Efficacy, effectiveness and safety of EU/EEA-authorised vaccines against COVID-19: living systematic review
Week 10, 2023. Produced on 13 March 2023 at 10.15.
1 Background
A living systematic review was carried out on the efficacy, effectiveness and safety of COVID-19 vaccines that were authorised in the EU/EEA between January 2021 up to February 2022. The aim of the review was to provide a living, continuously updated overview on the evidence by specific vaccine product, age groups and SARS-CoV-2 variants.
The review was conducted by the Robert Koch Institute (RKI), in collaboration with the EU/EEA NITAG Collaboration supported by ECDC.
The living systematic review is registered in the Prospective Register of Systematic Reviews (PROSPERO; Reg. No. CRD42020208935).
2 Methods
Participants/population
Male and female participants of all age groups are eligible.
Intervention
Any vaccine against COVID-19 which has been approved for use in the EU/EEA. Complete and incomplete dosing schedules will be eligible.
Comparators/control
The comparator was placebo, no vaccination or a vaccine not directed against COVID-19 (active comparator). In addition, head-to-head trials directly comparing different vaccines against COVID-19 will be included.
Main outcomes
1. Efficacy and effectiveness-related outcomes: SARS-CoV2 infection (PCR-confirmed); COVID-19 symptomatic disease; hospitalisation due to COVID-19 (PCR-confirmed); ICU admission due to COVID-19 (PCR-confirmed); intubation and oxygen supply due to COVID-19 (PCR-confirmed); death due to COVID-19 (PCR-confirmed).
2. Safety-related outcomes: local reactions; systemic events; severe adverse events; enhanced COVID-19 disease; adverse events of special interest (AESI)*. Solicited and unsolicited events will be included.
*An adverse event of special interest (serious or non-serious) is one of scientific and medical concern specific to the sponsor’s product or programme, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterise and understand it. Depending on the nature of the event, rapid communication by the trial sponsor to other parties (e.g. regulators) might also be warranted.
Measures of effect:
Effect measures for efficacy/effectiveness and safety: relative risk (RR), odds ratio (OR), hazard ratio (HR). These measures will be used to calculate vaccine efficacy/effectiveness (VE, in %) as (1-RR (or OR or HR)) x 100.
Additional outcomes
In addition, complications of COVID-19 (including, but not limited to thromboembolism) and viral shedding will be addressed if reported. Furthermore, other safety outcomes may also be reported if found, as part of the review.
Measures of effect:
Not applicable
Types of study to be included
All phase 2/3, phase 3 and phase 4 studies with designs that have a comparison group are eligible for inclusion. This includes, but is not limited to, randomised controlled trials, cohort studies and case-control studies. For safety data, only phase 2/3 studies, phase 3, phase 4 studies and non-randomised studies with control groups will be considered (including, e.g. self-controlled case series).
Searches
Bi-weekly searches were conducted in PubMed and Embase and supplemented by hand searches on the preprint servers arXiv, BioRxiv, ChemRxiv, MedRxiv, Preprints.org, ResearchSquare and SSRN and searching the reference lists of included studies and of relevant reviews. No limitations will be made regarding publication dates and languages of publications.
Analysis
Two reviewers initially screened studies by title and abstract for eligibility. Identified studies were retrieved in full text and the relevant data was extracted.
Study characteristics and effect measures were aggregated in tables. When statistical pooling was appropriate, pooled summary estimates were calculated with 95% confidence intervals, using fixed-effects and random-effects models. For RCTs, risk of bias were assessed using the Cochrane risk of bias tool-2 ( RoB-2) and for non-randomized studies, ROBINS-I was applied.
Quality of the evidence (per outcome) was assessed using the methodology developed by the Grading of Evidence Assessment Development and Evaluation (GRADE) Working Group.
