Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): Pfizer-BioNTech COVID-19 Vaccine

Grading of Recommendations, Assessment, Development, and Evaluation

Overview

A Grading of Recommendations, Assessment, Development and Evaluation (GRADE) review of the evidence for benefits and harms for Pfizer-BioNTech COVID-19 vaccine was presented to the Advisory Committee for Immunization Practices (ACIP) on December 11, 2020. GRADE evidence type indicates the certainty of estimates from the available body of evidence. Evidence certainty ranges from type 1 (high certainty) to type 4 (very low certainty) [1].

The policy question was, “Should vaccination with Pfizer-BioNTech COVID-19 vaccine be recommended for persons 16 years of age and older during an Emergency Use Authorization?” The potential benefits pre-specified by the ACIP COVID-19 Vaccines Work Group included prevention of symptomatic laboratory-confirmed COVID-19 (critical), hospitalization due to COVID-19 (critical), all-cause death (important), SARS-CoV-2 seroconversion (important), and asymptomatic SARS-CoV-2 infection (important). The two pre-specified harms were serious adverse events (critical) and reactogenicity grade ≥3 (important).

A systematic review of evidence on the efficacy and safety of a two-dose regimen of Pfizer-BioNTech COVID-19 vaccine among persons aged 16 years and older was conducted. The quality of evidence from one Phase I randomized controlled trial and one Phase II/III randomized controlled trial were assessed using a modified GRADE approach [2, 3, 4].

A lower risk of symptomatic COVID-19 was observed with vaccination compared to placebo (relative risk [RR] 0.05, 95% confidence interval [CI] 0.02 to 0.10, evidence type 1), corresponding to a vaccine efficacy of 95.0% (90.3%, 97.6%). This was observed with a median follow-up of 2 months, prompting concern for indirectness due to the short duration of follow-up (i.e., observed outcome of vaccine efficacy at two months does not directly inform vaccine efficacy for any duration longer than two months). The Phase II/III randomized controlled trial that generated this estimate is ongoing, thus the efficacy estimate may change with additional follow-up. However, given the strength of the association (i.e., high estimated vaccine efficacy), it is unlikely that the efficacy estimate for symptomatic COVID-19 would change substantially enough in the months following vaccination to fall below the FDA-defined efficacy threshold for an Emergency Use Authorization. The vaccine was also associated with a lower risk of hospitalization due to COVID-19 (RR 0.0; 95% CI 0.0 to 1.10; evidence type 3), corresponding to a vaccine efficacy of 100% (-9.9%, 100%). In addition, the vaccine was associated with a lower risk of all-cause death (RR 0.50, 95% CI 0.09 to 2.73; evidence type 4). The certainty of estimates regarding hospitalization due to COVID-19 and death was reduced due to indirectness and imprecision.

In terms of harms, the available data indicate that serious adverse events were balanced between the vaccine and placebo arms (RR 1.14; 95% CI 0.89 to 1.47, evidence type 2), and two serious adverse events were judged to be related to vaccination among over 21,000 persons vaccinated. The certainty of this estimate was reduced due to indirectness related to the short duration of follow-up and sample size to assess rare serious adverse events. Reactogenicity grade ≥3 was associated with vaccination (RR 4.27; 95% CI 3.39 to 5.38, evidence type 1). About 9% of vaccine recipients vs. 2% of placebo recipients reported grade ≥3 reactions.

The Phase II/III randomized controlled trial was designed to include multiple interim analyses to evaluate the primary endpoint of vaccine efficacy against symptomatic COVID-19. While the primary endpoint was reached early, the secondary efficacy endpoint for severe COVID-19, a less frequent event, had not been met. Hospitalizations due to COVID-19 and deaths are less common, thus, Phase III trials may not be designed or statistically powered to evaluate differences between vaccine and placebo groups. Since direct evidence is not expected from early results from Phase III studies, vaccine efficacy in preventing hospitalizations due to COVID-19 and deaths may be inferred from observed efficacy against symptomatic COVID-19. Additionally, no data were available for assessment of the important outcomes of SARS-CoV-2 seroconversion and asymptomatic infection, so they were not included in the evidence profile. Data on SARS-CoV-2 seroconversion will be available from an ongoing Phase II/III trial, but asymptomatic infection is not currently being studied.

