Covid-19 living Data

COVID-19 vaccine effectiveness
(Randomized evidence)

Methods

Protocol

Analyses are updated every two weeks

meta-COVID

Perform your own analysis using COVID-NMA data, create and download your forest plots by clicking below:

Vaccine types

Vaccine efficacy and safety for vaccine vs placebo / no vaccine (forest plots)

Vaccine efficacy and safety for vaccine vs vaccine (forest plots)

Vaccine efficacy and safety against variants of concern (forest plots)

Vaccine efficacy, immunogenicity and safety of heterologous vs homologous vaccination (tables)

Immunogenicity
Geometric mean titre specific antibodies

Reference	Intervention 1	Intervention 2	Follow up days	Participants	GMT1(N1)	GMT2(N2)	GMR [95% CI]	Evaluated by	Risk of bias
									A	B	C	D	E	Overall
Liu X, 2021	1 dose ChAdOx1/ 1 dose BNT162b2	2 doses ChAdOx1	28	Adults	12,995 (108)	1,387 (105)	9.3 [7.7, 11]	SARS-CoV-2 anti-spike IgG, ELISA -ELU/mL
Liu X, 2021	1 dose BNT162b2 /1 dose ChAdOx1	2 doses BNT162b2	28	Adults	7,133 (109)	13,938 (110)	0.51 [0.41, 0.6]	SARS-CoV-2 anti-spike IgG, ELISA -ELU/mL
Li J, 2022	1 dose CoronaVac / 1 dose Ad5-vectored	2 doses CoronaVac	14	Healthy adults	942 (51)	154 (50)	6.11 [3.90, 9.57]	RBD-specific IgG ELISA
Janssen C, 2022	1 dose BNT162b2/1 dose mRNA-1273	2 doses BNT162b2	28	Adults	3,706 (96)	2,698 (94)	1.37 [1.10, 1.72]	ELISA
Janssen C, 2022	1 dose mRNA-1273 /1 dose BNT162b2	2 doses mRNA-1273	28	Adults	2,690 (103)	3,995 (97)	0.67 [0.55, 0.82]	ELISA

N1: Number of patients analyzed in intervention 1; N2: Number of patients analyzed in intervention 2; GMT1: Geometric mean titre for intervention 1; GMT2: Geometric mean titre for intervention 2

Geometric mean titre neutralizing antibodies

Reference	Intervention 1	Intervention 2	Follow up days	Participants	GMT1(N1)	GMT2(N2)	GMR [95% CI]	Evaluated by	Risk of bias
									A	B	C	D	E	Overall
Liu X, 2021	1 dose ChAdOx1/ 1 dose BNT162b2	2 doses ChAdOx1	28	Adults	515 (101)	61 (101)	8.5 [6.5, 11]	Pseudotype virus neutralising antibody, NT50
Liu X, 2021	1 dose BNT162b2 /1 dose ChAdOx1	2 doses BNT162b2	28	Adults	383 (104)	574 (102)	0.67 [0.51, 0.88]	Pseudotype virus neutralising antibody, NT50
Li J, 2022	1 dose CoronaVac / 1 dose Ad5-vectored	2 doses CoronaVac	14	Healthy adults	54 (51)	13 (50)	4.3 [2.5, 7.3]	CPE-based microneutralization assay-wild-type
Janssen C, 2022	1 dose BNT162b2/1 dose mRNA-1273	2 doses BNT162b2	28	Adults	523 (96)	396 (94)	1.31 [1.02, 1.69]	CPE (cytopathic effect)-based virus neutralization test (VNT)

N1: Number of patients analyzed in intervention 1; N2: Number of patients analyzed in intervention 2; GMT1: Geometric mean titre for intervention 1; GMT2: Geometric mean titre for intervention 2

Safety
Serious adverse events

Reference	Intervention 1	Intervention 2	Follow up months	Participants	r1/N1	r2/N2	RR [95% CI]	Risk of bias
								A	B	C	D	E	Overall
Liu X, 2021	1 dose ChAdOx1/ 1 dose BNT162b2	2 doses ChAdOx1	NR	Adults	0 / 114	1 / 115	0.34 [0.01 - 8.17]
Liu X, 2021	1 dose BNT162b2 /1 dose ChAdOx1	2 doses BNT162b2	NR	Adults	0 / 115	0 / 119	NR
Macchia A, 2022	Gam-COVID-Vac rAd26-S	Gam-COVID-Vac rAd26-S/BBIBP-CorV	1	Adults	0 / 87	0 / 65	NR
Stuart A, 2021 a	1 dose ChAdOx1 followed by 1 dose NVX-CoV2373	2 doses ChAdOx1	NR	Older adults	1 / 179	3 / 180	0.34 [0.04 - 3.19]
Stuart A, 2021 a	1 dose ChAdOx1 followed by 1 dose mRNA-1273	2 doses ChAdOx1	NR	Older adults	3 / 181	3 / 180	0.99 [0.2 - 4.86]
Stuart A, 2021 b	1 dose BNT162b2 followed by 1 dose NVX-CoV2373	2 doses BNT162b2	NR	Older adults	3 / 180	2 / 175	1.46 [0.25 - 8.62]
Stuart A, 2021 b	1 dose BNT162b2 followed by 1 dose mRNA-1273	2 doses BNT162b2	NR	Older adults	3 / 177	2 / 175	1.48 [0.25 - 8.77]
Li J, 2022	1 dose CoronaVac / 1 dose Ad5-vectored	2 doses CoronaVac	1	Healthy adults	0 / 51	0 / 50	NR
Janssen C, 2022	1 dose BNT162b2/1 dose mRNA-1273	2 doses BNT162b2	0.9	Adults	0 / 102	0 / 101	NR
Janssen C, 2022	1 dose mRNA-1273 /1 dose BNT162b2	2 doses mRNA-1273	0.9	Adults	0 / 106	0 / 105	NR

r1: Number of events in intervention 1, r2: Number of events in intervention 2, N1: Number of patients analyzed in intervention 1; N2: Number of patients analyzed in intervention 2.

