International Journal of General Medicine Dovepress

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REVIEW

Adverse Reactions of COVID-19 Vaccines: A

Scoping Review of Observational Studies
International Journal of General Medicine downloaded from https://www.dovepress.com/ on 19-May-2023

1–3 4–6
Inge Dhamanti , Auliya A Suwantika , Amirah Adlia 7 , Laura Navika Yamani 8,9 , Fitri Yakub 10
1
Department of Health Policy and Administration, Faculty of Public Health, Universitas Airlangga, Surabaya, Indonesia; 2Center for Patient Safety
Research, Universitas Airlangga, Surabaya, Indonesia; 3School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia;
4
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia; 5Center of Excellence in
Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, Indonesia; 6Center for Health Technology Assessment,
Universitas Padjadjaran, Bandung, Indonesia; 7Department of Pharmaceutics, School of Pharmacy, Institut Teknologi Bandung, Bandung, Indonesia;
8
Division Epidemiology, Faculty of Public Health, Universitas Airlangga, Surabaya, Indonesia; 9Research Center on Global Emerging and Re-Emerging
Infectious Diseases, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia; 10Malaysia-Japan International Institute of Technology,
Universiti Teknologi Malaysia, Skudai, Malaysia

Correspondence: Inge Dhamanti, Tel +62315920948, Email [email protected]

For personal use only.

Abstract: The COVID-19 pandemic had a severe global impact. A range of campaigns and activities, including vaccines, are being
implemented to counteract this pandemic. Using observational data, the goal of this scoping review is to identify adverse events
connected with COVID-19 vaccinations. We conduct a scoping study and searched three databases from the start of the COVID-19
pandemic in 2020 through June 2022. Based on our criteria and searched keywords, the review included eleven papers in total, with
the majority of the studies being conducted in developed countries. The study populations varied and included general community
populations, healthcare professionals, military forces, and patients with systemic lupus and cancer. This study includes vaccines from
Pfizer-BioNTech, Oxford-AstraZeneca, Sinopharm, and Moderna. The COVID-19 vaccine-related adverse events were classified into
three types: local side effects, systemic side effects, and other side effects such as allergies. The adverse reactions to COVID-19
vaccines are mild to moderate in severity, with no significant influence or interference in individual daily activities and no unique
patterns in cause of death among vaccine-related deaths. According to the findings of these investigations, the COVID-19 vaccine is
safe to administer and induces protection. It is vital to convey accurate information to the public about vaccination side effects,
potential adverse responses, and the safety level of the vaccines supplied. Multiple strategies must be implemented at the individual,
organizational, and population levels to eliminate vaccine hesitance. Future studies could investigate the vaccine’s effect on people of
various ages and medical conditions.
Keywords: adverse effect, COVID-19 vaccines, vaccine reactions, vaccination impact

Introduction
COVID-19, which has been declared a global pandemic by WHO, has already infected over 38 million people and
claimed at least one million lives since the virus first emerged in late 2019 from Wuhan, China.1,2 The global infection
detection rate was close to 10%, and it is estimated that 66% of people have been infected at least once as of May 2022.3
Based on these findings, the world has been dealing with a devastating COVID-19 pandemic.
A variety of campaigns and actions are being undertaken to combat this pandemic, beginning with the establishment
of local lockdowns and mass testing.4,5 Furthermore, as a new promising way, COVID-19 vaccine can be called hope to
reduce the mortality rate of infected individuals and return to some forms of normal life.6 The United States has approved
the use of two COVID-19 vaccines, Pfizer-BioNTech and Moderna COVID-19 vaccines, both of which are to be
administered in a two-dose sequence. Following Phase III clinical trials in ten countries worldwide, China and a few
other countries approved the Sinopharm COVID-19 vaccine.7 Because these vaccines were modeled using various
processes and approaches, they differ in some aspects such as efficacy and storage conditions.8

