Comparing reactogenicity of COVID-19 vaccine boosters: a systematic review and meta-analysis

Figures & data

Figure 1. PRISMA flow diagram.

Table 1. Study characteristics.

Study	Phase	Registration ID	Country	Booster vaccine	Vaccine platform	Dose	Adjuvant	Control arm	Primary COVID-19 vaccine schedule	Months until booster	Age	Female %	Immuno- compromised
Ahi 2022* [21]	-	RCT20210206050259N4	Iran	BBIBP-CorV	Inactivated	4ug	Aluminium Hydroxide	-	2 doses of BBIBP-CorV	2.5–6	≥18	14.94	No
				FAKHARAVAC	Inactivated	10ug	-
Al Kaabi 2022 [43]	II	NCT05069129	UAE	BBIBP-CorV	Inactivated	4ug	Aluminium Hydroxide	-	2 doses of BBIBP-CorV	4–6,7–9,>9	18–59,≥60	1.04–4.81	No
				NVSI-06-08	Protein Sub-unit	20ug	Aluminium Hydroxide
Bonelli 2021 [36]	II	EudraCT2021–002348–57	Austria	BNT162b2	mRNA	30ug	-	-	2 doses of mRNA vaccine (mRNA-1273 or BNT162b2)	>1	≥18	66.7–82.1	Rituximab
				ChAdOx-1	Viral Vector	0.5 ml	-
				mRNA-1273	mRNA	50ug	-
Chuang 2022 [39]	I/II	NCT05132855	Taiwan	BNT162b2	mRNA	30ug	-	-	2 doses of ChAdOx-1	3–6.5	≥18	64–71	No
				mRNA-1273	mRNA	50ug	-
				mRNA-1273	mRNA	100ug	-
				MCV-COV1901	Protein Sub-unit	15ug	CpG-1018
Costa Clemens 2022 [38]	IV	RBR − 9nn3scw	Brazil	Ad26.COV2.S	Viral Vector	0.5 mL	-	-	2 doses of CoronaVac	5–7	18–60,>60	58.7–61.4	No
				BNT162b2	mRNA	30ug	-
				ChAdOx-1	Viral Vector	0.5 mL	-
				CoronaVac	Inactivated	0.5 mL	Aluminium Hydroxide
Hall 2021 [22]	IV	NCT04885907	Canada	mRNA-1273	mRNA	50ug	-	Normal Saline	2 doses of mRNA-1273	2	≥18	30–38.3	Transplant recipients
Hannawi 2022 [23]	I/II	NCT05043311	UAE	SCTV01C	Protein Sub-unit	20ug, 40ug	SCT-VA02B	Normal Saline	2 doses of mRNA vaccine (mRNA-1273 or BNT162b2)	3–24	18–59	0.90	No
Intapiboon 2021* [30]	I	CTR20211004001	Thailand	BNT162b2	mRNA	15ug, 30ug	-	-	2 doses of CoronaVac	>2	18–60	56	No
Jin 2022 [42]	IV	NCT04833101	China	ZF2001	Protein Sub-unit	25ug	Aluminium Hydroxide	Influenza vaccine	1 dose of AD5-nCOV	1,2	18–59,≥60	45–50	No
Kumar 2022* [24]	IV	NCT04885907	Canada	mRNA-1273	mRNA	50ug	-	Normal Saline	2 doses of mRNA-1273	2	≥18	32–38	Transplant recipients
Launay 2022 [33]	III	NCT05124171	France	BNT162b2	mRNA	30ug	-	-	2 doses of BNT162b2	>6	18–64,≥65	40.4	No
				MVB.1.351	Protein Sub-unit	0.5 mL	AS03
Li 2022 [44]	IV	NCT04892459	China	AD5-nCOV	Viral Vector	0.5 mL	-	-	1 or 2 doses of CoronaVac	1–3,3–6	18–50,51–59	52.9–62.8	No
				CoronaVac	Inactivated	0.5 mL	Aluminium Hydroxyde
Mallory 2022 [40]	II	NCT04368988	USA, Australia	NVX-CoV2373	Protein Sub-unit	5 ug	Matrix-M1	Normal saline	2 doses of NVX-CoV2373	6	18–59,60–84	45–58	No
Mok 2022* [29]	-	NCT04611243	Hong Kong	BNT162b2	mRNA	30ug	-	-	2 doses of CoronaVac	3	≥18	60–70	No
				CoronaVac	Inactivated	3ug	Aluminium Hydroxide			3
Moreira 2022 [25]	III	NCT04955626	USA, Brazil,South Africa	BNT162b2	mRNA	30ug	-	Normal saline	2 doses of BNT162b2	≥6	≥16	50.9	No
Munro 2021 [37]	II	ISRCTN 73,765,130	UK	Ad26.COV2.S	Viral vector	0.5 ml	-	Men ACWY	2 doses of BNT162b2 or ChAdOx-1	≥3	≥30	48.6–59.8	No
				BNT162b2	mRNA	30 ug, 15ug	-