Vaccine efficacy, immunogenicity and safety of booster vs no booster (tables)

Reference	Type of prime vaccination	Prime schedule	Intervention 1	Intervention 2	Follow up months	Participants	r1/N1	r2/N2	Vaccine efficacy [95% CI]	Risk of bias
	A	B	C	D	E	Overall
Toledo-Romani ME, 2021	Protein subunit	FINLAY-FR-2-25 mcg	Boost FINLAY-FR-1-50 mcg	Placebo	1.7	Adults	0 / 13883	6 / 14303	100.0 [, ]

Efficacy
Severe or critical COVID-19 after complete vaccination
Confirmed symptomatic COVID-19 after complete vaccination

Reference	Type of prime vaccination	Prime schedule	Intervention 1	Intervention 2	Follow up months	Participants	r1/N1	r2/N2	VE [95% CI]
	A	B	C	D	E	Overall
Moreira E D, 2022	RNA based vaccine	BNT162b2	Boost BNT162b2	Placebo	2.5	Adults and adolescents	6 / 4695	123 / 4671	95.3 [89.5, 98.3]
Toledo-Romani ME, 2021	Protein subunit	FINLAY-FR-2-25 mcg	Boost FINLAY-FR-1-50 mcg	Placebo	1.7	Adults	15 / 13883	155 / 14303	92.4 [86.9, 95.6]
Wang X-Y, 2022	Inactivated virus	BBIBP-CorV or CoronaVac	Boost V-01	Placebo	2	Healthy adults	38 / 4935	72 / 4934	47.8 [22.6, 64.7]

Reference	Type of prime vaccination	Prime schedule	Intervention 1	Intervention 2	Follow up days	Participants	GMT1(N1)	GMT2(N2)	GMR [95% CI]	Evaluated by
	A	B	C	D	E	Overall
Hall VG, 2021	RNA based vaccine	mRNA-1273	Boost mRNA-1273	Placebo	28	Transplant recipients	3,145 (60)	86 (57)	36.5 [ 12.9, 94]	Roche Elecsys
Vadrevu KM, 2022	Inactivated virus	BBV152	Boost BBV152	Placebo	28	Adolescents and adults	7,013 (80)	4,294 (87)	1.56 [1.06, 2.28]	ELISA

Immunogenicity
Geometric mean titre specific antibodies
Geometric mean titre neutralizing antibodies

Reference	Type of prime vaccination	Prime schedule	Intervention 1	Intervention 2	Follow up days	Participants	GMT1(N1)	GMT2(N2)	GMR [95% CI]	Evaluated by	Risk of bias
											A	B	C	D	E	Overall
Munro A, 2021 f	RNA based vaccine	BNT162b2	Boost mRNA1273	Placebo	28	Adults, elderly, health care workers	2,019 (91)	175 (98)	12.04 [9.95, 14.58]	PNA
Munro A, 2021 f	RNA based vaccine	BNT162b2	Boost CVnCov	Placebo	28	Adults, elderly, health care workers	487 (91)	175 (98)	2.57 [2.13, 3.12]	PNA
Munro A, 2021 f	RNA based vaccine	BNT162b2	Boost BNT162b2 half dose	Placebo	28	Adults, elderly, health care workers	1,339 (92)	175 (98)	6.91 [5.70, 8.37]	PNA
Munro A, 2021 b	RNA based vaccine	BNT162b2	Boost ChadOx1	Placebo	28	Adults, elderly, health care workers	950 (98)	157 (111)	6.01 [4.87, 7.41]	PNA
Munro A, 2021 b	RNA based vaccine	BNT162b2	Boost Novavax	Placebo	28	Adults, elderly, health care workers	766 (94)	157 (111)	5.39 [4.35, 6.67]	PNA
Munro A, 2021 b	RNA based vaccine	BNT162b2	Boost Novavax half dose	Placebo	28	Adults, elderly, health care workers	606 (89)	157 (111)	3.50 [2.81, 4.36]	PNA
Munro A, 2021 d	RNA based vaccine	BNT162b2	Boost BNT162b2	Placebo	28	Adults, elderly, health care workers	1,789 (95)	205 (93)	8.35 [6.88, 10.14]	PNA
Munro A, 2021 d	RNA based vaccine	BNT162b2	Boost VLA2001	Placebo	28	Adults, elderly, health care workers	289 (91)	205 (93)	1.38 [1.14, 1.68]	PNA
Munro A, 2021 d	RNA based vaccine	BNT162b2	Boost VLA2001 half dose	Placebo	28	Adults, elderly, health care workers	234 (87)	205 (93)	1.22 [1.00, 1.49]	PNA
Munro A, 2021 d	RNA based vaccine	BNT162b2	Boost Ad26.COV2.S	Placebo	28	Adults, elderly, health care workers	1,441 (75)	205 (93)	7.84 [6.37, 9.64]	PNA
Munro A, 2021 e	Non replicating viral vector	ChadOx1	Boost mRNA1273	Placebo	28	Adults, elderly, health care workers	2,368 (97)	80 (101)	26.98 [21.88, 33.26]	PNA
Munro A, 2021 e	Non replicating viral vector	ChadOx1	Boost CVnCov	Placebo	28	Adults, elderly, health care workers	373 (99)	80 (101)	5.06 [4.11, 6.23]	PNA
Munro A, 2021 e	Non replicating viral vector	ChadOx1	Boost BNT162b2 half dose	Placebo	28	Adults, elderly, health care workers	1,344 (103)	80 (101)	15.14 [12.32, 18.60]	PNA
Munro A , 2021 a	Non replicating viral vector	ChadOx1	Boost ChadOx1	Placebo	28	Adults, elderly, health care workers	193 (98)	85 (90)	2.47 [1.96, 3.11]	PNA
Munro A , 2021 a	Non replicating viral vector	ChadOx1	Boost Novavax	Placebo	28	Adults, elderly, health care workers	727 (87)	85 (90)	8.86 [7.00, 11.22]	PNA
Munro A , 2021 a	Non replicating viral vector	ChadOx1	Boost Novavax half dose	Placebo	28	Adults, elderly, health care workers	470 (86)	85 (90)	5.89 [4.64, 7.46]	PNA
Munro A, 2021 c	Non replicating viral vector	ChadOx1	Boost BNT162b2	Placebo	28	Adults, elderly, health care workers	1,621 (93)	70 (91)	21.58 [16.93, 27.51]	PNA
Munro A, 2021 c	Non replicating viral vector	ChadOx1	Boost VLA2001	Placebo	28	Adults, elderly, health care workers	202 (89)	70 (91)	2.68 [2.10, 3.43]	PNA
Munro A, 2021 c	Non replicating viral vector	ChadOx1	Boost VLA2001 half dose	Placebo	28	Adults, elderly, health care workers	147 (95)	70 (91)	2.01 [1.57, 2.55]	PNA
Munro A, 2021 c	Non replicating viral vector	ChadOx1	Boost Ad26.COV2.S	Placebo	28	Adults, elderly, health care workers	563 (95)	70 (91)	6.85 [5.37, 8.73]	PNA
Wang X-Y, 2022	Inactivated virus	BBIBP-CorV or CoronaVac	Boost V-01	Placebo	14	Healthy adults	1,453 (199)	157 (221)	NR	Live SARS-CoV-2 neutralization assay. A CPE assay was used to determine the 50% neutralization titer to live SARS-CoV-2. The neutralizing titer was set as the dilution number of the 50% protective condition using the Reed and Muench method. The neutralizing activity against ancestral strain was quantified by micro-dose cytopathogenic effect assays, with a limit of detection (LOD) of 10. Neutralizing activity against ancestral strain was quantified at the Wuhan Institute of Virology, Chinese Academy of Sciences by conducting micro-dose cytopathogenic effect assays, with a limit of detection (LOD) of 10.
Vadrevu KM, 2022	Inactivated virus	BBV152	Boost BBV152	Placebo	28	Adolescents and adults	746 (80)	101 (87)	7.41 [2.96, 18.51]	Plaque reduction neutralisation test