International Journal of General Medicine 2023:16 609–618 609

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The side effects of the COVID-19 vaccine were reported by 50% to 90% of participants in randomized clinical trials
of COVID-19 vaccines.9 Another study conducted worldwide (US, Argentina, Brazil, South Africa, Germany, and
Turkey) showed that more than 30% of participants had side effects.10 Clinical trials conducted in Argentina, Brazil,
Chile, Colombia, Mexico, Peru, South Africa, and the United States showed that the majority of participants had both
local and systemic reactions to the COVID-19 vaccine.11 Based on clinical trials, COVID-19 vaccines were found to be
extremely safe;9,10 however, there is less evidence comparing the safety of these vaccines in real-world settings.
Vaccine production is a difficult and lengthy. Rather than treating sick people, vaccines are given to large groups of healthy
people to prevent sickness. Thus, the protection barrier for a new vaccination must be high and apply to the whole target
population, regardless of age, gender, color, or ethnicity.8 Some people may refuse to receive a vaccine due to potential side
effects, while others may be apprehensive about adverse reactions due to allergies or comorbid diseases.12 As a result, vaccine
research and testing methodologies must be led carefully and deliberately by a primary focus on protection.
To date, no vaccine can be claimed to be completely free of adverse reactions, but the majority of them are either
preventable or treatable.13 In some vaccines, early side effects such as fever, pain, myalgias, headaches, and local or injection
site effects are related to immune surge.14 The adverse reactions to the COVID-19 vaccine are critical to public trust in the
vaccination. The rates of vaccine hesitancy and rejection are still high, which is associated with more negative beliefs that the
vaccination will cause adverse reactions;15 was found as the most significant potential barriers to getting vaccinated against
COVID-19.16 Adverse reactions were the most important factors in individuals’ vaccine choice decisions.17 Aside from that,
the possibility of a serious adverse reaction was discovered to be a variable cause of vaccination rejection.18
Therefore understanding the adverse effects will aid in increasing the vaccine’s success rate. The majority of studies on
vaccination adverse effects focused on clinical trials or pre-and post-intervention, with only a few focusing observational studies,
particularly those that examined the impact of vaccine on daily living in a real-world environment. As a result, the aim of this study
was to do analyze the adverse reactions to COVID-19 vaccines that have been reported in a number of observational studies.

Materials and Methods

Study Design
The current review was written using the Joanna Briggs Institute’s scoping review method (JBI).19 The concept of interest
was the challenges to discover the adverse reactions of the COVID-19 vaccines especially that using the observational
studies. We included only an observational quantitative study designs as most of the review were on clinical trials and pre-
and post-intervention.20,21 Observational studies has benefit for document the effects of naturally exposed outcomes, which
in this case are any outcomes produced by an intervention or treatment that were not originally intended by the person who
prescribed the intervention.22 This scoping review protocol was following the PRISMA-P guidelines.23

Search Strategy
On June 2022, we conducted initial research using all identifier keywords and relevant terms in the electronic databases
PubMed, Science Direct, and CINAHL. The search strategy for all databases was the same as shown in the PRISMA
Flowchart (Appendix I). In the search, keywords with Boolean operators (“OR” and “AND”) related to process
development and trigger tool validation were used (Table 1). We did not search the grey literature because we are

Table 1 Search Terms

Population Interest Outcomes

COVID-19 Vaccine Adverse Effect

COVID 19 Vaccination Adverse Event

COVID Adverse Reaction

Complication

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only interested in studies published in peer-reviewed journals that are based on scientific methods that use evidence to
develop conclusions.

Eligibility Criteria and Data Selection

The inclusion criteria were observational studies that clearly described the adverse reactions to COVID-19 vaccines
published in English between January 2020 and June 2022. Furthermore, studies were included if the outcome of the
adverse reactions was defined objectively such as the impact on daily life or the severity of the reactions. Two reviewers
assessed the eligibility of all studies (ID, AAS). Any conflicts or disagreements were handled and resolved by the third
reviewer (AA).

Data Extraction and Synthesis

Relevant data were extracted from the included studies to answer the review question using the JBI methodology.19 The
authors’ names, publication year, country of origin of the study, and characteristics (aim of study, vaccine types,
population, study design, adverse reaction, impact) were all retrieved (Table 2). To map the included research, we
extracted the key findings of the studies into the COVID-19’s adverse reaction. We also extracted the measured outcomes
of COVID-19 vaccine from all eleven studies.

Results
The initial search yielded 400 articles using the keywords in three databases. Mendeley Reference Manager identified
duplicates automatically, resulting in a total of 320 articles being evaluated and those that did not fulfill the inclusion
requirements being excluded. Eligibility was determined for a total of 55 full-text articles. Thirty-one publications were
deleted because they were not observational studies, and another 13 were excluded because the outcome did not include
adverse reactions to COVID-19 vaccinations. Finally, eleven articles were chosen after passing the eligibility criteria.
Appendix 1 depicts the entire study flow (Appendix).

