Introduction
Methods
Data sources and searches
Study selection
Data extraction and quality assessment
Data synthesis and analysis
Results
Study characteristics
Platform | Vaccine/manufacturer | Clinical stage | Trial number/study locations | Age range of participants | History of infection | Intervention schedule | Participants included in safety set | Placebo participants | Grading scale |
---|---|---|---|---|---|---|---|---|---|
Inactivated | |||||||||
BBIBP-CorV/Sinopharm | Phase 2/3 | ChiCTR2000032459 NCT04510207 ChiCTR2000034780 Global multi-centers | 18 years and older | Yes, 6.7% positive at baseline | 2 doses, 21 days interval | 13,555 (4 μg) | 13,481 (aluminum hydroxide) | CFDA, 2019 | |
WBIP/Sinopharm | Phase 2/3 | ChiCTR2000031809 NCT04510207 ChiCTR2000034780 Global | 18 years and older | Yes, 6.4% positive at baseline | 2 doses, 21 days interval | 13,548 (5 μg) | 13,481 (aluminum hydroxide) | CFDA, 2019 | |
CoronaVac/SinoVac | Phase 1/2/3 | NCT04352608 NCT04383574 NCT04651790 China, Brazil, Chile | 3–17 years old/18–59 years old/60 years and older | No | 2 doses, 14/28 days interval | 6958 (3 μg) | 6629 (aluminum hydroxide) | CFDA, 2019 | |
IBMCAMS vaccine/Institute of Medical Biology | Phase 1/2 | NCT04470609 NCT04412538 China | 18–59 years old | No | 2 doses, 14 days interval | 174 (150 EU) | 99 (aluminum hydroxide) | CFDA, 2019 | |
BBV152 (COVAXIN)/Bharat Biotech | Phase 2 | NCT04471519 India | 12–65 years old | No | 2 doses, 28 days interval | 190 (6 μg with Algel-IMDG) | No control groups | FDA and CTCAE | |
KCONVAC/Shenzhen Kangtai Biological Products Co., Ltd. | Phase 2 | ChiCTR2000038804 ChiCTR2000039462 China | 18–59 years old | No | 2 doses, 28 days interval | 100 (5 μg) | 50 (aluminum hydroxide) | CFDA, 2019 | |
RNA | |||||||||
BNT162b2/Pfizer-BioNTech | Phase 1/2/3 | NCT04368728 USA, Argentina, Brazil, Germany, S. Africa, Turkey | 12 years and older | Yes | 2 doses, 21 days interval | 22,752 (30 μg) | 22,760 (0.9% sodium chloride) | FDA | |
mRNA-1273/Moderna | Phase 3 | NCT04283461 USA | 18–95 years old | Yes | 2 doses, 28 days interval | 15,208 (100 μg) | 15,210 (0.9% saline) | FDA | |
mRNA-1273.351/Moderna | Phase 2 | NCT04405076 USA | 18 years and older | No | Booster dose | 20 (50 μg) | 20 (mRNA-1273) | FDA | |
CVnCoV/Curevac | Phase 1 | NCT04449276 Germany | 19–59 years old | No | 2 doses, 28 days interval | 28 (12 μg) | 32 (0.9% saline) | FDA | |
Non-replicating viral vector | |||||||||
Ad5 nCoV/CanSino Biological Inc. | Phase 1- 2 | NCT04341389 NCT04313127 China | 18–83 years old | No | 1 dose | 165 (5 × 1010 vp) | 126 (vaccine excipients) | CFDA, 2019 | |
