Adverse Reactions of COVID-19 Vaccines: A Scoping Review of Observational Studies

Figures & data

Table 1 Search Terms

Population	Interest	Outcomes
COVID-19	Vaccine	Adverse Effect
COVID 19	Vaccination	Adverse Event
COVID		Adverse Reaction
		Complication

Table 2 Summary Table of Adverse Reactions of COVID-19 Vaccines

Author, Year	Country	Aim	Vaccine Types	Population	Study Design	Adverse Reaction	Impact
Menni, et al; 2021^Citation24	United Kingdom	To investigate the adverse effects and infection rate of people in UK community after vaccinated with COVID-19 Pfizer-BioNTech (BNT162b2) and Oxford-AstraZeneca ChAdOx1 nCoV-19) vaccines.	Pfizer-BioNTech (BNT162b2) and Oxford-AstraZeneca ChAdOx1 nCoV-19) vaccines.	All UK COVID-19 symptom study app participants who received at least one dose of COVID-19 vaccine.	Prospective observational study that examined the proportion and probability of self-reported systemic and local side effects within 8 days of vaccination in individuals using COVID Symptom Study app.	a. The most commonly reported systemic side-effects were fatigue (8.4% and 21.1%) and headache (7.8% and 22.8%) of both vaccines and were most frequently reported within the first 24 h after vaccination and lasted a mean of 1.01 days. b. Tenderness (57.2%; 49.3%) and local pain (29.2%; 19.1%) around the injection site were the most frequently reported local effects of both vaccines occurring most often on the day after injection and lasting a mean of 1·02 days. c. Other side-effects including allergic skin reactions such as skin burning, rashes, and red welts on the lips and face were reported by 1.7% of users across both types of vaccine. d. Local effects were less commonly reported after the second dose than after the first dose of both vaccines. e. Local effects were similarly higher in individuals previously infected than in those without past infection for both vaccines.	Both vaccines have moderately frequent and mildly severe side effects.
Perrota, et al; 2021^Citation25	The US	To investigate the side-effects of COVID-19 vaccines among healthcare professionals and armed forces personnel.	mRNA and AdV vaccine or ChAdOx1 Astra-Zeneca-Oxford.	Healthcare professionals (HCPs) and armed forces personnel (AFP) worldwide.	Descriptive cross-sectional survey, using data from an online email or WhatsApp survey form that sent to healthcare professionals (HCPs) and armed forces personnel (AFP).	a. After the first dose of mRNA COVID-19 vaccine/Moderna, 65.6% participants experienced mild to moderate side-effects, with a large prevalence of mild ones. The most common local side effects reported after the first and second dose of mRNA vaccine were pain and/or paresthesia in the injection site (80.6% and 100%). b. The most commonly reported systemic events within 7 days after the two doses of mRNA vaccine were headache, asthenia and myalgia, which were significantly most often reported after the second dose than after the first one. c. After the first dose of AdV vaccine or ChAdOx1 Astra-Zeneca-Oxford 31 (81.6%) participants experienced mild to moderate side-effects, with a large prevalence of mild ones. d. The commonly reported systemic events within 7 days after the first dose of AdV vaccine were headache, myalgia, fever, and asthenia, which were frequently observed compared to both after the first and second dose of mRNA vaccine. e. No participant reported severe local or systemic reactions, irrespective of vaccine.	Mostly, the side effects are minor and do not interfere with daily activities or tasks.
Ganesan, et al; 2022^Citation26	United Arab Emirates	To investigate the nature and severity of the adverse effects reported and the differences based on the type of vaccine received.	Sinopharm and Pfizer-BioNTech vaccine.	Adult COVID-19 vaccine recipients (≥18 years) in the United Arab Emirates.	An observational cross-sectional study was conducted among ≥ 18 years old COVID-19 vaccine recipients using an online survey and telephone interviews.	a. The major adverse effects reported by the COVID-19 vaccine recipients were pain at the site of injection (47%), fatigue and drowsiness (28.2%), and joint/muscle pain (23.1%), followed by headache (17.7%) and fever (14.4%). b. A total of 61% of the Sinopharm vaccine recipients reported adverse effects following vaccination and people with associated comorbidities reported a statistically significant higher percentage (63.6%) of adverse effects than the others. c. A total of 68.5% reported adverse effects following the Pfizer-BioNTech vaccination and individuals who had a history of previous infection with COVID-19 reported a statistically significant higher percentage (75.4%) of adverse effects than the others. d. No statistically significant difference was observed with the local adverse effects reported after the first and second dose of the Sinopharm and Pfizer vaccine recipients. e. The average number of adverse effects reported between individuals who had received the Sinopharm and Pfizer-BioNTech vaccine was statistically significant difference was observed among people in the 35–54-years age group and ≥ 55-years age group.	Most adverse effects following vaccination were mild in nature and self-limiting. Only 5% of the adverse effects required consultation with a doctor or treatment at the hospital.