Study Characteristics
All of the research employed the observational study design. The 11 studies were undertaken the United States, the
United Kingdom, Canada, Peru, the United Arab Emirates, and South Korea and most of the studies taking place in
developed countries.24–34 The majority of the studies had similar contexts, but the populations varied and were conducted
in general community populations, with the remainder conducted in healthcare professionals, armed forces personnel,
and patients with systemic lupus and cancer. The objectives of most of the studies were to investigate the adverse
reactions after those populations vaccinated with COVID-19 vaccines.

Types of Adverse Reactions

Adverse reactions are classified into two types: vaccine-related events and allergic reactions. The majority of research has
been on negative vaccination reactions, and also no allergic reactions. The most commonly reported COVID-19 vaccine-
related adverse reactions include local injection and systemic side effects. Joint or muscle pain, tenderness, itching, and
paresthesia in the injection site.24–28,31,34 Local effects were also greater in previously infected individuals than in those
who had never been infected. Fever, chills, fatigue, headache, nausea, myalgia, pyrexia, and dyspnea are among the
systemic side effects.24–29,31–34 Some cardiovascular side effects like sinus tachycardia, premature ventricular contrac­
tions, and right bundle branch block may occur.33 The vast majority of patients who reported unfavorable cardiovascular
events were men. Males reported more unfavorable effects than females, such as chest pain or discomfort, dyspnea and
palpitation.33
Everyone in the community; health workers, students, and cancer or systemic lupus patients had the same adverse
reactions based on the data. The adverse responses seen by participants following the first dose of COVID-19
vaccinations are modest, with local pain and fever, according to the studies included.24–34 Another study, on the other
hand, discovered that moderate to severe reactogenicity was more typically observed after immunization dose two.27
These side effects were more common after the second dose than after the first.29,31 Patients who visited the ER for

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Table 2 Summary Table of Adverse Reactions of COVID-19 Vaccines
Author, Country Aim Vaccine Types Population Study Design Adverse Reaction Impact
Year
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Menni, et al; United To investigate the adverse Pfizer-BioNTech All UK COVID-19 Prospective a. The most commonly reported systemic side-effects were fatigue Both vaccines have
202124 Kingdom effects and infection rate of (BNT162b2) and symptom study app observational study that (8.4% and 21.1%) and headache (7.8% and 22.8%) of both vaccines moderately frequent and
people in UK community Oxford-AstraZeneca participants who examined the proportion and were most frequently reported within the first 24 h after mildly severe side effects.
after vaccinated with ChAdOx1 nCoV-19) received at least one and probability of self- vaccination and lasted a mean of 1.01 days.
COVID-19 Pfizer- vaccines. dose of COVID-19 reported systemic and b. Tenderness (57.2%; 49.3%) and local pain (29.2%; 19.1%) around
BioNTech (BNT162b2) and vaccine. local side effects within 8 the injection site were the most frequently reported local effects
Oxford-AstraZeneca days of vaccination in of both vaccines occurring most often on the day after injection
ChAdOx1 nCoV-19) individuals using COVID and lasting a mean of 1·02 days.
vaccines. Symptom Study app. 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.

Perrota, The US To investigate the side- mRNA and AdV Healthcare Descriptive cross- a. After the first dose of mRNA COVID-19 vaccine/Moderna, 65.6% Mostly, the side effects are
et al; 202125 effects of COVID-19 vaccine or ChAdOx1 professionals (HCPs) sectional survey, using participants experienced mild to moderate side-effects, with a minor and do not interfere
vaccines among healthcare Astra-Zeneca-Oxford. and armed forces data from an online email large prevalence of mild ones. The most common local side effects with daily activities or tasks.
professionals and armed personnel (AFP) or WhatsApp survey reported after the first and second dose of mRNA vaccine were
forces personnel. worldwide. form that sent to pain and/or paresthesia in the injection site (80.6% and 100%).
healthcare professionals b. The most commonly reported systemic events within 7 days after
(HCPs) and armed forces the two doses of mRNA vaccine were headache, asthenia and
personnel (AFP). 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.