Number of patients analyzed in intervention 1; N2: Number of patients analyzed in intervention 2; GMT1: Geometric mean titre for intervention 1; GMT2: Geometric mean titre for intervention 2; N1GMR: Geometric mean ratio

Safety
Serious adverse events

Reference	Type of prime vaccination	Prime schedule	Intervention 1	Intervention 2	Follow up months	Participants	r1/N1	r2/N2	RR [95% CI]	Risk of bias
										A	B	C	D	E	Overall
Moreira E D, 2022	RNA based vaccine	BNT162b2	Boost BNT162b2	Placebo	2.5	Adults and adolescents	16 / 5055	24 / 5020	0.66 [0.35 - 1.24]
Munro A, 2021 f	RNA based vaccine	BNT162b2	Boost mRNA1273	Placebo	2.7	Adults, elderly, health care workers	0 / 110	0 / 112	NR
Munro A, 2021 f	RNA based vaccine	BNT162b2	Boost CVnCov	Placebo	2.7	Adults, elderly, health care workers	1 / 106	0 / 112	3.17 [0.13 - 76.94]
Munro A, 2021 f	RNA based vaccine	BNT162b2	Boost BNT162b2 half dose	Placebo	2.7	Adults, elderly, health care workers	0 / 110	0 / 112	NR
Munro A, 2021 b	RNA based vaccine	BNT162b2	Boost ChadOx1	Placebo	2.7	Adults, elderly, health care workers	0 / 109	1 / 118	0.36 [0.01 - 8.76]
Munro A, 2021 b	RNA based vaccine	BNT162b2	Boost Novavax	Placebo	2.7	Adults, elderly, health care workers	1 / 114	1 / 118	1.04 [0.07 - 16.35]
Munro A, 2021 b	RNA based vaccine	BNT162b2	Boost Novavax half dose	Placebo	2.7	Adults, elderly, health care workers	2 / 112	1 / 118	2.11 [0.19 - 22.91]
Munro A, 2021 d	RNA based vaccine	BNT162b2	Boost BNT162b2	Placebo	2.7	Adults, elderly, health care workers	1 / 109	0 / 109	3 [0.12 - 72.84]
Munro A, 2021 d	RNA based vaccine	BNT162b2	Boost VLA2001	Placebo	2.7	Adults, elderly, health care workers	0 / 110	0 / 109	NR
Munro A, 2021 d	RNA based vaccine	BNT162b2	Boost VLA2001 half dose	Placebo	2.7	Adults, elderly, health care workers	1 / 110	0 / 109	2.97 [0.12 - 72.18]
Munro A, 2021 d	RNA based vaccine	BNT162b2	Boost Ad26.COV2.S	Placebo	2.7	Adults, elderly, health care workers	0 / 106	0 / 109	NR
Munro A, 2021 e	Non replicating viral vector	ChadOx1	Boost mRNA1273	Placebo	2.7	Adults, elderly, health care workers	1 / 112	0 / 114	3.05 [0.13 - 74.16]
Munro A, 2021 e	Non replicating viral vector	ChadOx1	Boost CVnCov	Placebo	2.7	Adults, elderly, health care workers	0 / 119	0 / 114	NR
Munro A, 2021 e	Non replicating viral vector	ChadOx1	Boost BNT162b2 half dose	Placebo	2.7	Adults, elderly, health care workers	0 / 116	0 / 114	NR
Munro A , 2021 a	Non replicating viral vector	ChadOx1	Boost ChadOx1	Placebo	2.7	Adults, elderly, health care workers	1 / 111	0 / 109	2.95 [0.12 - 71.54]
Munro A , 2021 a	Non replicating viral vector	ChadOx1	Boost Novavax	Placebo	2.7	Adults, elderly, health care workers	0 / 115	0 / 109	NR
Munro A , 2021 a	Non replicating viral vector	ChadOx1	Boost Novavax half dose	Placebo	2.7	Adults, elderly, health care workers	0 / 108	0 / 109	NR
Munro A, 2021 c	Non replicating viral vector	ChadOx1	Boost BNT162b2	Placebo	2.7	Adults, elderly, health care workers	0 / 106	1 / 105	0.33 [0.01 - 8.01]
Munro A, 2021 c	Non replicating viral vector	ChadOx1	Boost VLA2001	Placebo	2.7	Adults, elderly, health care workers	3 / 109	1 / 105	2.89 [0.31 - 27.34]
Munro A, 2021 c	Non replicating viral vector	ChadOx1	Boost VLA2001 half dose	Placebo	2.7	Adults, elderly, health care workers	0 / 111	1 / 105	0.32 [0.01 - 7.66]
Munro A, 2021 c	Non replicating viral vector	ChadOx1	Boost Ad26.COV2.S	Placebo	2.7	Adults, elderly, health care workers	1 / 108	1 / 105	0.97 [0.06 - 15.34]
Wang X-Y, 2022	Inactivated virus	BBIBP-CorV or CoronaVac	Boost V-01	Placebo	NR	Healthy adults	6 / 5108	8 / 5110	0.75 [0.26 - 2.16]
Vadrevu KM, 2022	Inactivated virus	BBV152	Boost BBV152	Placebo	1	Adolescents and adults	0 / 80	0 / 87	NR

