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Article

Prospective Evaluation of Side-Effects Following the First Dose


of Oxford/AstraZeneca COVID-19 Vaccine among Healthcare
Workers in Saudi Arabia
Majid A. Darraj 1, * and Hesham M. Al-Mekhlafi 2,3, *

1 Department of Internal Medicine, Faculty of Medicine, Jazan University, Jazan 45142, Saudi Arabia
2 Medical Research Centre, Jazan University, Jazan 45142, Saudi Arabia
3 Department of Parasitology, Faculty of Medicine and Health Sciences, Sana’a University, Sana’a 1247, Yemen
* Correspondence: [email protected] (M.A.D.); [email protected] (H.M.A.-M.)

Abstract: Background: Several different types of vaccines have been developed for the prevention
of coronavirus disease (COVID-19). Despite several local and systemic side-effects to COVID-19
vaccination reported, the vaccines are still considered the best intervention to tackle the spread
of the virus and reduce the severity of COVID-19 infection. However, the reported side-effects
continue to have a crucial role in public confidence in the vaccine and its acceptance. This study
aimed to investigate the short-term side-effects reported by the healthcare workers (HCWs) in Saudi
Arabia after receiving the first dose of the Oxford/AstraZeneca (ChAdOx1 nCoV-19) COVID-19
vaccine. Methods: A prospective cohort study was conducted among HCWs in the Jazan region of
southwestern Saudi Arabia. Healthcare workers who had received the first dose of the COVID-19
 vaccine and agreed to participate in the study were followed up for 3 weeks post vaccination through

a weekly online survey. Information was collected on local and/or systemic side-effects reported
Citation: Darraj, M.A.; Al-Mekhlafi,
H.M. Prospective Evaluation of
following vaccine administration. Participants’ general and demographic information was also
Side-Effects Following the First Dose collected. Results: A total of 57.2% (250/437) of the HCWs who participated in this study reported at
of Oxford/AstraZeneca COVID-19 least one side-effect. Injection site pain and redness (80.0%), fever (73.2%), whole-body pain/fatigue
Vaccine among Healthcare Workers (56.4%), and headache (48.8%) were the most commonly reported side-effects. Moreover, 12.4% of the
in Saudi Arabia. Vaccines 2022, 10, participants who reported side-effects needed to see a physician, and only one female participant
223. https://doi.org/10.3390/ was admitted to the hospital. Multivariate regression analyses revealed that nationality (Saudi,
vaccines10020223 adjusted odds ratio (aOR) = 3.65; 95% CI = 2.40, 5.55) and residency (Jazan governorate, aOR = 0.38;
Academic Editors: P Veeranna 95% CI = 0.15, 0.95) were the significant factors associated with reporting COVID-19 post-vaccination
Ravindra, Prashant Chikkahonnaiah side-effects, while the number of reported side-effects was found to be significantly influenced by
and Federico Pratesi occupation (medical, aOR = 0.42; 95% CI = 0.26, 0.66; p < 0.001) and gender (female, aOR = 0.61;
95% CI = 0.38, 0.97; p = 0.038). Conclusions: Findings of the present study support the safety of the
Received: 6 December 2021
Oxford/AstraZeneca COVID-19 vaccine among HCWs in Saudi Arabia. All the reported side-effects
Accepted: 27 January 2022
were mild-to-moderate side-effects. The findings may help convince vaccine-hesitant individuals
Published: 30 January 2022
and skeptics to accept the COVID-19 vaccine.
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in Keywords: COVID-19; vaccine; side-effects; healthcare workers; Saudi Arabia
published maps and institutional affil-
iations.

