Covid-19 living Data

COVID-19 vaccine effectiveness
(Randomized evidence)

Methods

Results of booster studies are available in the tables below and are updated on a daily basis.

As of December 14, 2022, the COVID-NMA revised its protocol and discontinued the inclusion of prime vaccination trials in its analysis. The analysis presented on this page for prime vaccines compared to placebo or other vaccines includes trials that were identified and included up to December 14, 2022. A list of studies that were eligible up to this date but not extracted is provided in detail here .

On December 7, 2022, we published results of the systematic review "Efficacy and safety of COVID‐19 vaccines" which included 41 preprints and published trials of 12 different COVID-19 used as prime vaccination and that were published before 5 November 2021.

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
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
Puthanakit T, 2022 a	CoronaVac followed by BNT162b2 30 at 6week interva	CoronaVac followed by BNT162b2 30 at 3week interva	21	Adolescents	112 (20)	77 (20)	1.28 [1.09, 1.51]	ELISA
Puthanakit T, 2022 a	CoronaVac followed by BNT162b2 20 at 3week interva	CoronaVac followed by BNT162b2 30 at 3week interva	21	Adolescents	84 (17)	77 (20)	0.95 [0.80, 1.13]	ELISA
Puthanakit T, 2022 a	CoronaVac followed by BNT162b2 20 at 6week interva	CoronaVac followed by BNT162b2 30 at 3week interva	21	Adolescents	74 (19)	77 (20)	1.10 [0.94, 1.30]	ELISA
Chen C, 2022	1 dose ChAdOx1 / 1 dose MVC-COV1901	ChAdOx1	10	Healthy adults	8 (50)	5 (50)	1.5 [1.2, 1.9]	ELISA
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]	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
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)
Jin P, 2022 b	CoronaVac/Ad5-nCoV	CoronaVac	14	Elderly	5 (30)	4 (30)	1.3 [1.0, 2.9]	Microneutralization assay against Omicron BA.1.1 variant
Chen C, 2022	1 dose ChAdOx1 / 1 dose MVC-COV1901	ChAdOx1	10	Healthy adults	202 (50)	78 (50)	2.6 [1.7, 4.0]	Plaque reduction neutralization
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

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
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]
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
Liu X, 2022	1 dose ChAdOx1/ 1 dose BNT162b2	2 doses ChAdOx1	8.3	Adults	2 / 114	1 / 115	2.02 [0.19 - 21.94]
Liu X, 2022	1 dose BNT162b2 /1 dose ChAdOx1	2 doses BNT162b2	8.3	Adults	2 / 115	1 / 119	2.07 [0.19 - 22.51]
Jin P, 2022 b	CoronaVac/Ad5-nCoV	CoronaVac	6	Elderly	1 / 50	2 / 50	0.5 [0.05 - 5.33]
Bánki Z, 2022	1 dose ChAdOx1/ 1 dose BNT162b2	ChAdOx1	1	Healthy adults	1 / 114	0 / 108	2.84 [0.12 - 69.03]
Chen C, 2022	1 dose ChAdOx1 / 1 dose MVC-COV1901	ChAdOx1	0.9	Healthy adults	0 / 50	0 / 50	NR
Li J, 2022	1 dose CoronaVac / 1 dose Ad5-vectored	2 doses CoronaVac	1	Healthy adults	0 / 51	0 / 50	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	Intervention 1	Intervention 2	Follow up months	Participants	r1/N1	r2/N2	RR [95% CI]	Risk of bias
	A	B	C	D	E	Overall
Chen C, 2022	1 dose ChAdOx1 / 1 dose MVC-COV1901	ChAdOx1	0.9	Healthy adults	0 / 50	0 / 50	NR

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, 2022 b Full text Full text	Protein subunit	FINLAY-FR-2-25 mcg	Boost FINLAY-FR-1-50 mcg	Placebo	*	Adults	0 / 13828	6 / 12486	100.0 [*, 100]

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]
Wang X-Y, 2022	Inactivated virus	BBIBP-CorV or CoronaVac	Boost V-01	Placebo	2	Healthy adults	NR	NR	47.8 [22.6, 64.7]
Toledo-Romani ME, 2022 b	Protein subunit	FINLAY-FR-2-25 mcg	Boost FINLAY-FR-1-50 mcg	Placebo	*	Adults	NR	NR	92.0 [80.4, 96.7]

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 neutralization assay against -wild type

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
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost ChAdTS-S	Placebo	14	Adults	290 (48)	5 (46)	56.8 [43.6, 74.1]	Micro-neutralisation assay
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost RQ3013	Placebo	14	Adults	950 (46)	5 (46)	190.9 [145.8, 249.9]	Micro-neutralisation assay
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost ZR202-CoV	Placebo	14	Adults	635 (47)	5 (46)	120.8 [92.6, 157.6]	Micro-neutralisation assay
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost CoronaVac	Placebo	14	Adults	75 (46)	5 (46)	15.1 [11.5, 19.8]	Micro-neutralisation assay
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
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 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 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
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.
Vadrevu KM, 2022	Inactivated virus	BBV152	Boost BBV152	Placebo	28	Adolescents and adults	746 (80)	101 (87)	7.41 [2.96, 18.51]	PRNT

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

Geometric mean titre neutralization assay- omicron

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
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost ChAdTS-S	Placebo	14	Adults	41 (48)	4 (46)	10.3 [7.6, 14.0]	Micro-neutralisation assay
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost RQ3013	Placebo	14	Adults	247 (46)	4 (46)	62.4 [45.8, 85.1]	Micro-neutralisation assay
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost ZR202-CoV	Placebo	14	Adults	104 (47)	4 (46)	26.0 [19.1, 35.4]	Micro-neutralisation assay
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost CoronaVac	Placebo	14	Adults	8 (46)	4 (46)	2.0 [1.5, 2.7]	Micro-neutralisation assay