Ganesan, United To investigate the nature Sinopharm and Pfizer- Adult COVID-19 An observational cross- a. The major adverse effects reported by the COVID-19 vaccine Most adverse effects
et al; 202226
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Arab and severity of the adverse BioNTech vaccine. vaccine recipients (≥18 sectional study was recipients were pain at the site of injection (47%), fatigue and following vaccination were
Emirates effects reported and the years) in the United conducted among ≥ 18 drowsiness (28.2%), and joint/muscle pain (23.1%), followed by mild in nature and self-
differences based on the Arab Emirates. years old COVID-19 headache (17.7%) and fever (14.4%). limiting. Only 5% of the
type of vaccine received. vaccine recipients using b. A total of 61% of the Sinopharm vaccine recipients reported adverse effects required
an online survey and adverse effects following vaccination and people with associated consultation with a doctor or
telephone interviews. comorbidities reported a statistically significant higher percentage treatment at the hospital.
(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

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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.

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Rosenblum, The USA To describe US surveillance Pfizer-BioNTech and US residents who Observational study, a. Among the reported cases, 3 92.1% were classified as non-serious; The effects of mRNA
et al; 202227 data collected through the Moderna. report to VAERS using the data reported 6.6% were serious, not resulting in death; and 1.3% were deaths. vaccination on daily-life
Vaccine Adverse Event following the receipt of on the Vaccine Adverse b. The most common MedDRA preferred terms assigned to non- activities among vaccine
Reporting System (VAERS) a mRNA vaccine. Event Reporting System serious reports were headache (20.4%), fatigue (16.6%), pyrexia recipients were most
on two mRNA COVID-19 and V-Safe. (16.3%), chills (15.7%), and pain (15.2%). frequently reported on day 1
vaccines. c. The most common MedDRA preferred terms assigned to serious after vaccination, with most
(BNT162b2 [Pfizer- reports were dyspnea (15.4%), death (14.1%), pyrexia (11.0%), side effects being mild.
BioNTech]; and mRNA- fatigue (9.7%), and headache (9.5%).
1273 [Moderna]) 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.

Lee, et al; South To assess the relationships ChAdOx1 nCoV-19 Healthcare workers in Prospective a. Most participants (n = 434, 97.1%) experienced at least one local The majority of participants
202128 Korea of antibody level with age, (AZD1222). Hanyang University observational study, using or systemic adverse reaction during days 0–7 after either injection reported experiencing local
sex, BMI, and adverse Hospital who received the data of self-reported (first or second). or systemic effects (0–7 days
reactions to the ChAdOx1 two doses of online adverse reaction b. The most frequently reported local AR was pain (91.8%), after vaccination) with
nCoV-19 (AZD1222) ChAdOx1 nCoV-19. survey after seven days of tenderness (86.3%), and induration (30.9%). tenderness and chills
vaccine. COVID-19 vaccination. c. The most frequently reported systemic AR was fatigue (87.5%), symptoms.
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%).

Bsoul, et al; The US Evaluate the Pfizer COVID- Pfizer COVID-19. Students and staff at An observational online a. The common adverse reactions after the COVID-19 vaccination a. Side effects after both
202229 19 vaccination experience the School of survey using the web- were injection site pain (75.0%), and the following general side doses of the vaccine were
related to safety, Dentistry, UT Health based survey platform. effects (66.7%) were fatigue/ tiredness, headache, muscle/ body reported by 36% of all
confidence levels, and side San Antonio. ache, and chills/fever. participants.
https://doi.org/10.2147/IJGM.S400458

effects among United b. About the 60% of participant reported the severity of side effects b. All reported side effect
States-based dental to be no worse than mild, and the vaccine did not interfere with were mild and did not
students, staff, and faculty. their life activities. interfere daily activities.
c. There were no differences in severity or impact of vaccine side
effects on participant life activities.

Flores, et al; Peru To identify post SARS-CoV- BioNTech and Pfizer. SLE patients at the Descriptive a. All patients received the vaccine presented symptoms within 10 Following SARS-CoV-2
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202130 2 vaccine BNT162b2 Immuno- observational study, using days after immunization with pain at the inoculation site being the immunization, the majority
(BioNTech and Pfizer) side Rheumatology the data of patients with most frequent (87%) with mild intensity. have local symptoms of an

Dhamanti et al
effects in patients with Department of the a diagnosis of systemic b. The pre-dominant type of flare presented after vaccination was adverse event with mild
systemic lupus Cayetano Heredia lupus erythematosus arthritis (85.1%) included synovitis, swelling, phlogosis, and severity and did not interfere
erythematosus (SLE). Hospital, Lima, Peru. (SLE) who attended at followed by dermal (18.5%). with daily activities.
the Immuno-
Rheumatology Service of
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the Cayetano Heredia

Hospital, Lima, Peru.