Publications linked to this living systematic review:
Harder Thomas, Koch Judith, Vygen-Bonnet Sabine, Külper-Schiek Wiebe, Pilic Antonia, Reda Sarah, Scholz Stefan, Wichmann Ole. Efficacy and effectiveness of COVID-19 vaccines against SARS-CoV-2 infection: interim results of a living systematic review, 1 January to 14 May 2021. Euro Surveill. 2021;26(28):pii=2100563. https://doi.org/10.2807/1560-7917.ES.2021.26.28.2100563
Harder Thomas, Külper-Schiek Wiebe, Reda Sarah, Treskova-Schwarzbach Marina, Koch Judith, Vygen-Bonnet Sabine, Wichmann Ole. Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B.1.617.2) variant: second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021. Euro Surveill. 2021;26(41):pii=2100920. https://doi.org/10.2807/1560-7917.ES.2021.26.41.2100920
Külper-Schiek W, Piechotta V, Pilic A, Batke M, Dreveton L-S, Geurts B, et al. Facing the Omicron variant – How well do vaccines protect against mild and severe COVID-19? Third interim analysis of a living systematic review. Available at: https://www.frontiersin.org/articles/10.3389/fimmu.2022.940562/full. Frontiers | Facing the Omicron variant—how well do vaccines protect against mild and severe COVID-19? Third interim analysis of a living systematic review (frontiersin.org)
3 COVID-19 vaccine efficacy and safety results from clinical trials
COVID-19 vaccines licensed for use in the EU/EEA were evaluated in tens of thousands of participants in clinical trials and have met EMA’s scientific standards for safety, efficacy and quality. The vaccines have been shown during clinical trials to be highly effective in providing protection against symptomatic COVID-19 and severe disease.
The EU/EEA authorised COVID-19 vaccines all showed a very good safety profile in clinical trials before receiving approval from the European Medicines Agency (EMA). Since licensing, EMA, other regulatory agencies and international bodies have been continuously monitoring the safety of COVID-19 vaccines. For further information on safety of COVID-19 vaccines please visit EMA.
3.1 Baseline characteristics for efficacy and safety studies included
3.2 Efficacy
3.2.1 Vaxzevria (AstraZeneca AB)
3.2.2 Cominarty (BioNTech Manufacturing GmbH)
3.2.3 COVID-19 Vaccine Janssen (Janssen-Cilag International NV)
3.2.4 Spikevax (Moderna Biotech Spain, S.L.)
3.2.5 Nuvaxovid (Novavax CZ A.S.)
3.3 Safety results
3.3.1 Vaxzevria (AstraZeneca AB)
[*] Medical events that have been observed after vaccination, but which are not necessarily related to or caused by the vaccine.
[~] Determining if an event is vaccine-related is made through a number of different methods including observing the rate of an adverse event in the vaccinated population and comparing it with the rate of this event among the unvaccinated population and calculating the background rate of an adverse event in the population and comparing this with the post-vaccination rates of the event. If the background rate of a particular adverse event is not known in a community, this can be compared with the observed rate in the study population with the ‘expected rate’ published by the vaccine regulatory authorities. The use of independent panels of experts are also used to assess if an adverse event may be associated with a vaccine.
3.3.2 Cominarty (BioNTech Manufacturing GmbH)
[^] Pooled results for all ages 16+ years who recevied Comirnaty
[*] Medical events that have been observed after vaccination, but which are not necessarily related to or caused by the vaccine.
[~] Determining if an event is vaccine-related is made through a number of different methods including observing the rate of an adverse event in the vaccinated population and comparing it with the rate of this event among the unvaccinated population and calculating the background rate of an adverse event in the population and comparing this with the post-vaccination rates of the event. If the background rate of a particular adverse event is not known in a community, this can be compared with the observed rate in the study population with the ‘expected rate’ published by the vaccine regulatory authorities. The use of independent panels of experts are also used to assess if an adverse event may be associated with a vaccine.
3.3.3 COVID-19 Vaccine Janssen (Janssen-Cilag International NV)
[*] Medical events that have been observed after vaccination, but which are not necessarily related to or caused by the vaccine.
[~] Determining if an event is vaccine-related is made through a number of different methods including observing the rate of an adverse event in the vaccinated population and comparing it with the rate of this event among the unvaccinated population and calculating the background rate of an adverse event in the population and comparing this with the post-vaccination rates of the event. If the background rate of a particular adverse event is not known in a community, this can be compared with the observed rate in the study population with the ‘expected rate’ published by the vaccine regulatory authorities. The use of independent panels of experts are also used to assess if an adverse event may be associated with a vaccine.
3.3.4 Spikevax (Moderna Biotech Spain, S.L.)
[^] Pooled results for all ages 16+ years who recevied Spikevax
[*] Medical events that have been observed after vaccination, but which are not necessarily related to or caused by the vaccine.