ChAdOx1-nCoV (AZD1222/Covishield)/AstraZeneca | Phase 1/2/3 | NCT04324606 NCT04400838 NCT04444674 ISRCTN 15281137 ISRCTN89951424 Brazil, South Africa, UK | 18 years and older | Yes, 3.0% positive at baseline | 2 doses, 28 days interval | 12,021 (5 × 1010 vp or 2.2 × 1010 vp) | 11,724 (MenACWY† plus saline) | FDA | |
Gam-COVID-Vac (Sputnik V)/Gamaleya Research Institute | Phase 1/2/3 | NCT04436471 NCT04437875 NCT04530396 Russia | 18 years and older | No | 2 doses, 21 days interval | 16,427 (1011 vp for rAd26-S and rAd5-S) | 5435 (vaccine buffer composition) | FDA, CTCAE | |
Ad26.COV2.S/Johnson & Johnson | Phase 1/2a/3 | NCT04436276 NCT04505722 Belgium, US, Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa | 18–83 years old | Yes, 1.2% positive at baseline | 1 dose | 21,895 (5 × 1010 vp) | 21,888 | FDA | |
Protein subunit | |||||||||
NVX-CoV2373/Novavax | Phase 1–2 | NCT04368988 USA, Australia | 18–84 years old | No | 2 doses, 21 days interval | 257 (5μg + 50 μg Matrix-M1) | 255 (0.9% saline) | FDA | |
SCB-2019/Clover Biopharmaceuticals Inc. | Phase 1 | NCT04405908 Australia | 18–74 years old | No | 2 doses, 21 days interval | 16 (30 μg SCB-2019 + CpG/Alum) | 30 (0.9% saline) | FDA | |
ZF2001/Anhui Zhifei Longcom Biopharmaceutical | Phase 1/2 | NCT04445194 NCT04466085 China | 20–59 years old | No | 3 doses, 30 days interval | 170 (25 μg) | 160 (aluminum hydroxide) | CFDA, 2019 | |
EpiVacCorona/Federal Budgetary Research Institution State Research Center of Virology and Biotechnology "Vector" | Phase 1/2 | NCT04527575 Russia | 18–60 years old | No | 2 doses, 21 days interval | 57 (225 ± 45 μg) | 43 (0.9% saline) | NA | |
Virus-like particle | |||||||||
CoVLP/Medicago Inc. | Phase 1 | NCT04450004 Canada | 19–49 years old | No | 2 doses, 21 days interval | 20 (3.75 μg + AS03) | No control group | FDA | |
DNA | |||||||||
INO-4800/Inovio Pharmaceuticals | Phase 1–2 | NCT04336410 NCT04642638 USA | 18–80 years old | No | 2 doses, 28 days interval | 167 (2.0 mg) | 50 | FDA, CTCAE |
Local and systemic reactions in clinical trials
Treatment comparison (reference: placebo) | Study group (N/total) | Pooled RR (95%CI) | |
---|---|---|---|
Treatment | Control | ||
Local reaction (16 vaccines on 5 platforms) | |||
Inactivated vaccines | 10,276/33,901 | 7674/20,033 | 0.9 (0.8–1.1) |
RNA vaccines | 18,442/20,443 | 5393/20,428 | 4.0 (2.9–5.4) |
Non-replicating vector vaccines | 3753/6169 | 1926/6003 | 2.6 (1.6–4.4) |
Protein subunit vaccines | 203/493 | 45/485 | 4.5 (3.4–5.9) |
DNA vaccines | 66/167 | 11/50 | 1.8 (1.0–3.1) |
Systemic reaction (16 vaccines on 5 platforms) | |||
Inactivated vaccines | 10,682/33,919 | 6764/20,033 | 1.0 (1.0–1.0) |
