• Scoping Review
  • Open access
  • Published: 14 November 2021

Effectiveness and safety of SARS-CoV-2 vaccine in real-world studies: a systematic review and meta-analysis

  • Qiao Liu 1   na1 ,
  • Chenyuan Qin 1 , 2   na1 ,
  • Min Liu 1 &
  • Jue Liu   ORCID: orcid.org/0000-0002-1938-9365 1 , 2  

Infectious Diseases of Poverty volume  10 , Article number:  132 ( 2021 ) Cite this article

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To date, coronavirus disease 2019 (COVID-19) becomes increasingly fierce due to the emergence of variants. Rapid herd immunity through vaccination is needed to block the mutation and prevent the emergence of variants that can completely escape the immune surveillance. We aimed to systematically evaluate the effectiveness and safety of COVID-19 vaccines in the real world and to establish a reliable evidence-based basis for the actual protective effect of the COVID-19 vaccines, especially in the ensuing waves of infections dominated by variants.

We searched PubMed, Embase and Web of Science from inception to July 22, 2021. Observational studies that examined the effectiveness and safety of SARS-CoV-2 vaccines among people vaccinated were included. Random-effects or fixed-effects models were used to estimate the pooled vaccine effectiveness (VE) and incidence rate of adverse events after vaccination, and their 95% confidence intervals ( CI ).

A total of 58 studies (32 studies for vaccine effectiveness and 26 studies for vaccine safety) were included. A single dose of vaccines was 41% (95% CI : 28–54%) effective at preventing SARS-CoV-2 infections, 52% (31–73%) for symptomatic COVID-19, 66% (50–81%) for hospitalization, 45% (42–49%) for Intensive Care Unit (ICU) admissions, and 53% (15–91%) for COVID-19-related death; and two doses were 85% (81–89%) effective at preventing SARS-CoV-2 infections, 97% (97–98%) for symptomatic COVID-19, 93% (89–96%) for hospitalization, 96% (93–98%) for ICU admissions, and 95% (92–98%) effective for COVID-19-related death, respectively. The pooled VE was 85% (80–91%) for the prevention of Alpha variant of SARS-CoV-2 infections, 75% (71–79%) for the Beta variant, 54% (35–74%) for the Gamma variant, and 74% (62–85%) for the Delta variant. The overall pooled incidence rate was 1.5% (1.4–1.6%) for adverse events, 0.4 (0.2–0.5) per 10 000 for severe adverse events, and 0.1 (0.1–0.2) per 10 000 for death after vaccination.

Conclusions

SARS-CoV-2 vaccines have reassuring safety and could effectively reduce the death, severe cases, symptomatic cases, and infections resulting from SARS-CoV-2 across the world. In the context of global pandemic and the continuous emergence of SARS-CoV-2 variants, accelerating vaccination and improving vaccination coverage is still the most important and urgent matter, and it is also the final means to end the pandemic.

Graphical Abstract

vaccine research paper covid

Since its outbreak, coronavirus disease 2019 (COVID-19) has spread rapidly, with a sharp rise in the accumulative number of infections worldwide. As of August 8, 2021, COVID-19 has already killed more than 4.2 million people and more than 203 million people were infected [ 1 ]. Given its alarming-spreading speed and the high cost of completely relying on non-pharmaceutical measures, we urgently need safe and effective vaccines to cover susceptible populations and restore people’s lives into the original [ 2 ].

According to global statistics, as of August 2, 2021, there are 326 candidate vaccines, 103 of which are in clinical trials, and 19 vaccines have been put into normal use, including 8 inactivated vaccines and 5 protein subunit vaccines, 2 RNA vaccines, as well as 4 non-replicating viral vector vaccines [ 3 ]. Our World in Data simultaneously reported that 27.3% of the world population has received at least one dose of a COVID-19 vaccine, and 13.8% is fully vaccinated [ 4 ].

To date, COVID-19 become increasingly fierce due to the emergence of variants [ 5 , 6 , 7 ]. Rapid herd immunity through vaccination is needed to block the mutation and prevent the emergence of variants that can completely escape the immune surveillance [ 6 , 8 ]. Several reviews systematically evaluated the effectiveness and/or safety of the three mainstream vaccines on the market (inactivated virus vaccines, RNA vaccines and viral vector vaccines) based on random clinical trials (RCT) yet [ 9 , 10 , 11 , 12 , 13 ].

In general, RNA vaccines are the most effective, followed by viral vector vaccines and inactivated virus vaccines [ 10 , 11 , 12 , 13 ]. The current safety of COVID-19 vaccines is acceptable for mass vaccination, but long-term monitoring of vaccine safety is needed, especially in older people with underlying conditions [ 9 , 10 , 11 , 12 , 13 ]. Inactivated vaccines had the lowest incidence of adverse events and the safety comparisons between mRNA vaccines and viral vectors were controversial [ 9 , 10 ].

RCTs usually conduct under a very demanding research circumstance, and tend to be highly consistent and limited in terms of population characteristics and experimental conditions. Actually, real-world studies differ significantly from RCTs in terms of study conditions and mass vaccination in real world requires taking into account factors, which are far more complex, such as widely heterogeneous populations, vaccine supply, willingness, medical accessibility, etc. Therefore, the real safety and effectiveness of vaccines turn out to be a major concern of international community. The results of a mass vaccination of CoronaVac in Chile demonstrated a protective effectiveness of 65.9% against the onset of COVID-19 after complete vaccination procedures [ 14 ], while the outcomes of phase 3 trials in Brazil and Turkey were 50.7% and 91.3%, reported on Sinovac’s website [ 14 ]. As for the Delta variant, the British claimed 88% protection after two doses of BNT162b2, compared with 67% for AZD1222 [ 15 ]. What is surprising is that the protection of BNT162b2 against infection in Israel is only 39% [ 16 ]. Several studies reported the effectiveness and safety of the COVID-19 vaccine in the real world recently, but the results remain controversial [ 17 , 18 , 19 , 20 ]. A comprehensive meta-analysis based upon the real-world studies is still in an urgent demand, especially for evaluating the effect of vaccines on variation strains. In the present study, we aimed to systematically evaluate the effectiveness and safety of the COVID-19 vaccine in the real world and to establish a reliable evidence-based basis for the actual protective effect of the COVID-19 vaccines, especially in the ensuing waves of infections dominated by variants.

Search strategy and selection criteria

Our methods were described in detail in our published protocol [PROSPERO (Prospective register of systematic reviews) registration, CRD42021267110]. We searched eligible studies published by 22 July 2021, from three databases including PubMed, Embase and Web of Science by the following search terms: (effectiveness OR safety) AND (COVID-19 OR coronavirus OR SARS-CoV-2) AND (vaccine OR vaccination). We used EndNoteX9.0 (Thomson ResearchSoft, Stanford, USA) to manage records, screen and exclude duplicates. This study was strictly performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

We included observational studies that examined the effectiveness and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among people vaccinated with SARS-CoV-2 vaccines. The following studies were excluded: (1) irrelevant to the subject of the meta-analysis, such as studies that did not use SARS-CoV-2 vaccination as the exposure; (2) insufficient data to calculate the rate for the prevention of COVID-19, the prevention of hospitalization, the prevention of admission to the ICU, the prevention of COVID-19-related death, or adverse events after vaccination; (3) duplicate studies or overlapping participants; (4) RCT studies, reviews, editorials, conference papers, case reports or animal experiments; and (5) studies that did not clarify the identification of COVID-19.

Studies were identified by two investigators (LQ and QCY) independently following the criteria above, while discrepancies reconciled by a third investigator (LJ).

Data extraction and quality assessment

The primary outcome was the effectiveness of SARS-CoV-2 vaccines. The following data were extracted independently by two investigators (LQ and QCY) from the selected studies: (1) basic information of the studies, including first author, publication year and study design; (2) characteristics of the study population, including sample sizes, age groups, setting or locations; (3) kinds of the SARS-CoV-2 vaccines; (4) outcomes for the effectiveness of SARS-CoV-2 vaccines: the number of laboratory-confirmed COVID-19, hospitalization for COVID-19, admission to the ICU for COVID-19, and COVID-19-related death; and (5) outcomes for the safety of SARS-CoV-2 vaccines: the number of adverse events after vaccination.

We evaluated the risk of bias using the Newcastle–Ottawa quality assessment scale for cohort studies and case–control studies [ 21 ]. and assess the methodological quality using the checklist recommended by Agency for Healthcare Research and Quality (AHRQ) [ 22 ]. Cohort studies and case–control studies were classified as having low (≥ 7 stars), moderate (5–6 stars), and high risk of bias (≤ 4 stars) with an overall quality score of 9 stars. For cross-sectional studies, we assigned each item of the AHRQ checklist a score of 1 (answered “yes”) or 0 (answered “no” or “unclear”), and summarized scores across items to generate an overall quality score that ranged from 0 to 11. Low, moderate, and high risk of bias were identified as having a score of 8–11, 4–7 and 0–3, respectively.

Two investigators (LQ and QCY) independently assessed study quality, with disagreements resolved by a third investigator (LJ).

Data synthesis and statistical analysis

We performed a meta-analysis to pool data from included studies and assess the effectiveness and safety of SARS-CoV-2 vaccines by clinical outcomes (rates of the prevention of COVID-19, the prevention of hospitalization, the prevention of admission to the ICU, the prevention of COVID-19-related death, and adverse events after vaccination). Random-effects or fixed-effects models were used to pool the rates and adjusted estimates across studies separately, based on the heterogeneity between estimates ( I 2 ). Fixed-effects models were used if I 2  ≤ 50%, which represented low to moderate heterogeneity and random-effects models were used if I 2  > 50%, representing substantial heterogeneity.

We conducted subgroup analyses to investigate the possible sources of heterogeneity by using vaccine kinds, vaccination status, sample size, and study population as grouping variables. We used the Q test to conduct subgroup comparisons and variables were considered significant between subgroups if the subgroup difference P value was less than 0.05. Publication bias was assessed by funnel plot and Egger’s regression test. We analyzed data using Stata version 16.0 (StataCorp, Texas, USA).

A total of 4844 records were searched from the three databases. 2484 duplicates were excluded. After reading titles and abstracts, we excluded 2264 reviews, RCT studies, duplicates and other studies meeting our exclude criteria. Among the 96 studies under full-text review, 41 studies were excluded (Fig.  1 ). Ultimately, with three grey literatures included, this final meta-analysis comprised 58 eligible studies, including 32 studies [ 14 , 15 , 17 , 18 , 19 , 20 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ] for vaccine effectiveness and 26 studies [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ] for vaccine safety. Characteristics of included studies are showed in Additional file 1 : Table S1, Additional file 2 : Table S2. The risk of bias of all studies we included was moderate or low.

figure 1

Flowchart of the study selection

Vaccine effectiveness for different clinical outcomes of COVID-19

We separately reported the vaccine effectiveness (VE) by the first and second dose of vaccines, and conducted subgroup analysis by the days after the first or second dose (< 7 days, ≥ 7 days, ≥ 14 days, and ≥ 21 days; studies with no specific days were classified as 1 dose, 2 dose or ≥ 1 dose).

For the first dose of SARS-CoV-2 vaccines, the pooled VE was 41% (95% CI : 28–54%) for the prevention of SARS-CoV-2 infection, 52% (95% CI : 31–73%) for the prevention of symptomatic COVID-19, 66% (95% CI : 50–81%) for the prevention of hospital admissions, 45% (95% CI : 42–49%) for the prevention of ICU admissions, and 53% (95% CI : 15–91%) for the prevention of COVID-19-related death (Table 1 ). The subgroup, ≥ 21 days after the first dose, was found to have the highest VE in each clinical outcome of COVID-19, regardless of ≥ 1 dose group (Table 1 ).

For the second dose of SARS-CoV-2 vaccines, the pooled VE was 85% (95% CI : 81–89%) for the prevention of SARS-CoV-2 infection, 97% (95% CI : 97–98%) for the prevention of symptomatic COVID-19, 93% (95% CI: 89–96%) for the prevention of hospital admissions, 96% (95% CI : 93–98%) for the prevention of ICU admissions, and 95% (95% CI : 92–98%) for the prevention of COVID-19-related death (Table 1 ). VE was 94% (95% CI : 78–98%) in ≥ 21 days after the second dose for the prevention of SARS-CoV-2 infection, higher than other subgroups, regardless of 2 dose group (Table 1 ). For the prevention of symptomatic COVID-19, VE was also relatively higher in 21 days after the second dose (99%, 95% CI : 94–100%). Subgroups showed no statistically significant differences in the prevention of hospital admissions, ICU admissions and COVID-19-related death (subgroup difference P values were 0.991, 0.414, and 0.851, respectively).

Vaccine effectiveness for different variants of SARS-CoV-2 in fully vaccinated people

In the fully vaccinated groups (over 14 days after the second dose), the pooled VE was 85% (95% CI: 80–91%) for the prevention of Alpha variant of SARS-CoV-2 infection, 54% (95% CI : 35–74%) for the Gamma variant, and 74% (95% CI : 62–85%) for the Delta variant. There was only one study [ 23 ] focused on the Beta variant, which showed the VE was 75% (95% CI : 71–79%) for the prevention of the Beta variant of SARS-CoV-2 infection. BNT162b2 vaccine had the highest VE in each variant group; 92% (95% CI : 90–94%) for the Alpha variant, 62% (95% CI : 2–88%) for the Gamma variant, and 84% (95% CI : 75–92%) for the Delta variant (Fig.  2 ).

figure 2

Forest plots for the vaccine effectiveness of SARS-CoV-2 vaccines in fully vaccinated populations. A Vaccine effectiveness against SARS-CoV-2 variants; B Vaccine effectiveness against SARS-CoV-2 with variants not mentioned. SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, COVID-19 coronavirus disease 2019, CI confidence interval

For studies which had not mentioned the variant of SARS-CoV-2, the pooled VE was 86% (95% CI: 76–97%) for the prevention of SARS-CoV-2 infection in fully vaccinated people. mRNA-1273 vaccine had the highest pooled VE (97%, 95% CI: 93–100%, Fig.  2 ).

Safety of SARS-CoV-2 vaccines

As Table 2 showed, the incidence rate of adverse events varied widely among different studies. We conducted subgroup analysis by study population (general population, patients and healthcare workers), vaccine type (BNT162b2, mRNA-1273, CoronaVac, and et al.), and population size (< 1000, 1000–10 000, 10 000–100 000, and > 100 000). The overall pooled incidence rate was 1.5% (95% CI : 1.4–1.6%) for adverse events, 0.4 (95% CI : 0.2–0.5) per 10 000 for severe adverse events, and 0.1 (95% CI : 0.1–0.2) per 10 000 for death after vaccination. Incidence rate of adverse events was higher in healthcare workers (53.2%, 95% CI : 28.4–77.9%), AZD1222 vaccine group (79.6%, 95% CI : 60.8–98.3%), and < 1000 population size group (57.6%, 95% CI : 47.9–67.4%). Incidence rate of sever adverse events was higher in healthcare workers (127.2, 95% CI : 62.7–191.8, per 10 000), Gam-COVID-Vac vaccine group (175.7, 95% CI : 77.2–274.2, per 10 000), and 1000–10 000 population size group (336.6, 95% CI : 41.4–631.8, per 10 000). Incidence rate of death after vaccination was higher in patients (7.6, 95% CI : 0.0–32.2, per 10 000), BNT162b2 vaccine group (29.8, 95% CI : 0.0–71.2, per 10 000), and < 1000 population size group (29.8, 95% CI : 0.0–71.2, per 10 000). Subgroups of general population, vaccine type not mentioned, and > 100 000 population size had the lowest incidence rate of adverse events, severe adverse events, and death after vaccination.

Sensitivity analysis and publication bias

In the sensitivity analyses, VE for SARS-CoV-2 infections, symptomatic COVID-19 and COVID-19-related death got relatively lower when omitting over a single dose group of Maria et al.’s work [ 33 ]; when omitting ≥ 14 days after the first dose group and ≥ 14 days after the second dose group of Alejandro et al.’s work [ 14 ], VE for SARS-CoV-2 infections, hospitalization, ICU admission and COVID-19-related death got relatively higher; and VE for all clinical status of COVID-19 became lower when omitting ≥ 14 days after the second dose group of Eric et al.’s work [ 34 ]. Incidence rate of adverse events and severe adverse events got relatively higher when omitting China CDC’s data [ 74 ]. P values of Egger’s regression test for all the meta-analysis were more than 0.05, indicating that there might not be publication bias.

To our knowledge, this is a comprehensive systematic review and meta-analysis assessing the effectiveness and safety of SARS-CoV-2 vaccines based on real-world studies, reporting pooled VE for different variants of SARS-CoV-2 and incidence rate of adverse events. This meta-analysis comprised a total of 58 studies, including 32 studies for vaccine effectiveness and 26 studies for vaccine safety. We found that a single dose of SARS-CoV-2 vaccines was about 40–60% effective at preventing any clinical status of COVID-19 and that two doses were 85% or more effective. Although vaccines were not as effective against variants of SARS-CoV-2 as original virus, the vaccine effectiveness was still over 50% for fully vaccinated people. Normal adverse events were common, while the incidence of severe adverse events or even death was very low, providing reassurance to health care providers and to vaccine recipients and promote confidence in the safety of COVID-19 vaccines. Our findings strengthen and augment evidence from previous review [ 75 ], which confirmed the effectiveness of the BNT162b2 mRNA vaccine, and additionally reported the safety of SARS-CoV-2 vaccines, giving insight on the future of SARS-CoV-2 vaccine schedules.

Although most vaccines for the prevention of COVID-19 are two-dose vaccines, we found that the pooled VE of a single dose of SARS-CoV-2 vaccines was about 50%. Recent study showed that the T cell and antibody responses induced by a single dose of the BNT162b2 vaccine were comparable to those naturally infected with SARE-CoV-2 within weeks or months after infection [ 76 ]. Our findings could help to develop vaccination strategies under certain circumstances such as countries having a shortage of vaccines. In some countries, in order to administer the first dose to a larger population, the second dose was delayed for up to 12 weeks [ 77 ]. Some countries such as Canada had even decided to delay the second dose for 16 weeks [ 78 ]. However, due to a suboptimum immune response in those receiving only a single dose of a vaccine, such an approach had a chance to give rise to the emergence of variants of SARS-CoV-2 [ 79 ]. There remains a need for large clinical trials to assess the efficacy of a single-dose administration of two-dose vaccines and the risk of increasing the emergence of variants.

Two doses of SARS-CoV-2 vaccines were highly effective at preventing hospitalization, severe cases and deaths resulting from COVID-19, while the VE of different groups of days from the second vaccine dose showed no statistically significant differences. Our findings emphasized the importance of getting fully vaccinated, for the fact that most breakthrough infections were mild or asymptomatic. A recent study showed that the occurrence of breakthrough infections with SARS-CoV-2 in fully vaccinated populations was predictable with neutralizing antibody titers during the peri-infection period [ 80 ]. We also found getting fully vaccinated was at least 50% effective at preventing SARS-CoV-2 variants infections, despite reduced effectiveness compared with original virus; and BNT162b2 vaccine was found to have the highest VE in each variant group. Studies showed that the highly mutated variants were indicative of a form of rapid, multistage evolutionary jumps, which could preferentially occur in the milieu of partial immune control [ 81 , 82 ]. Therefore, immunocompromised patients should be prioritized for anti-COVID-19 immunization to mitigate persistent SARS-CoV-2 infections, during which multimutational SARS-CoV-2 variants could arise [ 83 ].