r1: Number of events in intervention 1, r2: Number of events in intervention 2, N1: Number of patients analyzed in intervention 1; N2: Number of patients analyzed in intervention 2.

All-cause mortality

Reference	Type of prime vaccination	Prime schedule	Intervention 1	Intervention 2	Follow up months	Participants	r1/N1	r2/N2	RR [95% CI]	Risk of bias
										A	B	C	D	E	Overall
Vadrevu KM, 2022	Inactivated virus	BBV152	Boost BBV152	Placebo	1	Adolescents and adults	0 / 80	0 / 87	NR
Toledo-Romani ME, 2021	Protein subunit	FINLAY-FR-2-25 mcg	Boost FINLAY-FR-1-50 mcg	Placebo	5.2	Adults	11 / 13883	24 / 14303	0.47 [0.23 - 0.96]
Moreira E D, 2022	RNA based vaccine	BNT162b2	Boost BNT162b2	Placebo	2.5	Adults and adolescents	0 / 5055	1 / 5020	0.33 [0.01 - 8.12]
Wang X-Y, 2022	Inactivated virus	BBIBP-CorV or CoronaVac	Boost V-01	Placebo	2	Healthy adults	0 / 5108	0 / 5110	NR

r1: Number of events in intervention 1, r2: Number of events in intervention 2, N1: Number of patients analyzed in intervention 1; N2: Number of patients analyzed in intervention 2.

Vaccine efficacy, immunogenicity and safety of booster VS booster (tables)

Immunogenicity
Geometric mean titre specific antibodies

Reference	Type of prime vaccination	Prime schedule	Intervention 1	Intervention 2	Follow up days	Participants	GMT Boost1 (N1)	GMT Boost2 (N2)	GMR [95% CI]	Evaluated by	Risk of bias
											A	B	C	D	E	Overall
Al Kaabi N, 2022	Inactivated virus	BBIBP-CorV	Boost NVSI-06-07 (Interval 1-3 m)	Boost BBIBP-CorV (Interval 1-3 m)	14	Adults	0 (267)	0 (270)	NR	ELISA
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost BNT162b2	Boost CoronaVac	28	Healthy adults	674,267 (333)	48,405 (281)	13.4 [11.6, 15.3]	multiplex immunoassay
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost ChAdOx1	Boost CoronaVac	28	Healthy adults	335,213 (296)	48,405 (281)	7.0 [6.1, 8.1]	multiplex immunoassay
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost AD26.COV2-S	Boost CoronaVac	28	Healthy adults	336,851 (294)	48,405 (281)	6.7 [5.8, 7.7]	multiplex immunoassay
Nanthapisal S, 2022	Inactivated virus	2 doses of CoronaVac 21-28 days apart	Boost ChAdOx1-S standard dose	Boost ChAdOx1-S low-dose	14	Healthy adults	1,975 (209)	1,664 (209)	NR	ELISA
Shinkai M, 2022	RNA based vaccine	BNT162b2	Boost S-268019-b	Boost BNT162b2	28	Adults	48,465 (101)	55,215 (101)	0.87 [0.72, 1.06]	ELISA anti-spike IgG, LLOQ: 100
Li J, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored	Boost Coronavac	14	Healthy adults	3,090 (96)	369 (102)	8.37 [6.52, 10.75]	RBD-specific IgG ELISA
Li JX, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored high dose	Boost CoronaVac	14	Healthy adults	6,175 (140)	670 (140)	9.21 [6.87, 12.35]	ELISA
Li JX, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored low dose	Boost CoronaVac	14	Healthy adults	4,625 (140)	670 (140)	6.9 [5.01, 9.50]	ELISA
Toledo-Romani ME, 2021	Protein subunit	FR-1-50 mcg	Boost FINLAY-FR-2	Boost FR-1	14	Healthy adults	72 (51)	99 (58)	NR	ELISA
Cao Y, 2021	Inactivated virus	CoronaVac	Boost ZF2001	Boost CoronaVac	14	Healthcare workers	10,417 (81)	7,496 (40)	*1.38 [, ]*	ELISA
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost m-RNA-1273	Boost BNT162b2	28	Healthcare workers	4,379 (112)	2,671 (111)	40.95 [23.33, 71.78]	Liaison SARS CoV-2 TrimericS IgG
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S	Boost m-RNA-1273	28	Healthcare workers	403 (106)	4,379 (112)	3.76 [2.11, 6.69]	Liaison SARS CoV-2 TrimericS IgG
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S	Boost BNT162b2	28	Healthcare workers	403 (106)	2,671 (111)	3.76 [2.11, 6.69]	Liaison SARS CoV-2 TrimericS IgG