RNA vaccines | 16,440/20,443 | 10,505/20,429 | 1.6 (1.5–1.6) |
Non-replicating vector vaccines | 3843/6169 | 2694/6003 | 1.5 (1.2–1.9) |
Protein subunit vaccines | 148/493 | 105/485 | 1.4 (1.2–1.8) |
DNA vaccines | 49/167 | 19/50 | 0.8 (0.5–1.2) |
Medically attended events* (2 vaccines on 2 platformss) | |||
RNA vaccines | 140/15,185 | 83/15,166 | 1.7 (1.3–2.2) |
Non-replicating vector vaccines | 304/21,895 | 408/21,888 | 0.7 (0.6–0.9) |
SAE* (8 vaccines on 3 platforms) | |||
Inactivated vaccines | 156/33,137 | 109/19,647 | 0.8 (0.7–1.0) |
RNA vaccines | 223/37,937 | 201/37,926 | 1.1 (0.9–1.3) |
Non-replicating vector vaccines | 207/50,343 | 208/39,047 | 0.8 (0.7–1.0) |
SAE related to vaccination* (8 vaccines on 3 platforms) | |||
Inactivated vaccines | 2/33,137 | 0/19,647 | 5.0 (0.2–104.0) |
RNA vaccines | 10/37,937 | 4/37,926 | 2.3 (0.5–10.6) |
Non-replicating vector vaccines | 10/50,343 | 8/39,047 | 2.4 (0.7–7.8) |
Unsolicited AEFI, serious AEFI, and AESI in phase 3 clinical trials
Age subgroup analysis based on data from clinical trials
Post-authorization observational studies
Post-authorization national safety surveillance
Vaccine | Country | Cut-off date | Doses administrated | AEFIs | Crude rate | Pooled rate (95% CI) |
---|---|---|---|---|---|---|
Pfizer/BioNTech | 3424.5 (2725.7–4123.3) | |||||
Austria | May 28, 2021 | 3,495,168 | 7210 | 2062.8 | ||
Belgium | June 8, 2021 | 3,216,657 | 8496 | 2641.3 | ||
Canada | June 4, 2021 | 18,894,651 | 3763 | 199.2 | ||
Denmark | June 8, 2021 | 2,094,751 | 15,537 | 7417.1 | ||
Estonia | June 14, 2021 | 533,863 | 1333 | 2496.9 | ||
Finland | June 9, 2021 | 2,587,708 | 1533 | 592.4 | ||
France | June 3, 2021 | 29,685,000 | 23,947 | 806.7 | ||
Germany | May 31, 2021 | 36,865,276 | 34,735 | 942.2 | ||
Iceland | June 15, 2021 | 109,919 | 624 | 5676.9 | ||
Italy | May 26, 2021 | 22,285,723 | 47,631 | 2137.3 | ||
Netherlands | June 6, 2021 | 7,300,000 | 111,852 | 15,322.2 | ||
Norway | June 8, 2021 | 2,414,340 | 3302 | 1367.7 | ||
Spain | March 21, 2021 | 4,834,876 | 23,084 | 4774.5 | ||
Sweden | June 10, 2021 | 4,568,479 | 15,789 | 3456.1 | ||
UK | June 2, 2021 | 25,400,000 | 193,768 | 7628.7 | ||
USA | February 16, 2021 | 28,374,410 | 48,196 | 1698.6 | ||
Portugal | May 30, 2021 | 3,943,979 | 4782 | 1212.5 | ||
Slovakia | June 10, 2021 | 1,961,407 | 2493 | 1271.0 | ||
Moderna | 8231.3 (7530.6–8931.9) | |||||
Austria | May 28, 2021 | 507,987 | 1645 | 3238.3 | ||
Belgium | June 8, 2021 | 437,008 | 1787 | 4089.2 | ||
Canada | June 4, 2021 | 5,096,282 | 2151 | 422.1 | ||
Denmark | June 8, 2021 | 185,169 | 2510 | 13,555.2 | ||