Rosenblum, et al; 2022^Citation27	The USA	To describe US surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS) on two mRNA COVID-19 vaccines. (BNT162b2 [Pfizer-BioNTech]; and mRNA-1273 [Moderna])	Pfizer-BioNTech and Moderna.	US residents who report to VAERS following the receipt of a mRNA vaccine.	Observational study, using the data reported on the Vaccine Adverse Event Reporting System and V-Safe.	a. Among the reported cases, 3 92.1% were classified as non-serious; 6.6% were serious, not resulting in death; and 1.3% were deaths. b. The most common MedDRA preferred terms assigned to non-serious reports were headache (20.4%), fatigue (16.6%), pyrexia (16.3%), chills (15.7%), and pain (15.2%). c. The most common MedDRA preferred terms assigned to serious reports were dyspnea (15.4%), death (14.1%), pyrexia (11.0%), fatigue (9.7%), and headache (9.5%). d. The reporting rate to VAERS was 1049.2 non-serious reports per million vaccine doses, and 90.4 serious reports per million doses. e. Of the 4471 reports of deaths analyzed: 46.7% were reported following BNT162b2 and 53.3% following mRNA-1273. 42.6% deaths were in female vaccine recipients and 55.6% were in male recipients; the median age of participants who died was 76 years. f. Time to death following vaccination was available for 92.1% reports; median time was 10 days. The greatest number of death reports occurred on day 1 and day 2 following vaccination. g. Death certificates or autopsy reports were available for clinical review for 18.1% reports of deaths. Among these, causes of death were most commonly diseases of the heart and COVID-19. h. Among the rest of reports without a death certificate or autopsy, causes of death were 54.2%, most commonly unknown, 17.0% because of heart diseases and 8.7% COVID-19. i. Most reported symptoms were mild with participants reported moderate and severe reactogenicity most commonly on day 1 after dose two of either mRNA vaccine. Less than 1.0% reported receiving medical care after receiving either dose of either vaccine.	The effects of mRNA vaccination on daily-life activities among vaccine recipients were most frequently reported on day 1 after vaccination, with most side effects being mild.
Lee, et al; 2021^Citation28	South Korea	To assess the relationships of antibody level with age, sex, BMI, and adverse reactions to the ChAdOx1 nCoV-19 (AZD1222) vaccine.	ChAdOx1 nCoV-19 (AZD1222).	Healthcare workers in Hanyang University Hospital who received two doses of ChAdOx1 nCoV-19.	Prospective observational study, using the data of self-reported online adverse reaction survey after seven days of COVID-19 vaccination.	a. Most participants (n = 434, 97.1%) experienced at least one local or systemic adverse reaction during days 0–7 after either injection (first or second). b. The most frequently reported local AR was pain (91.8%), tenderness (86.3%), and induration (30.9%). c. The most frequently reported systemic AR was fatigue (87.5%), muscle pain (82.1%), chills (69.1%), and headache (69.1%). d. The most frequently reported grade 3 to grade 4 local AR was tenderness (26.8%), followed by pain (5.8%), and itching (4.4%), while the most frequently reported grade 3 to grade 4 systemic AR was chills (18.6%), followed by fatigue (18.2%), muscle pain (17%), and fever (6.1%). e. The ARs were less frequent after the second injection of the ChAdOx1 nCov-19 vaccine, both systemic (43.8%) and local (49.0%).	The majority of participants reported experiencing local or systemic effects (0–7 days after vaccination) with tenderness and chills symptoms.
Bsoul, et al; 2022^Citation29	The US	Evaluate the Pfizer COVID-19 vaccination experience related to safety, confidence levels, and side effects among United States-based dental students, staff, and faculty.	Pfizer COVID-19.	Students and staff at the School of Dentistry, UT Health San Antonio.	An observational online survey using the web-based survey platform.	a. The common adverse reactions after the COVID-19 vaccination were injection site pain (75.0%), and the following general side effects (66.7%) were fatigue/ tiredness, headache, muscle/ body ache, and chills/fever. b. About the 60% of participant reported the severity of side effects to be no worse than mild, and the vaccine did not interfere with their life activities. c. There were no differences in severity or impact of vaccine side effects on participant life activities.	a. Side effects after both doses of the vaccine were reported by 36% of all participants. b. All reported side effect were mild and did not interfere daily activities.
Flores, et al; 2021^Citation30	Peru	To identify post SARS-CoV-2 vaccine BNT162b2 (BioNTech and Pfizer) side effects in patients with systemic lupus erythematosus (SLE).	BioNTech and Pfizer.	SLE patients at the Immuno-Rheumatology Department of the Cayetano Heredia Hospital, Lima, Peru.	Descriptive observational study, using the data of patients with a diagnosis of systemic lupus erythematosus (SLE) who attended at the Immuno-Rheumatology Service of the Cayetano Heredia Hospital, Lima, Peru.	a. All patients received the vaccine presented symptoms within 10 days after immunization with pain at the inoculation site being the most frequent (87%) with mild intensity. b. The pre-dominant type of flare presented after vaccination was arthritis (85.1%) included synovitis, swelling, phlogosis, and followed by dermal (18.5%).	Following SARS-CoV-2 immunization, the majority have local symptoms of an adverse event with mild severity and did not interfere with daily activities.