[~] Determining if an event is vaccine-related is made through a number of different methods including observing the rate of an adverse event in the vaccinated population and comparing it with the rate of this event among the unvaccinated population and calculating the background rate of an adverse event in the population and comparing this with the post-vaccination rates of the event. If the background rate of a particular adverse event is not known in a community, this can be compared with the observed rate in the study population with the ‘expected rate’ published by the vaccine regulatory authorities. The use of independent panels of experts are also used to assess if an adverse event may be associated with a vaccine.
3.3.5 Nuvaxovid (Novavax CZ A.S.)
[^] Pooled results for all ages 16+ years who recevied Spikevax
[*] Medical events that have been observed after vaccination, but which are not necessarily related to or caused by the vaccine.
[~] Determining if an event is vaccine-related is made through a number of different methods including observing the rate of an adverse event in the vaccinated population and comparing it with the rate of this event among the unvaccinated population and calculating the background rate of an adverse event in the population and comparing this with the post-vaccination rates of the event. If the background rate of a particular adverse event is not known in a community, this can be compared with the observed rate in the study population with the ‘expected rate’ published by the vaccine regulatory authorities. The use of independent panels of experts are also used to assess if an adverse event may be associated with a vaccine.
3.4 Risk of bias
3.4.1 Vaxzevria (AstraZeneca AB)
[1] Parts of the study population received a different dose of vaccine. Consequences are unclear.
[2] A considerable proportion of randomised participants (both study arms) that was higher than the number of events did not contribute to data analysis. Due to unclear reporting risk bias cannot be completely excluded.
[3] Parts of the study personnel were not blinded. Since data are based on self report (diary) knowledge of group allocation could have influenced reporting.
3.4.2 Cominarty (BioNTech Manufacturing GmbH)
[1] Parts of the study staff were not blinded (e.g. people who administered vaccinations). It was estimated that this had no or only a negligible influence on the risk of bias for this outcome.
[2] A considerable part of the randomised study population (both study arms), which is also significantly larger than the total number of events, was not included in the analysis. The reporting is unclear here, so that a bias cannot be completely ruled out.
[3] Parts of the study personnel were not blinded. Since data are based on self report (diary) knowledge of group allocation could have influenced reporting.
3.4.3 COVID-19 Vaccine Janssen (Janssen-Cilag International NV)
3.4.4 Spikevax (Moderna Biotech Spain, S.L.)
[1] Parts of the study staff were not blinded (e.g. people who administered vaccinations). It was estimated that this had no or only a negligible influence on the risk of bias for this outcome.
[2] A considerable part of the randomised study population (both study arms), which is also significantly larger than the total number of events, was not included in the analysis. The reporting is unclear here, so that a bias cannot be completely ruled out.
[3] Parts of the study staff were not blinded (e.g. people who administered vaccinations). Since these are self-reported events (electronic study diary), possible knowledge of the group membership (knowingly or unknowingly communicated by study staff) could have influenced the reporting or evaluation of events by individual study participants.
3.4.5 Nuvaxovid (Novavax CZ A.S.)
[1] Unblinded personnel administered vaccination but deviations balanced between groups; per-protocol population analysed but unclear who was excluded due to protocol violations and substantial differences between ITT and PP-effect.
[2] Per-protocol population analysed, but only 7020/7406 (vaccine); 7019/7403 (placebo) that received both doses as assigned and did not discontinue trial after second dose due to other reason evaluated; other protocol deviations justifying exclusion not clearly described, thus missingness could depend on true value.
[3] Self-assessment of COVID-19 symptoms with subsequent PCR confirmation; observer-blinded study, but unblinded personnel administered intervention and could have informed study participants consciously or unconsciously about treatment assignment. “To maintain the blind, placebo vaccination via IM route will be included and unblinded site personnel will manage study vaccine”.
[4] Knowledge of treatment assignment possible; however due to severity of outcome influence through knowledge unlikely.
[5] Reported outcome should include participants regardless of serostatus at baseline, but only includes PP-population/seronegative participants admission or mechanical ventilation linked to any virologically confirmed (by PCR to SARS-CoV-2) COVID-19 with onset at least 7 days after second study vaccination).
[6] Unblinded personnel administered vaccination but deviations balanced between groups; subset of safety population analysed.