Recently, many countries, including Israel, the United States, China and the United Kingdom, have introduced a booster of COVID-19 vaccine, namely the third dose [ 84 , 85 , 86 , 87 ]. A study of Israel showed that among people vaccinated with BNT162b2 vaccine over 60 years, the risk of COVID-19 infection and severe illness in the non-booster group was 11.3 times (95% CI: 10.4–12.3) and 19.5 times (95% CI: 12.9–29.5) than the booster group, respectively [ 84 ]. Some studies have found that the third dose of Moderna, Pfizer-BioNTech, Oxford-AstraZeneca and Sinovac produced a spike in infection-blocking neutralizing antibodies when given a few months after the second dose [ 85 , 87 , 88 ]. In addition, the common adverse events associated with the third dose did not differ significantly from the symptoms of the first two doses, ranging from mild to moderate [ 85 ]. The overall incidence rate of local and systemic adverse events was 69% (57/97) and 20% (19/97) after receiving the third dose of BNT162b2 vaccine, respectively [ 88 ]. Results of a phase 3 clinical trial involving 306 people aged 18–55 years showed that adverse events after receiving a third dose of BNT162b2 vaccine (5–8 months after completion of two doses) were similar to those reported after receiving a second dose [ 85 ]. Based on V-safe, local reactions were more frequently after dose 3 (5323/6283; 84.7%) than dose 2 (5249/6283; 83.5%) among people who received 3 doses of Moderna. Systemic reactions were reported less frequently after dose 3 (4963/6283; 79.0%) than dose 2 (5105/6283; 81.3%) [ 86 ]. On August 4, WHO called for a halt to booster shots until at least the end of September to achieve an even distribution of the vaccine [ 89 ]. At this stage, the most important thing we should be thinking about is how to reach a global cover of people at risk with the first or second dose, rather than focusing on the third dose.

Based on real world studies, our results preliminarily showed that complete inoculation of COVID-19 vaccines was still effective against infection of variants, although the VE was generally diminished compared with the original virus. Particularly, the pooled VE was 54% (95% CI : 35–74%) for the Gamma variant, and 74% (95% CI : 62–85%) for the Delta variant. Since the wide spread of COVID-19, a number of variants have drawn extensive attention of international community, including Alpha variant (B.1.1.7), first identified in the United Kingdom; Beta variant (B.1.351) in South Africa; Gamma variant (P.1), initially appeared in Brazil; and the most infectious one to date, Delta variant (B.1.617.2) [ 90 ]. Israel recently reported a breakthrough infection of SARS-CoV-2, dominated by variant B.1.1.7 in a small number of fully vaccinated health care workers, raising concerns about the effectiveness of the original vaccine against those variants [ 80 ]. According to an observational cohort study in Qatar, VE of the BNT162b2 vaccine against the Alpha (B.1.1.7) and Beta (B.1.351) variants was 87% (95% CI : 81.8–90.7%) and 75.0% (95% CI : 70.5–7.9%), respectively [ 23 ]. Based on the National Immunization Management System of England, results from a recent real-world study of all the general population showed that the AZD1222 and BNT162b2 vaccines protected against symptomatic SARS-CoV-2 infection of Alpha variant with 74.5% (95% CI : 68.4–79.4%) and 93.7% (95% CI : 91.6–95.3%) [ 15 ]. In contrast, the VE against the Delta variant was 67.0% (95% CI : 61.3–71.8%) for two doses of AZD1222 vaccine and 88% (95% CI : 85.3–90.1%) for BNT162b2 vaccine [ 15 ].

In terms of adverse events after vaccination, the pooled incidence rate was very low, only 1.5% (95% CI : 1.4–1.6%). However, the prevalence of adverse events reported in large population (population size > 100 000) was much lower than that in small to medium population size. On the one hand, the vaccination population in the small to medium scale studies we included were mostly composed by health care workers, patients with specific diseases or the elderly. And these people are more concerned about their health and more sensitive to changes of themselves. But it remains to be proved whether patients or the elderly are more likely to have adverse events than the general. Mainstream vaccines currently on the market have maintained robust safety in specific populations such as cancer patients, organ transplant recipients, patients with rheumatic and musculoskeletal diseases, pregnant women and the elderly [ 54 , 91 , 92 , 93 , 94 ]. A prospective study by Tal Goshen-lag suggests that the safety of BNT162b2 vaccine in cancer patients is consistent with those previous reports [ 91 ]. In addition, the incidence rate of adverse events reported in the heart–lung transplant population is even lower than that in general population [ 95 ]. On the other hand, large scale studies at the national level are mostly based on national electronic health records or adverse event reporting systems, and it is likely that most mild or moderate symptoms are actually not reported.

Compared with the usual local adverse events (such as pain at the injection site, redness at the injection site, etc.) and normal systemic reactions (such as fatigue, myalgia, etc.), serious and life-threatening adverse events were rare due to our results. A meta-analysis based on RCTs only showed three cases of anaphylactic shock among 58 889 COVID-19 vaccine recipients and one in the placebo group [ 11 ]. The exact mechanisms underlying most of the adverse events are still unclear, accordingly we cannot establish a causal relation between severe adverse events and vaccination directly based on observational studies. In general, varying degrees of adverse events occur after different types of COVID-19 vaccination. Nevertheless, the benefits far outweigh the risks.

Our results showed the effectiveness and safety of different types of vaccines varied greatly. Regardless of SARS-CoV-2 variants, vaccine effectiveness varied from 66% (CoronaVac [ 14 ]) to 97% (mRNA-1273 [ 18 , 20 , 45 , 46 ]). The incidence rate of adverse events varied widely among different types of vaccines, which, however, could be explained by the sample size and population group of participants. BNT162b2, AZD1222, mRNA-1273 and CoronaVac were all found to have high vaccine efficacy and acceptable adverse-event profile in recent published studies [ 96 , 97 , 98 , 99 ]. A meta-analysis, focusing on the potential vaccine candidate which have reached to the phase 3 of clinical development, also found that although many of the vaccines caused more adverse events than the controls, most were mild, transient and manageable [ 100 ]. However, severe adverse events did occur, and there remains the need to implement a unified global surveillance system to monitor the adverse events of COVID-19 vaccines around the world [ 101 ]. A recent study employed a knowledge-based or rational strategy to perform a prioritization matrix of approved COVID-19 vaccines, and led to a scale with JANSSEN (Ad26.COV2.S) in the first place, and AZD1222, BNT162b2, and Sputnik V in second place, followed by BBIBP-CorV, CoronaVac and mRNA-1273 in third place [ 101 ]. Moreover, when deciding the priority of vaccines, the socioeconomic characteristics of each country should also be considered.

Our meta-analysis still has several limitations. First, we may include limited basic data on specific populations, as vaccination is slowly being promoted in populations under the age of 18 or over 60. Second, due to the limitation of the original real-world study, we did not conduct subgroup analysis based on more population characteristics, such as age. When analyzing the efficacy and safety of COVID-19 vaccine, we may have neglected the discussion on the heterogeneity from these sources. Third, most of the original studies only collected adverse events within 7 days after vaccination, which may limit the duration of follow-up for safety analysis.

Based on the real-world studies, SARS-CoV-2 vaccines have reassuring safety and could effectively reduce the death, severe cases, symptomatic cases, and infections resulting from SARS-CoV-2 across the world. In the context of global pandemic and the continuous emergence of SARS-CoV-2 variants, accelerating vaccination and improving vaccination coverage is still the most important and urgent matter, and it is also the final means to end the pandemic.

Availability of data and materials

All data generated or analyzed during this study are included in this published article and its additional information files.

Abbreviations

Coronavirus disease 2019

Severe Acute Respiratory Syndrome Coronavirus 2

Vaccine effectiveness

Confidence intervals

Intensive care unit

Random clinical trials

Preferred reporting items for systematic reviews and meta-analyses

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Acknowledgements

This study was funded by the National Natural Science Foundation of China (72122001; 71934002) and the National Science and Technology Key Projects on Prevention and Treatment of Major infectious disease of China (2020ZX10001002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the paper. No payment was received by any of the co-authors for the preparation of this article.

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Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, China

Qiao Liu, Chenyuan Qin, Min Liu & Jue Liu

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LQ and QCY contributed equally as first authors. LJ and LM contributed equally as correspondence authors. LJ and LM conceived and designed the study; LQ, QCY and LJ carried out the literature searches, extracted the data, and assessed the study quality; LQ and QCY performed the statistical analysis and wrote the manuscript; LJ, LM, LQ and QCY revised the manuscript. All authors read and approved the final manuscript.

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Supplementary Information

Additional file 1: table s1..

Characteristic of studies included for vaccine effectiveness.

Additional file 2: Table S2.

Characteristic of studies included for vaccine safety.

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Liu, Q., Qin, C., Liu, M. et al. Effectiveness and safety of SARS-CoV-2 vaccine in real-world studies: a systematic review and meta-analysis. Infect Dis Poverty 10 , 132 (2021). https://doi.org/10.1186/s40249-021-00915-3

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Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults

Affiliations.

  • 1 Thibodaux Regional Health System, Thibodaux, LA, USA. Electronic address: [email protected].
  • 2 Unit of Innovation and Organization, Navarre Health Service, Spain. Electronic address: [email protected].
  • 3 Institute of Evidence-Based Healthcare, Bond University, Gold Coast, QLD, Australia. Electronic address: [email protected].
  • 4 Fielding School of Public Health and College of Letters and Science, University of California, Los Angeles, CA, USA. Electronic address: [email protected].
  • 5 Geffen School of Medicine, University of California, Los Angeles, CA, USA. Electronic address: [email protected].
  • 6 Clinical Excellence Research Center, School of Medicine, Stanford University, CA, USA. Electronic address: [email protected].
  • 7 School of Pharmacy, University of Maryland, Baltimore, MD, USA. Electronic address: [email protected].
  • PMID: 36055877
  • PMCID: PMC9428332
  • DOI: 10.1016/j.vaccine.2022.08.036

Introduction: In 2020, prior to COVID-19 vaccine rollout, the Brighton Collaboration created a priority list, endorsed by the World Health Organization, of potential adverse events relevant to COVID-19 vaccines. We adapted the Brighton Collaboration list to evaluate serious adverse events of special interest observed in mRNA COVID-19 vaccine trials.

Methods: Secondary analysis of serious adverse events reported in the placebo-controlled, phase III randomized clinical trials of Pfizer and Moderna mRNA COVID-19 vaccines in adults ( NCT04368728 and NCT04470427 ), focusing analysis on Brighton Collaboration adverse events of special interest.

Results: Pfizer and Moderna mRNA COVID-19 vaccines were associated with an excess risk of serious adverse events of special interest of 10.1 and 15.1 per 10,000 vaccinated over placebo baselines of 17.6 and 42.2 (95 % CI -0.4 to 20.6 and -3.6 to 33.8), respectively. Combined, the mRNA vaccines were associated with an excess risk of serious adverse events of special interest of 12.5 per 10,000 vaccinated (95 % CI 2.1 to 22.9); risk ratio 1.43 (95 % CI 1.07 to 1.92). The Pfizer trial exhibited a 36 % higher risk of serious adverse events in the vaccine group; risk difference 18.0 per 10,000 vaccinated (95 % CI 1.2 to 34.9); risk ratio 1.36 (95 % CI 1.02 to 1.83). The Moderna trial exhibited a 6 % higher risk of serious adverse events in the vaccine group: risk difference 7.1 per 10,000 (95 % CI -23.2 to 37.4); risk ratio 1.06 (95 % CI 0.84 to 1.33). Combined, there was a 16 % higher risk of serious adverse events in mRNA vaccine recipients: risk difference 13.2 (95 % CI -3.2 to 29.6); risk ratio 1.16 (95 % CI 0.97 to 1.39).

Discussion: The excess risk of serious adverse events found in our study points to the need for formal harm-benefit analyses, particularly those that are stratified according to risk of serious COVID-19 outcomes. These analyses will require public release of participant level datasets.

Keywords: Adverse events of special interest; Brighton Collaboration; COVID-19; COVID-19 vaccines; Coalition for Epidemic Preparedness Innovations; Moderna COVID-19 vaccine mRNA-1273; NCT04368728 ; NCT04470427 ; Pfizer-BioNTech COVID-19 vaccine BNT162b2; SARS-CoV-2; Safety Platform for Emergency vACcines; Serious adverse events; Vaccines; mRNA vaccines.

Copyright © 2022 Elsevier Ltd. All rights reserved.

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Efficacy of COVID-19 vaccines: From clinical trials to real life

Dominique deplanque.

a Université de Lille, Inserm, CHU Lille, CIC 1403 – Clinical Investigation Center, 59000 Lille, France.

b F-CRIN IREIVAC/COVIREIVAC, 75679 Paris, France

Odile Launay

c Université de Paris, Inserm CIC 1417, Assistance publique – Hôpitaux de Paris, hôpital Cochin, 75679 Paris, France

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread around the globe leading to the COVID-19 pandemic. To mitigate the effects of the virus on public health and the global economy, vaccines were rapidly developed. In less than one year, with respect to usual clinical development rules, several vaccines have been put on the market and mass vaccination campaigns have been deployed. During the phase I to phase III clinical trials, most of these vaccines have demonstrated both their safety and efficacy. Despite questions remain about the impact of virus variants and the duration of the immune response, messenger RNA (mRNA)-based and adenoviral vectored vaccines have demonstrated an overall efficacy from 70 to 95% in both phase III trials and real life. In addition, all these vaccines also reduce the severe forms of the disease and might strongly impact the mortality which could change the course of the pandemic.

Abbreviations

Introduction.

Since December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread around the globe leading to the Coronavirus Disease 2019 (COVID-19) pandemic. From January 2020 to the beginning of second quarter of 2021, the intensity and rapidity of SARS-CoV-2 transmission have led to about 150,000,000 cases and more than 3,000,000 deaths in the world putting considerable pressure on public health systems and the global economy. In the context of extraordinary scientific and technical mobilization, the genetic sequence of SARS-CoV-2 was published on January 11 th 2020, triggering intense global Research and Development (R&D) activity to develop a vaccine against this disease. To date, World Health Organization (WHO) lists about 200 vaccine candidates in preclinical development, 100 in clinical evaluation and 13 received authorization [1] .

In Europe, 4 vaccines have already been authorized by the European Medicines Agency (EMA) and several mass vaccination campaigns are also underway worldwide. These rapid developments have been made possible by the important contribution of both public and private funding, high level of volunteers’ participation in clinical trials as well as by changes in the review process of regulatory agencies [2] . On the other hand, the success of messenger RNA (mRNA) vaccine platform is probably the consequence of previous researches for more than 15 years and their previous identification as vaccine platform of choice for emerging infectious diseases [3] . Since the mechanisms of action and undesirable effects of these vaccines are addressed in other articles of this special issue, we will focus on the efficacy of coronavirus disease 2019 (COVID-19) vaccines, more particularly on the four vaccines already available in Europe.

COVID-19 vaccine development: an unprecedented timeframe

In the last decade, there was a marked evolution of vaccine platforms including the development of nucleic acid-based vaccine candidates and vectored vaccines, a number of approaches that have been used to accelerate COVID-19 vaccines elaboration. Moreover, previous preclinical data from vaccine candidates for SARS-CoV and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) enabled the initial step of exploratory vaccine design to be largely overlooked, saving a considerable amount of time. In most cases, production processes were also adapted from those of existing vaccines [2] .

As a result, a first phase I clinical trial of a vaccine candidate for SARS-CoV-2 began in March 2020 testing the mRNA 1273 (Moderna) [4] . In April 2020, another phase I trial testing different sequences of the mRNA BNT 162 (BioNTech/Pfizer) has also begun [5] then followed by adenovirus vectored vaccines, in June and July 2020, respectively ChAdOx1nCov-19 (AstraZeneca/Oxford) and Ad26COVS1 (Janssen) [6] , [7] . One important particularity of this period was that clinical phases were overlapping and trial starts were staggered, with initial phase I/II trials followed by fast progression to phase III trials mainly considering interim analysis of the phase I/II data. Most of the manufacturers had also rapidly started the large-scale commercial production of vaccines despite the absence of any result from phase III trials [2] .

Finally, both Food and Drug Administration (FDA) and EMA implemented a rolling review process, which means that a drug company can submit completed sections of its new drug application for review, rather than waiting until every section of the application is completed before the entire application can be reviewed. Beyond these exceptional adaptations, one of the key factors of the accelerated development of COVID-19 vaccines was financial risk-taking that was greatly sustained by public funds, namely in Germany, UK and USA. Nonetheless, it should be underlined that despite these financial considerations but also the pandemic-associated emergency, no concession was made on safety.

Phase I/II clinical trials: safety and immunogenicity analysis

While phase I trials are usually designed to determine the safety profile at several dosages of a drug candidate, in the field of vaccines, the immunogenicity as a marker of drug-response is also evaluated. Indeed, this evaluation constitutes an essential step in the construction of future trials. In this context, phase II trials are intended to more precisely evaluate immunogenicity in relation to dose regimen in the way to determine the final dose to use in phase III trials. Here, most of the published studies were combined phase I/II trials aiming to determine safety and immunogenicity including the effect of a second vaccine dose according to different dosages and intervals [4] , [5] , [6] , [7] , [8] .

Phase I studies usually recruited a low number of subjects but during the early development of COVID-19 vaccines at least one study reported here included about 200 volunteers [5] and according to a phase II design, another study included more than 500 subjects [6] . Such an important recruitment clearly helped to provide stronger results and has probably facilitated the design of phase III studies. This large number of subjects also allowed to strengthen the excellent results about safety profile of these vaccine candidates whatever the platform used namely mRNA or adenoviral vector [4] , [5] , [6] , [7] , [8] .

As summarized in Table 1 , all the vaccine candidates reported here were able to induce an immune response against the spike protein of the SARS-CoV-2. Thus, there was a clear dose- or time-dependent increased in both specific Ig-G and neutralizing antibody titers ( Table 1 ) which are enhanced by the second dose of vaccine [4] , [5] , [6] , [7] , [8] . Some differences regarding Ig-G and neutralizing antibody titers may be discussed between these vaccines but it is important to point out that the assays used to perform these measures vary greatly and then comparisons must be made with caution. Nevertheless, an increase in specific Ig-G and neutralizing antibody titers has been shown in 90 to 100% of subjects while cellular responses were also observed. The phase I study on Ad26COVS1 vaccine also brings more details about immune response by analyzing the binding and functional profiles of vaccine-elicited antibodies by systems serology analyses. It was then showed the induction of S- and RBD-specific IgA1, IgA2, IgG1, IgG2, IgG3, IgG4, and IgM subclasses; FcγR2a, FcγR2b, FcγR3a, and FcγR3b binding; antibody-dependent complement deposition, antibody-dependent neutrophil phagocytosis, antibody-dependent cellular phagocytosis, and antibody-dependent NK cell activation functional antiviral responses [7] .