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Table 2 (Continued).
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Author, Country Aim Vaccine Types Population Study Design Adverse Reaction Impact
Year

Shulman The US To records short-term mRNA Pfizer Patients with two Prospective a. Local pain at the injection site was the most frequently reported Comparing patients with
et al; 202231 adverse reactions of the BNT162b2 vaccine. doses of the mRNA observational study using symptom for all respondents and did not distinguish patients with cancer to those without
COVID-19 vaccine in Pfizer BNT162b2 survey completed either cancer from those without cancer after either dose. cancer revealed few
patients with cancer, vaccine at the by telephone or online b. Muscle pain after the first vaccination was more frequent in differences in reported
compare these reactions to Comprehensive approximately 2 weeks patients with cancer than in those without but was of shorter adverse events. Active cancer
patients without cancer, Cancer Center. after the second dose of duration. treatment had little effect on
and determine whether COVID-19 vaccine. c. Joint pain, fever, chills, headache, and nausea were unrelated to the profiles of adverse events.
adverse reactions are cancer status.
associated with active d. For patients with cancer, adverse events that were reported
cancer therapy. more frequently after dose 2 included fatigue, joint pain, fever,
chills, headache, and nausea.

Jeong, S South To investigate the clinical Oxford/AstraZeneca Patients with fever and/ A retrospective a. The reported adverse reaction after the COVID-19 vaccination a. The number of patients
et al; 202232 Korea characteristics of older (AZD1222), Pfizer or febrile sensation observational study in was a fever which more experienced among younger adults age who visited the ED with
adults with self-reported BioNTech (BNT162b2) following COVID-19 three hospitals in Korea, than older adults (85.7% vs 75.5%, respectively). fever as a suspected
COVID-19 post and Moderna (mRNA- vaccination in three using the self-reported b. Post-vaccination fever symptoms most commonly occurred on COVID-19 vaccine-related
vaccination fever and/or 1273). South Korean data of patients with days 0 and 1. adverse reaction was lower
febrile sensation or rigors. hospitals. suspected adverse for older adults than for
reactions after COVID- younger adults.
19 vaccination. b. Older adults did not
require admission to the
hospital due to vaccine-
related adverse reactions.

Oh, et al; South To investigate clinical COVID-19 mRNA People were 65 years A Retrospective a. (51%) out of 1397 patients who visited the ED after receiving the Most patients reported
202233 Korea features of patients who vaccine, Pfizer- of age or younger at observational study, using COVID-19 mRNA vaccine reported cardiovascular symptoms as cardiovascular-adverse
visited the ED for BioNTech (BNT162b2) Incheon and Daejeon the data reported from adverse reactions. reactions within 7 days after
cardiovascular adverse and Moderna (mRNA- hospitals with the Immunization b. Most patients reported cardiovascular-adverse reactions within 7 vaccination, after both the
reactions after COVID-19 1273). cardiovascular adverse Registry System (IRS) on days after vaccination, after both the first and second doses (81.9% first and second doses.
m-RNA vaccination. reactions after the any suspected COVID-19 and 86.4%). Adverse reactions showed
COVID-19 vaccine. vaccine-related adverse c. Males presented adverse reaction with more chest pain/discomfort mild progression.
events. than females (81.7% vs 70%), while females presented with more
dyspnea and palpitation than males.
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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.

Park, et al; Daegu, To determine the ChAdOx1 and Hospital workers who Retrospective survey a. Participants who experienced significant levels of interference with The majority of the effects
202234 Republic association between the BNT162b2 COVID-19 received the first dose involving hospital work (5–10 points) reported all side effects (except urticaria) were visible within 24 hours
of Korea vaccination and vaccine. of ChAdOx1 at the workers that received more frequently with the ChAdOx1 vaccination, with the three of the vaccination. Individuals’
interference with work and University Hospital in ChAdOx1 and most common adverse events being local pain (83.2%), myalgia length of unpleasant effects
daily life. Daegu, Republic of BNT162b2 COVID-19 (78.3%), and fever (73.3%). varied, with around 50%
Korea. vaccine. b. The three most common side events for ChAdOx1 vaccine reporting that they were
participants who had severe levels of interference with everyday impacted for more than 24
living were local pain (84.4%), myalgia (77.7%), and fever (70.9%). hours. Effects on daily life
c. Myalgia, fever, chills, and local pain were the four most common activities were mild or low.
side events among those who got the BNT162b2 vaccination in
both the high interference with work and high interference with

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daily living groups.