Geometric mean titre neutralizing antibodies

Reference	Type of prime vaccination	Prime schedule	Intervention 1	Intervention 2	Follow up days	Participants	GMT Boost1 (N1)	GMT Boost2 (N2)	GMR [95% CI]	Evaluated by	Risk of bias
											A	B	C	D	E	Overall
Mok C K P, 2022	Inactivated virus	CoronaVac	Boost CoronaVac	Boost BNT162b2	30	Adults	17 (40)	207 (40)	NR	PRNT90
Al Kaabi N, 2022	Inactivated virus	BBIBP-CorV	Boost NVSI-06-07 (Interval 1-3 m)	Boost BBIBP-CorV (Interval 1-3 m)	14	Adults	1,335 (267)	296 (270)	4.36 [3.70, 5.13]	live-virus neutralization
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost BNT162b2	Boost CoronaVac	28	Healthy adults	4,326 (49)	211 (46)	21.5 [14.5, 31.9]	Pseudovirus neutralisation titres
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost ChAdOx1	Boost CoronaVac	28	Healthy adults	2,137 (52)	211 (46)	10.6 [7.2, 15.6]	Pseudovirus neutralisation titres
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost AD26.COV2-S	Boost CoronaVac	28	Healthy adults	1,844 (47)	211 (46)	8.7 [5.9, 12.9]	Pseudovirus neutralisation titres
Nanthapisal S, 2022	Inactivated virus	2 doses of CoronaVac 21-28 days apart	Boost ChAdOx1-S standard dose	Boost ChAdOx1-S low-dose	14	Healthy adults	96 (207)	97 (203)	NR	Surrogate virus neutralization test (sVNT)
Shinkai M, 2022	RNA based vaccine	BNT162b2	Boost S-268019-b	Boost BNT162b2	14	Adults	128 (101)	139 (101)	1.14 [0.94, 1.39]	Cytopathic effect-based virus neutralization test, LLOQ: 5
Li J, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored	Boost Coronavac	14	Healthy adults	197 (96)	34 (102)	5.9 [4.5, 7.7]	Cytopathic effect-based microneutralization assay- wild-type SARS-CoV-2
Li JX, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored high dose	Boost CoronaVac	14	Healthy adults	714 (140)	79 (140)	9.09 [5.65, 14.76]	CPE-based microneutralisation
Li JX, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored low dose	Boost CoronaVac	14	Healthy adults	744 (140)	79 (140)	*9.48 [6.09, ]**	CPE-based microneutralisation
Toledo-Romani ME, 2021	Protein subunit	FR-1-50 mcg	Boost FINLAY-FR-2	Boost FR-1	28	Healthy adults	33 (51)	43 (55)	NR	Conventional virus neutralization test
Cao Y, 2021	Inactivated virus	CoronaVac	Boost ZF2001	Boost CoronaVac	14	Healthcare workers	1,306 (81)	794 (40)	1.64 [1.09, 2.46]	CPE
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost m-RNA-1273	Boost BNT162b2	28	Healthcare workers	2,007 (54)	1,446 (53)	27.49 [15.23, 49.60]	PRNT
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S	Boost m-RNA-1273	28	Healthcare workers	235 (50)	2,007 (54)	3.21 [1.74, 5.93]	PRNT
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S	Boost BNT162b2	28	Healthcare workers	235 (50)	1,446 (53)	3.21 [1.74, 5.93]	PRNT

Safety
Serious adverse events

Reference	Type of prime vaccination	Prime schedule	Intervention 1	Intervention 2	Follow up months	Participants	r1/N1	r2/N2	RR [95% CI]	Risk of bias
										A	B	C	D	E	Overall
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost BNT162b2	Boost CoronaVac	1	Healthy adults	1 / 339	0 / 291	2.58 [0.11 - 62.99]
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost ChAdOx1	Boost CoronaVac	1	Healthy adults	1 / 304	0 / 291	2.87 [0.12 - 70.22]
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost AD26.COV2-S	Boost CoronaVac	1	Healthy adults	3 / 305	0 / 291	6.68 [0.35 - 128.75]
Intapiboon P, 2021	Inactivated virus	CoronaVac	CoronaVac 3mcg D0/14	CoronaVac	1	Healthy adults	0 / 30	0 / 30	NR
Intapiboon P, 2021	Inactivated virus	CoronaVac	CoronaVac 3mcg D0/14	CoronaVac	1	Healthy adults	0 / 31	0 / 30	NR
Munro APS, 2022	RNA based vaccine	BNT162b2 + boost BNT162b2	Boost BNT162b2	Boost half dose m-RNA 1273	1.7	Healthy adults	1 / 39	0 / 39	3 [0.13 - 71.37]
Munro APS, 2022	Non replicating viral vector	ChadOx1 + boost BNT162b2	Boost BNT162b2	Boost half dose m-RNA 1273	1.7	Healthy adults	2 / 44	0 / 44	5 [0.25 - 101.12]
Poh XY, 2022	RNA based vaccine	BNT162b2	Boost mRNA-1273	Boost BNT162b2	28	Adults	0 / 48	0 / 50	NR
Shinkai M, 2022	RNA based vaccine	BNT162b2	Boost S-268019-b	Boost BNT162b2	NR	Adults	0 / 101	0 / 103	NR
Li J, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored	Boost Coronavac	1	Healthy adults	0 / 96	0 / 102	NR
Li JX, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored high dose	Boost CoronaVac	1	Healthy adults	0 / 140	0 / 140	NR
Li JX, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored low dose	Boost CoronaVac	1	Healthy adults	0 / 140	0 / 140	NR
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost m-RNA-1273	Boost BNT162b2	1	Healthcare workers	0 / 112	0 / 111	NR
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S	Boost m-RNA-1273	1	Healthcare workers	0 / 106	0 / 112	NR
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S	Boost BNT162b2	1	Healthcare workers	0 / 106	0 / 111	NR
Reindl-Schwaighofer R, 2021	RNA based vaccine	BNT162b2 or mRNA-1273	Boost BNT162b2 or mRNA-1273	Boost Ad26COVS1	1	Kidney transplant recipients	2 / 99	3 / 99	0.67 [0.11 - 3.9]

r1: Number of events in intervention 1, r2: Number of events in intervention 2, N1: Number of patients analyzed in intervention 1; N2: Number of patients analyzed in intervention 2.