Main data from phases I/II clinical trials of the 4 vaccines available in Europe.

Ad26: adenovirus type-26; GMT: geometric mean titer; MNA: microneutralization assay; MT: microneutralization titer; ND: not determined; PRNT: plaque reduction neutralization testing; SFCs: spot-forming cells; VNA: virus neutralizing antibody; VP: viral particles; Y: years.

Another important information provided by these phase I/II studies was related to the effect of age. Among studies shown in Table 1 , only studies on BNT 162 b2 and ChAdOx1nCov-19 vaccines included subjects over 65 years of age [5] , [6] , [8] . These studies demonstrated both antigen-binding Ig-G and virus-neutralizing responses in older adults but also a possible decrease in such responses with increasing age [5] , [6] . Nevertheless, an elderly-dedicated phase I study showed that mRNA 1273 vaccine induces a good Ig-G response against the spike-protein as well as significative neutralizing antibody titers in adults older than 70 years of age [8] . Taken as a whole, these results suggested the possibility to demonstrate COVID-19 vaccines’ efficacy in phase III trials.

Phase III studies: evidence about a high level of efficacy

One of the main issues of phase III trials, particularly in the case of a new pathology, is to define the primary criterion to be used as efficacy markers as well as to define the level of efficacy that will be considered as pertinent. Undeniably, the definition of the primary criterion strongly impacts both the conduct of the trial and the future modalities of prescription of the vaccine. On June 2020, the FDA has released a guidance document for the development and licensure of COVID-19 vaccines [9] . This document stated that symptomatic laboratory-confirmed COVID-19 might be an acceptable primary endpoint for a COVID-19 vaccine efficacy trial with an efficacy level of at least 50% required. Moreover, other secondary criteria might be used to determine the possible efficacy on asymptomatic or severe infections. As a consequence, study sample sizes and timing of interim analyses had to be based on the statistical success criteria for primary and secondary efficacy analyses and realistic, data-driven estimates of vaccine efficacy and incidence of COVID-19 for the populations and locales in which the trials are conducted [9] .

According to these conditions, phase III studies have been conducted in countries where the virus spread was extremely high and have included in a few months several tens of thousands of subjects [10] , [11] , [12] , [13] . According to these studies and except unwanted effects related to usual reactogenicity, these vaccines appear safe. As summarized in Table 2 , among the four vaccines already authorized in Europe the overall efficacy defined as reduction of symptomatic COVID-19 varies from 67% to 95% [10] , [11] , [12] , [13] . These results are largely greater than the minimum efficacy level of 50% required by the FDA [9] . Furthermore, these levels of efficacy are also similar or even higher than that the mean 60% observed with the influenza vaccines [14] . It should be underlined that mRNA vaccines [10] , [11] appear to have a higher efficacy than that of adenoviral vectored vaccines [12] , [13] . Nevertheless, a definitive conclusion about any comparisons should be done with caution. The complexity of the design of ChAdOx1nCov-19 vaccine phase III study does not facilitate neither the interpretation nor any comparisons of data. On the other hand, regarding interim analyses of trials reported in the Table 2 , the protection against severe infection appears to be close to 100% for all vaccines but not for Ad26COVS1 vaccine where data recently published show protection against severe infection with one dose of vaccine of only 77% [13] . It remains to determine how this result is only representative of this vaccine rather than may be finally observed with all other COVID-19 vaccines when long-term follow-up data will be available.

Clinical efficacy observed in phase III studies of the 4 vaccines available in Europe.

ND: not determined; VP: viral particles; Y: years.

Some other elements remain to be clarified in real life conditions, namely the effect on mortality, the level of efficacy in the elderly and the clinical efficacy of vaccines according to emerging variants and the duration of protection. Concerning mortality, the studies have not been designed to answer this question, it may then be difficult to bring clear and conclusive result. Moreover, according to the drastic reduction of severe infections observed in vaccinated-people, these studies are probably under-powered to clearly demonstrate the effect of vaccines on mortality.

Regarding elderly, not all published phase III studies had included many elderly people but in studies with a significant number of elderly participants ( Table 2 ), the efficacy level remains relatively close to the one observed in younger subjects (86.4% and 94.7% in people of 65 or over, for mRNA 1273 and BNT 162 b2 respectively) [10] , [11] . Clinical efficacy of vaccines on emerging variants remains also to be more precisely evaluated. Due to the relatively recent emergence of different virus variants’, only few clinical data are available but they show the preservation of ChAdOx1nCov-19 vaccine efficacy on B.1.1.7 variant [15] and a possible decrease in efficacy of both Ad26COVS1 and ChAdOx1nCov-19 vaccines on B.1.351 variant ( Table 2 ) [13] , [16] .

COVID-19 vaccines effectiveness in real life

When a new drug comes on the market, it takes usually several years before it could be demonstrated the reproducibility of the phase III clinical trial results’ in real life. Here, according the pandemic situation and the rapid development of mass vaccination campaigns in Israel, USA and UK, we already have many data demonstrating this achievement and also providing supplementary informations. Indeed, as summarized in Table 3 , at least 4 studies that had included 20,000 to more than 1,300,000 vaccinated people provide us impressive results on symptomatic or asymptomatic infections, severe infections as well as on mortality [17] , [18] , [19] , [20] .

Effectiveness of SARS-CoV-2 vaccination in real life.

CI: confidence interval; ND: not determined; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

Israel was probably the country which developed the most rapid and extensive mass vaccination campaign in the world by using the BNT 162 b2 vaccine. All people recorded on the Clalit Health Services (53% of Israeli population) who were newly vaccinated during the period from December 20, 2020, to February 1, 2021, were matched to unvaccinated controls according to demographic and clinical characteristics leading to 2 study groups of 596,618 persons each [17] . Looking on results 7 days or more after the second dose of vaccine, symptomatic and asymptomatic as well as severe COVID-19 infections are reduced by 92%. Mortality was also reduced by 84% when regarding 21 to 27 days after the first dose [17] . Even if such results have to be strengthened by a longer-term follow-up, the present study also provides informations about a similar vaccine effectiveness across different age groups and a slightly lower effectiveness among patients with multiple coexisting pathological conditions [17] .

In another paper under review, similar results are provided with the Mayo Clinic Health Database showing a 90% decrease in the development of a symptomatic or asymptomatic COVID-19 infection after BNT 162 b2 or mRNA 1273 vaccination in 31 609 persons [18] . Same kind of results are also provided by both Scotland and England data where both BNT 162 b2 and ChAdOx1nCov-19 vaccines were largely used with evidence of 85% decrease in symptomatic and asymptomatic infections and about 90% decrease in severe infections ( Table 3 ) [19] , [20] . Interestingly, in the Scottish study, such results were observed while the vaccines were administered at only one dose to extend the number of subjects receiving at least one dose of vaccine. Besides the fact that all these data confirm the results of phase III clinical trials, they also help to discuss the question of the effect of vaccine on virus transmission. Because asymptomatic infections are also reduced, it may be that virus transmission is decreased. Moreover, a recently published paper brings supplemental arguments about an effect of vaccines on transmission. Indeed, people who develop a COVID-19 despite vaccination with the BNT 162 b2 vaccine have a clear reduction of viral load that might help to break the spread of the virus [21] . Complementary strategies, such as vaccines able to develop mucosal immunity are also under development [22] .

Several questions remain on hold

One of the first questions on hold is the duration of the protection afforded by the vaccination. According to studies follow-up duration, it might be supposed that this protection is as at least 6 to 12 months. This duration will determine the need of a new vaccine boost and possibly the need of annual boost. Some large population-based studies using test-negative designs might help to evaluate these different issues particularly the situations of vaccine failure [23] .

The question of using different vaccines than the one use initially is also crucial. New studies should be designed including studies for the evaluation of the impact of immunogenicity against adenoviral vector if such a vaccine is used for a third injection. Because phase III clinical studies provide no or only few data about immunogenicity, it remains important to also designed studies able to determine more precisely the immune response according to real life administration scheme namely regarding the role of both cellular and innate immunity. Actually, in France, 2 studies are in course to answer such questions by using BNT 162 b2 or mRNA 1273 vaccines in adults including a sub-population of elderly people over 75 years of age.

Besides older people, the question of the efficacy of vaccines in particular populations is also crucial. Several recently published studies bring some answers. To date, there is only few data about the efficacy of vaccine in young people under 18 years of age [10] . Studies evaluating COVID-19 mRNA vaccines in young people aged 12 to 16 years are actually in course but both FDA and EMA have already beenquestioned to provide an authorization of use. On the other hand, COVID-19 mRNA vaccines seem to generate robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women [24] . In this study, vaccine-induced immune responses were also significantly greater than the response to natural infection and immune transfer to neonates occurred via placenta and breastmilk [24] . Other data also suggest that a single dose of mRNA vaccine elicits rapid immune responses in SARS-CoV-2 seropositive participants, with post-vaccination antibody titers similar to or exceeding titers found in seronegative participants who received two vaccinations [25] . On the other hand, the immunization rate among kidney transplant recipients who received 2 doses of an mRNA vaccine can be as low as 48% [26] . Very low immune response is evidenced also in others immunocompromised populations. The issue of a third vaccine dose in these non-responsive patients is an intriguing one that will be usefully explored in further research. In this context, a large cohort has been opened in France (COV-POPART) to evaluate the immune response in a number of particular populations including patients with cancer, transplant recipients as well as patients with auto-immune disease receiving immune-modulator treatments.

Last, an important challenge also concerns the efficacy of vaccines regarding the emergence of viral variants [27] . We have previously described some data from clinical trials regarding the decrease or the absence of efficacy of the ChAdOx1nCov-19 namely on B.1.351 variant ( Table 2 ) [12] . Some similar concerns are discussed with the other vaccines but most of the data come from in vitro studies that are not able to consider the possible role of cellular immune response [27] , [28] . Besides to evaluate the effect of a boost particularly with new mRNA sequences, future trials should also explore more precisely the whole immune response against viral variants.

In less than one year, face to a worldwide pandemic due to an unknown virus, several vaccines have been put on the market and have been already used in several tens of millions of people. These vaccines are importantly effective and relatively safe according to the severity of the disease they prevent. Beyond this impressive efficacy of COVID-19 vaccines, notably those based on mRNA, such a technology may first contribute to modify the course of the pandemic but also could bring the world in a new era of specific treatments for numerous pathologies [3] .

Disclosure of interest

The authors declare that they have no competing interest.

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Pfizer, left, and Moderna bivalent COVID-19 vaccines are readied for use at a clinic, Nov. 17, 2022, in Richmond, Va. (AP)

Pfizer, left, and Moderna bivalent COVID-19 vaccines are readied for use at a clinic, Nov. 17, 2022, in Richmond, Va. (AP)

Sara Swann

Experts say mRNA COVID-19 vaccines have saved millions of lives, not caused mass deaths

If your time is short.

The research paper was based on COVID-19 vaccine claims that are false and misleading, experts told us. 

The mRNA COVID-19 vaccines have been rigorously tested and monitored for years, and public health experts worldwide have found them to be safe and effective. Adverse effects are rare.

The World Health Organization estimated that in 2021 alone the COVID-19 vaccines saved more than 14.4 million lives globally.

  • No spin, just facts you can trust. Here’s how we do it.

In the more than three years since COVID-19 vaccines first became available, billions of doses have been administered worldwide, protecting against severe disease and death. Still, social media posts claim the vaccines are causing more harm than good.

A Feb. 4 Instagram post shared a headline from conservative news outlet The Epoch Times that said, "mRNA COVID-19 vaccines caused more deaths than saved: study."

Another Instagram post shared a related headline that said, "Scientists call for global moratorium on mRNA vaccines, immediate removal from childhood schedule." The headline was from the Children’s Health Defense, a legal advocacy organization known for spreading vaccine misinformation. (The organization was created by Robert F. Kennedy Jr., who earned PolitiFact’s 2023 Lie of the Year for his movement to legitimize conspiracy theories.)

These Instagram posts were flagged as part of Meta’s efforts to combat false news and misinformation on its News Feed. (Read more about our partnership with Meta , which owns Facebook and Instagram.)

vaccine research paper covid

(Screengrab from Instagram)

The Epoch Times and Children’s Health Defense articles referred to a Jan. 24 research paper that said "for every life saved, there were nearly 14 times more deaths caused by" the mRNA COVID-19 vaccines. Two of the paper’s authors, Steve Kirsch and Peter McCullough , have often spread misinformation related to COVID-19 and the vaccine.

Experts on infectious diseases and vaccines told PolitiFact that the paper’s conclusion is based on misleading and false information about the mRNA COVID-19 vaccines. The paper repeats multiple claims that PolitiFact and other fact-checkers have debunked.

The paper "stands in contrast" to the global public health community’s consensus that the mRNA vaccines are safe and effective, said Dr. William Schaffner, a Vanderbilt University infectious diseases professor.

"And so, you have to ask why (the paper) is such an outlier," said Schaffner, who is also a spokesperson for the National Foundation for Infectious Diseases . "The reason it’s an outlier is … it’s a deeply flawed study."

The peer-reviewed research paper was published on Cureus, which Schaffner called "an obscure journal" that he’d never heard of in his 40 years of public health research. A 2022 Emory University study described Cureus as a "predatory" and "controversial" journal.

The paper claimed the Pfizer COVID-19 vaccine saved two lives and caused 27 deaths per 100,000 vaccinations. It said the Moderna vaccine saved 3.9 lives and caused 10.8 deaths per 100,000 vaccinations.

The paper’s authors based this conclusion on data from the Pfizer and Moderna COVID-19 vaccine clinical trials in the United States and reports of adverse effects from the United Kingdom. Although the datasets came from two different countries, the paper said, "it is unlikely that the adverse event rates would be different between the two populations."

The adverse effects reports came from the U.K.’s Yellow Card system , which lets members of the public report suspected safety concerns related to vaccines, medicines and medical devices.

This system is similar to the U.S. government’s Vaccine Adverse Event Reporting System , which the paper also cites to suggest the COVID-19 vaccines are unsafe.

With VAERS, anyone can report health effects after a vaccination, whether or not those effects are caused by the vaccine, the CDC said . And unlike other government data sources, these reports aren’t screened before they’re made public, making VAERS fertile ground for vaccine misinformation .

The paper claims the mRNA COVID-19 vaccines did not undergo adequate safety and efficacy testing.

This is inaccurate. We have rated multiple claims about this False or Pants on Fire, including  that mRNA technology was never tested in humans ; that the vaccines were released after only two months of testing in healthy humans; and that a safe vaccine can’t be developed in eight to 10 months.

Featured Fact-check

vaccine research paper covid

The Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines were thoroughly evaluated in clinical trials before receiving emergency use authorization from the U.S. Food and Drug Administration in December 2020. Since then, public health authorities have continued to closely monitor the vaccines’ safety.

"These vaccines have met rigorous scientific standards for safety and effectiveness. The available data continue to demonstrate that the benefits of these vaccines outweigh their risks," said Cherie Duvall-Jones, an FDA spokesperson.

Another claim in the paper is mRNA vaccines contain "DNA contamination." We previously fact-checked a similar claim and rated it False.

Decades of research has shown that the "biologically insignificant amounts of DNA" in the vaccines pose no known safety risk, said Dan Wilson, senior associate scientist at Janssen, which also developed a COVID-19 vaccine . Wilson also hosts "Debunk the Funk with Dr. Wilson," a YouTube show that covers science misinformation.

It’s not unusual for vaccines to contain DNA fragments. The measles, mumps, rubella, varicella and rotavirus vaccines also have minuscule amounts of DNA, said Dr. Paul Offit, director of the Vaccine Education Center and infectious diseases physician at Children’s Hospital of Philadelphia.

The chance that these DNA fragments could integrate into a person’s DNA is "zero," Offit said. "So, it’s just all a lot of hand-waving."

The paper also claims the spike proteins produced by COVID-19 vaccination linger in the body and cause adverse effects. PolitiFact has fact-checked several false claims that the spike proteins are harmful or toxic.

All coronaviruses, including COVID-19, have spikes known as spike proteins on their surfaces, which the viruses use to bind to cells and cause infection, the CDC said .

The mRNA vaccines contain neither the COVID-19 virus nor the spike protein. The vaccines’ mRNA technology gives the body genetic instructions for producing copies of the spike protein, which are harmless. Then, the body breaks down the mRNA and it leaves the body as waste.

The spike proteins trigger the body’s immune response, sparking antibody production. This helps the body recognize and fight off the real COVID-19 virus in future infections.

Schaffner said the spike protein claim is "far-fetched" because there’s no evidence the spike protein produced from the vaccines has caused adverse effects.

Public health authorities in the U.S. and worldwide have repeatedly found COVID-19 vaccines to be safe and effective.

The World Health Organization reported that as of November, more than 13 billion doses of the COVID-19 vaccine had been administered worldwide. In the U.S. alone, more than 676 million doses of the vaccine had been administered as of May. 

In 2021, the first full year the vaccines were widely available, the WHO estimated that COVID-19 vaccinations saved more than 14.4 million lives worldwide.

In rare instances, adverse effects, including myocarditis, or inflammation of the heart muscle, have been linked to mRNA COVID-19 vaccines, the CDC said . Myocarditis cases were more common among adolescent and young men within a week of receiving a second dose of the COVID-19 vaccine. Most patients had mild cases and recovered quickly .

An Instagram post claimed a research paper shows that "mRNA COVID-19 vaccines caused more deaths" than lives saved.

Experts said the paper’s conclusion is based on false and misleading claims. These claims have been repeatedly fact-checked and rated False by PolitiFact and other news outlets.

The COVID-19 vaccines have been rigorously tested and monitored for years and public health authorities worldwide continue to find them safe and effective. Billions of doses have been administered worldwide. The vaccines have saved millions of lives, and adverse effects are rare.

We rate this claim Pants on Fire!