Introduction

No vaccines are currently recommended for prevention of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus which emerged in late 2019.

On December 12, 2020, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Pfizer-BioNTech COVID-19 (BNT162b2) vaccine in persons aged ≥ 16 years, for prevention of symptomatic COVID-19 [5]. As part of the process employed by the Advisory Committee for Immunization Practices (ACIP), a systematic review and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment of the evidence for Pfizer-BioNTech COVID-19 vaccine was conducted and presented to ACIP. There were no conflicts of interest reported by CDC and ACIP COVID-19 Vaccines Work Group members involved in the GRADE analysis.

The ACIP adopted a modified GRADE approach in 2010 as the framework for evaluating the scientific evidence that informs recommendations for vaccine use. GRADE was used to evaluate the Pfizer-BioNTech COVID-19 vaccine. Evidence of benefits and harms were reviewed based on the GRADE approach [1].

The primary policy question was, “Should vaccination with Pfizer-BioNTech COVID-19 vaccine be recommended for persons 16 years of age and older during an Emergency Use Authorization?” (Table 1).

Methods

We conducted a systematic review of evidence on the efficacy and safety of a two-dose regimen of Pfizer-BioNTech COVID-19 vaccine. We assessed outcomes and evaluated the quality of evidence using the GRADE approach.

We identified studies in Medline, Embase, and Cochrane Library, written in English, without date restrictions. Search terms included coronavirus, COVID-19, SARS-CoV-2, respiratory (symptom, disease, illness, condition), vaccine, immunization, trial, double blind, single blind, placebo, comparative study, phase I, phase II, phase III, immunogenicity, efficacy, effective, adverse, evidence, and variations on these terms (see Appendix 2 for details).

Articles were included if they provided data on vaccination with the Pfizer-BioNTech COVID-19 vaccine and 1) involved human subjects; 2) reported primary data; 3) included adults (ages 18 and older) at risk for SARS-CoV-2 infection; 4) included data relevant to the efficacy and safety outcomes being measured; and 5) included data for the specific vaccine formulation, dosage, and timing being recommended (BNT162b2, 30 μg IM, 2 doses at 0 and 21 days).  In addition, efforts were made to obtain unpublished and other relevant data by hand-searching reference lists, and consulting with vaccine manufacturers and subject matter experts. Titles and abstracts were screened independently and in duplicate by two separate reviewers. Characteristics of the included studies are shown in Appendix 1.

Patient-important outcomes (including benefits and harms) for assessment were selected by the Work Group during Work Group calls and via online surveys where members were asked to rate and rank the importance of relevant outcomes. The GRADE assessment across the body of evidence for each outcome was presented in an evidence profile.

Results

The results of the GRADE assessment were presented to ACIP on December 11, 2020.

After title and abstract screening of 2,576 records, 17 studies were identified as eligible for full-text review. Of these, 14 were excluded because they assessed the wrong intervention (i.e. a different vaccine or a different dose). This left 2 studies for the evidence synthesis and GRADE evidence assessment [2-3]. Subsequent to the evidence synthesis, Phase II/III trial data were published [4]. Characteristics of the included studies are shown in Appendix 1.

Outcomes of interest included individual benefits and harms. Benefits of interest deemed critical were COVID-19 symptomatic laboratory-confirmed COVID-19 and hospitalization due to COVID-19 (Table 2). Other important outcomes included all-cause death; SARS-CoV-2 seroconversion to a non-spike protein; or asymptomatic SARS-CoV-2 infection. The critical harm of interest was serious adverse events, including vaccine-associated enhanced disease; reactogenicity grade ≥3 was deemed an important harm. SARS-CoV-2 seroconversion and asymptomatic SARS-CoV-2 infections were not included in the evidence profile because no data were available.