[7] Subset of safety population evaluated; data for 2.310 of approx. planned 2400 included (96%); only percentages reported and unclear how many participants were evaluated per group
[8] Self-reported outcome and knowledge of treatment assignment possible. Due to subjectiveness of outcome, influence through awareness of assignment possible
[9] Reported as per protocol only for a subset of included participants; according to SAP safety subset planned for “approximately 2,000 participants and in the seasonal influenza vaccine co-administration sub-study of approximately 400 participants”
[10] Reported up to data cutoff date of the final efficacy analysis (timepoint not reported); but planned for 28 days after dose 2
[11] Unblinded personnel administered vaccination, deviations not balanced between groups (eg number of withdrawals and number with major protocol deviations almost the same despite 2:1 randomisation); per-protocol population analysed.
[12] Unblinded personnel administered vaccination, deviations not balanced between groups (eg number of withdrawals and number with major protocol deviations almost the same despite 2:1 randomisation); Safety population (all participants that received at least one dose) analysed.
[13] Self-reported outcome and knowledge of treatment assignment possible. Due to subjectiveness of outcome, influence through awareness of assignment possible; further, according to trial report duplicate reporting by investigators possible
[14] Due to objectiveness of outcome, influence through awareness of assignment unlikely; however, according to trial report duplicate reporting of unsolicited Aes (potentially including SAEs) by investigators possible.
3.5 GRADE tables
3.5.1 GRADE Evidence Profile: Vaccination with Vaxzevria (AstraZeneca AB) against COVID-19
[1] Some participants received differing doses of the vaccine; consequences for VE are not completely clear
[2] Residual confounding cannot completely excluded
[3] Study investigated VE after dose 1, therefore indirectness regarding intervention
[4] Part of study personnel was not blinded (incl. vaccine administrators). This could have had an impact on recognition of events/reactions by participants if information on allocation was communicated to them.
[5] Part of control arm received MenACWY vaccine
3.5.2 GRADE Evidence Profile: Vaccination with Cominarty (BioNTech Manufacturing GmbH) against COVID-19
[1] Exclusion of participants in both arms not completely transparently described; impact on results cannot definitely be excluded
[2] Wide 95% confidence interval
[4] Residual confounding cannot be excluded.
[5] Part of study personnel was not blinded (incl. vaccine administrators). This could have had an impact on recognition of events/reactions by participants if information on allocation was communicated to them.
3.5.3 GRADE Evidence Profile: Vaccination with COVID-19 Vaccine Janssen (Janssen-Cilag International NV) against COVID-19
[1] Person-years as denominator
3.5.4 GRADE Evidence Profile: Vaccination with Spikevax (Moderna Biotech Spain, S.L.) against COVID-19
[1] Exclusion of participants in both arms not completely transparently described; impact on results cannot definitely be excluded
[2] Severe COVID-19 used as proxy for hospitalization (indirectness regarding outcome)
[3] Wide 95% confidence interval
3.5.5 GRADE Evidence Profile: Vaccination with Nuvaxovid (Novavax CZ A.S.) against COVID-19
[1] Both studies were rated with a high risk of bias for this outcome.
[2] In the 302-Trial, approximately 28% of the trial participants (vaccine arm: n=1.953) were 65 years of age or older. Overall vaccine efficacy against symptomatic disease was 88.9% (95% CI, 12.8 to 98.6). While supportive evidence (immunogenicity data in this age group) suggest that the vaccine elicits an immune response comparable to younger adults, the evidence was downgraded for imprecision due to large confidence intervals and the limited sample size. 301-Trial not adequately powered to assess vaccine efficacy in the age group 65 and older.
[3] No information about efficacy against currently circulating Variants of Concern or Variants of Interest, especially Delta and Omicron
[4] Serious imprecision due to very few observed events, resulting in a wide confidence interval.
[5] Imprecision due to the very low lower value of the confidence interval, which as a true value would not lead to recommendation.
[6] The effects here were only presented for one randomised trial, as for the other study the population in the two study arms have been not adequately presented (79,6% versus 16,4% for local events and 64% and 30% for systemic events in study 302)
[7] One study was rated with a high risk of bias and the other study with some concerns for bias for this outcome.
[8] Serious imprecision because of confidence interval including both, a potential benefit and harm for the intervention.
