Table 1.

Main studies and findings on vaccine efficacy.

Studies	Study Design	Vaccine Name	Vaccine Type	Main Inclusion/ Exclusion Criteria	No. of Subjects in Vaccine Group/No. of Subjects in Placebo Group	Outcome Type	Findings or Efficacy (%)
Saadat et al. [11]	Clinical research study	BNT162b2; mRNA-1273	mRNA vaccines	Healthcare workers previously enrolled in a hospital-wide serosurvey study and vaccinated with either the Pfizer/BioNTech or Moderna vaccine	N = 17 SARS-CoV-2 IgG antibody-negative (Ab-negative); N = 16 IgG-positive asymptomatic COVID-19 (asymptomatic); N = 26 IgG-positive with history of symptomatic COVID-19 (symptomatic)	Antibody responses	Healthcare workers with previous COVID-19 infection had higher antibody titer responses to a single dose of mRNA vaccine than those previously infected. Antibody titers started peaking at 7 days and achieved higher titers and neutralization in 14 days compared with Ab-negative volunteers.
Krammer et al. [12]	Short report	BNT162b2; mRNA-1273	mRNA vaccines	Subjects with and without documented pre- preexisting SARS-CoV-2, receiving their first vaccine dose in 2020	109 with/without documented preexisting SARS-CoV-2 (seronegative: 68, seropositive: 41)	Antibody responses	In seropositive subjects, the presence of post-vaccine antibody titers was comparable to or exceeded that in naïve subjects receiving two doses.
Parry et al. [13]	Clinical research study	BNT162b2 vaccine; ChAdOx1 nCoV-19 vaccine	mRNA vaccine and adenoviral vector vaccine	Subjects aged 80+ years who received a single dose of either BNT162b2 mRNA or ChAdOx1 adenovirus vaccine	165 participants N = 76 BNT162b2 mRNA N = 89 ChAdOx1 adenovirus vaccine	Immunogenicity (adaptive immune responses after 5 weeks)	Antibody responses against spike protein were detectable in 93% and 87% of mRNA or ChAdOx1 recipients, respectively, with median antibody titers of 19.3 and 19.6 U/mL (p = 0.41).
Sadoff et al. [14]	Randomized, double-blind, placebo-controlled, phase 3 trial	Ad26.COV2.S	Recombinant, adenoviral vector	SARS-CoV-2-negative adult subjects/RT-PCR-positive between days 1 and 14 or between days 1 and 28 were excluded from the analysis of cases with an onset at least 14 days after administration and at least 28 days after administration	per-protocol population: 39,321 SARS-CoV-2–negative participants N = 19,630 Ad26.COV2.S N = 19,691 placebo	Efficacy (against moderate to severe–critical coronavirus disease 2019 (COVID-19) with an onset at least 14 days and at least 28 days after administration)	Efficacy 66.9%.
Hall et al. [15]	Prospective cohort study	ChAdOx1 nCoV-19 (AZD1222) BNT162b2 mRNA	adenoviral vector vaccine and mRNA vaccine	Staff (aged ≥ 18 years) working in UK hospitals, assigned into either the positive cohort (antibody-positive or history of infection) or the negative cohort at the beginning of the follow-up period	23,324 participants N = 8203 assigned to the positive cohort N = 15,121 assigned to the negative cohort	Effectiveness	A single dose of BNT162b2 vaccine showed vaccine effectiveness of 70% (95% CI 55–85) 21 days after first dose and 85% (74–96) 7 days after two doses in the study population.
Fabiani et al. [16]	Retrospective cohort study	BNT162b2	mRNA vaccine	Adult healthcare workers (HCW) not infected/HCW infected with SARS-CoV-2 before the vaccination campaign, and HCW working outside hospitals	N = 6423 participants N = 1090 unvaccinated N = 147 vaccinated one dose N = 5186 vaccinated two doses	Effectiveness of one and two dose administration	84% in preventing asymptomatic and symptomatic SARS-CoV-2 infection (14–21 days from the first dose); 95% (7 days from the second dose).
Emary et al. [20]	Single-blind, multicenter, randomized phase 2/3 trial assessing the safety and efficacy of the ChAdOx1 nCoV-19 vaccine	ChAdOx1 nCoV-19 (AZD1222)	Adenoviral vector vaccine	Only participants in efficacy cohorts (n = 8534) were included; adults (≥18 years), with potentially high SARS-CoV-2 exposure, such as those in health and social care settings, enrolled at 19 study sites	8534 subjects randomly (1:1) assigned to receive standard-dose ChAdOx1 nCoV-19 vaccine (5 × 1010 viral particles) or a meningococcal group A, C, W, and Y conjugate vaccine (MenACWY) as control; 2773 subjects received a low-dose vaccine (2.2 × 1010 viral particles) as their first dose or control	The primary outcome: post hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against symptomatic COVID-19 disease for B.1.1.7	70.4% (95% CI 43.6–84.5%) efficacy against symptomatic NAAT positive infection for B.1.1.7 and 81.5% (67.9–89.4%) for non-B.1.1.7 lineage.