Two studies provided data on the outcomes (Appendix 1). Data were reviewed from one published Phase I randomized controlled trial, with additional data provided by the sponsor [2,3]. Data were reviewed from one Phase II/III randomized controlled trial using data provided by the sponsor [3].

The Pfizer-BioNTech COVID-19 vaccine reduced symptomatic COVID-19 when compared to no vaccination (vaccine efficacy: 95.0% (95% CI 90.3%, 97.6%)) (Table 3a). For hospitalization due to COVID-19, 5 events occurred, all in the placebo group. Vaccine effectiveness against hospitalization due to COVID-19 was 100% (95% CI: -9.9%, 100%) (Table 3b). Deaths were also uncommon, 2 in the vaccine group and 4 in the placebo group (relative risk: 0.50 (0.09, 2.73)) (Table 3c).

Numbers of serious adverse events were comparable between the vaccine group and the placebo group across the two studies (Phase II/III: 126/21621, 0.6% vs 111/21631, 0.5%; Phase II: 1/24, 4.2% vs. 0/18, 0.0%); there were no cases of vaccine-associated enhanced disease or vaccine-related deaths (Table 3d). Grade ≥3 reactions generally were uncommon, and occurred more frequently in the vaccine than placebo groups (Table 3e).

GRADE Summary

The initial GRADE evidence level was type 1 (high) for each outcome because the body of evidence was from randomized controlled trials (Table 4). In terms of benefits, the available data indicate that the vaccine is effective for preventing symptomatic COVID-19, and no serious concerns impacting certainty were identified in the context of the time frame of an Emergency Use Authorization for this outcome (type 1, high). The certainty of the evidence for hospitalization was downgraded 1 point for serious concern of indirectness related to the median 2-month follow-up and 1 point for serious concern of imprecision (type 3, low). The certainty of the evidence for all-cause death was downgraded 1 point for serious concern of indirectness related to the median 2-month follow-up and 2 points for very serious concern of imprecision (type 4, very low). The certainty of evidence for serious adverse events was downgraded one point due to serious concern of indirectness related to the median 2-month follow-up and sample size (type 2, moderate). No serious concerns impacted the certainty for estimates of reactogenicity (type 1, high) (Table 4).

References

  1. Ahmed F. U.S. Advisory Committee on Immunization Practices (ACIP) Handbook for Developing Evidence-based Recommendationspdf icon
  2. Walsh EE, Frenck RW, Falsey AR et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. NEJM. 2020. DOI: 1056/NEJMoa2027906external icon.​
  3. Pfizer, 2020.  personal communication,  November 25–December 11, 2020.
  4. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. NEJM. 2020. DOI: 10.1056/NEJMoa2034577external icon.
  5. U.S. Food and Drug Administration, Pfizer BioNTech COVID-19 Vaccine Emergency Use Authorizationexternal icon.

Table 1: Policy Question and PICO

Table 1: Policy Question and PICO
Policy question: Should vaccination with Pfizer BioNTech COVID-19 vaccine (2-doses, IM) be recommended for persons 16 years of age and older under an emergency use authorization?
Population Persons aged ≥16 years
Intervention Pfizer-BioNTech COVID-19 vaccine BNT162b2 (30 μg, 2 doses IM, 21 days apart)
Comparison No Pfizer-BioNTech COVID-19 vaccine
Outcomes Symptomatic laboratory-confirmed COVID-19
Hospitalization due to COVID-19
All-cause death
SARS-CoV-2 seroconversion to a non-spike protein
Asymptomatic SARS-CoV-2 infection
Serious adverse events
Reactogenicity grade ≥3

Abbreviations: IM = intramuscular.