All-cause mortality

Reference	Type of prime vaccination	Prime schedule	Intervention 1	Intervention 2	Follow up months	Participants	r1/N1	r2/N2	RR [95% CI]
	A	B	C	D	E	Overall
Shinkai M, 2022	RNA based vaccine	BNT162b2	Boost S-268019-b	Boost BNT162b2	*	Adults	0 / 101	0 / 103	NR
Toledo-Romani ME, 2021	Protein subunit	FR-1-50 mcg	Boost FINLAY-FR-2	Boost FR-1	1	Healthy adults	0 / 55	0 / 58	NR
Reindl-Schwaighofer R, 2021	RNA based vaccine	BNT162b2 or mRNA-1273	Boost BNT162b2 or mRNA-1273	Boost Ad26COVS1	3	Kidney transplant recipients	4 / 99	4 / 99	1 [0.26 - 3.88]

Search studies

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Trial	Type	Comparisons		Design	Participants	Sample size	Overall risk of bias Highest assessment	Full description
		Intervention 1	Intervention 2
NCT04649151 ModernaTX Ali K, N Engl J Med, 2021 Full text Commentary	RNA based vaccine	mRNA-1273	Placebo	RCT Phase 2-3	Healthy adolescents in 26 centers in the USA	N=3732	Some concerns Details	Full description
NCT04860739, EudraCT2021-001978-37 Pfizer/BioNTech+Fosun Pharma Borobia A M, Lancet, 2021 Full text Commentary	RNA based vaccine	BNT162b2 30 mcg 8-12 weeks after 1 dose ChAdOx1-S	No second vaccine dose	RCT Phase 2	Healthy, or clinically stable, adults (aged ≥18 and ≤60) that were SARS-COV-2 infection free and who had received a prime ChAdOx1-S vaccination between 8 and 12 weeks before the screening visit in 5 centers in Spain.	N=676	Some concerns Details	Full description
RBR–9nn3scw AstraZeneca+University of Oxford/Sinovac/Janssen Pharmaceutical Companies/Pfizer/BioNTech+Fosun Pharma Costa Clemens SA, Lancet, 2022 Full text Commentary Commentary	Non replicating viral vector	CoronaVac/Boost BNT162b2 CoronaVac/Boost ChAdOx1 CoronaVac/Boost AD26.COV2-S	CoronaVac/Boost CoronaVac	RCT Phase 4	Healthy adults with no history of confirmed covid-19 who had previously received 2 doses of CoronaVac at two centers in Brazil	N=1240	Some concerns Details	Full description
NCT04796896 ModernaTX Creech CB, N Engl J Med, 2022 KidCOVE Full text Commentary	RNA based vaccine	mRNA-1273 (50 mcg D0/28)	Placebo	RCT Phase 2-3	Children aged 6-11 years, healthy or with stable chronic conditions and no known recent history of COVID-19 infection, at 87 centers in Canada and USA.	N=4016	Some concerns Details	Full description
NCT04470427 ModernaTX El Sahly H, N Engl J Med, 2021 COVE Updated Full text Full text Commentary Commentary	RNA based vaccine	mRNA-1273 100 mcg D1/28	Placebo D1/28	RCT Phase 3	Healthy adults with no known history of SARS-CoV-2 infection in 99 centers in the US	N=30415	Some concerns Details	Full description
NCT04368728 Pfizer/BioNTech+Fosun Pharma Frenck R, N Engl J Med, 2021 Full text Commentary	RNA based vaccine	BNT162b2 3mcg D0/21	Placebo D0/21	RCT Phase 3	Adolescents aged 12 to 15 years with no previous Covid-19 diagnosis or SARS-CoV-2 infection in 29 centers in the USA	N=2264	Some concerns Details	Full description
NCT04885907 ModernaTX Hall VG, N Engl J Med, 2021 Full text Commentary Commentary	RNA based vaccine	mRNA-1273	Placebo	RCT Phase 4	Solid organ transplant recipients with no previous diagnosis of COVID-19 who has previously received two doses of mRNA-1273 at a single center in Canada	N=120	Some concerns Details	Full description
NCT04588480 Pfizer/BioNTech+Fosun Pharma Haranaka M, Nat. Commun., 2021 Full text Commentary Commentary	RNA based vaccine	BNT162b2	Placebo	RCT Phase 1-2	Adults including elderly and co-morbidities with no history of COVID-19 at 2 centres in Japan	N=160	Low Details	Full description
NCT04649021 Pfizer/BioNTech+Fosun Pharma Hui AH, SSRN, 2022 Full text Commentary Commentary	RNA based vaccine	BNT162b2	Placebo	RCT Phase 2	Healthy adults and those with a pre-existing stable condition, at 2 centers in China.	N=960	Low Details	Full description
NCT04900467; EudraCT: 2021-002174-52 Moderna;Pfizer/BioNTech Janssen C, EClinicalMedicine, 2022 Full text Full text Commentary	Heterologous vaccination scheme	1 dose BNT162b2/1 dose mRNA-1273 1 dose mRNA-1273 /1 dose BNT162b2	2 doses BNT162b2 2 doses mRNA-1273	RCT Phase 2	Adults with no known or suspected history of SARS-CoV-2 infection at 17 centers in France.	N=414	Some concerns Details	Full description
NCT04652102; EudraCT 2020-003998-22 CureVac AG Kremsner P, Lancet Infect Dis, 2022 HERALD Full text Commentary	RNA based vaccine	CVnCoV	Placebo	RCT Phase 2-3	Adults with no history of COVID-19 in 47 centers in Belgium, Germany, The Netherlands, Spain, Argentina, Colombia, Dominican Republic, Mexico, Panama and Peru	N=39680	Some concerns Details	Full description