1. Introduction
Copyright: © 2022 by the authors. The novel coronavirus (COVID-19), caused by severe acute respiratory syndrome
Licensee MDPI, Basel, Switzerland. coronavirus 2 (SARS-CoV-2), was declared a global pandemic on 11 March 2020 [1]. Since
This article is an open access article then, most countries have taken precautions to stop COVID-19 from spreading in the
distributed under the terms and hope of quickly developing safe and effective vaccines [2]. Extensive research has been
conditions of the Creative Commons condensed to bring a COVID-19 vaccine to market by late 2020 or early 2021, along with
Attribution (CC BY) license (https:// safety testing to prevent any serious side-effects [3]. Globally, Pfizer/BioNTech (BNT162b2)
creativecommons.org/licenses/by/ was the first vaccine authorized by the United States (US) Food and Drug Administration
4.0/).

Vaccines 2022, 10, 223. https://doi.org/10.3390/vaccines10020223 https://www.mdpi.com/journal/vaccines


Vaccines 2022, 10, 223 2 of 14

(FDA) in December 2020 [4], followed by Oxford/AstraZeneca being approved in January


2021 by the European Commission.
Many COVID-19 vaccine candidates have been developed by major global biophar-
maceutical companies. The Pfizer/BioNTech Comirnaty vaccine was the first vaccine for
COVID-19 listed on WHO’s Emergency Use Listing (EUL) on 31 December 2020. The As-
traZeneca AZD1222 and SII Covishield vaccines developed by AstraZeneca/Oxford were
given EUL on 16 February 2021. Moreover, the Johnson and Johnson’s Janssen Ad26.COV
2.S vaccine was listed for EUL on 12 March 2021, and the Moderna COVID-19 vaccine
(mRNA 1273) was listed on 30 April 2021. The Sinopharm COVID-19 vaccine produced by
Beijing Bio-Institute of Biological Products Co Ltd., a China National Biotec Group (CNBG)
subsidiary, was listed for EUL on 7 May 2021. The Sinovac/CoronaVac was listed for EUL
on 1 June 2021 [5].
These vaccines were developed using different technologies. The Pfizer/BioNTech
BNT162b2 and Moderna mRNA 1273 COVID-19 vaccines are messenger RNA (mRNA)-
based vaccines, which encode SARS-CoV-2 prefusion-stabilized full-length spike protein [6],
with efficacy rates of 95% and 94.1%, respectively [7]. Likewise, the vaccines developed
by Oxford/AstraZeneca and Johnson and Johnson are considered viral vector-based vac-
cines [8]. The Oxford/AstraZeneca vaccine consists of a replication-deficient chimpanzee
adenoviral vector ChAdOx1 containing the SARS-CoV-2 structural surface glycoprotein
antigen (spike protein; nCoV-19) gene, with an efficacy rate of 70% [9]. Both the Chinese
vaccines (Sinopharm and Sinovac/CoronaVac) are inactivated vaccines, which use killed
SARS-CoV-2 virus [8]. Overall, these vaccine types all met the necessary criteria for safety
and efficacy as evaluated by the WHO [10].
However, these vaccines were linked to various adverse events, as concluded in
clinical trials [11]. Moreover, several reports from different countries revealed that adverse
events reported following the first and/or the second dose of COVID-19 vaccines included
local side-effects, such as local pain at the site of injection, swelling, tenderness, redness,
warmth, itch, and swollen armpit glands. They also included nonspecific systemic side-
effects, such as headache, fever, fatigue, night sweats, chills and shivering, joint pain,
muscle pain, nausea, vomiting, and decreased appetite [6,12–17]. Despite being very rare,
a few clinical trials reported serious and life-threatening adverse events, such as vaccine-
induced immune thrombocytopenia and thrombosis (VIIT), following the first dose of
certain vaccines, mainly with viral vector vaccines [18,19]. Nonetheless, a recent interim
analysis of surveillance data from over six million individuals found no association between
VIIT and mRNA vaccines [20]. More information on adverse events is required at the global
level to understand better the factors associated with different vaccine-specific adverse
events, which could help guide further investigations and proper clinical management of
the cases.
In Saudi Arabia, COVID-19 cases reached 547,845 confirmed cases by mid-October
2021 and 8758 total deaths [21]. The country started its COVID-19 vaccination program
in December 2020 to stop the spread of COVID-19 [22]. Three vaccines are currently
available in Saudi Arabia: Pfizer/BioNTech, Oxford/AstraZeneca, and Moderna COVID-
19 vaccines [23]. About 45 million COVID-19 vaccine doses have been administered so far,
with nearly 60% of the country’s total population receiving two doses of the vaccines [24].
While there are data on COVID-19 vaccine views expressed by the general population and
their acceptability of vaccination [25], data on the attitude of healthcare workers (HCWs)
toward the Oxford/AstraZeneca and Pfizer/BioNTech COVID-19 vaccines are limited [26].
However, little is known about the factors associated with COVID-19 vaccine refusal or
hesitancy. Within this context, the present study aimed to identify short-term side-effects
among HCWs in Saudi Arabia after receiving their first dose of the Oxford/AstraZeneca
COVID-19 vaccine (ChAdOx1 nCoV-19).
Vaccines 2022, 10, 223 3 of 14