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
Tabarsi P, 2022	Any COVID-19 vaccine	Any Covid-19 vaccine	Boost SpikoGen	Placebo	0.5	Adults	0 / 250	0 / 50	NR
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost ChAdTS-S	Placebo	3	Adults	0 / 48	3 / 47	0.14 [0.01 - 2.63]
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost RQ3013	Placebo	3	Adults	0 / 47	3 / 47	0.14 [0.01 - 2.69]
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost ZR202-CoV	Placebo	3	Adults	0 / 47	3 / 47	0.14 [0.01 - 2.69]
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost CoronaVac	Placebo	3	Adults	0 / 46	3 / 47	0.15 [0.01 - 2.74]
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 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]
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 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 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
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
Toledo-Romani ME, 2022 b	Protein subunit	FINLAY-FR-2-25 mcg	Boost FINLAY-FR-1-50 mcg	Placebo	2.7	Adults	1 / 14677	3 / 14675	0.33 [0.03 - 3.2]
Sung J, 2022	Any COVID-19 vaccine	2 doses BNT162b2 or BBIBP	Boost Recombinant inactiv Bacillus subtilis spores	Boost active adjuvant	1.2	Healthy adults	0 / 9	0 / 7	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, 2022 b	Protein subunit	FINLAY-FR-2-25 mcg	Boost FINLAY-FR-1-50 mcg	Placebo	5.4	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
Sung J, 2022	Any COVID-19 vaccine	2 doses BNT162b2 or BBIBP	Boost Recombinant inactiv Bacillus subtilis spores	Boost active adjuvant	1.2	Healthy adults	0 / 9	0 / 7	NR
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost ChAdTS-S	Placebo	3	Adults	0 / 48	0 / 47	NR
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost RQ3013	Placebo	3	Adults	0 / 47	0 / 47	NR
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost ZR202-CoV	Placebo	3	Adults	0 / 47	0 / 47	NR
Zhang Y, 2022	Inactivated virus	CoronaVac	Boost CoronaVac	Placebo	3	Adults	0 / 46	0 / 47	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
Shinkai M, 2022	RNA based vaccine	BNT162b2	Boost S-268019-b	Boost BNT162b2	28	Adults	48464.8 / 101	NR	0.87 [0.72, 1.06]	ELISA
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	1975.1 / 209	NR	1.19 [1.07, 1.31]	ELISA
Cao Y, 2021	Inactivated virus	CoronaVac	Boost ZF2001	Boost CoronaVac	14	Healthcare workers	10417 / 81	NR	*1.38 [, ]*	ELISA
Anderson E, 2022	RNA based vaccine	mRNA-1273	Boost 50 mcg mRNA-1273.351	Boost 25 mcg mRNA-1273.351 and 25 mcg mRNA-1273	14	Healthy volunteers	9591 / 25	NR	1.06 [0.78, 1.43]	4-plex Mesoscale Discovery (MSD) 10-plex assay.
Anderson E, 2022	RNA based vaccine	mRNA-1273	Boost 100 mcg mRNA-1273	Boost 25 mcg mRNA-1273.351 and 25 mcg mRNA-1273	14	Healthy volunteers	8396 / 41	NR	0.93 [0.69, 1.24]	4-plex Mesoscale Discovery (MSD) 10-plex assay.
Li J, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored	Boost Coronavac	14	Healthy adults	3090.1 / 96	NR	8.37 [6.52, 10.75]	ELISA
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost m-RNA-1273	Boost Ad26.COV2.S	28	Healthcare workers	4379 / 112	NR	10.86 [8.22, 14.34]	Liaison SARS CoV-2 TrimericS IgG
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost BNT162b2	Boost Ad26.COV2.S	28	Healthcare workers	2671 / 111	NR	6.62 [4.93, 8.89]	Liaison SARS CoV-2 TrimericS IgG
Lien C, 2022 b	Protein subunit	MVC-COV1901	Boost MVC-COV1901+boost MVC-COV1901-Beta 15 mcg	Boost MVC-COV1901+boost MVC-COV1901	14	Adults including healthy or stable co-morbidities	28179.38 / 19	21078.01 / 21	1.33 [0.88, 2.01]	ELISA
Lien C, 2022 b	Protein subunit	MVC-COV1901	Boost MVC-COV1901+boost MVC-COV1901-Beta 25 mcg	Boost MVC-COV1901+boost MVC-COV1901	14	Adults including healthy or stable co-morbidities	21638.16 / 18	21078.01 / 21	1.02 [0.67, 1.55]	ELISA
Lien C, 2022 a	Protein subunit	MVC-COV1901	Boost MVC-COV1901-Beta 15 mcg	Boost MVC-COV1901	14	Adults including healthy or stable co-morbidities	32938.41 / 12	25878.60 / 15	1.27 [0.70, 2.83]	ELISA
Lien C, 2022 a	Protein subunit	MVC-COV1901	Boost MVC-COV1901-Beta 25 mcg	Boost MVC-COV1901	14	Adults including healthy or stable co-morbidities	43208.61 / 12	25878.60 / 15	1.66 [0.92, 3]	ELISA