3.6 Forest plot
Forest plot of Comirnaty (BNT162b2, BioNTech/Pfizer) and COVID-19 Vaccine Moderna (mRNA-1273) vaccine efficacy against COVID-19 infection in different age groups
4 Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection of any severity with the Delta variant (studies included up to 25 August 2021)
Current evidence shows that COVID-19 vaccines licensed in the EU are moderately effective in preventing SARS-CoV-2 infection with the Delta variant, however vaccine effectiveness against severe disease and hospitalisation remains high.
4.1 Vaccine effectiveness against SARS-CoV-2 infection of any type with the Delta variant
VE estimates against infection of any type (not specified in studies if symptomatic or asymptomatic) ranged between 49% and 82% (for 18-34 years: 90%), with pooled VE 66.9% (95% confidence interval (95%CI): 58.4-73.6%; I²=95.1%) across all studies. VE estimates against asymptomatic infection ranged between 35.9% and 80.2% with pooled VE across all studies 63.1% (95%CI: 40.9-76.9%; I²=93%).
4.1.1 Infection (any type)
4.1.2 Infection (any type)
aPreprint; CI, confidence interval; HCW, health care workers; NR, not reported
4.1.3 Forest Plot
4.2 Vaccine effectiveness against SARS-CoV-2 symptomatic infection, severe disease and hospitalisation with the Delta variant
VE against symptomatic infection ranged between 56% and 87.9% with the pooled VE estimate 75.7% (95%CI: 69.3-80.8%; I²=91.9%. VE against severe disease estimates ranged from 81.5% to 100% and the pooled VE was 93.8% (95%CI: 83-98%; I²=0%. VE estimates against hospitalisation ranged between 75% and 96%. Pooled effectiveness against hospitalisation was 90.9% (95%CI: 84.5-94.7%; I²=18.5%).
4.2.1 Symptomatic infection
4.2.2 Severe disease
4.2.3 Hospitalisation
aPreprint; CI, confidence interval; HCW, health care workers; NR, not reported
4.2.4 Forest Plot
4.3 Risk of Bias Assessments
1 adjusted estimates reported, but residual confounding possible; 2 VE not based on sequencing of Delta; 3 at least in in some participants, vaccination status was only self-reported; 4 no confounder-adjusted estimates reported; 5 vaccine (product) not reported; 6 test-negative design
5 Effectiveness of COVID-19 vaccines against mild and severe SARS-CoV-2 infections with the Omicron variant (studies included up to 11 February 2022)
Under the Omicron variant, effectiveness of EU-licensed COVID-19 vaccines in preventing any SARS-CoV-2 infection or mild disease is low and only short-lasting after primary immunization, but can be improved by booster vaccination. Vaccine effectiveness (VE) against severe COVID-19 remains high and is long-lasting, especially after receiving the booster vaccination.
5.1 Characteristics of studies
Characteristics of studies included for data extraction
5.2 Vaccine effectiveness against SARS-CoV-2 infection of any type with the Omicron variant
VE against any confirmed SARS-CoV-2 infection compared to no vaccination ranged between 0-62% after full primary immunization, and between 34-66% after a booster dose. VE-range for booster vs. primary immunization was 34-54.6%.
5.2.1 Vaccine effectiveness
[a] If not indicated otherwise, vaccine effectiveness (VE) estimates refer to the comparison of vaccinated (2 or 3 doses, respectively) vs. unvaccinated;
[b] Provided VE estimates refer to the last reported time point per observation period (e.g. if studies reported VE after 2-4 and 5-9 weeks, the estimate of 5-9 weeks was included in the depicted effect range)
[c] Several effect ranges are derived from single studies providing data for different vaccine types
[d] Time point closest to 14 days
[e] Comirnaty or Spikevax
[f] Vaxzevria or COVID-19-vaccine Janssen
[g] 1st dose with vector-based vaccine followed by prime booster dose of mRNA-based vaccine
[h] Studies include recipients of different vaccine types, and data was not further stratified
[i] Includes at least one study comparing booster vs. primary vaccination schedules (i.e., 3 vs. 2 doses)
[j] 1st dose with vector-based vaccine followed by prime booster dose, and 3rd dose of mRNA-based vaccine OR vector-based primary vaccination followed by one booster dose of mRNA-based vaccine
[k] One study estimated VE against vaccinated individuals who received second dose before =25 weeks, because of insufficient unvaccinated individuals available for analysis (Sheikh et al., 2021). VE against symptomatic infection with Omicron and Delta was estimated for 16-49 and 50+ year old’s, respectively. Estimates are provided for all reported observation periods in supplementary table 1
5.2.2 Forest plot
5.2.3 Risk of bias
5.3 Vaccine effectiveness against SARS-CoV-2 symptomatic infection with the Omicron variant
Against symptomatic COVID-19, VE ranged between 6-76% after full primary immunization, and between 19-73.9% after booster immunization, if compared to no vaccination. When comparing booster vs. primary immunization VE ranged between 56-69%.