Estonia | June 14, 2021 | 75,581 | 159 | 2103.7 | ||
Finland | June 9, 2021 | 298,480 | 82 | 274.7 | ||
France | June 3, 2021 | 3,492,000 | 3540 | 1013.7 | ||
Germany | May 31, 2021 | 3,972,764 | 8319 | 2094.0 | ||
Iceland | June 15, 2021 | 18,502 | 296 | 15,998.3 | ||
Italy | May 26, 2021 | 2,901,137 | 2564 | 883.8 | ||
Netherlands | June 6, 2021 | 300,000 | 20,799 | 69,330.0 | ||
Norway | June 8, 2021 | 318,193 | 497 | 1561.9 | ||
Portugal | May 30, 2021 | 521,683 | 387 | 741.8 | ||
Slovakia | June 10, 2021 | 296,050 | 559 | 1888.2 | ||
Spain | March 21, 2021 | 304,715 | 2741 | 8995.3 | ||
Sweden | June 10, 2021 | 597,293 | 4475 | 7492.1 | ||
UK | June 2, 2021 | 460,000 | 9243 | 20,093.5 | ||
USA | February 16, 2021 | 26,738,383 | 56,567 | 2115.6 | ||
Janssen | 2683.4 (2070.4–3296.4) | |||||
Austria | May 28, 2021 | 36,004 | 98 | 2721.9 | ||
Belgium | June 8, 2021 | 94,285 | 167 | 1771.2 | ||
Denmark | June 8, 2021 | 14,019 | 41 | 2924.6 | ||
Estonia | June 14, 2021 | 16,475 | 82 | 4977.2 | ||
France | June 3, 2021 | 336,038 | 80 | 238.1 | ||
Germany | May 31, 2021 | 472,941 | 733 | 1549.9 | ||
Iceland | June 15, 2021 | 35,726 | 125 | 3498.9 | ||
Italy | May 26, 2021 | 503,155 | 171 | 339.9 | ||
Netherlands | June 6, 2021 | 9,000 | 606 | 67,333.3 | ||
Portugal | May 30, 2021 | 109,409 | 17 | 155.4 | ||
USA | May 7, 2021 | 7,980,000 | 13,725 | 1719.9 | ||
Oxford/AstraZeneca | 13,996.5 (10,775.9–17,217.1) | |||||
Argentina | April 9, 2021 | 783,055 | 2069 | 2642.2 | ||
Austria | May 28, 2021 | 941,745 | 17,132 | 18,191.8 | ||
Belgium | June 8, 2021 | 1,348,696 | 7078 | 5248.0 | ||
Canada | June 4, 2021 | 2,346,032 | 874 | 372.5 | ||
Denmark | June 8, 2021 | 150,694 | 23.236 | 154.2 | ||
Estonia | June 14, 2021 | 203,897 | 2486 | 12,192.4 | ||
Finland | June 9, 2021 | 406,100 | 855 | 2105.4 | ||
France | June 3, 2021 | 5,318,878 | 17,727 | 3332.8 | ||
Germany | May 31, 2021 | 9,230,103 | 34,870 | 3777.9 | ||
Iceland | June 15, 2021 | 60,044 | 604 | 10,059.3 | ||
Italy | May 26, 2021 | 6,739,596 | 15,878 | 2355.9 | ||
Netherlands | June 6, 2021 | 1,300,000 | 145,423 | 111,863.8 | ||
Norway | June 8, 2021 | 261,624 | 6640 | 25,379.9 | ||
Portugal | May 30, 2021 | 1,215,009 | 1509 | 1242.0 | ||
Slovakia | June 10, 2021 | 641,528 | 2706 | 4218.1 | ||
Spain | March 21, 2021 | 985,528 | 6343 | 6436.1 | ||
Sweden | June 10, 2021 | 886,815 | 21,891 | 24,685.0 | ||
UK | June 2, 2021 | 40,200,000 | 717,250 | 17,842.0 | ||
Sinopharm | 316.4 (285.8–347.0) | |||||
Argentina | April 9, 2021 | 1,295,940 | 410 | 316.4 | ||
Sputnik V | 7447.2 (7356.0–7538.4) | |||||
Argentina | April 9, 2021 | 3,414,158 | 25,426 | 7447.2 |