Geometric mean titre neutralization assay against -wild type

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
Toledo-Romani ME, 2022 a	Protein subunit	FINLAY-FR-2-25 mcg	Boost FR-1	Boost FINLAY-FR-2	28	Healthy adults	43 (55)	33 (51)	1.29 [0.81, 2.06]	Conventional virus neutralization test
Al Kaabi N, 2023	Inactivated virus	BBIBP-CorV	Boost NVSI-06-09	Boost BBIBP-CorV	14	Healthy adults	2,349 (255)	506 (249)	4.64 [3.93, 5.47]	Live-virus microneutralization assay
Shinkai M, 2022	RNA based vaccine	BNT162b2	Boost S-268019-b	Boost BNT162b2	14	Adults	128 (101)	139 (101)	0.94 [0.76, 1.09]	Cytopathic effect-based virus neutralization test
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)	0.99 [0.97, 1.01]	Virus neutralization test (sVNT)
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
Anderson E, 2022	RNA based vaccine	mRNA-1273	Boost 50 mcg mRNA-1273.351	Boost 25 mcg mRNA-1273.351 and 25 mcg mRNA-1273	15	Healthy volunteers	2,111 (25)	2,435 (22)	0.87 [0.60, 1.24]	Neutralization assay (PsVN)
Anderson E, 2022	RNA based vaccine	mRNA-1273	Boost 100 mcg mRNA-1273	Boost 25 mcg mRNA-1273.351 and 25 mcg mRNA-1273	15	Healthy volunteers	2,842 (41)	2,435 (22)	1.17 [0.84, 1.62]	Neutralization assay (PsVN)
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
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
Al Kaabi N, 2022	Inactivated virus	BBIBP-CorV	Boost NVSI-06-07 (Interval 4-6 m)	Boost BBIBP-CorV (Interval 4-6 m)	14	Adults	1,813 (279)	328 (290)	5.75 [4.99, 6.63]	live-virus neutralization
Niyomnaitham S, 2022	Inactivated virus	CoronaVac	Boost ChAdOx1 (1/5 dose ID)	Boost BNT162b2 (1/6 dose ID)	14	Healthy adults	206 (45)	288 (45)	0.71 [0.48, 1.07]	Plaque reduction neutralization test
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost m-RNA-1273	Boost Ad26.COV2.S	28	Healthcare workers	5,686 (11)	614 (12)	9.26 [5.20, 16.48]	PRNT
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost BNT162b2	Boost Ad26.COV2.S	28	Healthcare workers	2,204 (12)	614 (12)	3.58 [1.11, 11.59]	PRNT
Al Kaabi N, 2022 b	Inactivated virus	BBIBP-CorV	Boost NVSI-06-08 4-6 months	Boost BBIBP-CorV 4-6 months	15	Healthy adults	3,142 (285)	197 (289)	15.96 [13.34, 19.08]	Live-virus neutralization assay
Al Kaabi N, 2022 b	Inactivated virus	BBIBP-CorV	Boost NVSI-06-08 7-9 months	Boost BBIBP-CorV 7-9 months	15	Healthy adults	4,908 (270)	505 (270)	9.72 [8.04, 11.77]	Live-virus neutralization assay
Al Kaabi N, 2022 b	Inactivated virus	BBIBP-CorV	Boost NVSI-06-08 >9 months	Boost BBIBP-CorV >9 months	15	Healthy adults	4,185 (286)	375 (278)	11.17 [9.44, 13.22]	Live-virus neutralization assay
Niyomnaitham S, 2022	Inactivated virus	Coronavac	Boost ChAdOx1	Boost BNT162b2	28	Healthy adults	575 (97)	928 (99)	0.61 [0.49, 0.77]	Micro Neutralizing Antibody Titer
Corominas J, 2023	RNA based vaccine	BNT162b2	Boost PHH-1V	Boost BNT162b2	14	Healthy adults	1,966 (500)	3,309 (241)	0.59 [0.51, 0.69]	Pseudovirion-based neutralisation assay
Tang R, 2023	Inactivated virus	Coronavac	Boost Coronovac/BoostAd5-nCoV IN	Boost Coronovac/boost Coronavac	14	Healthy adults	292 (117)	78 (116)	3.7 [2.6, 5.1]	Cytopathic effect-based microneutralization assay
Tang R, 2023	Inactivated virus	Coronavac	Boost Coronovac/Ad5-nCoV INCoV IM	Boost Coronovac/boost Coronavac	14	Healthy adults	746 (118)	78 (116)	9.5 [7.3, 12.3]	Cytopathic effect-based microneutralization assay
Lien C, 2022 b	Protein subunit	MVC-COV1901	Boost MVC-COV1901+boost MVC-COV1901-Beta 15 mcg	Boost MVC-COV1901+boost MVC-COV1901	28	Adults including healthy or stable co-morbidities	1,125 (19)	868 (18)	1.29 [0.82, 2.02]	Plaque reduction neutralization test
Lien C, 2022 b	Protein subunit	MVC-COV1901	Boost MVC-COV1901+boost MVC-COV1901-Beta 25 mcg	Boost MVC-COV1901+boost MVC-COV1901	28	Adults including healthy or stable co-morbidities	929 (18)	868 (18)	1.06 [0.68, 1.67]	Plaque reduction neutralization test
Lien C, 2022 a	Protein subunit	MVC-COV1901	Boost MVC-COV1901-Beta 15 mcg	Boost MVC-COV1901	28	Adults including healthy or stable co-morbidities	1,805 (12)	1,352 (14)	1.33 [0.61, 2.89]	Plaque reduction neutralization test
Lien C, 2022 a	Protein subunit	MVC-COV1901	Boost MVC-COV1901-Beta 25 mcg	Boost MVC-COV1901	28	Adults including healthy or stable co-morbidities	3,603 (12)	1,352 (14)	2.64 [1.22, 5.79]	Plaque reduction neutralization test
Amplify, 2023 b	RNA based vaccine	BNT162b2	Boost Ad26.COV2.S 1*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	14	Adults including elderly and stable co-morbidities	3,218 (88)	4,439 (299)	0.725 [0.570, 0.922]	Virus neutralization assay (VNA)
Amplify, 2023 b	RNA based vaccine	BNT162b2	Boost Ad26.COV2.S 2.5*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	14	Adults including elderly and stable co-morbidities	3,566 (295)	4,439 (299)	0.803 [0.696, 0.927]	Virus neutralization assay (VNA)
Amplify, 2023 a	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S 1*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	14	Adults including elderly and stable co-morbidities	734 (93)	1,130 (298)	0.649 [0.484, 0.827]	Virus neutralization assay (VNA)
Amplify, 2023 a	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S 2.5*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	14	Adults including elderly and stable co-morbidities	915 (297)	1,130 (298)	0.810 [0.665, 0.986]	Virus neutralization assay (VNA)