Shulman et al; 2022^Citation31	The US	To records short-term adverse reactions of the COVID-19 vaccine in patients with cancer, compare these reactions to patients without cancer, and determine whether adverse reactions are associated with active cancer therapy.	mRNA Pfizer BNT162b2 vaccine.	Patients with two doses of the mRNA Pfizer BNT162b2 vaccine at the Comprehensive Cancer Center.	Prospective observational study using survey completed either by telephone or online approximately 2 weeks after the second dose of COVID-19 vaccine.	a. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose. b. Muscle pain after the first vaccination was more frequent in patients with cancer than in those without but was of shorter duration. c. Joint pain, fever, chills, headache, and nausea were unrelated to cancer status. d. For patients with cancer, adverse events that were reported more frequently after dose 2 included fatigue, joint pain, fever, chills, headache, and nausea.	Comparing patients with cancer to those without cancer revealed few differences in reported adverse events. Active cancer treatment had little effect on the profiles of adverse events.
Jeong, S et al; 2022^Citation32	South Korea	To investigate the clinical characteristics of older adults with self-reported COVID-19 post vaccination fever and/or febrile sensation or rigors.	Oxford/AstraZeneca (AZD1222), Pfizer BioNTech (BNT162b2) and Moderna (mRNA-1273).	Patients with fever and/or febrile sensation following COVID-19 vaccination in three South Korean hospitals.	A retrospective observational study in three hospitals in Korea, using the self-reported data of patients with suspected adverse reactions after COVID-19 vaccination.	a. The reported adverse reaction after the COVID-19 vaccination was a fever which more experienced among younger adults age than older adults (85.7% vs 75.5%, respectively). b. Post-vaccination fever symptoms most commonly occurred on days 0 and 1.	a. The number of patients who visited the ED with fever as a suspected COVID-19 vaccine-related adverse reaction was lower for older adults than for younger adults. b. Older adults did not require admission to the hospital due to vaccine-related adverse reactions.
Oh, et al; 2022^Citation33	South Korea	To investigate clinical features of patients who visited the ED for cardiovascular adverse reactions after COVID-19 m-RNA vaccination.	COVID-19 mRNA vaccine, Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273).	People were 65 years of age or younger at Incheon and Daejeon hospitals with cardiovascular adverse reactions after the COVID-19 vaccine.	A Retrospective observational study, using the data reported from the Immunization Registry System (IRS) on any suspected COVID-19 vaccine-related adverse events.	a. (51%) out of 1397 patients who visited the ED after receiving the COVID-19 mRNA vaccine reported cardiovascular symptoms as adverse reactions. b. Most patients reported cardiovascular-adverse reactions within 7 days after vaccination, after both the first and second doses (81.9% and 86.4%). c. Males presented adverse reaction with more chest pain/discomfort than females (81.7% vs 70%), while females presented with more dyspnea and palpitation than males. d. Both males (70.8%) and females (65.7%) visited the ED after experiencing adverse reaction more frequently after the first vaccine dose than after the second dose, except for the 17–19 age group.	Most patients reported cardiovascular-adverse reactions within 7 days after vaccination, after both the first and second doses. Adverse reactions showed mild progression.
Park, et al; 2022^Citation34	Daegu, Republic of Korea	To determine the association between the vaccination and interference with work and daily life.	ChAdOx1 and BNT162b2 COVID-19 vaccine.	Hospital workers who received the first dose of ChAdOx1 at the University Hospital in Daegu, Republic of Korea.	Retrospective survey involving hospital workers that received ChAdOx1 and BNT162b2 COVID-19 vaccine.	a. Participants who experienced significant levels of interference with work (5–10 points) reported all side effects (except urticaria) more frequently with the ChAdOx1 vaccination, with the three most common adverse events being local pain (83.2%), myalgia (78.3%), and fever (73.3%). b. The three most common side events for ChAdOx1 vaccine participants who had severe levels of interference with everyday living were local pain (84.4%), myalgia (77.7%), and fever (70.9%). c. Myalgia, fever, chills, and local pain were the four most common side events among those who got the BNT162b2 vaccination in both the high interference with work and high interference with daily living groups.	The majority of the effects were visible within 24 hours of the vaccination. Individuals’ length of unpleasant effects varied, with around 50% reporting that they were impacted for more than 24 hours. Effects on daily life activities were mild or low.