VE was characterized by a moderate to strong decline within three to six months for SARS-CoV-2 infections and symptomatic COVID-19. Waning immunity was more profound after primary than booster immunization.
5.3.1 Vaccine effectiveness
[a] If not indicated otherwise, vaccine effectiveness (VE) estimates refer to the comparison of vaccinated (2 or 3 doses, respectively) vs. unvaccinated;
[b] Provided VE estimates refer to the last reported time point per observation period (e.g. if studies reported VE after 2-4 and 5-9 weeks, the estimate of 5-9 weeks was included in the depicted effect range)
[c] Several effect ranges are derived from single studies providing data for different vaccine types
[d] Time point closest to 14 days
[e] Comirnaty or Spikevax
[f] Vaxzevria or COVID-19-vaccine Janssen
[g] 1st dose with vector-based vaccine followed by prime booster dose of mRNA-based vaccine
[h] Studies include recipients of different vaccine types, and data was not further stratified
[i] Includes at least one study comparing booster vs. primary vaccination schedules (i.e., 3 vs. 2 doses)
[j] 1st dose with vector-based vaccine followed by prime booster dose, and 3rd dose of mRNA-based vaccine OR vector-based primary vaccination followed by one booster dose of mRNA-based vaccine
[k] One study estimated VE against vaccinated individuals who received second dose before =25 weeks, because of insufficient unvaccinated individuals available for analysis (Sheikh et al., 2021). VE against symptomatic infection with Omicron and Delta was estimated for 16-49 and 50+ year old’s, respectively. Estimates are provided for all reported observation periods in supplementary table 1
5.3.2 Forest plot
5.3.3 Risk of bias
5.4 Vaccine effectiveness against SARS-CoV-2 severe disease infection with the Omicron variant
VE against severe COVID-19 compared to no vaccination ranged between 3-84% after full primary immunization, and between 12-100% after a booster dose. One study compared booster vs. primary immunization (VE 100%, 95% CI 71.4-100).
Against severe COVID-19 protection remained robust at least for up to six months. Waning immunity was more profound after primary than booster immunization.
5.4.1 Vaccine effectiveness
[a] If not indicated otherwise, vaccine effectiveness (VE) estimates refer to the comparison of vaccinated (2 or 3 doses, respectively) vs. unvaccinated;
[b] Provided VE estimates refer to the last reported time point per observation period (e.g. if studies reported VE after 2-4 and 5-9 weeks, the estimate of 5-9 weeks was included in the depicted effect range)
[c] Several effect ranges are derived from single studies providing data for different vaccine types
[d] Time point closest to 14 days
[e] Comirnaty or Spikevax
[f] Vaxzevria or COVID-19-vaccine Janssen
[g] 1st dose with vector-based vaccine followed by prime booster dose of mRNA-based vaccine
[h] Studies include recipients of different vaccine types, and data was not further stratified
[i] Includes at least one study comparing booster vs. primary vaccination schedules (i.e., 3 vs. 2 doses)
[j] 1st dose with vector-based vaccine followed by prime booster dose, and 3rd dose of mRNA-based vaccine OR vector-based primary vaccination followed by one booster dose of mRNA-based vaccine
[k] One study estimated VE against vaccinated individuals who received second dose before =25 weeks, because of insufficient unvaccinated individuals available for analysis (Sheikh et al., 2021). VE against symptomatic infection with Omicron and Delta was estimated for 16-49 and 50+ year old’s, respectively. Estimates are provided for all reported observation periods in supplementary table 1
5.4.2 Forest plot
5.4.3 Risk of bias
