vaccines - versus control - for COVID-19 prophylaxis (excluding children) pdf   xlsx method abbreviations

Outcome Relative effect 95%CI LoD Trt. better when I2 k (RCT/OBS) Bayesian probability Overall ROB Publication bias Degree of certainty Endpoint importance Published MA

efficacy endpoints 00

6 months symptomatic COVID 0.09 [0.07, 0.11]< 10%1 study (1/-)100.0 %NAnot evaluable crucial-
confirmed Covid-19, from 1st dose 0.10 [0.03, 0.35]< 193%2 studies (3/-)100.0 %some concernnot evaluable moderatecrucial-
death D28 0.41 [0.37, 0.46]< 10%1 study (-/1)100.0 %NAnot evaluable crucial-
deaths 0.28 [0.11, 0.72]< 10%4 studies (4/-)99.6 %some concernnot evaluable moderatecrucial-
deaths (time to event analysis only) 0.12 [0.06, 0.24]< 10%1 study (-/1)100.0 %NAnot evaluable crucial-
hospitalization or death 0.39 [0.33, 0.46]< 10%1 study (-/1)100.0 %NAnot evaluable crucial-
vaccine efficacy from randomization (ITT) 0.11 [0.04, 0.29]< 191%2 studies (3/-)100.0 %some concernnot evaluable moderatecrucial-
clinical deterioration 0.44 [0.37, 0.52]< 10%1 study (-/1)100.0 %NAnot evaluable important-
confirmed COVID (any severity) 0.10 [0.05, 0.17]< 10%1 study (2/-)100.0 %NAnot evaluable important-
death or ventilation 0.56 [0.46, 0.68]< 10%1 study (-/1)100.0 %NAnot evaluable important-
hospitalization 0.18 [0.03, 1.17]< 10%1 study (3/-)96.3 %NAnot evaluable important-
new illness compatible with Covid-19 0.23 [0.23, 0.24]< 10%1 study (-/1)100.0 %NAnot evaluable important-
symptomatic Covid-19 0.18 [0.10, 0.35]< 193%5 studies (11/-)100.0 %some concernnot evaluable moderateimportant-
6 months severe COVID-19 0.03 [0.00, 0.46]< 10%1 study (1/-)99.4 %NAnot evaluable non important-
asymptomatic COVID case 0.33 [0.23, 0.48]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
ICU admission 0.07 [0.02, 0.25]< 10%1 study (-/1)100.0 %NAnot evaluable non important-
infection (PCR positive symptomatic or not) 0.44 [0.33, 0.59]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
severe COVID-19 occurrence 0.21 [0.11, 0.41]< 10%5 studies (8/-)100.0 %some concernnot evaluable moderatenon important-
transmission (hospitalization for COVID19) 0.77 [0.53, 1.11]< 10%1 study (-/1)92.0 %NAnot evaluable non important-
transmission (symptomatic confirmed COVID19) 0.58 [0.47, 0.72]< 182%3 studies (-/3)100.0 %seriousnot evaluable lownon important-
vaccine efficacy after dose 1 (and before dose 2) 0.35 [0.18, 0.68]< 175%2 studies (2/-)99.9 %some concernnot evaluable moderatenon important-