Table 2: Outcomes and Rankings

Table 2: Outcomes and Rankings
Outcome Importance Included in evidence profile
Symptomatic laboratory-confirmed COVID-19 Critical Yes
Hospitalization due to COVID-19 Critical Yesa
All-cause death Important Yesa
SARS-CoV-2 seroconversion Important Nob
Asymptomatic SARS-CoV-2 infection Important Nob
Serious adverse events Critical Yes
Reactogenicity grade ≥3 Important Yes

aLimited number of events were observed in studies identified in the review of evidence.

bData on outcome not available in studies identified in the review of evidence.

Table 3a: Summary of Studies Reporting Symptomatic Laboratory-confirmed COVID-19

Table 3a: Summary of Studies Reporting Symptomatic COVID-19 (PCR-confirmed)
Authors last name, pub year Age or other characteristic of importance n/N intervention n/N comparison Comparator Vaccine Efficacy (95% CI) [100 x (1-IRR)] Study limitations (Risk of Bias)
Pfizer, 2020 [3] Primarya: SARS-CoV-2 RT-PCR-positive symptomatic illnessb, in seronegative persons aged ≥16, ≥7 days post second dose 8/17411 162/17511 Placebo 95.0% (90.3%, 97.6%) Not serious

Abbreviations: RT-PCR = real-time polymerase chain reaction; CI = confidence interval; IRR = incidence rate ratio.

aPrimary outcome, defined as SARS-CoV-2 RT-PCR-positive symptomatic illness, in seronegative adults, ≥7 days post second dose.

bSymptomatic illness defined as least one respiratory or other COVID-19-related symptom (fever, cough, shortness of breath, chills, muscle pain, loss of taste/smell, sore throat, diarrhea, vomiting), confirmed with PCR during or +/-4 days of symptom onset

Table 3b: Summary of Studies Reporting Hospitalization due to COVID-19

Table 3b: Summary of Studies Reporting Hospitalization due to COVID-19
Authors last name, pub year Age or other characteristic of importance n/N intervention n/N comparison Comparator Vaccine Efficacy (95% CI) [100 x (1-IRR)] Study limitations (Risk of Bias)
Pfizer, 2020 [3] No evidence of prior infection, ≥7 d after dose 2a 0/17399 (0.0%) 5/17495 (0.0%) Placebo 100% (-9.9%, 100%) Not serious

Abbreviations: CI = confidence interval; IRR = incidence rate ratio

aParticipants aged ≥16 years, without evidence of prior infection, ≥7 days after dose 2

Table 3c: Summary of Studies Reporting All-cause Deatha

Table 3c: Summary of Studies Reporting All-cause Death
Authors last name, pub year Age or other characteristic of importance n/N intervention n/N comparison Comparator RR (95% CI) Study limitations (Risk of Bias)
Pfizer, 2020 [3] Persons aged ≥16 years 2/21621 4/21631 Placebo 0.50 (0.09, 2.73) Not serious

Abbreviations: RR = relative risk; CI = confidence interval.

aDeath from any cause, including COVID-related or serious adverse event.

Table 3d: Summary of Studies Reporting Serious Adverse Eventsa

Table 3d: Summary of Studies Reporting Serious Adverse Events
Authors last name, pub year Age or other characteristic of importance n/N (%) intervention n/N (%) comparison Comparator RR (95% CI) Study limitations (Risk of Bias)
Walsh, 2020 [2] Aged ≥18 1/24 (4.2) 0/18 (0.0) Placebo 2.28 (0.10, 52.92) Not serious
Pfizer, 2020 [3] Aged ≥16 126/21621 (0.6)b 111/21631 (0.5) Placebo 1.14 (0.88, 1.46) Not serious

Abbreviations: RR = relative risk; CI = confidence interval.

aDeath, life-threatening event, hospitalization, incapacity to perform normal life functions, medically important event, or congenital anomaly/birth defect

bFour serious adverse events were deemed by blinded investigators to be related to vaccination. These included: shoulder injury related to vaccine administration, ventricular arrhythmia, lymphadenopathy, and lower back pain and bilateral lower extremity pain with radicular paresthesia. Through further investigation by the FDA, only two were classified as related to vaccination: shoulder injury and lymphadenopathy.