Our Sources

Instagram post ( archived ), Feb. 4, 2024

Instagram post ( archived ), Feb. 5, 2024

Interview with Dr. William Schaffner, an infectious diseases professor at Vanderbilt University and spokesperson for the National Foundation for Infectious Diseases, Feb. 7, 2024

Interview with Dr. Paul Offit, director of the Vaccine Education Center and physician in the Division of Infectious Diseases at the Children’s Hospital of Philadelphia, Feb. 7, 2024

Email interview with Dan Wilson, a senior associate scientist at Janssen and host of the YouTube show " Debunk the Funk with Dr. Wilson ," Feb. 7, 2024

Email interview with Cherie Duvall-Jones, spokesperson for the U.S. Food and Drug Administration, Feb. 7, 2024

The Epoch Times, " mRNA COVID-19 Vaccines Caused More Deaths Than Saved: Study ," Feb. 6, 2024

Children’s Health Defense, " Scientists Call for Global Moratorium on mRNA Vaccines, Immediate Removal From Childhood Schedule ," Jan. 29, 2024

Cureus, " COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign ," Jan. 24, 2024

The Centers for Disease Control and Prevention, " CDC COVID Data Tracker ," May 11, 2023

The Centers for Disease Control and Prevention, " End of the Federal COVID-19 Public Health Emergency (PHE) Declaration ," Sept. 12, 2023

The Centers for Disease Control and Prevention, " Clinical Considerations: Myocarditis after COVID-19 Vaccines ," Oct. 10, 2023

The Centers for Disease Control and Prevention, " Myocarditis and Pericarditis After mRNA COVID-19 Vaccination ," Nov. 3, 2023

The Centers for Disease Control and Prevention, " Reporting Adverse Events to VAERS | Vaccine Safety ," March 13, 2023

The Centers for Disease Control and Prevention, " How Protein Subunit COVID-19 Vaccines Work ," accessed Feb. 8, 2024 

Vaccine Adverse Event Reporting System website , accessed Feb. 8, 2024

The U.S. Food and Drug Administration, " Emergency Use Authorization for Vaccines Explained ," Nov. 20, 2020 

The U.S. Food and Drug Administration, " Janssen COVID-19 Vaccine ," June 2, 2023

The World Health Organization, " COVID-19 vaccines | WHO COVID-19 dashboard ," Nov. 26, 2023

The World Health Organization, " COVID-19 Vaccines Advice ," Dec. 5, 2023

U.K. Medicines and Healthcare products Regulatory Agency, " Yellow Card system ," accessed Feb. 8, 2024

Emory University, " Assessing Predatory Journal Publishing Within Health Sciences Authors ," August 2022

PolitiFact, " Robert F. Kennedy Jr.’s campaign of conspiracy theories: PolitiFact’s 2023 Lie of the Year ," Dec. 21, 2023

PolitiFact, " No, the COVID-19 vaccine is not the deadliest vaccine ever made ," Dec. 10, 2021

PolitiFact, " No evidence of COVID-19 vaccines causing deaths ," Sept. 20, 2021

PolitiFact, " Activist misuses federal data to make Pants on Fire claim that COVID-19 vaccines killed 676,000 ," Aug. 14, 2023

PolitiFact, " mRNA COVID-19 vaccines were tested in humans, have proven to be safe, effective ," June 25, 2021

PolitiFact, " COVID-19 vaccine testing included people with underlying health conditions ," Aug. 31, 2021

PolitiFact, " Yes, data shows COVID-19 vaccines are safe despite quick timeline ," March 26, 2021

PolitiFact, " Experts rebut claims that mRNA COVID-19 vaccines are ‘adulterated’ ," Oct. 27, 2023

PolitiFact, " Ditch the detox. The spike proteins produced from COVID-19 vaccination aren’t toxins. ," Aug. 2, 2023

PolitiFact, " Claim that children will be harmed by spike proteins from COVID-19 vaccines is false ," Jan. 7, 2022

PolitiFact, " Claim that spike proteins will cause illness to spread like wildfires in kids is False ," Nov. 2, 2021

PolitiFact, " No sign that the COVID-19 vaccines’ spike protein is toxic or ‘cytotoxic’ ," June 16, 2021

PolitiFact, " Snarky posts about Travis Kelce’s heart-hand gesture mislead about COVID-19 vaccine effects ," Jan. 29, 2024

NPR, " As the pandemic winds down, anti-vaccine activists are building a legal network ," May 4, 2023

Agence France-Presse, " US cardiologist makes sweeping false claims about effects of Covid-19 vaccinations ," Nov. 8, 2023

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Study Finds Moderna Vaccine Reduced Symptomatic COVID-19 In Young Adults

A photo of five young adults sitting around a table with books while laughing.

The COVID-19 pandemic spurred rapid development of different vaccines, including the messenger RNA (mRNA)-1273 vaccine produced by Moderna.

In a new  study , a team of researchers including  Rebecca Fischer , Ph.D., assistant professor in the Department of Epidemiology and Biostatistics at the Texas A&M University School of Public Health , analyzed the mRNA-1273 vaccine’s efficacy at preventing infection and symptomatic COVID-19 in healthy young adults. The study, published in the journal  Open Forum Infectious Diseases , followed adults aged 18-29 with no known history of COVID-19 infection or prior vaccination for a six-month period to determine the effect of vaccination on the incidence of SARS-CoV-2 infection and on symptomatic COVID-19.

The research team recruited 1,149 young adults from 44 sites around the United States, mostly on college campuses, who were then randomly assigned to a group receiving immediate vaccination or one following the standard of care for vaccination. The researchers also included an observational group of participants who intended to decline COVID-19 vaccination altogether.

During the study period, participants were to collect nasal swab samples each day, which were then analyzed using quantitative PCR testing to detect COVID-19 infection. Infected individuals completed daily symptom diaries. Additionally, participants were surveyed about how often they followed recommendations like wearing masks indoors, maintaining physical distancing and avoiding large gatherings.

Initial  studies  of the mRNA-1273 vaccine conducted earlier in the pandemic showed a 94.1 percent efficacy for preventing symptomatic COVID-19 over the first two months, with efficacy decreasing to around 93 percent up to six months after vaccination. Later  research  found lower efficacy with the Delta and Omicron variants of COVID-19 at around 80 percent and 60 percent, respectively. However, these studies did not focus solely on young adults, who are often at risk of catching and spreading COVID-19. This study aimed to fill that gap and determine the efficacy of the mRNA-1273 vaccine in young adults.

“Importantly, a primary goal of this study was to assess efficacy of the vaccine at preventing infection as well as illness, since vaccines are generally evaluated on how effectively they prevent illness or severe disease,” Fischer said.

The analysis found 93 cases of SARS-CoV-2 infection, including 11 participants who had received both vaccine doses, 13 who had received only their first dose, and 69 who were unvaccinated. Of the 93 infected individuals, 51 were considered to have symptomatic COVID-19, including four participants who had received both vaccine doses, four who had received a first dose and 41 unvaccinated participants. No participants were hospitalized or required emergency room visits for COVID-19. Ultimately, this study found that two doses of the mRNA-1273 vaccine had an efficacy of nearly 53 percent against infection and around 71 percent against symptomatic COVID-19.

“These efficacy rates were lower than other studies conducted around the same time, probably due to the uniquely rigorous testing design of this study, with increased ability to detect even transient infections, and differences in COVID-19 variants present at the time,” Fischer said. “Notably, this study employed a randomized controlled trial, the gold standard of study designs for making such assessments, while many earlier studies were observational in nature.”

In the vaccine-declined group alone, 45 infections occurred among the 311 participants, nearly double (1.8 times as many) the incidence observed in similarly unvaccinated participants in the standard of care group. This result not only shows that unvaccinated young adults were more likely to contract infection but also highlights important behavioral differences in that group that could underlie increased infection risk, such as less frequent use of masking and physical distancing. The researchers also note that socioeconomic factors that increase odds of exposure could be involved.

The research team noted a few limitations to their study. For example, the study had a short duration and was limited to healthy young adults, which limits the ability to generalize its findings to older or sicker populations. Additionally, recommendations for the standard of care cohort changed over the study period, such that about 58 percent of participants sought vaccinations later in the study, leading to some uncertainty in efficacy calculations for that group. The study was also limited to a single vaccine and variants that were present during the study period. Further research will be needed to better understand efficacy for other vaccines and later COVID-19 variants.

“Despite these limitations, the findings of this analysis indicate that vaccination reduced the incidence of COVID-19 infection and illness during the study period,” Fischer said. “Additional research is needed on other vaccines and variants that also include other factors affecting infection risk. However, this study provides solid evidence for the value of vaccination in preventing COVID-19 in young adults.”

This story by Rae Lynn Mitchell originally appeared in  Vital Record .

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COVID-19 vaccines: Get the facts

Looking to get the facts about COVID-19 vaccines? Here's what you need to know about the different vaccines and the benefits of getting vaccinated.

As the coronavirus disease 2019 (COVID-19) continues to cause illness, you might have questions about COVID-19 vaccines. Find out about the different types of COVID-19 vaccines, how they work, the possible side effects, and the benefits for you and your family.

COVID-19 vaccine benefits

What are the benefits of getting a covid-19 vaccine.

Staying up to date with a COVID-19 vaccine can:

  • Help prevent serious illness and death due to COVID-19 for both children and adults.
  • Help prevent you from needing to go to the hospital due to COVID-19 .
  • Boost your body's protection, also called immunity, against catching the virus that causes COVID-19 .
  • Be a safer way to protect yourself compared to getting sick with the virus that causes COVID-19 .

How much protection a COVID-19 vaccine gives depends on different factors. Factors that can affect how much you're protected with a vaccine can include your age, if you've had COVID-19 before or if you have medical conditions such as cancer.

How well a COVID-19 vaccine protects you also depends on how the virus that causes COVID-19 changes and what variants the vaccine protects against. Your level of protection also depends on timing, such as when you got the shot.

Talk to your healthcare team about how you can stay up to date with COVID-19 vaccines.

Should I get the COVID-19 vaccine even if I've already had COVID-19?

Yes. After you've had COVID-19 , getting vaccinated can boost your body's protection against catching the virus that causes COVID-19 another time.

Getting COVID-19 or getting a COVID-19 vaccination gives you protection, also called immunity, from being infected again with the virus that causes COVID-19 . But over time, that protection seems to fade. Getting COVID-19 again may cause serious illness or medical complications, especially for people with risk factors for severe COVID-19 .

Researchers continue to study what happens when someone has COVID-19 a second time. Reinfections are generally milder than the first infection. But severe illness can still happen. Some people may see their risk of having to go to the hospital and having medical problems such as diabetes go up with each COVID-19 infection.

Research has found that people who have had COVID-19 and then have had all of the suggested COVID-19 vaccinations are less likely to be treated in the hospital due to COVID-19 than people who are not vaccinated or who haven't had all the suggested shots. This protection wears off in the months after getting the vaccine.

Also, because the virus that causes COVID-19 can change, also called mutate, a vaccination with the latest strain, or variant, that is spreading or expected to spread can help keep you from getting sick again.

Safety and side effects of COVID-19 vaccines

What covid-19 vaccines have been authorized or approved.

The COVID-19 vaccines available in the United States are:

  • 2023-2024 Pfizer-BioNTech COVID-19 vaccine, available for people age 6 months and older.
  • 2023-2024 Moderna COVID-19 vaccine, available for people age 6 months and older.
  • 2023-2024 Novavax COVID-19 vaccine, available for people age 12 years and older.

In general, people age 5 and older with typical immune systems can get any vaccine that is approved or authorized for their age. They usually don't need to get the same vaccine each time.

Some people should get all their vaccine doses from the same vaccine maker, including:

  • Children ages 6 months to 4 years.
  • People age 5 years and older with weakened immune systems.
  • People age 12 and older who have had one shot of the Novavax vaccine should get the second Novavax shot in the two-dose series.

Talk to your healthcare professional if you have any questions about the vaccines for you or your child. Your healthcare team can help you if:

  • The vaccine you or your child got earlier isn't available.
  • You don't know which vaccine you or your child received.
  • You or your child started a vaccine series but couldn't finish it due to side effects.

At the start of the COVID-19 pandemic, COVID-19 vaccines were needed right away. But the U.S. Food and Drug Administration's (FDA's) vaccine approval process can take years.

To provide vaccines sooner, the FDA gave emergency use authorization to COVID-19 vaccines based on less data than is typically required. But the data still has to show that the vaccines are safe and effective.

In August 2022, the FDA authorized an update to the Moderna and the Pfizer-BioNTech COVID-19 vaccines. Both included the original and omicron variants of the virus that causes COVID-19 .

In June 2023, the FDA directed vaccine makers to update COVID-19 vaccines. The vaccines were changed to target a strain of the virus that causes COVID-19 called XBB.1.5.

In September and October 2023, the FDA authorized the use of the updated 2023-2024 COVID-19 vaccines made by Novavax, Moderna and Pfizer-BioNTech.

Vaccines with FDA emergency use authorization or approval include:

2023-2024 Pfizer-BioNTech COVID-19 vaccine. This vaccine was first tested against the original strain of the COVID-19 virus. That strain began spreading at the end of 2019. In December 2020, the Pfizer-BioNTech COVID-19 vaccine two-dose series was found to be both safe and 91% to 95% effective in preventing COVID-19 infection in people age 18 and older. This data helped predict how well the vaccines would work for younger people. The effectiveness varied by age.

The Pfizer-BioNTech vaccine is approved under the name Comirnaty for people age 12 and older. It is authorized for people age 6 months to 11 years. The number of shots in this vaccination series varies based on a person's age and COVID-19 vaccination history.

2023-2024 Moderna COVID-19 vaccine. This vaccine also was first tested against the original strain of the virus that causes COVID-19 . In December 2020, the Moderna COVID-19 vaccine was found to be both safe and about 93% effective in preventing infection among study volunteers, all age 18 or older.

Based on the comparison between people who got COVID-19 in the placebo group, the Moderna COVID-19 vaccine was 98% effective at preventing serious COVID-19 illness. Vaccine effect was predicted for younger people based on that clinical trial data as well.

The vaccine is approved under the name Spikevax for people age 12 and older. The vaccine is authorized for use in people age 6 months to 11 years. The number of shots needed varies based on a person's age and COVID-19 vaccination history.

  • 2023-2024 Novavax COVID-19 vaccine, adjuvanted. This vaccine is available under an emergency use authorization for people age 12 and older. It requires two shots, given 3 to 8 weeks apart. Research done before the spread of the delta and omicron variants has shown that the vaccine is 90% effective at preventing mild, moderate and severe disease with COVID-19 . For people age 65 and older, the vaccine is 79% effective.

How do the COVID-19 vaccines work?

Both the Pfizer-BioNTech and the Moderna COVID-19 vaccines use genetically engineered messenger RNA (mRNA). Coronaviruses have a spikelike structure on their surface called an S protein. COVID-19 mRNA vaccines give your cells instructions for how to make a harmless piece of an S protein.

After vaccination, your muscle cells begin making the S protein pieces and displaying them on cell surfaces. The immune system recognizes the protein and begins building an immune response and making antibodies. After delivering instructions, the mRNA is immediately broken down. It never enters the nucleus of your cells, where your DNA is kept.

The Novavax COVID-19 , adjuvanted vaccine is a protein subunit vaccine. These vaccines include only the parts (proteins) of a virus that best stimulate your immune system. The Novavax COVID-19 vaccine contains harmless S proteins. It also has an ingredient called an adjuvant that helps with your immune system response.

Once your immune system recognizes the S proteins, this vaccine creates antibodies and defensive white blood cells. If you later become infected with the COVID-19 virus, the antibodies will fight the virus.

Protein subunit COVID-19 vaccines don't use any live virus and can't cause you to become infected with the COVID-19 virus. The protein pieces also don't enter the nucleus of your cells, where your DNA is kept.

Can a COVID-19 vaccine give you COVID-19?

No. The COVID-19 vaccines currently being developed and used in the U.S. don't use the live virus that causes COVID-19 . Because of this, the COVID-19 vaccines can't cause you to become sick with COVID-19 or shed any vaccine parts.

It can take a few weeks for your body to build immunity after getting a COVID-19 vaccination. As a result, it's possible that you could become infected with the virus that causes COVID-19 just before or after being vaccinated.

What are the possible general side effects of a COVID-19 vaccine?

Many people have no side effects from the COVID-19 vaccine. For those who get them, most side effects go away in a few days. A COVID-19 vaccine can cause mild side effects after the first or second dose, including:

  • Pain, redness or swelling where the shot was given.
  • Muscle pain.
  • Joint pain.
  • Nausea and vomiting.
  • Feeling unwell.
  • Swollen lymph nodes.

Babies ages 6 months through 3 years old also might cry, feel sleepy or lose their appetite after vaccination. Children in this age group also may have the common side effects seen in adults. These include pain, redness or swelling where the shot was given, fever, or swollen lymph nodes.

A healthcare team watches you for 15 minutes after getting a COVID-19 vaccine to see if you have an allergic reaction.

If the redness or tenderness where the shot was given gets worse after 24 hours or you're worried about any side effects, contact your healthcare professional.

Are there any long-term side effects of the COVID-19 vaccines?

The vaccines that help protect against COVID-19 are safe and effective. The vaccines were tested in clinical trials. People continue to be watched for rare side effects, even after more than 650 million doses have been given in the United States.

Side effects that don't go away after a few days are thought of as long term. Vaccines rarely cause any long-term side effects.

If you're concerned about side effects, safety data on COVID-19 vaccines is reported to a national program called the Vaccine Adverse Event Reporting System in the U.S. This data is available to the public. The CDC also has created v-safe, a smartphone-based tool that allows users to report COVID-19 vaccine side effects.

If you have other questions or concerns about your symptoms, talk to your healthcare professional.

Can COVID-19 vaccines affect the heart?

In some people, COVID-19 vaccines can lead to heart complications called myocarditis and pericarditis. Myocarditis is the swelling, also called inflammation, of the heart muscle. Pericarditis is the swelling, also called inflammation, of the lining outside the heart.

The risk of myocarditis or pericarditis after a COVID-19 vaccine is rare. These conditions have been reported after a COVID-19 vaccination with any of the three available vaccines. Most cases have been reported in males ages 12 to 39.

If you or your child develops myocarditis or pericarditis after getting a COVID-19 vaccine, talk to a healthcare professional before getting another dose of the vaccine.

Of the cases reported, the problem happened more often after the second dose of the COVID-19 vaccine and typically within one week of COVID-19 vaccination. Most of the people who got care felt better after receiving medicine and resting.

Symptoms to watch for include:

  • Chest pain.
  • Shortness of breath.
  • Feelings of having a fast-beating, fluttering or pounding heart.

If you or your child has any of these symptoms within a week of getting a COVID-19 vaccine, seek medical care.

Things to know before a COVID-19 vaccine

Are covid-19 vaccines free.

In the U.S., COVID-19 vaccines may be offered at no cost through insurance coverage. For people whose vaccines aren't covered or for those who don't have health insurance, options are available. Anyone younger than 18 years old can get no-cost vaccines through the Vaccines for Children program. Adults can get no-cost COVID-19 vaccines through the temporary Bridges to Access program, which is scheduled to end in December 2024.

Can I get a COVID-19 vaccine if I have an existing health condition?

Yes, COVID-19 vaccines are safe for people who have existing health conditions, including conditions that have a higher risk of getting serious illness with COVID-19 .

Your healthcare team may suggest you get added doses of a COVID-19 vaccine if you have a moderately or severely weakened immune system. Talk to your healthcare team if you have any questions about when to get a COVID-19 vaccine.

Is it OK to take an over-the-counter pain medicine before or after getting a COVID-19 vaccine?

Don't take medicine before getting a COVID-19 vaccine to prevent possible discomfort. It's not clear how these medicines might impact the effectiveness of the vaccines. However, it's OK to take this kind of medicine after getting a COVID-19 vaccine, as long as you have no other medical reason that would prevent you from taking it.