Geometric mean titre neutralization assay- omicron

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, 2023	Inactivated virus	BBIBP-CorV	Boost NVSI-06-09	Boost BBIBP-CorV	14	Healthy adults	1,714 (255)	143 (249)	11.96 [9.60, 14.90]	Live-virus microneutralization assay
Jin P, 2022 a	Inactivated virus	CoronaVac	Boost Ad5-vectored 5×10^10 vp	Boost CoronaVac	14	Elderly	33 (50)	4 (50)	7.5 [3.5, 18.0]	Microneutralization assay
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost BNT162b2	Boost CoronaVac	28	Healthy adults	223 (20)	17 (20)	13.12 [5.66, 30.40]	Pseudovirus neutralisation titres
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost ChAdOx1	Boost CoronaVac	28	Healthy adults	102 (20)	17 (20)	6 [2.91, 12.36]	Pseudovirus neutralisation titres
Costa Clemens SA, 2022	Inactivated virus	CoronaVac	Boost AD26.COV2-S	Boost CoronaVac	28	Healthy adults	138 (20)	17 (20)	8.12 [3.72, 17.69]	Pseudovirus neutralisation titres
Jin L, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored high dose	Boost CoronaVac	28	Healthy adults	23 (37)	4 (40)	5.63 [3.83, 8.29]	CPE-based microneutralisation
Jin L, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored low dose	Boost CoronaVac	28	Healthy adults	52 (40)	4 (40)	12.68 [9.06, 17.75]	CPE-based microneutralisation
Launay O, 2022	RNA based vaccine	BNT162b2	Boost MV B.1.351	Boost BNT162b2	15	Adults including healthy or stable co-morbidities	253 (71)	140 (76)	1.81 [1.34, 2.44]	Microneutralization test
Launay O, 2022	RNA based vaccine	BNT162b2	Boost MV D614	Boost BNT162b2	15	Adults including healthy or stable co-morbidities	124 (76)	140 (76)	0.88 [0.67, 1.17]	Microneutralization test
Chuang C-H, 2022	Non replicating viral vector	ChAdOx1	Boost mRNA-1273 (half dose)	Boost BNT162b2	28	Healthcare workers	204 (30)	146 (30)	5.51 [3.42, 8.90]	Live virus neutralization
Chuang C-H, 2022	Non replicating viral vector	ChAdOx1	Boost mRNA-1273	Boost BNT162b2	28	Healthcare workers	250 (30)	146 (30)	6.75 [4.30, 10.61]	Live virus neutralization
Chuang C-H, 2022	Non replicating viral vector	ChAdOx1	Boost MVC-COV1901	Boost BNT162b2	28	Healthcare workers	37 (30)	146 (30)	0.25 [0.16, 0.38]	Live virus neutralization
Al Kaabi N, 2022	Inactivated virus	BBIBP-CorV	Boost NVSI-06-07 (Interval >6m)	Boost BBIBP-CorV (Interval >6m)	14	Adults	293 (96)	38 (96)	7.71 [5.42, 10.97]	Live-virus neutralizationn against Omicron variant
Branche A, 2022 a	Any COVID-19 vaccine	Completed primary and booster COVID-19 vaccine series, either homologous or heterologous	Boost mRNA Omicron + Beta vaccine	Boost Original mRNA-1273 vaccine	15	Adults	4,784 (198)	2,699 (97)	1.77 [1.24, 2.53]	Pseudovirion-based neutralisation assay
Branche A, 2022 a	Any COVID-19 vaccine	Completed primary and booster COVID-19 vaccine series, either homologous or heterologous	Boost mRNA Omicron + Delta vaccine	Boost Original mRNA-1273 vaccine	15	Adults	4,503 (99)	2,699 (97)	1.67 [1.09, 2.54]	Pseudovirion-based neutralisation assay
Branche A, 2022 a	Any COVID-19 vaccine	Completed primary and booster COVID-19 vaccine series, either homologous or heterologous	Boost mRNA Omicron + Original mRNA-1273 vaccine	Boost Original mRNA-1273 vaccine	15	Adults	5,322 (96)	2,699 (97)	1.97 [1.31, 2.95]	Pseudovirion-based neutralisation assay
Branche A, 2022 a	Any COVID-19 vaccine	Completed primary and booster COVID-19 vaccine series, either homologous or heterologous	Boost mRNA Omicron vaccine	Boost Original mRNA-1273 vaccine	15	Adults	6,011 (96)	2,699 (97)	2.23 [1.52, 3.26]	Pseudovirion-based neutralisation assay
Niyomnaitham S, 2022	Inactivated virus	CoronaVac	Boost ChAdOx1 (1/5 dose ID)	Boost BNT162b2 (1/6 dose ID)	14	Healthy adults	46 (45)	53 (45)	0.87 [0.55, 1.38]	Plaque reduction neutralization test
Al Kaabi N, 2022 b	Inactivated virus	BBIBP-CorV	Boost NVSI-06-08 7-9 months	Boost BBIBP-CorV 7-9 months	15	Healthy adults	368 (270)	45 (270)	8.17 [6.03, 11.06]	Live-virus neutralization assay
Niyomnaitham S, 2022	Inactivated virus	Coronavac	Boost ChAdOx1	Boost BNT162b2	28	Healthy adults	119 (97)	256 (99)	0.46 [0.36, 0.59]	Micro Neutralizing Antibody Titer
Corominas J, 2023	RNA based vaccine	BNT162b2	Boost PHH-1V	Boost BNT162b2	14	Healthy adults	2,036 (500)	1,211 (241)	1.70 [1.41, 2]	Pseudovirion-based neutralisation assay
Tang R, 2023	Inactivated virus	Coronavac	Boost Coronovac/BoostAd5-nCoV IN	Boost Coronovac/boost Coronavac	14	Healthy adults	63 (117)	21 (116)	3.0 [2.3, 3.8]	Cytopathic effect-based microneutralization assay
Tang R, 2023	Inactivated virus	Coronavac	Boost Coronovac/Ad5-nCoV INCoV IM	Boost Coronovac/boost Coronavac	14	Healthy adults	117 (118)	21 (116)	5.6 [4.6, 7.3]	Cytopathic effect-based microneutralization assay
Lien C, 2022 b	Protein subunit	MVC-COV1901	Boost MVC-COV1901+boost MVC-COV1901-Beta 15 mcg	Boost MVC-COV1901+boost MVC-COV1901	28	Adults including healthy or stable co-morbidities	222 (19)	137 (18)	1.62 [0.86, 3.05]	Plaque reduction neutralization test
Lien C, 2022 b	Protein subunit	MVC-COV1901	Boost MVC-COV1901+boost MVC-COV1901-Beta 25 mcg	Boost MVC-COV1901+boost MVC-COV1901	28	Adults including healthy or stable co-morbidities	155 (18)	137 (18)	1.13 [0.67, 1.89]	Plaque reduction neutralization test
Lien C, 2022 a	Protein subunit	MVC-COV1901	Boost MVC-COV1901-Beta 15 mcg	Boost MVC-COV1901	28	Adults including healthy or stable co-morbidities	240 (12)	139 (14)	1.72 [0.76, 3.91]	Plaque reduction neutralization test
Lien C, 2022 a	Protein subunit	MVC-COV1901	Boost MVC-COV1901-Beta 25 mcg	Boost MVC-COV1901	28	Adults including healthy or stable co-morbidities	426 (12)	139 (14)	3.05 [1.44, 6.47]	Plaque reduction neutralization test