Table 3e: Summary of Studies Reporting Reactogenicitya

Table 3e: Summary of Studies Reporting Reactogenicity
Authors last name, pub year Age or other characteristic of importance n/N (%) intervention n/N (%) comparison Comparator RR (95% CI) Study limitations (Risk of Bias)
Walsh, 2020 [2] Any local reaction or systemic eventsb,c post dose 1 or 2 2/24 (8.3) 1/18 (5.6) Placebo 1.50 (0.15, 15.28) Not serious
Pfizer, 2020 [3] Any local reaction or systemic eventsb,c, post dose 1 or 2 362/4108 (8.8) 84/4106 (2.1) Placebo  4.31 (3.41, 5.44) Not serious

Abbreviations: RR = relative risk; CI = confidence interval.

Reactogenicity grade ≥3. Both trials assessed reactogenicity by soliciting the following events through electronic diaries for 7 days following each dose: local reactions (pain at injection site, redness, swelling) and systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain, new or worsened joint pain).

Grade 3 local reactions included pain at injection site that prevented daily activity; redness >10 cm; and swelling >10 cm. Grade 4 local reactions included emergency room visit or hospitalization for severe pain at the injection site, necrosis (redness and swelling categories) or exfoliative dermatitis (redness category only).

c Grade 3 systemic events included fever >38.9°C to 40.0°C , vomiting that required intravenous hydration; diarrhea of ≥6 loose stools in 24 hours; severe fatigue, severe headache, severe muscle pain, or severe joint pain that prevented daily activity; Grade 4 systemic events included: fever >40.0°C, fatigue, headache, muscle pain, joint pain, diarrhea, or vomiting that required emergency room visit or hospitalization.

Table 4. Grade Summary of Findings Table

Table 4. Grade Summary of Findings Table
Certainty assessment № of patients Effect Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Pfizer BioNTech COVID-19 vaccine, 30 mcg, 2 doses 21 days apart No vaccine Relative
(95% CI)
Absolute
(95% CI)
Symptomatic COVID-19 (PCR-confirmed)
1 RCT not serious a not serious Not serious b,c,d not serious none 8/17411 (0.0%) 162/17511 (0.9%) c RR 0.05
(0.02 to 0.10)
9 fewer per 1,000
(from 9 fewer to 8 fewer)e
Type 1
High certainty
CRITICAL
Hospitalization due to COVID-19
1 RCT not serious a not serious serious c,f,g serious h none 0/17399 (0.0%) 5/17495 (0.0%) RR 0.00
(0.00, 1.10)
e Type 3
Low certainty
CRITICAL
All-cause death
1 RCT not serious not serious serious c,i very serious h,j none 2/21621 (0.0%) 4/21631 (0.0%) RR 0.50
(0.09 to 2.73)
e Type 4
Very low certainty
IMPORTANT
Serious adverse events
2 RCT not serious
k
not serious serious
c,l
not serious none 127/21645 (0.6%) 111/21649 (0.5%) RR 1.14
(0.89 to 1.47)
1 more per 1,000
(from 1 fewer to 2 more)e
Type 2
Moderate certainty
CRITICAL
Reactogenicity, grade ≥3
2 RCT not serious not serious not serious c,m not serious none 364/4132 (8.8%) 85/4124 (2.1%) RR 4.27
(3.39 to 5.38)
68 more per 1,000
(from 50 fewer to 91 more)e
Type 1
High certainty
IMPORTANT