Allergic reactions and COVID-19 vaccines

What are the signs of an allergic reaction to a covid-19 vaccine.

You might be having an immediate allergic reaction to a COVID-19 vaccine if you experience these symptoms within four hours of getting vaccinated:

  • Swelling of the lips, eyes or tongue.

If you have any signs of an allergic reaction, get help right away. Tell your healthcare professional about your reaction, even if it went away on its own or you didn't get emergency care. This reaction might mean you are allergic to the vaccine. You might not be able to get a second dose of the same vaccine. However, you might be able to get a different vaccine for your second dose.

Can I get a COVID-19 vaccine if I have a history of allergic reactions?

If you have a history of severe allergic reactions not related to vaccines or injectable medicines, you may still get a COVID-19 vaccine. You're typically monitored for 30 minutes after getting the vaccine.

If you've had an immediate allergic reaction to other vaccines or injectable medicines, ask your healthcare professional about getting a COVID-19 vaccine. If you've ever had an immediate or severe allergic reaction to any ingredient in a COVID-19 vaccine, the CDC recommends not getting that specific vaccine.

If you have an immediate or severe allergic reaction after getting the first dose of a COVID-19 vaccine, don't get the second dose. But you might be able to get a different vaccine for your second dose.

Pregnancy, breastfeeding and fertility with COVID-19 vaccines

Can pregnant or breastfeeding women get the covid-19 vaccine.

If you are pregnant or breastfeeding, the CDC recommends that you get a COVID-19 vaccine. Getting a COVID-19 vaccine can protect you from severe illness due to COVID-19 . Vaccination also can help pregnant women build antibodies that might protect their babies.

COVID-19 vaccines don't cause infection with the virus that causes COVID-19 , including in pregnant women or their babies. None of the COVID-19 vaccines contains the live virus that causes COVID-19 .

Children and COVID-19 vaccines

If children don't often experience severe illness with covid-19, why do they need a covid-19 vaccine.

While rare, some children can become seriously ill with COVID-19 after getting the virus that causes COVID-19 .

A COVID-19 vaccine might prevent your child from getting the virus that causes COVID-19 . It also may prevent your child from becoming seriously ill or having to stay in the hospital due to the COVID-19 virus.

After a COVID-19 vaccine

Can i stop taking safety precautions after getting a covid-19 vaccine.

You are considered up to date with your vaccines if you have gotten all recommended COVID-19 vaccine shots when you become eligible.

After getting vaccinated, you can more safely return to doing activities that you might not have been able to do because of high numbers of people with COVID-19 in your area. However, if you're in an area with a high number of people with COVID-19 in the hospital, the CDC recommends wearing a well-fitted mask indoors in public, whether or not you're vaccinated.

If you have a weakened immune system or have a higher risk of serious illness, wear a mask that provides you with the most protection possible when you're in an area with a high number of people with COVID-19 in the hospital. Check with your healthcare professional to see if you should wear a mask at other times.

The CDC recommends that you wear a mask on planes, buses, trains and other public transportation traveling to, within or out of the U.S., as well as in places such as airports and train stations.

If you've gotten all recommended vaccine doses and you've had close contact with someone who has the COVID-19 virus, get tested at least five days after the contact happens.

Can I still get COVID-19 after I'm vaccinated?

COVID-19 vaccination will protect most people from getting sick with COVID-19 . But some people who are up to date with their vaccines may still get COVID-19 . These are called vaccine breakthrough infections.

People with vaccine breakthrough infections can spread COVID-19 to others. However, people who are up to date with their vaccines but who have a breakthrough infection are less likely to have serious illness with COVID-19 than those who are not vaccinated. Even when people who are vaccinated develop symptoms, they tend to be less severe than those experienced by unvaccinated people.

Are the new COVID-19 vaccines safe?

Andrew Badley, M.D., COVID-19 Research Task Force Chair, Mayo Clinic: The safety of these vaccines has been studied extensively. They've been tested now in about 75,000 patients in total, and the incidence of adverse effects is very, very low.

These vaccines were fast-tracked, but the parts that were fast-tracked were the paperwork; so the administrative approvals, the time to get the funding — those were all fast-tracked. Because these vaccines have such great interest, the time it took to enroll patients was very, very fast. The follow up was as thorough as it is for any vaccine, and we now have months of data on patients who received the vaccine or placebo, and we've compared the incidence of side effects between patients who received the vaccine and placebo, and that incidence of side effects, other than injection site reaction, is no different.

The side effects to the vaccines are very mild. Some of them are quite common. Those include injection site reactions, fevers, chills, and aches and pains. In a very, very small subset of patients — those patients who've had prior allergic reactions — some patients can experience allergic reaction to the vaccine. Right now we believe that number is exceedingly low.

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FactCheck.org

Review Article By Misinformation Spreaders Misleads About mRNA COVID-19 Vaccines 

By Catalina Jaramillo

Posted on February 16, 2024

SciCheck Digest

The mRNA COVID-19 vaccines have a good safety record and have saved millions of lives. But viral posts claim the contrary, citing a recent peer-reviewed article authored by known COVID-19 misinformation spreaders and published in a controversial journal. The paper repeats previously debunked claims.

vaccine research paper covid

More than  half a billion doses of COVID-19 vaccines have now been administered in the U.S. and only a few, very rare, safety concerns have emerged. The vast majority of people experience only minor, temporary side effects such as pain at the injection site, fatigue, headache, or muscle pain — or no side effects at all. As the Centers for Disease Control and Prevention has said , these vaccines “have undergone and will continue to undergo the most intensive safety monitoring in U.S. history.”

A small number of severe allergic reactions known as anaphylaxis, which are expected with any vaccine, have occurred with the authorized and approved COVID-19 vaccines. Fortunately, these reactions are rare, typically occur within minutes of inoculation and can be treated. Approximately 5 per million people vaccinated have experienced anaphylaxis after a COVID-19 vaccine, according  to the CDC.

To make sure serious allergic reactions can be identified and treated, all people receiving a vaccine should be observed for 15 minutes after getting a shot, and anyone who has experienced anaphylaxis or had any kind of immediate allergic reaction to any vaccine or injection in the past should be monitored for a half hour. People who have had a serious allergic reaction to a previous dose or one of the vaccine ingredients should not be immunized. Also, those who shouldn’t receive one type of COVID-19 vaccine should be monitored for 30 minutes after receiving a different type of vaccine.

There is evidence that the Pfizer/BioNTech and Moderna mRNA vaccines may rarely cause inflammation of the heart muscle (myocarditis) or of the surrounding lining (pericarditis), particularly in male adolescents and young adults .

Based on data collected through August 2021, the reporting rates of either condition in the U.S. are highest in males 16 to 17 years old after the second dose (105.9 cases per million doses of the Pfizer/BioNTech vaccine), followed by 12- to 15-year-old males (70.7 cases per million). The rate for 18- to 24-year-old males was 52.4 cases and 56.3 cases per million doses of Pfizer/BioNTech and Moderna vaccines, respectively.

Health officials have emphasized that vaccine-related myocarditis and pericarditis cases are rare and the benefits of vaccination still outweigh the risks. Early evidence suggests these myocarditis cases are less severe than typical ones. The CDC has also noted that most patients who were treated “responded well to medicine and rest and felt better quickly.”

The Johnson & Johnson vaccine has been linked to an  increased risk of rare blood clots combined with low levels of blood platelets, especially in women ages 30 to 49 . Early symptoms of the condition, which is known as thrombosis with thrombocytopenia syndrome, or TTS, can appear as late as three weeks after vaccination and  include  severe or persistent headaches or blurred vision, leg swelling, and easy bruising or tiny blood spots under the skin outside of the injection site.

According to the CDC, TTS has occurred in around 4 people per million doses administered. As of early April ,  the syndrome has been confirmed in 60 cases, including nine deaths, after more than 18.6 million doses of the J&J vaccine. Although TTS remains rare, because of the availability of mRNA vaccines, which are not associated with this serious side effect, the FDA on May 5 limited authorized use of the J&J vaccine to adults who either couldn’t get one of the other authorized or approved COVID-19 vaccines because of medical or access reasons, or only wanted a J&J vaccine for protection against the disease. Several months earlier, on Dec. 16, 2021 ,  the CDC had recommended the Pfizer/BioNTech and Moderna shots over J&J’s.

The J&J vaccine has also been linked to an increased risk of Guillain-Barré Syndrome, a rare disorder in which the immune system attacks nerve cells.  Most people  who develop GBS fully recover, although some have permanent nerve damage and the condition can be fatal.

Safety surveillance data suggest that compared with the mRNA vaccines, which have not been linked to GBS, the J&J vaccine is associated with 15.5 additional GBS cases per million doses of vaccine in the three weeks following vaccination. Most reported cases following J&J vaccination have occurred in men 50 years old and older.

Link to this

The  safety  of the mRNA COVID-19 vaccines from Pfizer/BioNTech and Moderna is supported by the rigorous clinical trials run prior to their release and numerous studies conducted since. Hundreds of millions of people have been vaccinated in the U.S., many with multiple doses, and serious side effects are rare .

vaccine research paper covid

COVID-19 vaccines have also been shown to be  effective  in reducing the risk of severe forms of the disease. Multiple studies have estimated that the COVID-19 vaccines saved millions of lives across the globe.

But an  article  — written by misinformation spreaders who oppose COVID-19 vaccination — that claims to have reviewed the original trials and “other relevant studies” largely ignores this body of evidence. Instead, the review, which calls for a “global moratorium” on the mRNA vaccines, cites multiple flawed or criticized studies —  many   of   which   we’ve   written about before — to falsely claim the mRNA COVID-19 vaccines have caused “extensive, well-documented” serious adverse events and have killed nearly 14 times as many people as they saved.

The article was peer-reviewed and published in Cureus, an open-access online medical journal that prioritizes fast publication and has published problematic studies before, as we will explain.

Social   media   posts  that share the incorrect conclusions of the review have gone viral. 

“mRNA COVID-19 vaccines caused more deaths than saved: study,” reads a Feb. 4  Instagram post  that shared a screenshot of a headline by the Epoch Times. 

One author of the review — as well as other social media users — are also using the fact that the paper was published as proof that the mRNA COVID-19 vaccines are unsafe.

“People have said I’m a misinformation spreader because since  May 2021, I have been publicly saying the COVID vaccines are not safe . Now the medical peer-reviewed literature shows I was right.  Do you believe me now? ” Steve Kirsch, a review co-author and a former tech entrepreneur who lacks biomedical training, said in a post on X, formerly known as Twitter, on Jan. 30 (emphasis is his). 

“!! TRUST THE #SCIENCE !!,” the author of a  viral post  wrote on Instagram on Feb. 7. The post included a screenshot of a news story titled “Mainstream science mulls ‘global moratorium’ on COVID vaccines as cancers rise, boosters flub,” and the statement “Covid vaccines *may* cause cancer. You don’t say.” 

Just because a paper is published does not make it correct. While peer review is useful in weeding out bad science, it’s not foolproof, and the rigor and processes vary by journal. This review, which many experts have criticized, is an outlier, not “mainstream science.” And as  we’ve   written , there’s no evidence mRNA COVID-19 vaccines cause cancer and resulted in millions of deaths. 

Anti-Vaccine Authors and Debunked Claims

Many of the review’s authors have a history of spreading COVID-19 or vaccine misinformation. This includes Kirsch , who has repeatedly pushed the incorrect idea that the COVID-19 vaccines have killed millions of people worldwide, as well as Dr. Peter McCullough , Stephanie Seneff and Jessica Rose.

McCullough still   recommends  treating COVID-19 patients with hydroxychloroquine and ivermectin, even though both have been shown not to work against the disease. He also promotes and sells “spike protein detoxification” products for people who have been vaccinated, despite no evidence that vaccinated people need any such detox.

Seneff is a computer scientist who has promoted the false notion that vaccines cause autism. She previously co-authored a review paper with McCullough, which the Cureus review cites, that misused data from the Vaccine Adverse Event Reporting System to baselessly claim the mRNA COVID-19 vaccines suppress the innate immune system, as we  reported . Rose has also been  accused  of misusing VAERS data to claim vaccines are not safe — a common deception among the anti-vaccination community.

The Cureus review cites and even republishes a figure from one of Rose’s Substack posts about the supposedly alarming number of VAERS reports for “autoimmune disorders” following COVID-19 vaccination compared with influenza vaccines. The review claims the increased reporting “represents an immense safety signal.” But as we’ve explained   before , the higher number of VAERS reports for the COVID-19 vaccines can be explained by multiple factors, such as increased awareness and stricter reporting requirements – and does not in and of itself constitute a safety signal. A report can be submitted by anyone and does not mean that a vaccine caused a particular problem.

The review paper, titled “COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign,” repeats many claims we’ve already written about, based on studies or analyses that have been widely criticized or debunked. 

To claim the vaccines cause “serious harms to humans,” for example, the review draws on a problematic reanalysis of the adverse events reported in the original trials that was published in the journal Vaccine in 2022. Florida Gov. Ron DeSantis and Dr. Joseph Ladapo, the state’s surgeon general, have cited the paper to argue that the vaccines are too risky. But as  we’ve   written — and is detailed in a commentary article published in the same journal — the paper has multiple methodological flaws, including how it counted the adverse events.

The review also uncritically cites an unpublished analysis by former physics professor Denis Rancourt that alleged that some 17 million people died from the COVID-19 vaccines. We recently explained that the report erroneously ignored deaths from COVID-19 and that such estimates are implausible. And the review recycles unsupported claims about “high levels of DNA contamination” in the mRNA vaccines and the possibility that such DNA fragments “will integrate into the human genome” and cause cancer. As we’ve detailed , trace amounts of residual DNA are expected in vaccines, but there is no evidence the DNA can alter a person’s DNA or cause cancer.

vaccine research paper covid

Finally, the review highlighted findings from a Cleveland Clinic observational study that it called the “best evidence for the failure of the COVID-19 mRNA vaccine’s ability to confer protection against COVID-19.” The study, which identified a correlation between more COVID-19 vaccine doses and a higher rate of testing positive for a coronavirus infection, has frequently been cited by those opposed to vaccination. But as  we’ve   explained , the finding runs counter to that of many other studies, which have generally found increased protection with more doses. And the paper did not demonstrate that more doses actually cause an increased risk of infection. In fact, many experts suspect that the association is likely the result of other differences between people who received a different number of doses. Moreover, the primary purpose of vaccination is to protect against severe disease — and there is abundant evidence that the COVID-19 vaccines have been very successful on that front.

“Lessons learned? More like conspiracies spun,” wrote surgical oncologist Dr.  David Gorski  in a  post  about the review in his blog Respectful Insolence.

The authors of the review have also been criticized for citing their own studies in the review and for including non-scientific publications as primary sources. 

“BTW, the McCullough, Kirsch, etc. Cureus paper that is purportedly a scientific review article references trialsitetnews, epoch times, brownstone, the spectator, children’s health defense, and conservative review as primary sources for some of their points, as well as 11 substack articles/blogs, a youtube/twitter video, and 2 explicit anti-vaccine books, plus a large number of self-citations from the review authors,”  Jeffrey S. Morris , director of the division of biostatistics in the department of biostatistics, epidemiology and informatics at the University of Pennsylvania Perelman School of Medicine,  wrote on X  on Feb. 1.

Peer Review Doesn’t Guarantee Scientific Quality

Much of the complimentary coverage of the review paper by some of the usual misinformation spreaders has emphasized that it was published in a peer-reviewed journal.

“A review paper published last week in the journal Cureus is the first peer-reviewed paper to call for a global moratorium on the COVID-19 mRNA vaccines,” declared a Jan. 29  article  published on Robert F. Kennedy’s anti-vaccine website, Children’s Health Defense. The story also received attention on  social media .

Peer review , or the process of having fellow scientists provide feedback on a manuscript and whether it is good enough to publish, can be immensely helpful in ensuring that a given paper does not contain major flaws or errors. But peer review is only as good as the feedback provided — and it does not automatically mean the paper can be trusted. Nor are all peer-reviewed journals  the same , since each has different standards and reputations.

Cureus is unusual in that it focuses on publishing papers quickly and advertises “efficient” peer review and a “hassle-free” publishing experience. The journal’s metrics for the last six months indicate that the average time from submission to publication is 33 days and that the acceptance rate is 51%. For context, the prestigious journal  Nature — which some posts have misleadingly likened Cureus to, as they share the same parent publisher — has a median time of 267 days for submission to acceptance and an 8%  acceptance rate . Per the  article information  for this review paper, the peer-review process took  77  days.

In 2015, responding to concerns about the journal and its fast peer-review process, the founder, president and co-editor-in-chief of Cureus, Dr. John R. Adler, said that “by design peer rejection is not a big part of our review process,” and that the journal also relies on post-publication review to “sort out what is quality/important.”

A paper by Emory University librarians that was presented at a 2022 conference classified Cureus as potentially “untrustworthy or predatory.” The journal is available on PubMed Central, the National Institutes of Health’s database of biomedical research, but is not indexed on MEDLINE, which requires some vetting for inclusion. (A paper’s appearance in either database does not imply any kind of endorsement by the NIH.)

Cureus, notably, published  two problematic  studies about ivermectin for COVID-19 in 2022. As we reported at the time, the results of the studies were inconsistent with stronger studies that did not find any benefit of using ivermectin for COVID-19. Both studies had methodological flaws and were authored by ivermectin activists —  a fact that was not disclosed  at the time of publication.

Although even the best journals occasionally retract published studies, Cureus has ended up  multiple   times  in the pages of Retraction Watch, a blog and online database of retractions — most recently on Jan. 26 for  56 studies  retracted for faked authorship nearly two years after they were first flagged. In 2022, Retraction Watch  reported  that a study retracted by Frontiers in Medicine was later updated and published in Cureus.

Editor’s note: SciCheck’s articles providing accurate health information and correcting health misinformation are made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over FactCheck.org’s editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation.

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ORIGINAL RESEARCH article

Vaccine side effects following covid-19 vaccination among the residents of the uae—an observational study.

\nSubhashini Ganesan,*&#x;

  • 1 G42 Healthcare, Abu Dhabi, United Arab Emirates
  • 2 Insights Research Organization and Solutions, Abu Dhabi, United Arab Emirates
  • 3 Sheikh Khalifa Medical City, SEHA, Abu Dhabi, United Arab Emirates
  • 4 College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
  • 5 Ambulatory Healthcare Services, SEHA, Abu Dhabi, United Arab Emirates
  • 6 College of Medicine and Health Sciences, UAE University, Abu Dhabi, United Arab Emirates

COVID-19 vaccines have proven to be very safe in the clinical trials, however, there is less evidence comparing the safety of these vaccines in real-world settings. Therefore, we aim to investigate the nature and severity of the adverse effects reported and the differences based on the type of vaccine received. A survey was conducted among 1,878 adult (≥18 years) COVID-19 vaccine recipients through online survey platforms and telephonic interviews during March to September 2021. The factors potentially associated with the reported side effects like age, gender, ethnicity, comorbidities, and previous COVID-19 infection were analyzed based on the type of vaccine received. Differences in adverse events and the severity were compared between inactivated and mRNA vaccine recipients. The major adverse effects reported by the COVID-19 vaccine recipients were pain at the site of injection, fatigue and drowsiness, and headache followed by joint/muscle pain. The adverse effects were more common among recipients of mRNA Pfizer-BioNTech vaccine than among recipients of inactive Sinopharm vaccine with the odds ratio of 1.39 (95% CI 1.14–1.68). The average number of adverse effects reported between individuals who had received Sinopharm and Pfizer-BioNTech vaccines was 1.61 ± 2.08 and 2.20 ± 2.58, respectively, and the difference was statistically significant ( p <0.001). Severe adverse effects after COVID-19 vaccinations were rare and 95% of the adverse effects reported after either an inactivated or mRNA vaccine were mild requiring no or home-based treatment. The study found that individuals less than 55 years of age, female gender, with history of one or more comorbid conditions, who had received mRNA Pfizer- BioNTech vaccine, and with history of COVID-19 infections are at higher odds of developing an adverse effect post COVID-19 vaccination compared to the others.