Voysey et al. [26]	Three single-blind randomized controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and one phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005)	ChAdOx1 nCoV-19	Adenoviral vector vaccine	Participants in three single-blind randomized controlled trials	24,422 participants were recruited and vaccinated across the four studies, of whom 17,178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine)	Virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom	Efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76.0% (59.3–85.9%). Protection did not wane during this initial 3 month period.
Kuodi et al. [27]	A cross-sectional study nested in a prospective longitudinal cohort study	Mainly the BNT162b2	mRNA vaccine	All subjects (age ≥ 18 year) tested for SARS-CoV-2 infection by RT-PCR between 15 March 2020 and 15 November 2021 in the three major government hospitals in northern Israel were eligible	951 infected and 2437 uninfected subjects	Health outcomes according to vaccination and infection status	Fatigue (22%), headache (20%), weakness (13%), and persistent muscle pain (10%) were the most common symptoms. Subjects receiving two doses are less likely than unvaccinated individuals to report any of these symptoms by 64%, 54%, 57%, and 68%, respectively (Risk ratios: 0.36, 0.46, 0.43, 0.32, p < 0.04 in the listed sequence).
Choi et al. [29]	(1) mRNA-1273 booster open-label phase: booster dose of 50 µg mRNA-1273 (2) mRNA-1273 variant booster open-label phase: booster dose of mRNA-1273.351 20 or 50 µg or mRNA-1273.211 50 µg	mRNA-1273 mRNA-1273.351 mRNA-1273.211	mRNA vaccines	(1) Inclusion in the mRNA-1273 booster phase: only participants receiving 100 µg doses of mRNA-1273 in the P201 study were included in this analysis (2) Inclusion in the mRNA-1273 variant booster phase: participants must have been enrolled in the mRNA-1273-P301 COVE (NCT04470427) study and received two doses of mRNA-1273, with their second dose ≥6 months before enrollment in P201	(1) N = 600 randomized 1:1:1 to placebo or 50 or 100 µg mRNA-1273 in phase 2 study; n = 587 received 2 injections in the blinded phase; n = 558 proceeded to mRNA-1273 booster phase and offered option of unblinding at participant decision visit (2) N = ~30,400 randomized 1:1 to placebo or 100 µg mRNA-1273 in phase 3 COVE study; n = ~29,300 completed blinded phase; n = ~28,600 proceeded to open-label phase and offered option of unblinding at participant decision visit	Exploratory interim analysis of the preliminary safety and immunogenicity of single booster doses of mRNA-1273 (50 µg), modified mRNA-1273.351 and multivalent mRNA-1273.211	Boosters increased neutralization titers against VOCs and VOIs (B.1.351, P.1., and B.1.617.2), equivalent to peak titers measured after the primary vaccine series against wildtype D614G virus, and superior against some VOIs.
Patalon et al. [31]	Case–control study	BNT162b2	mRNA vaccine	306,710 members of Maccabi Healthcare Services (age ≥40 years; 55% female), receiving either 2 or 3 doses of BNT162b2 vaccine and without a positive PCR test result for SARS-CoV-2 before the follow-up period	500,232 PCR tests performed, 227,380 in subjects receiving 2 doses and 272,852 in those receiving 3 doses, with 14.989 (6.6%) and 4941 (1.8%) positive test results in each group, respectively	Retrospective study evaluating additional protection of a third booster dose of the BNT162b2 vaccine compared with a 2-dose regimen over the short term	Estimated odds ratio of 0.14 (95% CI, 0.13–0.15) 28 to 65 days following receipt of the booster (86% reduction in the odds of testing positive for SARS-CoV-2).
Doria-Rose et al. [34]	Laboratory study	mRNA-1273	mRNA vaccines	Participants receiving two doses of mRNA-1273	Serum samples from 30 vaccine recipients 4 weeks after second dose of mRNA-1273 in the phase 3 COVE study (NCT04470427) were assayed against D614G, Beta, or Omicron spike of SARS-CoV-2 in two independent laboratories; in a separate analysis, sequential serum samples from the 7 participants vaccinated and boosted under EUA were tested against D614G, Beta, and Omicron	To assess potential risk of Omicron variant to existing vaccines, serum samples from mRNA-1273 vaccine recipients were tested for neutralizing activity against Omicron and compared to neutralization titers against D614G and Beta	Neutralizing titers to Omicron were 49–84 times lower than neutralization titers to D614G after 2 doses of mRNA-1273, leading to an increased risk of symptomatic breakthrough infections. A booster dose of mRNA-1273 increases Omicron neutralization titers and may substantially reduce this risk.