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cardiovascular adverse events, on the other hand, did so more frequently after the first vaccine dose than after the
second.33 Some deaths were also reported, however an examination of death certificates found that the most common
reasons of death were heart disease and COVID-19.27

Type of Vaccine Associated with Adverse Reactions

This study included reports indicating the type of vaccine used was linked to adverse reactions among participants. Types
of vaccines included in this study are Pfizer-BioNTech, Oxford-AstraZeneca, Sinopharm, and Moderna.24–34 According
to the studies, the type of vaccine given was connected to adverse reactions among participants. Side effects are 2.9 times
more prevalent in first-time Sinopharm vaccination recipients.26 However, Pfizer-BioNTech vaccination recipients were
1.4 times more likely to suffer an adverse reaction following the second dosage.26 According to Sinopharm vaccine
recipients, people with connected comorbidities had a statistically significant higher percentage of adverse effects than
others.26 According to Pfizer-BioNTech vaccine recipients, individuals having a history of past infection with COVID-19
reported a statistically significant higher percentage of adverse effects than the others.24,26
Dyspnea, death, pyrexia, tiredness, and headache were the most prevalent serious reports of Pfizer-BioNTech.27,29
Another study found that the majority of Pfizer-BioNTech users have mild-to-moderate negative effects.30 Side effects of
the Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccinations include fatigue, headache, tenderness, local discomfort,
myalgia, fever, asthenia, induration, and allergic skin.24,25,28 Local effects were observed less frequently after the second
dosage of both vaccines than after the first dose, as was the case with Pfizer-BioNTech.24,28
Moderna, another mRNA vaccine, had similar adverse effects as Oxford-AstraZeneca (ChAdOx1 nCoV-19), includ­
ing headache, asthenia, and myalgia.25 However, no participant experienced serious local or systemic reactions after
receiving both mRNA vaccines, chadOx1-ncov-19 (astraZeneca) and Moderna.25 Another study revealed that persons
who received Moderna vaccinations (who had heart disease and COVID-19) had serious outcomes, such as fatalities.27
The majority of BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna] mRNA vaccination patients experienced
cardiovascular-adverse responses within 7 days of receiving both the first and second doses.33

Impact of the Adverse Reactions

We looked at the severity of the reactions or the impact of adverse reactions on daily life as vaccination side effects can
impair one’s capacity to conduct daily tasks. The majority of the reactions were mild to moderate in nature and did not
affecting daily tasks,27 appearing within 1–2 days following vaccination and dissipating within a few days. On the first
day following vaccination, the impact of mRNA vaccination, BNT162b2 [Pfizer-BioNTech] and mRNA-1273
[Moderna], on everyday life activities was most often reported among vaccine recipients.27 60% of Pfizer vaccination
participants experienced moderate side effects, and 75% felt the vaccine had little influence on their regular lives.29
Another study described the effect of vaccines on work and daily life for participants who had received ChAdOx1 and
BNT162b2 COVID-19, with the majority of adverse effects occurring within 24 hours of vaccination, with varying
duration of symptoms, and approximately half indicating that they were impacted for more than 24 hours.34 Women were
more likely than males to experience moderate-to-severe side effects that interfered with their daily activities. However,
the majority of individuals, regardless of gender, reported that the COVID-19 vaccine had no effect on their everyday
activities and that any adverse effects were minor.29