Introduction

In the world's fight against the COVID-19 pandemic, vaccines emerged as the greatest savior for humankind and many vaccine candidates were developed and entered clinical trials in early 2020. Many of these vaccines obtained emergency approval and governments around the world started vaccination campaigns against COVID-19 ( 1 , 2 ).

The United Arab Emirates (UAE) government had successfully completed the vaccination trial for the BBIBP-CorV or Sinopharm vaccine which was approved for general public in December 2020 ( 3 ). Since then, vigorous vaccination of the population was undertaken and the UAE tops the world in the vaccine distribution rate per 100 people ( 4 )and has effectively vaccinated more than 90% of the population so far ( 5 ). Apart from Sinopharm, the UAE government has also approved mRNA Pfizer-BioNTech, adenovirus-based AstraZeneca, and Sputnik V and other vaccines and made them accessible for all people in the UAE.

The worldwide vaccination coverage for COVID-19 vaccination is still low and as of 24 November 2021, only 42% of the world population have received initial two doses of COVID-19 vaccination ( 6 ). Data published from the vaccine trials have demonstrated that the adverse effects of the COVID-19 vaccine most commonly include fever, fatigue, muscle pain, joint pain, and headache and serious adverse events were rarely reported ( 7 – 10 ). In the Sinopharm inactivated vaccine trial, the most common adverse reaction observed was injection site pain followed by fever and all the adverse reactions reported were mild and self-limiting and did not require any treatment ( 7 ). The Pfizer-BioNTech mRNA vaccine trial has reported that the most common adverse effect was mild to moderate fatigue and headache ( 8 ). Similarly, AstraZeneca and Sputnik vaccine trials have also reported only mild/moderate side effects ( 9 , 10 ).

Global safety studies on vaccine reactogenicity have shown that the mRNA COVID-19 vaccine recipients have reported injection site or local reactions more frequently than systemic reactions and serious adverse events were rare ( 11 , 12 ). Younger population and females have reported more side effects than the others ( 13 ). Despite published safety data on COVID-19 vaccines, people around the globe have expressed their concerns and hesitancy in vaccination, and studies have shown that the intention to get vaccinated is associated with positive vaccination beliefs ( 14 ). Surveys have shown that people worry about the potential adverse effects of the COVID-19 vaccine which they believe would be worse than the disease itself ( 15 , 16 ). Even among healthcare professionals, vaccine acceptance has been found to be sub-optimal with doubts about vaccine safety, the quality control, and potential adverse effects given its rapid development ( 17 , 18 ).

A survey done in the UAE on vaccine perception for COVID-19 vaccine showed that safety of the vaccine with no major side effects emerged as the greatest motivating factor to get vaccinated ( 19 ). As vaccine-related fears on safety and side effects play a role in determining the decision regarding vaccination, studies are conducted to monitor the safety of COVID-19 vaccines globally ( 20 ). All these reports establish that the major concern for people to get vaccinated is the side effects or adverse events following COVID-19 vaccination.

Therefore, this survey would give an insight into the actual adverse effects experienced by the recipients of the COVID-19 vaccine and will help us understand the nature of the adverse effects of these different vaccines. This insight would also help instill confidence in people on getting vaccinated against COVID-19.

Study Design and Study Setting

A cross-sectional study based on an online survey and telephonic interviews was conducted between 14 March 2021 and 4 September 2021 among the residents of the UAE. The survey was designed to identify the side effects reported after receiving a COVID-19 vaccination and no personal identification details were collected. An electronic consent was obtained during the online survey and only participants who agreed entered the survey. Participants in telephonic interviews also consented orally before they were presented with the survey. The study was approved by the Medical Research Department, DOH, Abu Dhabi, UAE (approval number: DOH/CVDC/2021/329).

Study Participants

Participants from all nationalities, gender, and age 18 years and above, who had received at least one dose of the COVID-19 vaccination, who were able to give consent and were currently residing in the UAE were included in the survey. The survey form was designed using Google Forms and the participants were approached through social media platforms. A total of 744 participants consented and completed the survey online. Apart from this, telephonic interviews were conducted and the participants were selected randomly from the vaccine database of those who had received the COVID-19 vaccination during the period of the study available at the Ambulatory Healthcare Services, SEHA. This is Abu Dhabi's largest health services provider, which operates all public hospitals and clinics in the emirate of Abu Dhabi. It provides vaccination against COVID-19, manages vaccine-related complications, and operates all COVID-19 dedicated hospitals in Abu Dhabi. Stratified random sampling was used to ensure good representation and samples were stratified based on age group and type of vaccine received. The selected participants were contacted, and among those who were willing to participate, the survey was completed through a telephone interview. A total of 1,796 vaccine recipients were selected from the database based on the stratification criteria and were approached. The response rate was 63.1% with 1,134 completing the interview. Of the others who did not participate, 4.7% refused to participate, 20% did not answer the phone calls, and the rest were identified as having wrong numbers or having language barriers. The interviews were done by family medicine residents who were trained for this purpose. Therefore, a total of 1,878 participants completed the survey, of which 1,134 participants were interviewed through a telephonic survey and 744 participants completed the online survey form.

The Survey Tool

The questionnaire was designed to capture the reactogenicity to the COVID-19 vaccine and the factors that were related to the development of the vaccine's side effects. Based on the literature review of the side effects reported post-COVID-19 vaccination ( 8 – 14 ), the adverse effects were listed in our survey and avenues to add additional side effects were provided. The factors that were studied in the literature and found to be associated with the development of the side effects were captured by designing specific questions on age, gender, nationality, educational status, monthly income, comorbid conditions, previous history of COVID-19 infection, type of COVID-19 vaccine received, and the number of doses received to elicit the responses ( 11 – 13 , 21 ).

The questionnaire was prepared both in English and Arabic languages. The Arabic translation was done by language experts and back-translated by two native speakers to understand any discrepancies and then corrected and approved by the language experts.

The construct validity of the questionnaire was established by four experts with epidemiology, public health, and family medicine background and experience in vaccine trials and vaccination programs. The questionnaire was pilot tested among 5 participants to understand the feasibility and was refined based on feedback.

The survey had a screening question on vaccination which screened all participants who were not vaccinated. Only the participants who had received at least one dose of the COVID-19 vaccine were presented further for the survey.

The first part of the survey included questions on demographic variables like age, sex, education, and nationality. The second part of the survey included questions on comorbid conditions like diabetes, hypertension, chronic lung diseases, cardiovascular, cancer, autoimmune diseases, and other chronic diseases. This section also included a question on the previous history of allergies and associated immunodeficiency or taking medication like high-dose corticosteroids, immunosuppressants, or cancer medicines to rule out any immunocompromised state. The third section included questions on the previous infection with COVID-19 and the severity of the infection. The fourth section of the survey was on vaccination, the type of vaccination taken against COVID-19, the number of doses taken, and the adverse effects experienced after vaccination for COVID-19. The final section of the survey was only for people who had experienced any adverse effects. This section included more questions to understand the nature of adverse effects. Questions on doses of vaccination after which they developed adverse effects and the severity of the adverse effects were included. Participants were asked to grade the severity of side effects by using a Likerts scale of 1–10, where 1 denotes “mild symptoms” and 10 denotes “extremely severe symptoms”. To assess severity more objectively, we also asked the participants whether the side effects required any treatment, if so, was it home-based treatment, consultation with a health professional, or hospital-based treatment.

The age of the participants was stratified into three groups <35 years, 35–54 years, and 55 years and above, which was based on previous literature and the age stratification widely employed in the studies reviewed on systematic review and metanalysis of the impact of age difference on COVID-19 vaccine safety ( 12 , 22 ). The adverse effects were classified into local and systemic side effects for analysis. The local side effects included injection site reactions like pain at the site of vaccination, redness, swelling/lymph node enlargement, and itch. The systemic side effects included fever, headache, muscle, and joint pain, flu-like symptoms, etc.

Sample Size

The study was conducted only among residents of the UAE, which has a population of approximately 10 million people, and at the time of the study, 4 million doses were administered, that is approximately 40% of the total population had received at least one dose of their vaccination against COVID-19 ( 23 ). Hence, with 40 % vaccination coverage with power 80% and relative precision of 10%, the sample size was calculated to be 1,200 which accommodated a non-response rate of 50%.

Statistical Analysis

The adverse effects experienced post-COVID-19 vaccination are expressed in percentage (%) and a chi-square test was used to test the significance of the difference between the demographics and other variables of interest (comorbid conditions, previous history of COVID-19 infection, etc.) against adverse effects. The difference in adverse effects based on the type of vaccine and doses was also compared using the chi-square test and the odds ratio was calculated. p value < 0.05 was considered statistically significant. All statistical analyses were done using SPSS software version 28.0.

Of the 1,878 participants who completed our survey, 940 (50 %) belonged to the 35–55-year age group, 1,151 (61.3%) were females, 526 (28%) had associated comorbid conditions, and 332(17.7%) had a history of a previous infection with COVID-19. The demographical details of all the participants are described in Supplementary Table S1 .

A total of 941 (50.1%) people received inactivated Sinopharm vaccine, 890 (47.4%) received mRNA Pfizer-BioNTech vaccine, and 11 (0.6%) received Adenovirus vector AstraZeneca vaccine; 36 (1.9%) were not aware of the details of the vaccine received. Among the study participants, 1,795 (95.6%) had received two or more doses of COVID-19 vaccination and 83 (4.4%) had received one dose of vaccination.

Adverse Reactions Following COVID-19 Vaccination

A total of 1,217 (64.8%) study participants reported one or more side effects following COVID-19 vaccination. The major adverse effects reported by the COVID-19 vaccine recipients were pain at the site of injection (47%), fatigue and drowsiness (28.2%), and joint/muscle pain (23.1%) followed by headache (17.7%) and fever (14.4%) ( Supplementary Table S2 ). The percentage of side effects reported based on the type of vaccine is shown in Figure 1 . Since most of the study participants either received an inactivated Sinopharm or mRNA Pfizer-BioNTech vaccine and only a negligible percentage of the people had received other vaccines further analyses were done on these two vaccine groups only.

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Figure 1 . Adverse effects reported post-COVID-19 vaccination.

Adverse Effects Following Inactivated Sinopharm Vaccine and the Factors Associated

A total of 574 (61%) of the Sinopharm vaccine recipients reported adverse effects following vaccination. The analysis of various factors related to reactogenicity among the participants who received the Sinopharm vaccine found that younger age group (<55 years), female gender, individuals with higher educational status (graduate/postgraduate), and people with associated comorbidities reported a statistically significant higher percentage of adverse effects than the others ( Table 1 ).

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Table 1 . Association of factors with the adverse effects after receiving the inactive Sinopharm vaccine.

Adverse Effects Following Pfizer-BioNTech (MRNA) Vaccine and the Factors Associated

A total of 610 (68.5%) reported adverse effects following the Pfizer-BioNTech vaccination. The association of demographic variables, comorbid conditions, and previous history of COVID-19 infection with the adverse effects following the Pfizer-BioNTech vaccine showed that age of <35 years, higher educational status, higher income, individuals with comorbidities, and individuals who had a history of previous infection with COVID-19 reported a statistically significant higher percentage of adverse effects than the others ( Table 2 ).

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Table 2 . Association of the risk factors with adverse effects after receiving the mRNA Pfizer vaccine.

Comparison of Adverse Effects Between Sinopharm and Pfizer-BioNTech Vaccine Recipients

The adverse effects were more common among recipients of the mRNA Pfizer-BioNTech vaccine than among recipients of the inactive Sinopharm vaccine with the odds ratio of 1.39 (95% CI 1.14–1.68); 4 out of 10 participants reported no side effects after receiving the Sinopharm vaccine compared to the Pfizer-BioNTech vaccine recipients among which 3 out of 10 reported no side effects ( Supplementary Table S3 ).

Vaccine Dose and Adverse Effects

Among the recipients of inactivated Sinopharm vaccine 214 (22.7%), 208 (22.1%) and 128 (13.6%) reported adverse effects after the first, second, and both doses, respectively. Similarly, among the recipients of mRNA Pfizer-BioNTech vaccine, 103 (11.6%), 268 (30.1%), and 232 (26.1%) reported adverse effects after the first, second, and both doses, respectively ( Supplementary Table S3 ).

The first-dose Sinopharm vaccine recipients are 2.9 times more likely to develop adverse effects compared to the first-dose recipients of the Pfizer-BioNTech vaccine ( p < 0.001), however, after the second dose, recipients of the Pfizer-BioNTech vaccine were 1.4 times more likely to develop an adverse effect than the second-dose Sinopharm vaccine recipients ( p : 0.007) ( Supplementary Table S3 ).

Local and Systemic Side Effects

The Sinopharm vaccine recipients reported 393 (41.8%) and 417(44.3%) local and systemic symptoms, respectively. Among the Pfizer vaccine recipients, 478(53.7%) reported local symptoms and 432 (48.5%) reported systemic symptoms after vaccination.

While no statistically significant difference was observed with the local adverse effects reported after the first and second dose of the Sinopharm and Pfizer vaccine recipients, respectively, a statistically significant higher percentage of systemic adverse effects was reported after the first dose in the Sinopharm vaccine recipients (78.5%) compared to the first-dose Pfizer vaccine recipients (64.1%) (odds ratio 2.04 p -value-0.007). However, after the second dose of the Pfizer vaccine, recipients reported more systemic side effects (86.6%), which was statistically significant compared to the systemic side effects reported after the second dose of the Sinopharm vaccine (72.1%) (odds ratio 1.12, p -value <0.001) ( Supplementary Table S3 ).

Age and Vaccine Adverse Effects

Based on age group, among people <35 years of age, there was no significant difference in the occurrence of the side effects based on the type of vaccine but among people in the 35–54 age group and in the age group ≥55 years, those who received the Pfizer-BioNTech vaccine were 1.44 (95% CI 1.18,1.75) and 1.83 (95% CI 1.38, 2.43) times more at risk of having an adverse effect than those who received the Sinopharm vaccine ( Supplementary Table S4 ). Similar results were seen when the average number of side effects reported were considered among the different age groups based on the vaccine received.

Number of Sides Effects Reported

Considering the number of side effects reported, 54.5 and 6.5% of the inactive vaccine recipients reported 1–5 side effects and 6–14 side effects, respectively, compared to the mRNA vaccine recipients of which 55.9 and 12.7% reported 1–5 side effects and 6–14 side effects, respectively. The average number of adverse effects reported between individuals who had received the Sinopharm and Pfizer-BioNTech vaccine was 1.61 ± 2.08 and 2.20 ± 2.58, respectively, and the difference was statistically significant ( p < 0.001).

Statistically significant difference was observed among people in the 35–54-years age group and ≥ 55-years age group. Based on the number of side effects reported in the 35–54-years age group and 55-years age group, those who received the Pfizer-BioNTech vaccine on an average reported 3.49± 2.70 and 2.93 ± 2.34 adverse effects, respectively, compared to 2.42 ± 1.76 and 2.18 ±1.55, among those who received the Sinopharm vaccine. No statistically significant difference was observed in the <35 years of age cohort ( Figure 2 ).

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Figure 2 . Adverse effects reported based on the age group and severity. The blue line represents the median of the number of adverse events reported across all age groups.

Severity of Side Effects

A total of 1,137 (62.2%) graded the severity of the symptoms, of which 924 (81%) graded it with a score below 5; 1,154 (63.0%) answered the question on the treatment for side effects, of which only 59 (5.0%) required consultation or hospital visit, 1,095 (95.0%) did not require any treatment or only home-based treatments. No severe adverse events were reported ( Figure 2 and Supplementary Figure S1 ).

The observed proportion of adverse effects that required either a doctor's advice or a hospital-based treatment was slightly higher in the age group ≥55 years but no statistical significance was observed between the two vaccine recipients among the different age groups ( Supplementary Table S5 ).

Vaccine reactogenicity represents various local and systemic manifestations because of the inflammatory response to vaccination. The reactogenicity depends on various factors like the host characteristics (age, gender, etc.), type of vaccine, composition, route of administration, and many others ( 24 ). Therefore, it is likely that most individuals would exhibit vaccine reaction post-COVID-19 vaccination. The survey shows that around 65% of the study participants experienced some adverse reaction due to the COVID-19 vaccination. None of the study participants reported severe allergic reactions to the COVID-19 vaccines. The most common adverse effects experienced among both the inactivated and the mRNA vaccine recipients were pain at the site of vaccination followed by fever, fatigue, and headache among the mRNA Pfizer-BioNTech recipients and fatigue and headache among the inactivated Sinopharm vaccine recipients, respectively. The rarest adverse effect reported among the Sinopharm vaccine recipients was enlarged swollen lymph nodes and change or loss of taste; while among the mRNA Pfizer-BioNTech vaccine recipients, temporary one-sided facial weakness was reported by one participant followed by enlarged swollen lymph nodes. Similar rare adverse effects were also reported in a study from Saudi Arabia on the Pfizer-BioNTech vaccine recipients ( 25 ). The nature of the adverse effects reported were similar to the adverse events mentioned in the safety and efficacy study of the Sinopharm and Pfizer-BioNTech vaccines but the percentage observed in this study was higher than reported in the trials ( 7 , 8 ). However, other reports on real-world data have reported a similar percentage of adverse effects observed among both inactivated and mRNA vaccine recipients ( 26 – 28 ).

Among the participants who received the Sinopharm vaccine, younger age group (<55 years), female gender, individuals with higher educational status, higher income, and people with comorbidities had reported a statistically significant higher percentage of adverse effects which was again supported by evidence from other studies on the inactivated vaccine ( 21 , 29 ). Among the Pfizer-BioNTech vaccine recipients, statistically significant associations with the vaccine's adverse effects were observed among participants in the age group of 35 years and above with higher educational status, higher income, individuals with comorbidities, and among individuals who had a history of a previous infection with COVID-19. Studies have demonstrated similar findings where higher vaccine reactogenicity was observed among individuals previously infected with the COVID-19 infection ( 26 , 30 , 31 ).