safety endpoints 00

cerebrovascular thromboembolic events 0.84 [0.55, 1.29]< 10%1 study (-/1)78.8 %NAnot evaluable important-
related AE (TRAE) 4.91 [4.58, 5.26]< 10%1 study (1/-)0.0 %NAnot evaluable important-
related SAE (TRSAE) 8.00 [0.42, 151.43]< 10%1 study (1/-)8.5 %NAnot evaluable important-
serious adverse events 1.02 [0.87, 1.20]< 10%3 studies (3/-)38.9 %some concernnot evaluable moderateimportant-
acute kidney injury 0.44 [0.25, 0.78]< 10%1 study (-/1)99.7 %NAnot evaluable non important-
adverse events 1.73 [0.77, 3.91]< 1100%2 studies (6/-)9.4 %some concernnot evaluable moderatenon important-
Anemia 0.79 [0.67, 0.93]< 10%1 study (-/1)99.8 %NAnot evaluable non important-
arrhythmia 0.89 [0.75, 1.06]< 10%1 study (-/1)91.0 %NAnot evaluable non important-
Arthritis or arthropathy 0.95 [0.66, 1.36]< 10%1 study (-/1)60.9 %NAnot evaluable non important-
ATE (Myocardial infarction or ischemic stroke) 0.50 [0.12, 2.00]< 10%1 study (4/-)83.6 %NAnot evaluable non important-
ATE with thrombocytopenia 1.57 [0.65, 3.79]< 10%1 study (-/1)15.8 %NAnot evaluable non important-
convulsions/seizures 1.03 [0.85, 1.26]< 10%2 studies (-/2)37.8 %criticalnot evaluable very lownon important-
deep vein thrombosis 3.00 [0.61, 14.86]< 10%1 study (1/-)9.0 %NAnot evaluable non important-
disseminated intravascular coagulation 0.70 [0.39, 1.27]< 10%1 study (-/1)88.0 %NAnot evaluable non important-
Guillain-Barré syndrome 1.00 [0.06, 15.98]< 10%1 study (2/-)50.0 %NAnot evaluable non important-
Herpes simplex infection 1.13 [0.94, 1.36]< 10%1 study (-/1)10.0 %NAnot evaluable non important-
herpes zoster infection 1.25 [0.94, 1.66]< 173%2 studies (-/2)6.3 %moderatenot evaluable moderatenon important-
immune thrombocytopenia 1.55 [0.93, 2.59]< 163%4 studies (-/4)4.7 %seriousnot evaluable lownon important-
intracranial hemorrhage 0.27 [0.05, 1.33]< 10%5 studies (5/-)94.6 %lownot evaluable highnon important-
ischemic stroke 0.67 [0.11, 3.99]< 10%1 study (7/-)67.1 %NAnot evaluable non important-
life-threatening SAE 0.91 [0.51, 1.65]< 10%1 study (1/-)61.8 %NAnot evaluable non important-
Myocardial infarction 1.00 [0.02, 50.39]< 10%1 study (8/-)50.0 %NAnot evaluable non important-
myocarditis 2.11 [1.19, 3.74]< 176%5 studies (-/5)0.6 %moderatenot evaluable moderatenon important-
neutropenia 0.87 [0.46, 1.65]< 10%1 study (-/1)66.5 %NAnot evaluable non important-
paresthesia 1.18 [1.09, 1.28]< 120%2 studies (-/2)0.0 %moderatenot evaluable moderatenon important-
pericarditis 2.00 [0.07, 59.60]< 10%1 study (1/-)34.7 %NAnot evaluable non important-
pulmonary embolism 4.00 [0.45, 35.79]< 10%1 study (8/-)10.9 %NAnot evaluable non important-
serious adverse events (SAE), any 0.88 [0.72, 1.08]< 10%5 studies (5/-)88.8 %NAnot evaluable non important-
severe adverse events 1.74 [1.41, 2.14]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
splanchnic vein thrombosis (SVT) 1.38 [0.72, 2.65]< 10%1 study (-/1)16.7 %NAnot evaluable non important-
stroke (non-specific, hemorrhagic, and ischemic) 0.99 [0.88, 1.10]< 112%2 studies (-/2)59.1 %criticalnot evaluable very lownon important-
stroke with thrombocytopenia 2.21 [0.99, 4.92]< 10%1 study (-/1)2.6 %NAnot evaluable non important-
thrombocytopenia 1.24 [1.00, 1.54]< 188%4 studies (-/4)2.7 %criticalnot evaluable very lownon important-
Transverse myelitis 1.45 [0.07, 31.68]< 10%1 study (-/1)40.8 %NAnot evaluable non important-
uveitis 1.27 [0.64, 2.52]< 10%1 study (-/1)24.7 %NAnot evaluable non important-
venous thromboembolism 2.75 [0.88, 8.64]< 10%1 study (2/-)4.2 %NAnot evaluable non important-
VTE with thrombocytopenia 0.91 [0.64, 1.28]< 10%2 studies (-/2)71.2 %criticalnot evaluable very lownon important-

