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

Figures & data

Figure 1. Study selection flow chart.

Figure 2. World map of countries hosting vaccine trial sites by vaccine type (note: some trials took place in more than one country).

Table 1. Study characteristics.

Vaccine characteristics							Participant characteristics
Vaccine platform	Vaccine name (developer)	Study	Phase	Dose (b)	Dosing schedule	Control	Age	% Female	Ethnicity (%) (c)
Viral Vector	Ad26.COV2.S (Janssen Pharmaceutical Companies)	Sadoff et al [15].	I/IIa	5 × 10^10 vp	Single dose	0.9% Saline	18–55, ≥65	51.3	White (94.5), Black (2.9)
		Sadoff et al (d) [27].	III	5 × 10^10 vp	Single dose	0.9% Saline	18–59, ≥60	45	White (58.7), Black (19.4)
	Ad5-nCov (CanSino Biological Inc, Beijing Institute of Biotechnology)	Halperin et al [31].	III	5 × 10^10 vp	Single dose	Vaccine excipients	≥18	29.2	Hispanic/Latino (37), Other (63)
		Zhu et al [30].	II	5 × 10^10 vp	Single dose	Vaccine excipients	≥18	50	Not reported
		Zhu et al [29].	IIb	5 × 10^10 vp	D0-D56	Vaccine excipients	18–55, >56	41	Not reported
	ChAdOx1 (University of Oxford, AstraZeneca)	Asano et al [36].	I/II	5 × 10^10 vp	D0-D28	0.9% Saline	18–55, 56–69, ≥70	33.9	Japanese (100)
		Falsey et al [16].	III	5 × 10^10 vp	D0-D28	0.9% Saline	18–64, ≥65	44.4	White (79), Black (8.3)
		Folegatti et al [32].	I/II	5 × 10^10 vp	D0-D28	MenACWY Vaccine	18–55	49.8	White (90.9), South Asian (3.2)
		Madhi et al [34].	Ib/II	5 × 10^10 vp	D0-D28	0.9% Saline	18–64	43.5	Black African (70.6), Mixed (15.0)
		Madhi et al [33].	Ib/IIa	5 × 10^10 vp	D0-D28	0.9% Saline	18–65	61	Black (99), White (1)
		Ramasamy et al [35].	II	5 × 10^10 vp	D0-D28	MenACWY Vaccine	18–55, 56–69, ≥70	49.8	White (94.9), Asian (3.4)
	Gam-COVID-Vac (Gamaleya Research Institute)	Logunov et al (e) [21].	III	10^11 vp	D0-D21	Vaccine excipients	≥18	38.8	White (98.5), Asian (1.4)
Inactivated	BBV152 (Bharat Biotech)	Ella et al [49].	I	6 µg	D0-D14	Algel-IMDG only	18–55	20.8	Not reported
		Ella et al [50].	III	6 µg	D0-D28	Algel only	18–60, ≥60	32.7	Indian (100)
	BIBP (Sinopharm’s Beijing Institute of Biological Products)	Al Kaabi et al [28].	III	4 µg	D0-D21	Aluminum Hydroxyde	≥18	15.3	Not reported
		Xia et al [56].	I + II	4 µg	D0-D21	Aluminum Hydroxyde	18–59	55	Not reported
		Xia et al [44].	I/II	4 µg	D0-D28-56	Aluminum Hydroxyde	13–17	47.9	Han Chinese (97.5), Hui (2.3)
	CoronaVac (Sinovac)	Bueno et al [48].	III	3 µg	D0-D14	Aluminum Hydroxyde	18–59, ≥60	61.8	White (93.8), Other (6.2)
		Fadlyana et al [47].	III	3 µg	D0-D14	Water for Injection	18–59	35.4	Not reported
		Han et al [62].	I/II	3 µg	D0-D28	Aluminum Hydroxyde	12–17	46.0	Han Chinese (100)
		Tanriover et al [57].	III	3 µg	D0-D14	Aluminum Hydroxyde	18–59	42.2	Not reported
		Wu et al [45].	I/II	3 µg	D0-D28	Aluminum Hydroxyde	≥60	51.1	Han Chinese (99.8)
		Zhang et al [46].	I/II	3 µg	D0-D14, D0-D28	Aluminum Hydroxyde	18–59	53.4	Han Chinese (100)
	Inactivated Vaccine (IMBCAMS(a))	Che et al (e) [22].	II	150 U	D0-D14	Aluminum Hydroxyde	18–59	62.3	Han Chinese (70.1), Yi (19.2)
		Pu et al [20].	I	150 U	D0-D14	Aluminum Hydroxyde	18–59	55.2	Han Chinese (96.9), Tibetan (1.6)
	QazCovid-in (Scientific Research Institute for Biological Safety Problems of the Republic of Kazakhstan)	Zakarya et al (e) [23].	I	5 µg	D0-21	0.9% Saline	18–50	34.1	Not reported