The mRNA vaccine when first developed was considered safer than inactivated vaccines as it is noninfectious and there is no potential risk of infection ( 32 ). However, in our study, the mRNA Pfizer-BioNTech vaccine showed a statistically significant higher percentage of adverse effects compared to the inactivated Sinopharm vaccine but 53.7% reported the adverse effects among the mRNA Pfizer-BioNTech vaccine recipients were local adverse effects. The mRNA Pfizer-BioNTech vaccine recipients also reported a greater number of side effects compared to inactive Sinopharm vaccine recipients. A study that has compared the Sinopharm and Pfizer-BioNTech vaccines has reported more moderate to severe adverse effects after the Pfizer-BioNTech vaccination ( 33 ) and another has reported a similar higher percentage of local adverse effects with the Pfizer-BioNTech vaccination than systemic adverse effects ( 26 ).

While the percentage of side effects reported did not vary with the number of doses among the inactive Sinopharm vaccine recipients, it was observed that among the mRNA vaccine recipients, the number of adverse effects reported after the second dose was 2.6 times higher than after the first dose of the vaccine. Furthermore, local side effects were reported after the first dose and more systemic side effects were reported after the second dose, which was in agreement with the findings reported in a survey conducted in the United Kingdom ( 26 ).

This study showed that among the inactive Sinopharm vaccine recipients, individuals in the younger age group reported significantly higher side effects than the older age groups. Among the mRNA vaccine recipients, individuals in the 35–54-year age group reported more adverse effects than the older individuals but the difference was not statistically significant and the younger individuals (<35 years) reported statistically significantly lesser side effects than the older individuals. On the contrary, another study published on the mRNA vaccine showed that younger age was associated with greater odds of adverse effects. This might be due to the difference in the age group among which the study was conducted as most of the study participants of this study were between 38 and 66 years ( 34 ). Now that COVID-19 vaccination for children is recommended, a similar survey is needed to understand the response of the younger age group, especially that in this study we found that among the Sinopharm vaccine recipients, the younger age group of <35 years reported more side effects than among those in the age group of ≥35 years.

In our survey, only 5% of the adverse effects required consultation with a doctor or treatment at the hospital and more than 80% of the participants reported a severity score of <5 supporting the fact that most adverse effects following vaccination were mild in nature and self-limiting.

The strength of this study is the comparison of the adverse effects between inactive and mRNA COVID-19 vaccines, the availability of both inactive Sinopharm and mRNA Pfizer-BioNTech vaccines in the UAE allowed cross-vaccine comparison in the same population. To the best of our knowledge, this is the first study to do a detailed comparison of these two different types of vaccines with a relatively large sample size. Another strength of this study is that the information bias was controlled to a large extent by cross-verification. Among all the participants who were contacted through a telephone interview, the survey details on the side effects and medical advice or treatment of the same were verified using the electronic medical records (EMR). The highly electronically integrated healthcare system in Abu Dhabi ensures easy accessibility for researchers to report more accurate and comprehensive data. Our study also has some limitations as the survey was on voluntary basis individuals who are more concerned about their health or have better health-seeking behaviors are most likely to participate in these surveys creating a participant bias. The results of the study are based on survey-based results, so with any other cross-sectional study, the results do not allow for causality interpretation.

In conclusion, the adverse effects of both the inactivated and mRNA vaccines developed mostly within 24 h of vaccination and about 95% were mild requiring no or home-based treatment. The adverse effects are more likely to be systemic side effects and younger individuals, females, and people with comorbidities are more likely to report adverse effects following inactivated Sinopharm vaccine. Among the mRNA Pfizer-BioNTech vaccine recipients, the adverse effects are more likely to be local after the first dose and systemic after the second dose and observed more among people with associated comorbid conditions and with a previous history of COVID-19 infection.

Thus, most adverse effects reported are mild and this public knowledge on the nature of side effects and the factors associated with greater odds of side effects would instill confidence and overcome vaccine hesitancy among people and enhance vaccine coverage which is the need of the hour.

Data Availability Statement

The data supporting the conclusion of this article is available with the corresponding author, which shall be provided on approval upon request.

Ethics Statement

The studies involving human participants were reviewed and approved by Institutional Review Board, Department of Health, Abu Dhabi, UAE. The patients/participants provided their informed consent to participate in this study.

Author Contributions

SG, LK, and WZ: conception, design of work, and acquisition. MM, NM, MS, AS, HE, RM, NS, KS, and AF: design of work and acquisition. FC, SG, LK, and WZ: analysis. NK, KW, FC, SG, LK, WZ, and FA: interpretation of data. NK, KW, SG, LK, WZ, and FA: drafting and substantively revising the manuscript. All authors read and approved the final manuscript.

Conflict of Interest

SG, FC, KW, FA, and WZ were employed by G42 Healthcare. SG and WZ was employed by Insights Research Organization and Solutions. MM, NM, MS, AS, HE, RM, NS, KS, and AF were employed by Ambulatory Healthcare Services, SEHA.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

We thank Mr. Santosh Elavalli and Mr. Rohaan Pereira for their support in conducting this study.

Supplementary Material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpubh.2022.876336/full#supplementary-material

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Keywords: SARS-CoV-2, COVID-19, adverse (side) effects, Pfizer-BioNTech vaccine, Sinopharm vaccine

Citation: Ganesan S, Al Ketbi LMB, Al Kaabi N, Al Mansoori M, Al Maskari NN, Al Shamsi MS, Alderei AS, El Eissaee HN, Al Ketbi RM, Al Shamsi NS, Saleh KM, Al Blooshi AF, Cantarutti FM, Warren K, Ahamed F and Zaher W (2022) Vaccine Side Effects Following COVID-19 Vaccination Among the Residents of the UAE—An Observational Study. Front. Public Health 10:876336. doi: 10.3389/fpubh.2022.876336

Received: 15 February 2022; Accepted: 31 March 2022; Published: 06 May 2022.

Reviewed by:

Copyright © 2022 Ganesan, Al Ketbi, Al Kaabi, Al Mansoori, Al Maskari, Al Shamsi, Alderei, El Eissaee, Al Ketbi, Al Shamsi, Saleh, Al Blooshi, Cantarutti, Warren, Ahamed and Zaher. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Subhashini Ganesan, Subhashini.g@g42.ai

† These authors have contributed equally to this work and share first authorship

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Early Estimates of Updated 2023–2024 (Monovalent XBB.1.5) COVID-19 Vaccine Effectiveness Against Symptomatic SARS-CoV-2 Infection Attributable to Co-Circulating Omicron Variants Among Immunocompetent Adults — Increasing Community Access to Testing Program, United States, September 2023–January 2024

Weekly / February 1, 2024 / 73(4);77–83

Ruth Link-Gelles, PhD 1 ; Allison Avrich Ciesla, PhD 1 ,2 ; Josephine Mak, MPH 1 ; Joseph D. Miller, PhD 3 ; Benjamin J. Silk, PhD 1 ; Anastasia S. Lambrou, PhD 1 ; Clinton R. Paden, PhD 1 ; Philip Shirk, PhD 1 ; Amadea Britton, MD 1 ; Zachary R. Smith, PhD 3 ; Katherine E. Fleming-Dutra, MD 1 ( View author affiliations )

What is already known about this topic?

In September 2023, CDC’s Advisory Committee on Immunization Practices recommended updated 2023–2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. Many variants co-circulated during fall 2023; the JN.1 lineage became predominant in January 2024. Few estimates of updated 2023–2024 vaccine effectiveness (VE) are available.

What is added by this report?

Receipt of updated COVID-19 vaccine provided approximately 54% increased protection against symptomatic SARS-CoV-2 infection compared with no receipt of updated vaccine. Vaccination provides protection against JN.1 and other circulating lineages.

What are the implications for public health practice?

All persons aged ≥6 months should receive updated 2023–2024 COVID-19 vaccine. CDC will continue monitoring COVID-19 VE, including against severe disease and for expected waning.

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The figure is an illustration of a magnifying glass over virus cells with text about updated COVID-19 vaccine effectiveness.

On September 12, 2023, CDC’s Advisory Committee on Immunization Practices recommended updated 2023–2024 (updated) COVID-19 vaccination with a monovalent XBB.1.5–derived vaccine for all persons aged ≥6 months to prevent COVID-19, including severe disease. During fall 2023, XBB lineages co-circulated with JN.1, an Omicron BA.2.86 lineage that emerged in September 2023. These variants have amino acid substitutions that might increase escape from neutralizing antibodies. XBB lineages predominated through December 2023, when JN.1 became predominant in the United States. Reduction or failure of spike gene ( S -gene) amplification (i.e., S -gene target failure [SGTF]) in real-time reverse transcription–polymerase chain reaction testing is a time-dependent, proxy indicator of JN.1 infection. Data from the Increasing Community Access to Testing SARS-CoV-2 pharmacy testing program were analyzed to estimate updated COVID-19 vaccine effectiveness (VE) (i.e., receipt versus no receipt of updated vaccination) against symptomatic SARS-CoV-2 infection, including by SGTF result. Among 9,222 total eligible tests, overall VE among adults aged ≥18 years was 54% (95% CI = 46%–60%) at a median of 52 days after vaccination. Among 2,199 tests performed at a laboratory with SGTF testing, VE 60–119 days after vaccination was 49% (95% CI = 19%–68%) among tests exhibiting SGTF and 60% (95% CI = 35%–75%) among tests without SGTF. Updated COVID-19 vaccines provide protection against symptomatic infection, including against currently circulating lineages. CDC will continue monitoring VE, including for expected waning and against severe disease. All persons aged ≥6 months should receive an updated COVID-19 vaccine dose.

Introduction

On September 12, 2023, CDC’s Advisory Committee on Immunization Practices recommended that all persons aged ≥6 months receive the updated 2023–2024 (updated) monovalent COVID-19 vaccine ( 1 ). Most persons aged ≥5 years are recommended to receive 1 updated dose. These vaccines contain a component from the SARS-CoV-2 Omicron XBB.1.5 lineage and unlike previous COVID-19 vaccines, do not contain the ancestral SARS-CoV-2 strain. During the period of analysis, XBB lineages predominated early, many with evolutionarily advantageous amino acid changes in the spike gene ( S -gene). In September 2023, the divergent JN.1 lineage was detected in the United States. JN.1 has more than 30 mutations in the spike protein compared with XBB.1.5, including a change (L455S) similar to one found in circulating XBB lineages (L455F).* JN.1 accounted for 69% (range = 65%–73%) of SARS-CoV-2 infections nationally by the 2-week period ending January 6, 2024. † Results of spike gene ( S -gene) amplification in real-time reverse transcription–polymerase chain reaction (RT-PCR) can be used to distinguish certain SARS-CoV-2 lineages over time ( 2 ). Detection of S -gene target presence (SGTP) by a widely used commercial test was noted in most lineages that circulated in 2023, including XBB lineages, § whereas S -gene target failure (SGTF), resulting from a mutation in the S -gene, is detected in JN.1 and other BA.2.86 lineages. ¶ Vaccine effectiveness (VE) of receipt of updated COVID-19 vaccine in preventing symptomatic SARS-CoV-2 infection was assessed in adults aged ≥18 years, by time since dose and by SGTF and SGTP as a proxy for likely JN.1 versus other lineages. Whereas the goal of the U.S. COVID-19 vaccination program is to prevent severe disease, VE against symptomatic infection can provide useful insights into protection early after introduction of updated vaccines and during the emergence of new lineages, such as JN.1.

Overall Assessment of VE

Increasing Community Access to Testing (ICATT) is a CDC program that provides access to no-cost SARS-CoV-2 testing at pharmacies nationwide to persons who are uninsured,** prioritizing socially vulnerable areas. †† ICATT VE methods have been described §§ ( 3 ). Tests conducted at participating CVS Pharmacy and Walgreen Co. (Walgreens) locations during September 21, 2023–January 14, 2024, among adults who reported ≥1 symptom of COVID-19 were included in the test-negative design study. For the full analysis, case-patients were persons who received a positive nucleic acid amplification test (NAAT) result; control patients were those who received a negative NAAT result. Tests among persons fulfilling any of the following criteria were excluded from analyses: 1) self-reported immunocompromising condition ¶¶ ; 2) reported receipt of Novavax as the most recent dose and reported receipt of <2 total COVID-19 vaccine doses***; 3) reported receipt of a Janssen (Johnson & Johnson) COVID-19 vaccine dose after May 12, 2023 ††† ; 4) receipt of the most recent dose <7 days before the date of testing or during September 1–12, 2023; 5) receipt of a COVID-19 vaccine <2 months before date of testing for those who did not receive an updated COVID-19 vaccine dose; or 6) registration for testing with a version of the questionnaire that only reported month and year of the most recent vaccine dose rather than calendar date. In addition, tests from persons reporting receipt of a positive SARS-CoV-2 test result during the preceding 90 days §§§ were excluded. Type of most recent vaccine dose (original monovalent, bivalent, or updated monovalent) was determined by the reported date of receipt of the dose. ¶¶¶

VE against symptomatic disease was calculated by comparing odds of receipt versus nonreceipt of the updated COVID-19 vaccine among case- and control patients. Secondary analyses examined alternative reference groups, including 1) receipt of a bivalent dose and 2) being either unvaccinated or having received only original COVID-19 vaccines. Odds ratios (ORs) were estimated using multivariable logistic regression****; VE was calculated separately based on SGTF or SGTP status as (1 − OR) x 100%.

Analysis of VE by SGTF and Time Since Vaccination

A subanalysis of VE by SGTF status and time since last dose included RT-PCR tests performed by one pharmacy chain during October 27, 2023–January 12, 2024, and analyzed at a commercial laboratory that used the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific). Quantitative results were reported as cycle threshold (Ct) values for each of three SARS-CoV-2 gene targets ( S, N , and ORF1ab ). Only specimens with Ct values available for both N and ORF1ab were included in the SGTF subanalysis. SARS-CoV-2–positive specimens with either null or reduced amplification of the S -gene (Ct for S -gene >4 cycles from the average of N and ORF1ab Ct values) were considered to have SGTF ( 2 , 4 ), an indication of a particular deletion in the SARS-CoV-2 spike protein, which currently indicates an infection with BA.2.86, JN.1, and their sublineages. SARS-CoV-2–positive specimens without SGTF were considered to exhibit SGTP, which likely indicates infection with previously dominant XBB.1.5 lineages (Supplementary Figure; https://stacks.cdc.gov/view/cdc/145936 ).

For the SGTF and SGTP subanalysis, overall VE (regardless of time since dose) and VE during the 7–59 days after an updated dose were not calculated because the emergence of JN.1 parallels time since dose; statistical power for SGTF (likely JN.1) during the 7–59 days was therefore limited. Analyses were conducted using R software (version 4.1.2; R Foundation). This activity was reviewed by CDC, deemed not research, and was conducted consistent with applicable federal law and CDC policy. ††††

Among 9,222 NAAT results for persons with COVID-19–like illness symptoms eligible for the full analysis, 3,295 (36%) were positive for SARS-CoV-2 ( Table 1 ). Among 1,125 persons who had received updated COVID-19 vaccine ≥7 days earlier, more control patients (844; 14%) reported having received the vaccine than did case-patients (281; 9%). Among those who received updated vaccine, the median interval since the last dose was 60 days (IQR = 32–79 days) for case-patients and 51 days (IQR = 28–73) for control patients. Among the 8,097 persons who reported that they had not received an updated vaccine dose, 2,435 (30%) were unvaccinated. Among the remaining 5,662 (70%) who were vaccinated but had not received an updated vaccine dose, the median interval since the last dose was 378 days (IQR = 321–413 days) for case-patients and 363 days (IQR = 254–402 days) for control patients. In the full analysis, VE for persons aged 18–49 years was 57% (95% CI = 48%–65%) and for persons aged ≥50 years was 46% (95% CI = 31%–58%) ( Table 2 ). Overall VE was 58% (95% CI = 48%–65%) among those who received testing 7–59 days after receipt of updated vaccine and 49% (95% CI = 36%–58%) among those who received testing 60–119 days after receipt of updated vaccine.

VE by SGTF Status

In the subanalysis, 679 tests with S -gene target results from eligible persons were available, including 258 (38%) exhibiting SGTF (likely JN.1 lineages) and 421 (62%) with SGTP (likely non-JN.1 lineages) ( Table 3 ). Because of recent emergence of JN.1 in the United States, VE was imprecise for tests with SGTF during the 7–59 days after receipt of updated vaccine. VE during the 60–119 days since receipt of updated vaccine was 49% (95% CI = 19%–68%) for tests with SGTF (median interval since dose = 80 days) and 60% (95% CI = 35%–75%) for tests with SGTP (median interval since dose = 73 days).

Secondary VE Analyses

Secondary analyses showed similar VE estimates for receipt of updated vaccine compared with those who previously received only original monovalent doses and those who received original monovalent and bivalent doses. (Supplementary Table; https://stacks.cdc.gov/view/cdc/145937 ).

This report provides early estimates of effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and the first estimates of VE against symptomatic infection with the JN.1 lineage. These preliminary estimates from pharmacy testing conducted during September 2023–January 2024 showed updated monovalent COVID-19 vaccine provided protection for JN.1 and other circulating lineages.

VE against symptomatic infection provides helpful information about the range of protection provided by updated vaccines and against emerging lineages. An important strength of ICATT SARS-CoV-2 testing data is the ability to distinguish JN.1 from XBB lineages, allowing for comparison of VE during the same period after vaccination. Monitoring the potential impact on VE of JN.1 is critical because of the spike mutations in JN.1 (as compared with XBB lineages), which might be associated with increased immune escape §§§§ ( 5 ). Recent laboratory data show that the updated vaccines elicit neutralizing antibodies against emerging XBB lineages and JN.1 ( 6 ). Although point estimates during the 60–119 days after vaccination were lower for SGTF than SGTP results in this analysis, CIs overlapped, indicating no statistically significant difference. These data provide reassurance that updated vaccines are providing protection against JN.1 and XBB lineages.

These early estimates include the period only through 119 days since vaccination, a relatively brief postvaccination period, with no substantial waning. Because consistent patterns of waning VE were observed after original monovalent and bivalent COVID-19 vaccination, waning of VE is expected with more time since updated vaccination, especially against less severe outcomes such as symptomatic infection. Additional analyses conducted at longer intervals since authorization of updated vaccines are needed for continued monitoring of expected waning and to determine how well vaccines are working to prevent severe disease.