Menni C, Klaser K, May A, et al. Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. Lancet Infect Dis. 2021;21(7):939–949. doi:10.1016/S1473-3099(21)00224-3

 PubMed Web of Science ®Google Scholar

Perrotta A, Biondi-Zoccai G, Saade W, et al. A snapshot global survey on side effects of cOvid-19 vaccines among healthcare professionals and armed forces with a focus on headache. Panminerva Med. 2021;63(3):324–331. doi:10.23736/S0031-0808.21.04435-9

 PubMed Web of Science ®Google Scholar

Ganesan S, Al Ketbi LMB, Al Kaabi N, et al. Vaccine side effects following COVID-19 vaccination among the residents of the UAE—an observational study. Front Public Health. 2022;10. doi:10.3389/fpubh.2022.876336

 PubMed Web of Science ®Google Scholar

Rosenblum HG, Gee J, Liu R, et al. Safety of mRNA vaccines administered during the initial 6 months of the US COVID-19 vaccination programme: an observational study of reports to the vaccine adverse event reporting system and v-safe. Lancet Infect Dis. 2022;22(6):802–812. doi:10.1016/S1473-3099(22)00054-8

 PubMed Web of Science ®Google Scholar

Lee SW, Moon JY, Lee SK, et al. Anti-SARS-CoV-2 Spike Protein RBD antibody levels after receiving a second dose of ChAdOx1 nCov-19 (AZD1222) vaccine in healthcare workers: lack of association with age, sex, obesity, and adverse reactions. Front Immunol. 2021;12. doi:10.3389/fimmu.2021.779212

 Web of Science ®Google Scholar

Bsoul EA, Loomer PM, Patel SKS. COVID-19 vaccination experience among United States dental professionals and students: safety, confidence, concerns, and side effects. PLoS One. 2022;17(2):e0264323. doi:10.1371/journal.pone.0264323

 PubMed Web of Science ®Google Scholar

Zavala-Flores E, Salcedo-Matienzo J, Quiroz-Alva A, Berrocal-Kasay A. Side effects and flares risk after SARS-CoV-2 vaccination in patients with systemic lupus erythematosus. Clin Rheumatol. 2022;41(5):1349–1357. doi:10.1007/s10067-021-05980-5

 PubMed Web of Science ®Google Scholar

Shulman RM, Weinberg DS, Ross EA, et al. Adverse events reported by patients with cancer after administration of a 2-dose mRNA COVID-19 vaccine. J Natl Comprehen Cancer Netw. 2022;20(2):160–166. doi:10.6004/jnccn.2021.7113

 PubMed Web of Science ®Google Scholar

Jeong S, Hong S, Oh T, et al. Analysis of older adults visiting the emergency department with fever as a suspected Covid-19 vaccine-related adverse reaction: a retrospective multicenter study. J Infect Chemother. 2022;28(8):1159–1164. doi:10.1016/j.jiac.2022.04.022

 PubMed Web of Science ®Google Scholar

Oh TH, Woo SH, Hong S, Lee C, Lee WJ, Jeong SK. Clinical features of patients presenting to the emergency department with cardiovascular adverse reactions after COVID-19 mRNA vaccination. J Korean Med Sci. 2022;37(9). doi:10.3346/jkms.2022.37.e73

 Web of Science ®Google Scholar

Park C, Sakong J, Jo S, Kim M, Baek K. Adverse effects on work and daily life interference among healthcare workers after the first and second chadox1 and bnt162b2 covid-19 vaccine doses. Vaccines. 2021;9(8):926. doi:10.3390/vaccines9080926

 Web of Science ®Google Scholar