ChiCTR2000034825 ; NCT04523571 BioNTech RNA Pharmaceuticals Li J, Nature Medicine, 2021 Full text Commentary	RNA based vaccine	BNT162b1 10 mcg D0/21	BNT162b1 10 mcg D0/21	RCT Phase 1	Healthy young adults between 18 and 55 years of age, and older adults between 65 and 85 that were SARS-COVID-2 infection-free at a single center in China.	N=144	Low Details	Full description
ISRCTN69254139, EudraCT: 2020-005085-33 AstraZeneca+University of Oxford; Pfizer/BioNTech+Fosun Pharma Liu X, Lancet, 2021 Com-COV Full text Commentary	RNA based vaccine	1 dose ChAdOx1/ 1 dose BNT162b2 1 dose BNT162b2 /1 dose ChAdOx1	2 doses ChAdOx1 2 doses BNT162b2	RCT Phase 2	Adults 50 years or older with no previous SARS-CoV-2 infection, no or well-controlled mild-moderate comorbidities and HIV-negative in 8 centers in the UK	N=463	Some concerns Details	Full description
NCT04480957 Arcturus Therapeutics Inc. Low J, medRxiv, 2021 a Full text Commentary Commentary	RNA based vaccine	ARCT-021 1mcg ARCT-021 5mcg ARCT-021 7.5mcg ARCT-021 10mcg	Placebo	RCT Phase 1	Healthy HIV-negative adults at a single Center in Singapore.	N=42	Some concerns Details	Full description
NCT04480957 Arcturus Therapeutics Inc. Low J, medRxiv, 2021 b Full text Commentary Commentary	RNA based vaccine	ARCT-021 3mcg ARCT-021 5mcg	Placebo	RCT Phase 2	Healthy HIV-negative adults at a single Center in Singapore.	N=64	Some concerns Details	Full description
NCT04962906; NCT05027672 Gamaleya Research Institute, AstraZeneca+University of Oxford;Moderna;Sinopharm Macchia A, Lancet Reg Health Am, 2022 Full text Commentary	Non replicating viral vector	Gam-COVID-Vac rAd26-S	Gam-COVID-Vac rAd26-S/BBIBP-CorV	RCT Phase 2	Adults who had received the first dose (rAd26) of the Sputnik V vaccine at least 30 days earlier and no history of SARS-CoV-2 at a single centre in Argentina	N=540	Some concerns Details	Full description
NCT04677660 ModernaTX Masuda T, Vaccine, 2022 a Full text Commentary	RNA based vaccine	mRNA-1273	Placebo	RCT Phase 1-2	Healthy adults aged ≥ 20 years with no known history/risk of SARS-CoV-2 infection at 2 centers in Japan.	N=200	Some concerns Details	Full description
NCT04611243 Sinovac/Pfizer/BioNTech+Fosun Pharma Mok C K P, Am. J. Respir. Crit., 2022 Full text Commentary	Inactivated virus	CoronaVac/Boost CoronaVac	CoronaVac/Boost BNT162b2	RCT *	Adults that had received two doses of CoronaVac but had low immune response against SARS-CoV-2 at two centres in Hong Kong, China	N=80	Some concerns Details	Full description
NCT04955626 Pfizer/BioNTech+Fosun Pharma Moreira E D, N Engl J Med, 2022 Full text Commentary	RNA based vaccine	Boost BNT162b2 after prime vaccination with BNT162b2	BNT162b2	RCT Phase 3	Adults and adolescents (from age of 16 years) that had received two doses BNT162b2 in a previous trial at least 6 months previously and had no history of COVID-19 at 123 sites in Brazil, South Africa, and the USA	N=10136	Some concerns Details	Full description
NCT04368728 Pfizer/BioNTech + Fosun Pharma Mulligan MJ, Nature, 2020 Full text Commentary	RNA based vaccine	*	*	RCT phase 1/2	Healthy adult volunteers with HIV-negative and SARS-CoV-2 infection-free in multiple centres in the USA.	N=45	High Details	Full description
ISRCTN73765130 AstraZeneca + University of Oxford; Janssen Pharmaceutical; Novovax; Moderna + NIAID; Pfizer BioNTech + Fosun Pharma; CureVac AG; Valneva, NIHR, UK Munro A, Lancet, 2021 d COV-BOOST Full text Commentary	RNA based vaccine	BNT162b2/boost BNT162b2 BNT162b2/boost VLA2001 BNT162b2/boost VLA2001 half dose BNT162b2/boost Ad26.COV2.S	BNT162b2/Placebo	RCT Phase 2	Adults aged ≥30 years in good physical health at 18 centers in the UK.	N=545	Some concerns Details	Full description
ISRCTN73765130 ; EudraCT 2021-002175-19 Pfizer/BioNTech;ModernaTX Munro APS, Lancet Infect Dis, 2022 COV-BOOST Full text Commentary Commentary (22)00282-1/fulltext	RNA based vaccine	BNT162b2 + 2 booster doses BNT162b2 ChadOx1 + boost 2 doses BNT162b2	BNT162b2 + booster dose BNT162b2+ 2nd booster half mRNA-1273 ChadOx1 + boost 1 dose BNT162b2+ half dose m-RNA 1273	RCT Phase 2	Healthy adults aged 30 years or over, including elderly and those with well controlled or mild-moderate comorbidity, who had received a 2-dose primary schedule of either BNT162b2 or ChAdOx1 and a BNT162b2 booster at 18 centers in the UK	N=166	Some concerns Details	Full description
NCT05142319 Pfizer/BioNTech+Fosun Pharma; ModernaTX Poh XY, Clin. Infect. Dis., 2022 PRIBIVAC Full text Commentary	RNA based vaccine	Boost mRNA-1273 after prime vaccination with BNT162b2	Boost BNT162b2 after prime vaccination with BNT162b2	RCT 3	Adults at a single center in Singapore with no previous history of COVID-19 who had received a primary series of BTN162b2 at least 6 months previously	N=100	Some concerns Details	Full description