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
Al Kaabi N, 2023	Inactivated virus	BBIBP-CorV	Boost NVSI-06-09	Boost BBIBP-CorV	1	Healthy adults	0 / 260	0 / 256	NR
Jin P, 2022 a	Inactivated virus	CoronaVac	Boost Ad5-vectored 5×10^10 vp	Boost CoronaVac	6	Elderly	1 / 99	0 / 100	3.03 [0.12 - 73.49]
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]
Jin L, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored high dose	Boost CoronaVac	12	Healthy adults	1 / 137	1 / 137	1 [0.06 - 15.83]
Jin L, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored low dose	Boost CoronaVac	6	Healthy adults	2 / 139	1 / 137	1.97 [0.18 - 21.49]
Kho M, 2022	RNA based vaccine	mRNA-1273 or BNT162b2	Boost mRNA-1273 (2 doses)	Boost mRNA-1273	0.9	Adult kidney transplant recipients	0 / 75	3 / 71	0.14 [0.01 - 2.57]
Kho M, 2022	RNA based vaccine	mRNA-1273 or BNT162b2	Boost Ad26.COV2-S	Boost mRNA-1273	0.9	Adult kidney transplant recipients	1 / 78	3 / 71	0.3 [0.03 - 2.85]
Launay O, 2022	RNA based vaccine	BNT162b2	Boost MV B.1.351	Boost BNT162b2	0.5	Adults including healthy or stable co-morbidities	1 / 80	0 / 82	3.07 [0.13 - 74.36]
Launay O, 2022	RNA based vaccine	BNT162b2	Boost MV D614	Boost BNT162b2	0.5	Adults including healthy or stable co-morbidities	1 / 85	0 / 82	2.89 [0.12 - 70.04]
Costa Clemens, 2022	Non replicating viral vector	ChadOx1	Boost 9 mcg SCB-2019 + alum	Boost ChadOx1	0.92	Adults	0 / 30	0 / 29	NR
Costa Clemens, 2022	Non replicating viral vector	ChadOx1	Boost 9 mcg SCB-2019 + CpG + alum	Boost ChadOx1	0.92	Adults	1 / 29	0 / 29	3 [0.13 - 70.59]
Costa Clemens, 2022	Non replicating viral vector	ChadOx1	Boost 30 mcg SCB-2019 + CpG + alum	Boost ChadOx1	0.92	Adults	0 / 32	0 / 29	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]
Shinkai M, 2022	RNA based vaccine	BNT162b2	Boost S-268019-b	Boost BNT162b2	NR	Adults	0 / 101	0 / 103	NR
Poh XY, 2022	RNA based vaccine	BNT162b2	Boost mRNA-1273	Boost BNT162b2	28	Adults	0 / 48	0 / 50	NR
Anderson E, 2022	RNA based vaccine	mRNA-1273	Boost 50 mcg mRNA-1273.351	Boost 25 mcg mRNA-1273.351 and 25 mcg mRNA-1273	1	Healthy volunteers	0 / 25	1 / 23	0.31 [0.01 - 7.16]
Anderson E, 2022	RNA based vaccine	mRNA-1273	Boost 100 mcg mRNA-1273	Boost 25 mcg mRNA-1273.351 and 25 mcg mRNA-1273	1	Healthy volunteers	0 / 48	1 / 23	0.16 [0.01 - 3.81]
Bruminhent J, 2022	Inactivated virus	2 doses of CoronaVac (3–5 weeks apart) or followed by 1 dose of ChAdOx1 or 2 doses of ChAdOx1	CoronaVac or ChAdOx1/Boost BNT162b2 or mRNA-1273	Boost ChAdOx1	0.2	Kidney transplant recipients	0 / 40	0 / 37	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]
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
Li J, 2022	Inactivated virus	CoronaVac	Boost Ad5-vectored	Boost Coronavac	1	Healthy adults	0 / 96	0 / 102	NR
Fadlyana E, 2023	Inactivated virus	CoronaVac	boost BNT162b2	boost CoronaVac	28	Healthy adults	1 / 193	0 / 191	2.97 [0.12 - 72.43]
Fadlyana E, 2023	Inactivated virus	CoronaVac	boost BNT162b2	boost BNT162b2	28	Healthy adults	1 / 193	1 / 193	1 [0.06 - 15.87]
Fadlyana E, 2023	Inactivated virus	CoronaVac	boost BNT162b2 (half dose)	boost CoronaVac	28	Healthy adults	0 / 186	0 / 191	NR
Fadlyana E, 2023	Inactivated virus	CoronaVac	boost ChAdOx1 (half dose)	boost CoronaVac	28	Healthy adults	1 / 192	0 / 191	2.98 [0.12 - 72.8]
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost m-RNA-1273	Boost Ad26.COV2.S	1	Healthcare workers	0 / 112	0 / 106	NR
Sablerolles R, 2022	Non replicating viral vector	Ad26.COV2.S	Boost BNT162b2	Boost Ad26.COV2.S	1	Healthcare workers	0 / 111	0 / 106	NR
Niyomnaitham S, 2022	Inactivated virus	Coronavac	Boost ChAdOx1	Boost BNT162b2	3	Healthy adults	0 / 307	0 / 308	NR
Corominas J, 2023	RNA based vaccine	BNT162b2	Boost PHH-1V	Boost BNT162b2	3.2	Healthy adults	1 / 513	0 / 252	1.48 [0.06 - 36.09]
Tang R, 2023	Inactivated virus	Coronavac	Boost Coronovac/BoostAd5-nCoV IN	Boost Coronovac/boost Coronavac	0.9	Healthy adults	0 / 117	0 / 119	NR
Tang R, 2023	Inactivated virus	Coronavac	Boost Coronovac/Ad5-nCoV INCoV IM	Boost Coronovac/boost Coronavac	0.9	Healthy adults	0 / 120	0 / 119	NR
Lien C, 2022 b	Protein subunit	MVC-COV1901	Boost MVC-COV1901+boost MVC-COV1901-Beta 15 mcg	Boost MVC-COV1901+boost MVC-COV1901	0.9	Adults including healthy or stable co-morbidities	0 / 21	0 / 21	NR
Lien C, 2022 b	Protein subunit	MVC-COV1901	Boost MVC-COV1901+boost MVC-COV1901-Beta 25 mcg	Boost MVC-COV1901+boost MVC-COV1901	0.9	Adults including healthy or stable co-morbidities	0 / 20	0 / 21	NR
Lien C, 2022 a	Protein subunit	MVC-COV1901	Boost MVC-COV1901-Beta 15 mcg	Boost MVC-COV1901	0.9	Adults including healthy or stable co-morbidities	0 / 15	0 / 15	NR
Lien C, 2022 a	Protein subunit	MVC-COV1901	Boost MVC-COV1901-Beta 25 mcg	Boost MVC-COV1901	0.9	Adults including healthy or stable co-morbidities	0 / 15	0 / 15	NR
Amplify, 2023 b	RNA based vaccine	BNT162b2	Boost Ad26.COV2.S 1*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	4.5	Adults including elderly and stable co-morbidities	1 / 106	3 / 326	1.03 [0.11 - 9.75]
Amplify, 2023 b	RNA based vaccine	BNT162b2	Boost Ad26.COV2.S 2.5*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	4.5	Adults including elderly and stable co-morbidities	1 / 326	3 / 326	0.33 [0.03 - 3.19]
Amplify, 2023 a	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S 1*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	4.5	Adults including elderly and stable co-morbidities	0 / 116	1 / 330	0.95 [0.04 - 23.05]
Amplify, 2023 a	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S 2.5*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	4.5	Adults including elderly and stable co-morbidities	3 / 328	1 / 330	3.02 [0.32 - 28.87]