AE of interest endpoints 00

cerebral venous sinus thrombosis (CVST) 2.00 [0.07, 59.60]< 10%1 study (1/-)34.7 %NAnot evaluable important-
appendicitis 1.33 [0.62, 2.84]< 10%3 studies (3/-)23.5 %some concernnot evaluable moderatenon important-
arthralgia, grade 3-4 18.37 [13.54, 24.91]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
Bell's palsy 1.76 [0.65, 4.75]< 10%4 studies (5/-)13.3 %some concernnot evaluable moderatenon important-
hypersensitivity, all terms 1.43 [1.18, 1.74]< 10%2 studies (2/-)0.0 %some concernnot evaluable moderatenon important-
immediate allergic reaction 1.47 [0.11, 19.07]< 10%2 studies (2/-)38.6 %some concernnot evaluable moderatenon important-
lymphadenopathy, any 10.69 [4.63, 24.69]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
lymphadenopathy, grade 3-4 1.00 [0.06, 15.97]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
multiple sclerosis 1.95 [0.07, 58.15]< 10%1 study (1/-)35.2 %NAnot evaluable non important-
musculoskeletal and connective tissue disorders, any 3.64 [3.25, 4.08]< 10%2 studies (2/-)0.0 %some concernnot evaluable moderatenon important-
myalgia, grade 3-4 27.64 [20.93, 36.50]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
myelitis 1.95 [0.18, 21.52]< 10%1 study (1/-)29.4 %NAnot evaluable non important-
Potential Immune Gastrointestinal disorders 0.33 [0.03, 3.13]< 10%1 study (2/-)83.3 %NAnot evaluable non important-
Potential Immune Musculoskeletal disorders 0.98 [0.06, 15.60]< 10%1 study (1/-)50.7 %NAnot evaluable non important-
Potential Immune Neuroinflammatory disorders 1.22 [0.33, 4.54]< 10%1 study (1/-)38.4 %NAnot evaluable non important-
Potential Immune Skin disorders 0.73 [0.16, 3.27]< 10%1 study (1/-)65.8 %NAnot evaluable non important-
Potential Immune Vasculitides 0.49 [0.02, 14.54]< 10%1 study (1/-)65.9 %NAnot evaluable non important-
Thromboembolic events 0.49 [0.15, 1.62]< 10%1 study (1/-)87.9 %NAnot evaluable non important-

reactogenicity (vaccines) endpoints 00

fever, grade 3-4 43.29 [17.83, 105.10]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
local adverse reaction, any, dose 1 24.90 [22.13, 28.03]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
local adverse reaction, any, dose 2 27.99 [19.26, 40.68]< 196%2 studies (2/-)0.0 %some concernnot evaluable moderatenon important-
local adverse reaction, grade 3-4, dose 2 15.04 [11.83, 19.12]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
systemic adverse reaction, any, dose 1 1.63 [1.50, 1.78]< 10%1 study (2/-)0.0 %NAnot evaluable non important-
systemic adverse reaction, any, dose 2 5.53 [3.79, 8.06]< 198%2 studies (3/-)0.0 %some concernnot evaluable moderatenon important-
systemic adverse reaction, grade 3-4, dose 2 9.50 [8.38, 10.77]< 10%1 study (1/-)0.0 %NAnot evaluable non important-

immunogenicity (vaccines) endpoints 00

serologic response (seroconversion) 0.09 [0.00, 5.02]> 170%2 studies (-/2)12.4 %NAnot evaluable non important-

LoD: level of statistical demonstration: Statistically conclusive: statistically significant with a strict control of overall risk of type 1 error (statistically demonstrated), does not take into account the risk of bias; suggested: nominally statistically significant but without a strict control of overall risk of type 1 error; inconclusive: not nominally statistically significant; safety concerns;
Bayesian probability: Bayesian posterior probability of treatment effect (computed with a noninformative prior); ROB: risk of bias; k: number of studies; published MA: number of published meta-analysis on the same topic; degree of certainty adapted from GRADE. Trt. better when: indicates when the relative treatment effect shows that the studied treatment is better than control.