NCT04368728 Pfizer/BioNTech+Fosun Pharma Polack F, N Engl J Med, 2020 Full text Commentary ; Commentary ; Commentary ; Commentary ; Commentary	RNA based vaccine	BNT162b2 10mcg D1/D21	Normal saline (0.9% sodium chloride) D1/D21	RCT Phase 2/3	Healthy SARS-CoV-2 DNA negative adults in multiple centres in Argentina, Brazil, Germany, South Africa, Turkey, and the USA	N=43448	Some concerns Details	Full description
EudraCT021-002927-39 Pfizer/BioNTech+Fosun Pharma/Moderna/Janssen Pharmaceutical Companies Reindl-Schwaighofer R, JAMA, 2021 Updated Full text Full text Commentary Commentary	RNA based vaccine	mRNA-1273 or BNT162b2/homologous booster	mRNAorBNT/Ad26COVS1 booster	RCT Phase 2	Adult kidney transplant recipients with no history of COVID-19 infection and without an antibody response 4 weeks after a 2-dose mRNA vaccine schedule at a single center in Austria.	N=201	Some concerns Details	Full description
NCT04927936 Janssen Pharmaceutical;Moderna ;Pfizer/BionTech+Fosun Pharma Sablerolles R, N Engl J Med, 2022 Full text Commentary	Non replicating viral vector	Ad26.COV2.S/m-RNA-1273 Ad26.COV2.S/Ad26.COV2.S Ad26.COV2.S/Ad26.COV2.S	Ad26.COV2.S/BNT162b2 Ad26.COV2.S/m-RNA-1273 Ad26.COV2.S/BNT162b2	RCT Phase 3	Healthcare workers aged 18-65 years, without severe comorbidities, and no known history of SARS-CoV-2 infection who received a single Ad26.COV2.S primary vaccination at 4 centers in the Netherlands.	N=461	Some concerns Details	Full description
jRCT2031210470 Shionogi;Pfizer/BioNTech+Fosun Pharma Shinkai M, Vaccine, 2022 Updated Full text Full text Commentary Commentary	Protein subunit	BNT162b2/booster S-268019-b	BNT162b2/boostBNT	RCT Phase 2-3	Adults who had received 2 doses of BNT162b2 vaccine at least 6 months earlier with no history of SARS-CoV-2 infection at a single centre in Japan	N=204	Some concerns Details	Full description
NCT04805125 Pfizer/BioNTech+Fosun Pharma; ModernaTX Speich B, Clin. Infect. Dis., 2022 Full text Commentary Commentary	RNA based vaccine	BNT162b2	mRNA-1273	RCT Phase 3	Adult patients living with HIV (PLWH) or solid organ transplant recipients who were SARS-CoV-2 infection-free for the last 3 months in 3 centres in Switzerland.	N=430	Some concerns Details	Full description
ISRCTN27841311; EudraCT 2021-001275-16 AstraZeneca + University of Oxford / Novavax / Moderna + NIAID Stuart A, Lancet, 2021 a Com-COV2 Full text Commentary Commentary	Protein subunit	1 dose ChAdOx1 followed by 1 dose NVX-CoV2373 1 dose ChAdOx1 followed by 1 dose mRNA-1273	2 doses ChAdOx1	RCT Phase 2	Healthy adults over 50 years previously vaccinated with one dose of ChAdOx1 nCoV-19 in 9 centres in the UK	N=540	Some concerns Details	Full description
ISRCTN27841311; EudraCT 2021-001275-16 Pfizer BioNTech + Fosun Pharma / Novavax / Moderna + NIAID Stuart A, Lancet, 2021 b Com-COV2 Full text Commentary Commentary	Protein subunit	1 dose BNT162b2 followed by 1 dose NVX-CoV2373 1 dose BNT162b2 followed by 1 dose mRNA-1273	2 doses BNT162b2	RCT Phase 2	Adults over 50 years previously vaccinated with one dose of BNT162b2 at 9 centres in the UK	N=532	Some concerns Details	Full description
NCT04368728 Pfizer/BioNTech+Fosun Pharma Thomas S, N Engl J Med, 2021 Full text Commentary Commentary	RNA based vaccine	BNT162b2	Placebo	RCT Phase 2-3	Children (>=12Y yo), adolescentes and adults, with no history or SARS-CoV 2 infection at 152 sites in Argentina, Brazil, Germany, South Africa, Turkey and USA	N=44165	Some concerns Details	Full description
NCT04368728 Pfizer/BioNTech+Fosun Pharma Walsh E, N Engl J Med, 2020 Full text Commentary	RNA based vaccine	RNA-based COVID-19 vaccine BNT162b1 - 10mcg x 2 doses on day 1/22	Normal saline placebo (0.9% sodium chloride) x 2 doses on day 1/21	RCT Phase 1	Healthy SARS-CoV-2 serology/DNA negative adults in four centres in USA	N=195	Low Details	Full description
NCT04816643 Pfizer/BioNTech+Fosun Pharma Walter E, N Engl J Med, 2021 Full text Commentary	RNA based vaccine	BNT162b2 10 mcg	Placebo	RCT Phase 2-3	Children aged 5-11 years with or without stable co-morbidities with no history of COVID-19 in 81 centres in the USA, Spain, Finland, and Poland	N=2285	Some concerns Details	Full description
NCT04523571 ; ChiCTR Pfizer/BioNTech + Fosun Pharma Zhu F, ResearchSquare, 2021 Full text Commentary ; Commentary	RNA based vaccine	BNT126b1 30 mcg/0.5 ml 2-dose Days 0,21	Saline 0.5 m l Days 0,21	RCT Phase 1	Healthy SARS-CoV-2 infection-free adults aged 18-55 and 65-85 at a single center in China	N=144	Low Details	Full description

COVID-19 vaccine effectiveness(Randomized evidence)

Methods

meta-COVID

Vaccine types

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COVID-19 vaccine effectiveness
(Randomized evidence)