Abbreviations: CI = confidence interval; COVID-19 = coronavirus disease 2019; PCR = polymerase chain reaction; RR = relative risk; RCT = randomized controlled trial.

a. Risk of bias related to blinding of participants and personnel was present. Although participants and study staff were blinded to intervention assignments, they may have inferred receipt of vaccine or placebo based on reactogenicity. This was deemed unlikely to overestimate efficacy or underestimate risk of serious adverse events, therefore the risk of bias was rated as not serious.

b. The effect shown in the table is from an analysis of the evaluable efficacy population with outcomes assessed at least 7 days post dose 2 among persons who received two doses and had no evidence of prior SARS-CoV-2 infection. In an analysis using the all-available efficacy population (including persons who received at least 1 dose, with or without evidence of prior SARS-CoV-2 infection), there were 50 cases reported among 21,314 persons who received the vaccine, and 275 cases among 21,258 persons who received the placebo, for a relative risk of 0.18 (95% CI: 0.13 to 0.24).

c. The RCT excluded persons with prior COVID-19 diagnosis, pregnant or breastfeeding women, and persons who were immunocompromised. The population included in the RCT may not represent all persons aged ≥16 years.

d. Concern for indirectness was noted due to the short duration of observation in the available body of evidence. The vaccine efficacy observed at a median 2-month follow-up may differ from the efficacy observed with ongoing follow-up. However, in consideration of the strength of association and precision observed, it is unlikely that the efficacy estimate for symptomatic COVID-19 would change substantially enough to fall below the FDA-defined efficacy threshold for Emergency Use Authorization (i.e., to <50% efficacy).

e. Absolute risk was calculated using the observed risk among placebo recipients in the available body of evidence. Absolute risk estimates should be interpreted in this context. Absolute risks were not presented for hospitalizations and deaths due to their low incidence.

f. The effect shown is from an analysis of the evaluable efficacy population, with outcomes assessed at least 7 days post dose 2, among persons who received 2 doses, and had no evidence of prior SARS-CoV-2 infection. In an analysis using the all-available efficacy population (including persons who received at least 1 dose, among those with or without evidence of prior infection), 1 hospitalized case occurred among 21,299 persons who received the vaccine, and 14 hospitalized cases occurred among 21,238 persons who received the placebo (RR=0.07; 95% CI: 0.02 to 0.47).

g. Serious concern for indirectness was noted due to the short duration of follow-up in the available body of evidence. Severe COVID-19 cases leading to hospitalization may not have had time to occur in a median 2-month follow-up.

h. Serious concern for imprecision was present due to the small number of events that were observed.

i. Serious concern for indirectness was noted due to the short duration of follow-up in the available body of evidence. Deaths due to COVID-19 may not have had time to occur in a median 2-month follow-up.

j. Death from all causes was considered a descriptive outcome in the clinical trial data. The sponsor provided counts of total deaths but appropriate denominators for analysis to evaluate benefits for this outcome are not clear, further increasing concern for imprecision.

k. Risk of bias related to blinding of participants was present. Although participants and study staff were blinded to intervention assignments, they may have inferred receipt of vaccine or placebo based on reactogenicity. Some reactogenicity outcomes may also have been reported as serious adverse events, and experiences of reactions immediately after vaccination could have influenced recall or reporting of subsequent serious adverse events. This was rated as not serious.

l. Serious concern of indirectness was noted. The body of evidence does not provide certainty that rare serious adverse events were captured due to the median 2-month follow-up and the sample size.

m. Reactogenicity data were not solicited from persons aged 16-17 years, raising some concern of indirectness. However, their reactions to vaccination are expected to be similar to those of young adults who were included. In addition, reactogenicity data from adolescents aged 12-15 years were obtained and reviewed, and were similar to those from adults aged 18-55 years.

