Table 2.
Grade III and IV AEs of COVID-19 vaccines in the latest clinical trials
| Vaccine platform | Vaccine | Location | Age | Study phase | Sample size (vaccine group vs. placebo group) | Grade III and IV AEs except neurological AEs (cases, n) | Grade III and IV neurological AEs (cases, n) | Reference | |
|---|---|---|---|---|---|---|---|---|---|
| Nonreplicating viral vector | AZD1222 | US, Chile, and Peru | ≥18 | 3 | 32,451 (21,635 vs. 10,816) | Fever (DNP), chills (DNP), muscle pain (DNP), malaise (DNP), tenderness (DNP), and fatigue (DNP) | Chronic inflammatory demyelinating polyradiculoneuropathy (1), hypoesthesia (1), and headache (DNP) | [39] | |
| Ad5-vectored COVID-19 vaccine | Argentina, Chile, Mexico, Pakistan, and Russia | ≥18 | 3 | 36,717 (18,363 vs. 18,354) | Fever (27), drowsiness (66), nausea (15), diarrhea (7), vomiting (1), generalized muscle aches (65), redness (4), swelling (3), and pain (49) | Headache (85) | [40] | ||
| Sputnik V | Russia | ≥18 | 3 | 21,977 (16,501 vs. 5,476) | None | None | [41] | ||
| Ad26.COV2.S | Belgium, Brazil, Colombia, France, Germany, The Philippines, South Africa, Spain, UK, and US | ≥18 | 3 | 31,300 (15,708 vs. 15,592) | Injection site swelling (1), pyrexia (1), hemoptysis (1), pulmonary embolism (1), pericarditis (1), vertigo (1), allergy to vaccine (1), increased myocardial necrosis marker (1), nausea (2), fatigue (1), vaccination site erythema (1), acute sinusitis (1), localized infection (1), and myalgia (1) | Cerebrovascular accident (1), headache (1), and facial paresis (1) | [42] | ||
| Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa, and US | ≥18 | 3 | 43,783 (21,895 vs. 21,888) | Fatigue (2), chills (1), malaise (1), pyrexia (1), nausea (2), diarrhea (1), dyspepsia (1), vomiting (1), myalgia (1), vaccination site hypersensitivity (1), pain in extremity (1), tendon disorder (1), pericarditis (1), post-vaccination syndrome (1), tachycardia (1), and nasal congestion (1) | Guillain-Barré syndrome (1), syncope (1), Bell's palsy (2), brachial radiculitis (1), and headache (4) | [43] | |||
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| RNA | mRNA-1273 | US | ≥18 | 3 | 30,415 (15,209 vs. 15,206) | Pain (606), erythema (287), swelling (255), axillary swelling (68), fever (216), fatigue (1,433), myalgia (1,321), arthralgia (775), nausea (22), and chills (191) | Headache (666), cerebrovascular accident (1), and syncope (1) | [44] | |
| BNT162b2 | Argentina, Brazil, South Africa, Germany, Turkey, and US | ≥16 | 2/3 | 44,165 (22,085 vs. 22,080) | Fever (DNP), fatigue (DNP), chills (DNP), vomiting (DNP), diarrhea (DNP), pain (DNP), redness (DNP), swelling (DNP), shoulder injury (1), right axillary lymphadenopathy (1), paroxysmal ventricular arrhythmia (1), and right leg paresthesia (1) | Headache (DNP) | [45] | ||
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| RNA | CVnCoV | Belgium, Germany, The Netherlands, Spain, Argentina, Colombia, Dominican, Republic, Mexico, Panama, and Peru | ≥18 | 2/3 | 39,680 (19,846 vs. 19,834) | Pain (10), swelling (1), fatigue (176), myalgia (99), chills (135), arthralgia (40), fever (67), nausea (6), diarrhea (5), acute myocardial infarction (1), atrial fibrillation (1), cardiac arrest (1), supraventricular extrasystoles (1), ventricular tachycardia (1), appendicitis (1), and cellulites (1) | Headache (143) and seizure (1) | [46] | |
| ARCoV | China | 18–59 | 1 | 120 (100 vs. 20) | Injection site pain (1) and fever (22) | None | [47] | ||