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
Toledo-Romani ME, 2022 a	Protein subunit	FINLAY-FR-2-25 mcg	Boost FR-1	Boost FINLAY-FR-2	1	Healthy adults	0 / 58	0 / 55	NR
Launay O, 2022	RNA based vaccine	BNT162b2	Boost MV B.1.351	Boost BNT162b2	0.5	Adults including healthy or stable co-morbidities	0 / 80	0 / 82	NR
Launay O, 2022	RNA based vaccine	BNT162b2	Boost MV D614	Boost BNT162b2	0.5	Adults including healthy or stable co-morbidities	0 / 85	0 / 82	NR
Costa Clemens, 2022	Non replicating viral vector	ChadOx1	Boost 9 mcg SCB-2019 + alum	Boost ChadOx1	2.53	Adults	0 / 30	0 / 29	NR
Costa Clemens, 2022	Non replicating viral vector	ChadOx1	Boost 9 mcg SCB-2019 + CpG + alum	Boost ChadOx1	2.53	Adults	0 / 29	0 / 29	NR
Costa Clemens, 2022	Non replicating viral vector	ChadOx1	Boost 30 mcg SCB-2019 + CpG + alum	Boost ChadOx1	2.53	Adults	0 / 32	0 / 29	NR
Chuang C-H, 2022	Non replicating viral vector	ChAdOx1	Boost mRNA-1273 (half dose)	Boost BNT162b2	5.9	Healthcare workers	0 / 85	0 / 83	NR
Chuang C-H, 2022	Non replicating viral vector	ChAdOx1	Boost mRNA-1273	Boost BNT162b2	5.9	Healthcare workers	0 / 85	0 / 83	NR
Chuang C-H, 2022	Non replicating viral vector	ChAdOx1	Boost MVC-COV1901	Boost BNT162b2	5.9	Healthcare workers	0 / 85	0 / 83	NR
Shinkai M, 2022	RNA based vaccine	BNT162b2	Boost S-268019-b	Boost BNT162b2	*	Adults	0 / 101	0 / 103	NR
Mrak D, 2022	RNA based vaccine	mRNA-1273 or BNT162b2	Boost ChAdOx1	Boost homologous mRNA-1273 or BNT162b2	0.9	Immunosuppressed adults	0 / 22	0 / 24	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]
Al Kaabi N, 2022	Inactivated virus	BBIBP-CorV	Boost NVSI-06-07 (Interval 1-3 m)	Boost BBIBP-CorV (Interval 1-3 m)	*	Adults	NR	NR	NR
Al Kaabi N, 2022	Inactivated virus	BBIBP-CorV	Boost NVSI-06-07 (Interval 4-6 m)	Boost BBIBP-CorV (Interval 4-6 m)	*	Adults	NR	NR	NR
Al Kaabi N, 2022	Inactivated virus	BBIBP-CorV	Boost NVSI-06-07 (Interval >6m)	Boost BBIBP-CorV (Interval >6m)	*	Adults	NR	NR	NR
Al Kaabi N, 2022 b	Inactivated virus	BBIBP-CorV	Boost NVSI-06-08 4-6 months	Boost BBIBP-CorV 4-6 months	1	Healthy adults	0 / 299	0 / 301	NR
Al Kaabi N, 2022 b	Inactivated virus	BBIBP-CorV	Boost NVSI-06-08 7-9 months	Boost BBIBP-CorV 7-9 months	1	Healthy adults	0 / 297	0 / 303	NR
Al Kaabi N, 2022 b	Inactivated virus	BBIBP-CorV	Boost NVSI-06-08 >9 months	Boost BBIBP-CorV >9 months	1	Healthy adults	0 / 300	0 / 300	NR
Niyomnaitham S, 2022	Inactivated virus	Coronavac	Boost ChAdOx1	Boost BNT162b2	3	Healthy adults	0 / 307	0 / 308	NR
Corominas J, 2023	RNA based vaccine	BNT162b2	Boost PHH-1V	Boost BNT162b2	3.2	Healthy adults	0 / 513	0 / 252	NR
Tang R, 2023	Inactivated virus	Coronavac	Boost Coronovac/BoostAd5-nCoV IN	Boost Coronovac/boost Coronavac	0.9	Healthy adults	0 / 117	0 / 119	NR
Tang R, 2023	Inactivated virus	Coronavac	Boost Coronovac/Ad5-nCoV INCoV IM	Boost Coronovac/boost Coronavac	0.9	Healthy adults	0 / 120	0 / 119	NR
Lien C, 2022 b	Protein subunit	MVC-COV1901	Boost MVC-COV1901+boost MVC-COV1901-Beta 15 mcg	Boost MVC-COV1901+boost MVC-COV1901	0.9	Adults including healthy or stable co-morbidities	0 / 21	0 / 21	NR
Lien C, 2022 b	Protein subunit	MVC-COV1901	Boost MVC-COV1901+boost MVC-COV1901-Beta 25 mcg	Boost MVC-COV1901+boost MVC-COV1901	0.9	Adults including healthy or stable co-morbidities	0 / 20	0 / 21	NR
Lien C, 2022 a	Protein subunit	MVC-COV1901	Boost MVC-COV1901-Beta 15 mcg	Boost MVC-COV1901	0.9	Adults including healthy or stable co-morbidities	0 / 15	0 / 15	NR
Lien C, 2022 a	Protein subunit	MVC-COV1901	Boost MVC-COV1901-Beta 25 mcg	Boost MVC-COV1901	0.9	Adults including healthy or stable co-morbidities	0 / 15	0 / 15	NR
Amplify, 2023 b	RNA based vaccine	BNT162b2	Boost Ad26.COV2.S 1*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	4.5	Adults including elderly and stable co-morbidities	0 / 106	0 / 326	NR
Amplify, 2023 b	RNA based vaccine	BNT162b2	Boost Ad26.COV2.S 2.5*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	4.5	Adults including elderly and stable co-morbidities	0 / 326	0 / 326	NR
Amplify, 2023 a	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S 1*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	4.5	Adults including elderly and stable co-morbidities	0 / 116	0 / 330	NR
Amplify, 2023 a	Non replicating viral vector	Ad26.COV2.S	Boost Ad26.COV2.S 2.5*10^10 vp	Boost Ad26.COV2.S 5*10^10 vp	4.5	Adults including elderly and stable co-morbidities	0 / 328	0 / 330	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.