Appendix 1. Studies Included in the Review of Evidence

Appendix 1. Studies Included in the Review of Evidence
Last name first author, Publication year Study design Country (or more detail, if needed) Age (measure central tendency – mean/SD; range) Total population N Intervention N comparison Outcomes Funding source
Polack, 2020 [4]

Pfizer, 2020 [3]

RCT United States
Brazil
Argentina
Turkey
South
Africa
Germany
Intervention:
50.6 (15.70)
aged 12-89 years
Placebo:
50.4 (15.81)
12-91 years
All-Available
Efficacy Population:
43355
Evaluable
Efficacy
Population:
36621
Safety
Population: 37706
All-Available
Efficacy
Population:
21669
Evaluable
Efficacy
Population:
18242
Safety
Population: 18860
All-Available
Efficacy
Population:
21686
Efficacy
Population:
18379
Safety
Population:
18846
  • Symptomatic laboratory-confirmed COVID-19
  • Hospitalization due to COVID-19
  • All-cause death
  • Serious Adverse Events1
  • Reactogenicity
Industry funded
Walsh, 2020 [2]2 RCT United States
Age 18-55 years
Group:
Intervention
(30 μg):
37.3 (9.85)
23-54 years<
Placebo:
34.4 (13.22)
19-53 years
Age 65-85 years
Group:
Intervention
(30 μg):
68.5 (2.81)
65-74 years
Placebo:
70.0 (3.84)
65-77 years
90 72
(36 in each
age group,
with 12
each in 3
dose
groups: 10,
20, and
30 μg)
18
  • Serious Adverse Events1
  • Reactogenicity
Industry funded

Appendix 2. Databases and strategies used for systematic review

 

Appendix 2. Databases and strategies used for systematic review
Database Strategy Records
09/28/2020
Medline
(OVID)
1946-
And
Embase
(OVID)
1988-
exp coronavirus/ OR ((corona* or corono*) adj1 (virus* or viral* or virinae*)).ti,ab,kw OR (coronavirus* or coronovirus* or coronavirinae* or Coronavirus* or Coronovirus* or Wuhan* or Hubei* or Huanan or “2019-nCoV” or 2019nCoV or nCoV2019 or “nCoV-2019” or “COVID-19” or COVID19 or “CORVID-19” or CORVID19 or “WN-CoV” or WNCoV or “HCoV-19” or HCoV19 or CoV or “2019 novel*” or Ncov or “n-cov” or “SARS-CoV-2” or “SARSCoV-2” or “SARSCoV2” or “SARS-CoV2” or SARSCov19 or “SARS-Cov19” or “SARSCov-19” or “SARS-Cov-19” or Ncovor or Ncorona* or Ncorono* or NcovWuhan* or NcovHubei* or NcovChina* or NcovChinese*).ti,ab,kw OR (((respiratory* adj2 (symptom* or disease* or illness* or condition*)) or “seafood market*” or “food market*”) adj10 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)).ti,ab,kw OR ((outbreak* or wildlife* or pandemic* or epidemic*) adj1 (China* or Chinese* or Huanan*)).ti,ab,kw. OR “severe acute respiratory syndrome*”.ti,ab,kw. OR exp Coronavirus Infections/
AND
Vaccin* OR immunization*
AND
Trial* OR rct* OR randomi?ed OR double blind OR single blind OR clinical stud* OR comparative stud* OR placebo* OR phase 3 OR phase III OR safe* OR immunogenicity OR efficacy OR effective* OR adverse OR evidence
Limit 2020 – current
Cochrane Library “novel coronavir*” OR “novel corona virus*” OR “2019 coronavirus” OR “coronavirus disease” OR “coronavirus 2019” OR covid19 OR “covid 19” OR nCoV OR “novel CoV” OR “CoV 2” OR CoV2 OR sarscov2 OR sars-cov* OR sarscov OR 2019nCoV OR 2019-nCoV
AND
Vaccin* OR immunization*

duplicates
=
unique items
Page last reviewed: December 15, 2020