Limitations

The findings in this report are subject to at least five limitations. First, vaccination status, previous infection history, and underlying medical conditions were self-reported and might be subject to recall bias. Self-reported frequency of previous infections >90 days before testing differed by vaccination status and SGTF status, but statistical power was not adequate for stratification of results. Further, previous infection is likely underreported ( 7 ). Previous infection provides some protection against repeat infection ( 8 ) and U.S. adults have a high prevalence of infection-induced SARS-CoV-2 immunity. ¶¶¶¶ Thus, VE in this analysis reflects the current situation among U.S. adults and can be interpreted as the incremental benefit of receipt of updated COVID-19 vaccine beyond existing vaccination-induced, infection-induced, or hybrid immunity. Second, test registration questionnaires did not ask registrants about the number of updated vaccine doses received; therefore, the analysis might have included some persons who received >1 updated dose. Third, these estimates are derived from a population choosing to be tested for SARS-CoV-2 and are potentially subject to selection biases related to these factors. In addition, updated vaccination coverage to date has been low (approximately 22% as of January 13, 2024*****) among persons aged ≥18 years and varies by age, which could bias results if persons being vaccinated earlier are systematically different from those vaccinated later. Thus, residual confounding might be present and could affect these early estimates. Fourth, this analysis used a subset of data with SGTF status as a proxy for infection with a JN.1 lineage. Although SGTF identifies other BA.2.86 lineage viruses, JN.1 represents the majority of these and was the primary lineage increasing in proportion during the analytic period. Finally, this analysis did not control for time since receipt of the most recent dose before the updated dose; however, because of waning effectiveness of previous doses, particularly against symptomatic infection ††††† ( 9 ), this limitation likely had a minimal effect on results.

Implications for Public Health Practice

Updated monovalent COVID-19 vaccines provided 54% (95% CI = 46–60%) protection against symptomatic SARS-CoV-2 infection in persons recently vaccinated compared with those who did not receive an updated vaccine dose. Vaccination provided protection for infections caused by JN.1 and infections caused by XBB-related lineages. Waning of effectiveness is expected with additional elapsed time since vaccination, especially against less severe disease. CDC will continue to monitor trends in VE. All persons aged ≥6 months should stay up to date with COVID-19 vaccination, including receiving a dose of updated vaccine.

Acknowledgments

CVS Health; Walgreen Co.

Corresponding author: Ruth Link-Gelles, [email protected] .

1 National Center for Immunization and Respiratory Diseases, CDC; 2 Eagle Health Analytics, San Antonio, Texas; 3 Office of Readiness and Response, CDC.

All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

* https://www.cdc.gov/respiratory-viruses/whats-new/SARS-CoV-2-variant-JN.1.html

† https://covid.cdc.gov/covid-data-tracker/#variant-proportions

§ XBB sublineages representing >1% of all sequenced variants include HV.1, JD.1.1, HK.3, JG.3, and EG.5 (last updated January 9, 2024).

¶ SGTF lineages are defined by the presence of a deletion at positions 69–70 in the spike protein.

** ICATT vendors also report data for tests administered to people with medical insurance. Tests for persons with and without health insurance are included in this analysis.

†† The Social Vulnerability Index (SVI) is a composite measure that uses U.S. Census Bureau data on 16 social factors to rank social vulnerability by U.S. Census Bureau tract. The scale is from 0 to 1; higher SVIs represent more vulnerable communities. Tests with missing SVI data (<1% of total) were excluded from all analyses. https://www.atsdr.cdc.gov/placeandhealth/svi/data_documentation_download.html

§§ At test registration, adults report information on COVID-19 vaccination history, current COVID-19–like illness symptoms, history of previous positive SARS-CoV-2 test results, and underlying medical conditions. At Walgreens, comprising 95% of tests meeting inclusion criteria, test registrants who reported receiving COVID-19 vaccines were asked to report the total number of doses received and for the most recent dose, the manufacturer and the date of receipt as part of test registration. At CVS Pharmacy, comprising 5% of tests meeting inclusion criteria, test registrants’ vaccination status was ascertained from a visit with a nurse practitioner or physician associate.

¶¶ Test registration forms asked persons to report whether they had an immunocompromising condition and provided the following examples: immunocompromising medications, solid organ or blood stem cell transplant, HIV, or other immunocompromising conditions.

*** Persons aged ≥12 years without immunocompromise and receiving updated Novavax COVID-19 vaccination are recommended to receive 2 updated COVID-19 vaccine doses if previously unvaccinated and 1 updated dose if previously vaccinated with any COVID-19 vaccine. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us-appendix.html

††† On May 12, 2023, CDC removed guidance for use of Janssen COVID-19 vaccine because the vaccine was no longer available in the United States. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us-appendix.html

§§§ Tests from persons reporting a positive SARS-CoV-2 test result during the preceding 90 days were excluded to avoid analyzing multiple tests for the same illness episode or reinfections within a relatively short time frame. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/testing.html

¶¶¶ Persons were assumed to have received only original monovalent COVID-19 vaccine doses if they reported receiving their last dose before September 2, 2022, or if they reported receiving 1 or 2 total doses before April 18, 2023; persons were assumed to have received a bivalent dose and no updated monovalent dose if they reported receiving >2 total doses with their last dose during September 2, 2022–April 18, 2023, or reported receiving any number of doses with their last dose during April 19–September 12, 2023; persons reporting receipt of a dose after September 12, 2023, were assumed to have received an updated monovalent dose because these were the only authorized COVID-19 doses in the United States during that period. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us-appendix.html

**** Multivariable logistic regression models were controlled for age (as a continuous variable), gender, race and ethnicity, SVI of the testing location (<0.5 versus ≥0.5), pharmacy contractor, underlying conditions (presence versus absence), U.S. Department of Health and Human Services region of testing location, and date of testing. The following underlying conditions were included on the test registration questionnaire: heart conditions, high blood pressure, overweight or obesity, diabetes, current or former smoker, kidney failure or end stage renal disease, cirrhosis of the liver, and chronic lung disease (such as chronic obstructive pulmonary disease, moderate to severe asthma, cystic fibrosis, or pulmonary embolism).

†††† 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.

§§§§ JN.1 is a sublineage of BA.2.86, defined by the spike substitution L455S. Changes at this amino acid position have conferred immune escape advantages to other lineages and might be associated with increased immune escape.

¶¶¶¶ https://covid.cdc.gov/covid-data-tracker/#nationwide-blood-donor-seroprevalence-2022

***** https://www.cdc.gov/vaccines/imz-managers/coverage/covidvaxview/interactive/adult-coverage-vaccination.html

††††† https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2023-09-12/05-COVID-Link-Gelles-508.pdf

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  • Scobie HM, Ali AR, Shirk P, et al. Spike gene target amplification in a diagnostic assay as a marker for public health monitoring of emerging SARS-CoV-2 variants—United States, November 2021–January 2023. MMWR Morb Mortal Wkly Rep 2023;72:125–7. https://doi.org/10.15585/mmwr.mm7205e2 PMID:36730050
  • Link-Gelles R, Ciesla AA, Roper LE, et al. Early estimates of bivalent mRNA booster dose vaccine effectiveness in preventing symptomatic SARS-CoV-2 infection attributable to Omicron BA.5– and XBB/XBB.1.5–related sublineages among immunocompetent adults—Increasing Community Access to Testing program, United States, December 2022–January 2023. MMWR Morb Mortal Wkly Rep 2023;72:119–24. https://doi.org/10.15585/mmwr.mm7205e1 PMID:36730051
  • Clark C, Schrecker J, Hardison M, Taitel MS. Validation of reduced S-gene target performance and failure for rapid surveillance of SARS-CoV-2 variants. PLoS One 2022;17:e0275150. https://doi.org/10.1371/journal.pone.0275150 PMID:36190984
  • Kaku Y, Okumura K, Padilla-Blanco M, et al.; Genotype to Phenotype Japan (G2P-Japan) Consortium. Virological characteristics of the SARS-CoV-2 JN.1 variant. Lancet Infect Dis 2024;S1473–3099:00813–7. https://doi.org/10.1016/S1473-3099(23)00813-7 PMID:38184005
  • Wang Q, Guo Y, Bowen A, et al. XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants. bioRxiv [Preprint posted online November 27, 2023]. https://doi.org/10.1101/2023.11.26.568730
  • Clarke KEN, Jones JM, Deng Y, et al. Seroprevalence of infection-induced SARS-CoV-2 antibodies—United States, September 2021–February 2022. MMWR Morb Mortal Wkly Rep 2022;71:606–8. https://doi.org/10.15585/mmwr.mm7117e3 PMID:35482574
  • Bobrovitz N, Ware H, Ma X, et al. Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the Omicron variant and severe disease: a systematic review and meta-regression. Lancet Infect Dis 2023;23:556–67. https://doi.org/10.1016/S1473-3099(22)00801-5 PMID:36681084
  • Ciesla AA, Wiegand RE, Smith ZR, et al. Effectiveness of booster doses of monovalent mRNA COVID-19 vaccine against symptomatic severe acute respiratory syndrome Coronavirus 2 infection in children, adolescents, and adults during Omicron subvariant BA.2/BA.2.12.1 and BA.4/BA.5 predominant periods. Open Forum Infect Dis 2023;10:ofad187. https://doi.org/10.1093/ofid/ofad187 PMID:37213428

Abbreviations: HHS = U.S. Department of Health and Human Services; ICATT = Increasing Community Access to Testing program; NA = not applicable; NAAT = nucleic acid amplification test; SGT = spike gene target; SVI = Social Vulnerability Index. * Tests included in the subanalysis represent a subset of those included in the full analysis. † Persons of Hispanic or Latino (Hispanic) origin might be of any race but are categorized as Hispanic; all racial groups are non-Hispanic. § Regions are defined by HHS and include only states and territories with ICATT sites. U.S. Virgin Islands (Region 2) and American Samoa, Federated States of Micronesia, Guam, Marshall Islands, Northern Mariana Islands, and Palau (Region 9) were not included because they did not have pharmacies participating in ICATT. https://www.hhs.gov/about/agencies/iea/regional-offices/index.html . ¶ SVI is a composite measure that uses U.S. Census Bureau data on 16 social factors to rank social vulnerability by U.S. Census Bureau tract. The scale is from 0 to 1; higher SVIs represent more vulnerable communities. Tests with missing SVI data (<1% of total) were excluded from all analyses. https://www.atsdr.cdc.gov/placeandhealth/svi/data_documentation_download.html ** Rapid NAAT was performed on-site on self-collected nasal swabs using ID Now (Abbott Diagnostics Scarborough, Inc.), Xpert Xpress (Cepheid), and Accula (Thermo Fisher Scientific). †† Laboratory-based NAAT was performed on self-collected nasal swabs at contracted laboratories using a variety of testing platforms. §§ Persons were assumed to have received only original monovalent COVID-19 vaccine doses if they reported receiving their last dose before September 2, 2022, or if they reported receiving 1 or 2 total doses before April 18, 2023; persons were assumed to have received a bivalent dose and no updated dose if they reported receiving >2 total doses with their last dose during September 2, 2022–April 18, 2023, or receiving any number of doses with their last dose during April 19–September 12, 2023; persons reporting receipt of a dose after September 12, 2023, were assumed to have received an updated dose because these were the only authorized COVID-19 doses in the United States. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us-appendix.html ¶¶ “Updated” refers to 2023–2024 monovalent COVID-19 vaccine.

Abbreviations: Ref = referent group; VE = vaccine effectiveness. * VE = (1 − adjusted odds ratio) x 100. Odds ratios were calculated using multivariable logistic regression, adjusting for age (as a continuous variable), gender, race and ethnicity, Social Vulnerability Index of the testing location (<0.5 versus ≥0.5), pharmacy contractor, underlying conditions (presence versus absence), U.S. Department of Health and Human Services region of testing location, and date of testing. Previous analyses from this platform included local SARS-CoV-2 incidence in regression models; however, this variable is no longer available since the end of the public health emergency declaration in May 2023.

Abbreviations: Ref = referent group; SGT = spike gene target; VE = vaccine effectiveness. * VE = (1 – adjusted odds ratio) x 100. Odds ratios were calculated using multivariable logistic regression, adjusting for age (as a continuous variable), gender, race and ethnicity, Social Vulnerability Index of the testing location (<0.5 versus ≥0.5), pharmacy contractor, underlying conditions (presence versus absence), U.S. Department of Health and Human Services region of testing location, and date of testing. Previous analyses from this platform included local SARS-CoV-2 incidence in regression models; however, this variable is no longer available since the end of the public health emergency declaration in May 2023. † Overall VE, regardless of time since dose, and VE during the 7–59 days since vaccination were not calculated for the subanalysis based on SGT presence or SGT failure. Because of the timing of JN.1 spread in the United States, JN.1 VE estimates would be inherently weighted as longer time since dose and non-JN.1 VE estimates as shorter time since dose, biasing overall estimates of VE by lineage. Similarly, because of the timing of JN.1 spread, statistical power for VE for JN.1 lineages during the 7–59 days after receipt of vaccination was limited.

Suggested citation for this article: Link-Gelles R, Ciesla AA, Mak J, et al. Early Estimates of Updated 2023–2024 (Monovalent XBB.1.5) COVID-19 Vaccine Effectiveness Against Symptomatic SARS-CoV-2 Infection Attributable to Co-Circulating Omicron Variants Among Immunocompetent Adults — Increasing Community Access to Testing Program, United States, September 2023–January 2024. MMWR Morb Mortal Wkly Rep 2024;73:77–83. DOI: http://dx.doi.org/10.15585/mmwr.mm7304a2 .

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  • Assessing America's Vaccine Safety Systems, Part 1 - 02/15/2024

Testimony | In Person

Event Title Assessing America's Vaccine Safety Systems, Part 1 February 15, 2024

Introduction.

Chair Wenstrup, Ranking Member Ruiz, and members of the Subcommittee, thank you for the opportunity to testify before you to discuss the Food and Drug Administration’s (FDA or the Agency) coronavirus disease 2019 (COVID-19) response and vaccine safety and surveillance efforts to date and moving forward.

The American public can be assured of the simple fact that FDA-approved and authorized vaccines are high quality, effective, and safe. Vaccines work and save the lives of millions of children and adults every year by producing immune responses to bacteria or viruses that cause disease.  While they may not always prevent an infection or mild disease, vaccines often can prevent hospitalization and death. The vaccine development process, and FDA’s stringent regulatory and scientific evaluation process, ensure that the health benefits of available approved and authorized vaccines far outweigh any risks.

Vaccines approved or authorized by FDA, including the COVID-19 vaccines, have undergone a rigorous research and development process and have been thoroughly evaluated by FDA prior to authorization for emergency use and prior to approval, in accordance with the Agency’s rigorous policies, procedures, and standards. Furthermore, vaccine safety is closely and continuously monitored through multiple surveillance systems, which alert both FDA and the Centers for Disease Control and Prevention (CDC) should a potential concern arise. 

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    Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the inter …

  12. COVID-19 Vaccines

    By the end of November 2021, scientists estimate that mRNA COVID-19 vaccines had prevented at least 1 million deaths, 10 million hospitalizations, and 36 million SARS-CoV-2 infections in the United States. Sometimes people who are fully vaccinated get a breakthrough infection, meaning that they test positive for SARS-CoV-2 or become ill with ...

  13. Coronavirus disease (COVID-19): Vaccine research and development

    In a human challenge vaccine study, healthy volunteers are given an experimental vaccine, and then deliberately exposed to the organism causing the disease to see if the vaccine works. Some scientists believe that this approach could accelerate COVID-19 vaccine development, in part because it would require far fewer volunteers than a typical study.

  14. SARS-CoV-2

    Here, the authors enhance their nasally delivered chimpanzee adenoviral-vectored SARS-CoV-2 vaccine with an Omicron-matched vaccine (ChAd-SARS-CoV-2-BA.5-S) that stimulates mucosal immunity...

  15. Serious adverse events of special interest following mRNA COVID-19

    Pfizer and Moderna mRNA COVID-19 vaccines were associated with an excess risk of serious adverse events of special interest of 10.1 and 15.1 per 10,000 vaccinated over placebo baselines of 17.6 and 42.2 (95 % CI -0.4 to 20.6 and -3.6 to 33.8), respectively.

  16. Efficacy of COVID-19 vaccines: From clinical trials to real life

    Despite questions remain about the impact of virus variants and the duration of the immune response, messenger RNA (mRNA)-based and adenoviral vectored vaccines have demonstrated an overall efficacy from 70 to 95% in both phase III trials and real life.

  17. Experts say mRNA COVID-19 vaccines have saved millions of lives, not

    The research paper was based on COVID-19 vaccine claims that are false and misleading, experts told us. The mRNA COVID-19 vaccines have been rigorously tested and monitored for years, and public ...

  18. PDF Next Generation COVID-19 Vaccines

    Scalability: The feasibility to rapidly manufacture next-generation platforms on a large scale is currently unclear. Vaccine effectiveness: Data on vaccine efficacy and real-world effectiveness against emerging variants is sparse and mostly from high-income nations. SARS-CoV-2 genome: A key bottleneck is the rapidly evolving mutational change in the SARS-

  19. Study Finds Moderna Vaccine Reduced Symptomatic COVID-19 In Young

    The COVID-19 pandemic spurred rapid development of different vaccines, including the messenger RNA (mRNA)-1273 vaccine produced by Moderna. In a new study, a team of researchers including Rebecca Fischer, Ph.D., assistant professor in the Department of Epidemiology and Biostatistics at the Texas A&M University School of Public Health, analyzed the mRNA-1273 vaccine's efficacy at preventing ...

  20. Cureus

    Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged.

  21. Get the facts about COVID-19 vaccines

    2023-2024 Pfizer-BioNTech COVID-19 vaccine. This vaccine was first tested against the original strain of the COVID-19 virus. That strain began spreading at the end of 2019. In December 2020, the Pfizer-BioNTech COVID-19 vaccine two-dose series was found to be both safe and 91% to 95% effective in preventing COVID-19 infection in people age 18 ...

  22. Review Article By Misinformation Spreaders Misleads About mRNA COVID-19

    "A review paper published last week in the journal Cureus is the first peer-reviewed paper to call for a global moratorium on the COVID-19 mRNA vaccines," declared a Jan. 29 article published ...

  23. Global impact of the first year of COVID-19 vaccination: a mathematical

    The first COVID-19 vaccine outside a clinical trial setting was administered on Dec 8, 2020. To ensure global vaccine equity, vaccine targets were set by the COVID-19 Vaccines Global Access (COVAX) Facility and WHO. However, due to vaccine shortfalls, these targets were not achieved by the end of 2021.

  24. Frontiers

    Comparison of Adverse Effects Between Sinopharm and Pfizer-BioNTech Vaccine Recipients. The adverse effects were more common among recipients of the mRNA Pfizer-BioNTech vaccine than among recipients of the inactive Sinopharm vaccine with the odds ratio of 1.39 (95% CI 1.14-1.68); 4 out of 10 participants reported no side effects after receiving the Sinopharm vaccine compared to the Pfizer ...

  25. Early Estimates of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19

    Abstract. On September 12, 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (updated) COVID-19 vaccination with a monovalent XBB.1.5-derived vaccine for all persons aged ≥6 months to prevent COVID-19, including severe disease.

  26. Assessing America's Vaccine Safety Systems, Part 1

    Vaccines approved or authorized by FDA, including the COVID-19 vaccines, have undergone a rigorous research and development process and have been thoroughly evaluated by FDA prior to authorization ...

  27. Could alternating arms for multidose vaccines boost your immunity?

    A new study examines whether alternating arms for multidose vaccines could improve immunity. Researchers say that switching arms for the initial and booster doses of mRNA COVID-19 vaccines helped ...