Trials reports under extraction

In addition to the below included trials, we have included and presently extracting 15 new vaccine randomized trials

Description of primary studies

In this table, we report the main characteristics of the COVID-19 vaccine candidates from RCTs identified, in addition to the overall risk of bias assessment.

For prime vaccination, early phase trials were extracted only when the dose has been selected. Results from phase 1-2 studies are included in forest plots for the chosen vaccine dose and schedule only. List of early phases included but not extracted are detailed on here .

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
NCT04999111 Janssen Pharmaceutical Companies Amplify, Unpublished, 2023 b New Full text	Heterologous booster	BNT162b2/ Boost Ad26.COV2.S 110^10 vp BNT162b2/ Boost Ad26.COV2.S 2.510^10 vp	BNT162b2/ Boost Ad26.COV2.S	RCT Phase 2	Adults including elderly and stable co-morbidities with no history of COVID-19 in 21 centres in USA.	N= 764	Some concerns Details	Full description
NCT04999111 Janssen Pharmaceutical Companies Amplify, Unpublished, 2023 a New Full text	Homologous booster	Ad26.COV2.S/Boost Ad26.COV2.S 110^10 vp Ad26.COV2.S/Boost Ad26.COV2.S 2.510^10 vp	Ad26.COV2.S//Boost Ad26.COV2.S	RCT Phase 2	Adults including elderly and stable co-morbidities with no history of COVID-19 in 21 centres in USA.	N= 777	Some concerns Details	Full description
NCT05069129 Sinopharm-Beijing/ National Vaccine and Serum Institute, China Al Kaabi N, Nat Commun, 2022 b New Full text Commentary Commentary	Heterologous booster	BBIBP-CorV/boostNVSI-06-08 4-6m BBIBP-CorV/boostNVSI-06-08 7-9m BBIBP-CorV/boostNVSI-06-08 >9m	BBIBP-CorV/boostBBIBP-CorV 4-6 months BBIBP-CorV/boostBBIBP-CorV 7-9m BBIBP-CorV/boostBBIBP-CorV >9m	RCT Phase 2	Healthy adults that were HIV-negative and with no previous history of COVID-19 in a single centre in the United Arab Emirates.	N= 1833	Some concerns Details	Full description
NCT05216601 Medigen Vaccine Biologics+Dynavax+NIAID Lien C, SSRN, 2022 b New Full text Full text Commentary Commentary Commentary Commentary	Heterologous booster	Prime series MVC-COV1901+boost MVC-COV1901+boost MVC-COV1901 Beta 15mcg Prime series MVC-COV1901+boost MVC-COV1901+boost MVC-COV1901 Beta 25mcg	Prime series MVC-COV1901+boost MVC-COV1901+boost MVC-COV1901	RCT Phase 1	Healthy adults or with stable co-morbidities that were HIV-negative and with no history of COVID-19 in 2 centres in Taiwan (China).	N= 62	Some concerns Details	Full description
NCT05216601 Medigen Vaccine Biologics+Dynavax+NIAID Lien C, SSRN, 2022 a New Full text Full text Commentary Commentary Commentary Commentary	Heterologous booster	MVC-COV1901/boost MVC-COV1901-Beta 15 mcg MVC-COV1901/boost MVC-COV1901-Beta 25 mcg	MVC-COV1901/boost MVC-COV1901	RCT Phase 1	Healthy adults or with stable co-morbidities that were HIV-negative and with no history of COVID-19 in 2 centres in Taiwan (China).	N= 45	Some concerns Details	Full description
NCT05303584 CanSino Biological Inc Tang R, Lancet Resp Med, 2023 New Full text Full text Commentary Commentary	Heterologous booster	Coronavac/boost Coronovac/boost Ad5-nCoV IN Coronavac/boost Coronovac/boost Ad5-nCoV IM	Coronavac/boost Coronovac/boost Coronavac	RCT Phase 4	Healthy adults previously in receipt of 3 doses of CoronaVac and with no history of SARS-CoV-2/COVID-19 in multiple centres in China.	N= 356	Some concerns Details	Full description
TCTR20210907003, TCTR20211102006 AstraZeneca + University of Oxford ; Pfizer/BioNTech + Fosun Pharma Niyomnaitham S, Vaccines, 2022 Full text Commentary Commentary	Non replicating viral vector	Prime Coronavac/Boost ID 1/5 ChAdOx1	Prime Coronavac/Boost ID 1/6 BNT162b2	RCT Phase 1-2	Healthy adults with no known history of previous SARS-CoV-2 infection at a single center in Thailand.	N= 90	Some concerns Details	Full description
EudraCT 2021-002693-10 Moderna+NIAID; Pfizer/BioNTech+Fosun Pharma; AstraZeneca + University of Oxford Mrak D, Nat Commun, 2022 Full text Commentary Commentary	Homologous booster	BNT162b2 or mRNA-1273/Boost ChAdOx1	mRNA-1273 or BNT162b2/Homologous boost	RCT Phase 2	Immunosuppressed adults including elderly with no history of COVID-19 in a single centre in Austria.	N= 51	Low Details	Full description
NCT05049226 AstraZeneca + University of Oxford ; Pfizer/BioNTech + Fosun Pharma Niyomnaitham S, medRxiv, 2022 Full text Commentary Commentary	Heterologous booster	Coronavac/Boost ChAdOx1	CoronaVac/Boost BNT162b2	RCT Phase 2	Healthy adults without recent (3 months) COVID-19 at 7 centers in Thailand.	N= 1243	Some concerns Details	Full description
ChiCTR2200057758 Walvax Biotech Co., Ltd ; Walvax Biotechnology + Shanghai RNACure Biopharma ; Shanghai Zerun Biotechnology + Walvax Biotechnology + CEPI ; Sinovac Research an Zhang Y, EClinicalMedicine, 2022 Full text Commentary	Non replicating viral vector	CoronaVac/Boost ChAdTS-S CoronaVac/Boost RQ3013 CoronaVac/Boost ZR202-CoV CoronaVac/Boost CoronaVac	CoronaVac/Boost placebo	RCT Phase 2	Adults aged 18-59, healthy or with stable pre-existing disease and with no history of SARS-CoV-2 infection, at a single center in China.	N= 250	Some concerns Details	Full description