	WIBP (Sinopharm’s Wuhan Institute of Biological Products)	Al Kaabi et al [28].	III	4 µg	D0-D21	Aluminum Hydroxyde	≥18	15.6	Not reported
		Guo et al [58].	II	5 µg	D0-21, D0-28	Aluminum Hydroxyde	18–59	50.4	Not reported
mRNA	BNT162b2 (Pfizer, BioNTech)	Frenck et al [38].	III	30 µg	D0-D21	0.9% Saline	12–15	50.1	White (84.7), Black (6.1)
		Haranaka et al [40].	I/II	30 µg	D0-D21	0.9% Saline	20–64, 65–85	49.3	Asian (100)
		Polack et al (d) [26].	II/III	30 µg	D0-D21	0.9% Saline	16–55, ≥55	49.4	White (82.9), Black (9.3)
		Thomas et al (d) [25].	II/III	30 µg	D0-D21	0.9% Saline	≥16	49.1	White (82), Black (9.6)
		Walsh et al [39].	I	30 µg	D0-D21	0.9% Saline	18–55, 65–85	55.2	White (88.6); Asian (8.6)
	CVnCoV (CureVac N.V.)	Kremsner et al [37].	IIb	12 µg	D0-D28	0.9% Saline	18–60, >61	45	White (25.3), Latin American (74.7)
	mRNA-1273 (Moderna)	Ali et al [41].	II/III	100 µg	D0-D28	0.9% Saline	12–17	49	White (84), Asian (6)
		Chu et al [42].	II	100 µg	D0-D28	0.9% Saline	18-<55, ≥55	65.0	White (94.8), Black (2.7)
		El Sahly et al [43].	III	100 µg	D0-D28	0.9% Saline	18-<65, ≥65	47.4	White (79.2), Black (10.2)
Protein Subunit	EpiVacCorona (Vector Institute)	Ryzhikov et al (e) [24].	I/II	225 μg	D0-D21	0.9% Saline	18–60	44.0	Not reported
	MVC-COV1901 (Medigen Vaccine Biologics Corporation, Dynavax, NIAID)	Hsieh et al [55].	II	15 µg	D0-D28	0.9% Saline	20–64, ≥65	43.5	Asian (99.9)
	NVX-CoV2373 (Novavax)	Dunkle et al [54].	III	5 µg	D0-D21	0.9% Saline	18–64, ≥65	48.2	White (75.9), Black (11)
		Formica et al [53].	II	5 µg	D0-D21	0.9% Saline	18–59, 60–84	50.9	White (86.8), Asian (7.6)
		Heath et al [51].	III	5 µg	D0-D21	0.9% Saline	18–84	48.4	White (94.5), Asian (2.9)
		Keech et al [17].	I/II	5 µg	D0-D21	0.9% Saline	18–59	49.6	White (78.6), Hispanic/Latino (14.5)
		Shinde et al [52].	II	5 µg	D0-D21	0.9% Saline	18–84	42.6	Black (95.3), White (3.5)
	S-Trimer/SCB-2019 (Clover Biopharmaceuticals, GSK, Dinavax)	Richmond et al [18].	I	30 µg	D0-D21	0.9% Saline	18–54, 55–75	65	Asian (13), White (87)
	Sf9 (West China Hospital, Sichuan University)	Meng et al [19].	I/II	40 µg	D0-D14-D28	Aluminum Hydroxyde	18–55, ≥56	60.2	Not reported
	V-01 (Guandong Provincial CDC, Gaozhou CDC, Livson Pharmaceutical Group)	Zhang et al [46].	I	10 µg	D0-D21	Aluminum Hydroxyde	18–59, >60	40	Han Chinese (100)
		Ya-Jun et al [61].	II	10 µg	D0-D21	Aluminum Hydroxyde	18–59, >60	47	Han Chinese (100)
	ZF2001 (Anhui Zhifei Longcom Biopharmaceutical, Chinese Academy of Sciences)	Yang et al [59].	II	25 μg	D0-D30-D60	Aluminum Hydroxyde	18–59	58.0	Han Chinese (99.3)

a- IMBCAMS – Institute of Medical Biology, Chinese Academy of Medical Sciences; b– Dose which is being taken forward to Phase 3 trials; c– The top two ethnicities are listed; d– Not included in meta-analysis due to missing data; e- Not included in meta-analysis due to high risk of bias; vp = viral particles

Forest plot 1. Risk ratio of fever compared to control, by vaccine type and dose.

Forest plot 2. Risk ratio of fatigue compared to control, by vaccine type and dose.

Forest plot 3. Risk ratio of headache compared to control, by vaccine type and dose.

Forest plot 4. Risk ratio of pain at injection site compared to control, by vaccine type and dose.

Forest plot 5. Risk ratio of redness compared to control, by vaccine type and dose.

Forest plot 6. Risk ratio of swelling compared to control, by vaccine type and dose.

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