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| Inactivated | CoronaVac | Brazil | ≥18 | 3 | 12,408(6,201 vs. 6,207) | None | None | [48] | |
| Turkey | 18–59 | 3 | 10,218 (6,650 vs. 3,568) | Systemic allergic reaction (1) | None | [49] | |||
| Chile | ≥18 | 3 | 434 (270 vs. 164) | None | None | [50] | |||
| WIV04 | UAE and Bahrain | ≥18 | 3 | 26,941 (13,470 vs. 13,471) | Pain (6), induration (1), swelling (1), fever (28), diarrhea (12), constipation (1), vomiting (3), myalgia (9), arthralgia (2), dyspnea (7), pruritus (4), skin and mucosal abnormalities (1), and fatigue (11) | Headache (14) | [51] | ||
| HB02 | UAE and Bahrain | ≥18 | 3 | 26,941 (13,470 vs. 13,471) | Emesis (1), pain (1), rash (1), itching (1), fever (23), diarrhea (8), constipation (1), dysphagia (1), vomiting (3), nausea (1), myalgia (8), arthralgia (2), dyspnea (6), pruritus, (1) and fatigue (19) | Headache (13) | [51] | ||
| SARS-CoV-2 vaccine (vero cells) | China | 18–59 | 2 | 750 (600 vs. 150) | None | None | [52] | ||
| QazCovid-ine | RK | ≥18 | 3 | 3,000 (2,400 vs. 600) | None | None | [53] | ||
| BBV152 | India | 18–98 | 3 | 25,798 (12,899 vs. 12,899) | DNP | DNP | [54] | ||
| KCONVAC | China | 18–59 | 2 | 500 (400 vs. 100) | None | None | [55] | ||
| NDV-HXP-S | Thailand | 18–59 | 1/2 | 210 (175 vs. 35) | None | None | [56] | ||
| CoviVac | Russia | 18–60 | 1/2 | 398 (298 vs. 100) | None | None | [57] | ||
| Protein subunit | NVX-CoV2373 | UK | 18–84 | 3 | 15,187 (7,593 vs. 7,594) | Myocarditis (1), fatigue (DNP), malaise (DNP), muscle pain (DNP), joint pain (DNP), elevated temperature (DNP), pain (DNP), tenderness (DNP), erythema (DNP), and swelling (DNP) | Headache (DNP) | [58] | |
| US and Mexico | ≥18 | 3 | 29,949 (19,965 vs. 9,984) | Pain (302), tenderness (837), erythema (143), swelling (91), fatigue (1,423), malaise (1,082), muscle pain (846), joint pain (417), fever (64), and nausea (36) | Headache (518) | [59] | |||
| ZF2001 | China | 18–59 | 2 | 900 (600 vs. 300) | Redness (6), swelling (3), injection site pain (1), induration (1), rash (1), and fever (1) | Headache (1) | [60] | ||
| CoV2 preS dTM | USCo | ≥18 | 1/2 | 441 (378 vs. 63) | Pain (8), erythema (23), swelling (12), fever (11), malaise (31), and myalgia | (25) | Headache (17) | [61] | |
| SCB-2019 | Belgium, Brazil, Colombia, Philippines, and South Africa | ≥18 | 3 | 30,128 (15,064 vs. 15,064) | DNP | DNP | [62] | ||
| MVC-COV1901 | China | ≥20 | 2 | 3,854 (3,304 vs. 550) | None | None | [63] | ||
| SOBERANA 02 | Cuba | 19–80 | 3 | 44,031 (29,356 vs. 14,675) | DNP | DNP | [64] | ||
| Recombinant COVID-19 vaccine (Sf9 cells) | China | ≥18 | 2 | 960 (800 vs. 160) | Redness (1) and swelling (1) | None | [65] | ||
| Abdala | Cuba | 19–80 | 2 | 726 (484 vs. 242) | None | None | [66] | ||
| Nanocovax | Vietnam | ≥18 | 2 | 560 (480 vs. 80) | Pain (DNP), redness (1), fatigue (DNP), and swelling (DNP) | None | [67] | ||
| MF59-adjuvanted subunit vaccine | Australia | 18–55 | 1 | 120 (96 vs. 24) | Injection site pain (1) and malaise (1) | None | [68] | ||
| Recombinant fusion protein vaccine (V-01) | China | ≥18 | 2 | 880 (720 vs. 160) | DNP | DNP | [69] | ||
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| Virus-like particle | CoVLP | Argentina, Brazil, Canada, Mexico, UK, and US | 18–86 | 3 | 24,076 (12,036 vs. 12,040) | None | None | [70] | |
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| DNA | INO-4800 | US | ≥18 | 2/3 | 399 (298 vs. 101) | Arthralgia (1) | None | [71] | |
UAE, the United Arab Emirates; UK, the United Kingdom; US, the United States; RK, the Republic of Kazakhstan; DNP, data not provided.