Akahata W, SSRN, 2023	Safety and Immunogenicity of SARS-CoV-2 Self-Amplifying RNA Vaccine Expressing Anchored RBD: A Randomised, Observer-Blind, Phase 1 Study
Al Kaabi N, Vaccines, 2023	Efficacy and Safety of a Booster Vaccination with Two Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: Results of a Double-Blind, Randomized, Placebo-Controlled, Phase 3 Trial in Abu Dhabi
Barda N, Clin Microbiol Infect, 2023	Immunogenicity of Omicron BA.1-adapted BNT162b2 vaccines; randomized trial, 3 months follow-up.
Branche A, medRxiv, 2023	Immunogenicity of the BA.1 and BA.4/5 Bivalent Boosts: A Brief Report of Preliminary Results from the COVAIL Randomized Clinical Trial
Hannawi S, J Infect, 2022	Safety and Immunogenicity of a Bivalent SARS-CoV-2 Protein Booster Vaccine, SCTV01C in Adults Previously Vaccinated with Inactivated Vaccine: a Randomized, Double-blind, Placebo-controlled Phase 1/2 Clinical Trial
Kulkarni P, ResearchSquare, 2023	A randomized, controlled study to evaluate the safety and immunogenicity of a heterologous booster dose of an adjuvanted SARS CoV-2 recombinant spike protein vaccine in adults
Lee I, medRxiv, 2023a	A Randomized Trial Comparing Omicron-Containing Boosters with the Original Covid-19 Vaccine mRNA-1273
Leung N H L, medrxiv, 2022	Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)
Niyomnaitham S, Hum Vaccin Immunother, 2022	Immunogenicity and reactogenicity against the SARS-CoV-2 variants following heterologous primary series involving CoronaVac, ChAdox1 nCov-19 and BNT162b2 plus BNT162b2 booster vaccination: An open-label randomized study in healthy Thai adul
Omma A, Hum Vaccin Immunother, 2022	Safety and immunogenicity of inactive vaccines as booster doses for COVID-19 in Türkiye: A randomized trial
Rao CC, medRxiv, 2022	Heterologous boosting of neutralizing activity against Delta and Omicron SARS-CoV-2 variants in CoronaVac-primed adults; a randomized study with SCB-2019 vaccine
Tawinprai K, Expert Rev Vaccines, 2022	Reactogenicity, immunogenicity, and humoral immune response dynamics after the third dose of heterologous COVID-19 vaccines in participants fully vaccinated with inactivated vaccine.
Thuluva S, medRxiv, 2023	"Immunogenicity and safety of Biological Es CORBEVAX vaccine as a heterologous booster dose in adult volunteers previously vaccinated with two doses of either COVISHIELD or COVAXIN: a Prospective double-blind randomised phase III clinical s
Wang L, SSRN, 2022	Safety and Cross-Reactive Immune Response Against the Omicron Variant of a Third Dose of CoronaVac, and Immune Persistence of Primary Immunization in Healthy Children and Adolescents: Interim Results from a Double-Blind, Randomised, Placebo
Winokur P, N Engl J Med, 2023	Bivalent Omicron BA.1-Adapted BNT162b2 Booster in Adults Older than 55 Years

COVID-19 vaccine effectiveness(Randomized evidence)

Methods

meta-COVID

Vaccine types

Trials reports under extraction

Description of primary studies

Search studies

COVID-19 vaccine effectiveness
(Randomized evidence)