				ChAdOx-1	Viral vector	0.5 ml	-
				mRNA-1273	mRNA	100 ug	-
				NVX-CoV2373	Protein Sub-unit	5ug	Matrix-M1
				VLA2001	Inactivated	0.5 mL	CpG
Munro 2022 [34]	II	ISRCTN 73,765,130	UK	BNT162b2	mRNA	30 ug,15 ug	-	-	2 doses of BNT162b2 or ChAdOx1 + BNT162b2 as third dose	6–7	≥30	52	No
				mRNA-1273	mRNA	50 ug	-
Nantanee 2022 [32]	II	TCTR20211027002	Thailand	BNT162b2	mRNA	15 ug	-	-	2 doses of ChAdOx-1	>2	18–69	61	No
						30 ug	-
Nanthapisal 2022 [45]	II	TCTR20210722003	Thailand	ChAdOx-1	Viral Vector	0.25 ml	-	-	2 doses CoronaVac	>2	18–59	52.1	No
						0.5 ml	-
Omma 2022 [46]	II	NCT04979949	Turkey	CoronaVac	Inactivated	3ug		-	2 doses CoronaVac	<4, 4–6 > 6	18–60	29.6–32.5	No
				Turkovac	Inactivated	3ug	Aluminium Hydroxyde
Poh 2022 [35]	III	NCT05142319.	Singapore	BNT162b2	mRNA	30ug	-	-	2 doses BNT162b2	6–9	21–59, 60–84	35–54	No
				mRNA-1273	mRNA	50ug	-
Reindl-Schwaighofer 2021 [26]	II	NCT05324319	Austria	Ad26.COV2.S	Viral Vector	0.5 mL	-	-	2 doses of mRNA vaccine (mRNA-1273 or BNT162b2)	2–3	≥18	42	Transplant recipients
				BNT162b2	mRNA	30ug	-
				mRNA-1273	mRNA	100ug	-
Sablerolles 2022 [47]	-	NCT04927936	Netherlands	Ad26.COV2.S	Viral Vector	0.5 mL	-	-	1 dose of Ad26.COV2.S	3	18–65	59–67	No
				BNT162b2	mRNA	30ug	-
				mRNA-1273	mRNA	100ug	-
Shinkai 2022* [31]	II/III	RCT203121047	Japan	BNT162b2	mRNA	30ug		-	2 doses of BNT162b2	6–7, >7–8, >8	20–40,>40	29.7	No
				S-268019-b	Protein Sub-unit	10ug	Squalene-based (A-91082)
Tabarsi 2022 [27]	III	NCT05175625	Iran	Spikogen	Protein Sub-unit	25ug	Advax-CpG55.2	Normal Saline	2 doses of Spikogen or Inactivated (BIBP-CorV,COVIran Barekat) or Viral Vector (ChAdOx-1,Sputnik V)	4–9	≥18	36–45.6	No
Wang 2022 [28]	III	NCT05096832	Malaysia, Pakistan	V-01	Protein Sub-unit	10ug	Aluminium Hydroxyde	Aluminium Hydroxide + fusion protein	2 doses of BBIBP-CorV or Coronavac	3–6	18–59, ≥60	28.3	No
Zhang Yuemiao 2022 [41]	II	ChiCTR2200057758	China	CoronaVac	Inactivated	0.5 mL	Aluminium Hydroxyde	Normal Saline	2 doses CoronaVac	3–9	18–59	45.7–60.9	No
Zhang Zhiren 2022 [48]	III	NCT05238649	China	CoronaVac	Inactivated	0.5 mL	Aluminium Hydroxyde	-	2 doses of BBIBP-CorV or CoronaVac	5–7	18–59, ≥60	30–50	No
				V-01	Protein Sub-unit	10ug	Aluminium Hydroxyde

*excluded from meta-analysis.

Figure 2. Map of countries with included studies.

Forest plot 1. Risk ratios for fever – BNT162b2 30ug control.

Forest plot 2. Risk ratios for fatigue – BNT162b2 30ug control.

Forest plot 3. Risk ratios for headache – BNT162b2 30ug control.

Forest plot 4. Risk ratios for injection site pain – BNT162b2 30ug control.

Forest plot 5. Risk ratios for redness – BNT162b2 30ug control.

Forest plot 6. Risk ratios for swelling – BNT162b2 30ug control.#Redness grading criteria for Chuang 2022 were based on impact during daily activities while the other trials used milimeter measurements.

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Data availability statement

Study data is available via reasonable requests directed to the corresponding author.