Discussion
Several adverse reactions to COVID-19 vaccines have been identified in this review. Local and systemic side effects are
among the most common adverse reactions to all COVID-19 vaccines, as previously stated in the studies included. Local
side effects includes joint or muscle pain tenderness, itching, induration and paresthesia in the injection site.24–28,30,31
Meanwhile fever, chills, fatigue, headache, nausea, myalgia, pyrexia, and dyspnea are among the systemic side effects.24–
29,31–34
Local and systemic adverse events occurred within 7 days of receiving COVID-19 vaccines, with fever, fatigue,
and headache being the most common systemic adverse reactions.35 This finding is consistent with other study that
confirmed the incidence rate of frequent adverse effects among healthcare workers was 32.1% for fever, 69.1% for
muscle ache, and 48.7% for headache.36 While injection-site pain was the most common local adverse effect.37

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Other adverse reactions previously mentioned were allergic, such as skin burning, rashes, and red welts on the lips
and face also cardiovascular adverse reactions.24,31,33 Severe allergic reactions following COVID-19 vaccination are
extremely rare, but have garnered attention due to potentially fatal outcomes and a high level of uncertainty.38 Other
research indicates that cardiovascular side effects such as tachycardia, flushing, hypertension, hypotension, and periph­
eral coldness have also been reported.39 Other studies found that people who received the Pfizer/BioNTech vaccine had a
higher rate of cardiovascular adverse events than people who received other types of vaccines.39 However, all reported
adverse events were mostly mild, and did not following by hospital admission.
Vaccine type and dose were also linked to different patterns of interference with work and daily life.34 There were
fewer adverse reactions reported after the second dose of ChAdOx1 vaccination than after the first dose, and the effects
on daily life and work were minor.34 Another form of COVID-19 vaccine linked to mild or moderate severity adverse
effects reported following Moderna vaccination, with no influence or interference in work-life activities.40 Another study
discovered that 79.7% of health workers who were immunized with the BNT162b2 mRNA vaccine were able to return to
work.41
Previous study backs up our findings that COVID-19 vaccination adverse responses are modest and have no effect on
the recipient’s everyday life.41 This finding is also supported by another study which described the efficacy of vaccines
ranged from 60% to 90% which are always efficient against asymptomatic (SARS-CoV-2) infection, symptomatic
COVID-19, COVID-19 hospitalization, severe or critical hospitalization, and death.42 Deaths following COVID-19
vaccination, as reported in one study, have no connection to the vaccine, but rather to heart disease or COVID-19.
The issue of excess death from COVID-19 immunization is a scientifically challenging matter that is influenced by the
type of vaccines used, the age and health condition of the vaccinated population.43 It can be interpreted that host
immunity and the type of vaccine are known to influence COVID-19 vaccine adverse responses.
Inconsistencies in adverse reactions may also be caused by symptoms connected with culture or languages.34 The
majority of studies were conducted in developed countries where citizens have a greater understanding and awareness of
vaccine adverse reactions therefore the adverse event reporting rate might be higher. Whereas the public may be
perplexed by the disparities in results, which are dependent on the research design and subject studies. Therefore, as
recommendation, it is critical to disseminate clear information to the public, about vaccine side effects, potential adverse
reactions, and safety level of the vaccines provided. Multi-strategies at individual, organization and population level need
to be employed to reduce vaccine hesitancy.
There are various limitations to this study. First, this analysis only gathered evidence from observational studies,
which are prone to biases such as confounding, information, and selection bias. Observational studies, on the other hand,
aid in finding adverse events or negative effects that demand a longer time of follow-up. Second, due to the limitations of
the keywords and database, the findings may not have captured all of the evidence in the literature; however, this study
did aid in mapping the available evidence in observational studies.

Conclusion
This study confirmed prior findings that the COVID-19 immunization caused mostly mild or non-severe side effects. This
review discovered some adverse reactions to COVID-19 vaccinations with most prevalent adverse reactions to all
COVID-19 vaccinations are local and systemic side effects. Other previously cited side events included allergic
responses and cardiovascular problems. The type of vaccine and dose were linked to the various adverse reaction
patterns. Individual daily activities are not severely influenced or interfered with. Deaths following COVID-19 vaccina­
tion have nothing to do with the vaccine, but rather with heart disease or COVID-19. It is critical to give the public with
accurate information on vaccine side effects, probable adverse reactions, and the safety level of the vaccines provided. To
reduce vaccine hesitancy, multiple measures must be implemented at the individual, organizational, and population
levels. Future research could look into the impact of the vaccine on patients of various ages and medical conditions.

Acknowledgments
The authors would like to express their gratitude to the Indonesia Research Collaboration scheme.

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Disclosure
The authors report no conflicts of interest in this work.

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