2. Materials and Methods


2.1. Study Settings
A prospective cohort study was conducted among HCWs in the Jazan region of Saudi
Arabia from May through June 2021. All vaccinated HCWs who had received their first
dose of vaccination with the Oxford/AstraZeneca vaccine were followed up for 3 weeks
post vaccination through a weekly online survey where the participants were asked to
self-report any symptoms they developed. Those who had mild-to-moderate symptoms
notified their clinic at the respective hospital via WhatsApp, SMS, or in person to set
an appointment to be seen by a physician. A thorough assessment was performed and
documented in their medical record for further follow-up by an infection control team for
the specified 3 week period.
The target populations of the present study were all clinical (including physicians,
nurses, medical technicians, and pharmacists) and nonclinical HCWs (including adminis-
trative and medical record professionals, workers, security, and nonmedical technicians)
who were actively serving at participating private and public hospitals in Jazan region
during the time of the study. The eligible participants were to have not received their first
dose of COVID-19 vaccine before accepting the invitation to participate and filling in the
questionnaire. Healthcare workers who were vaccinated before the study period were
excluded. At the participating hospitals, an invitation message and information about
the study objective and procedures were sent to all HCWs via their WhatsApp and email
groups. Those who were eligible and willing to participate were listed, and their contact
information was obtained. The participants were instructed to contact the survey team
after they made appointments to get vaccinated.
Ethical approval was granted by the research ethics committee of Jazan University. A
signed written informed consent was obtained from all participants prior to completing
the survey. This procedure was approved by the research ethics committee. Participation
in this survey was not compensated financially or by any other incentives.

2.2. Sample Size


The minimum sample size required for this survey was calculated according to Lwanga
and Lemeshow [27]. As previous data on COVID-19 post-vaccination side-effects in the
HCWs in Saudi Arabia were unavailable, a 0.50 assumed proportion was considered [28],
with a 5% margin of error and 95% confidence level. Accordingly, 384 was yielded as the
minimum number of participants required for this study. Considering a drop-out rate of
10%, the final sample size was determined as 422. During the study period, 485 eligible
HCWs agreed to participate in the survey.

2.3. Instrument and Data Collection


A structured self-administered questionnaire of this survey was created after extensive
review of the literature on adverse events of various COVID-19 vaccines [11,12,29]. The
questionnaire was designed using Google Forms and was written in English and Arabic.
The final versions were reviewed by four different experts in the field to check for face and
content validity. The questions addressed the demographic characteristics of respondents
(age, sex, job category, marital status, residence, and nationality), medical anamnesis data
(history of chronic diseases, and medical treatment taken regularly) and COVID-19-related
anamnesis data (history of previous diagnosis with COVID-19, the type of vaccine they
received, and vaccination date). The questionnaire also included questions for reporting
short-term local and systemic side-effects associated with the COVID-19 vaccine, time of
onset post vaccination, the duration of symptoms, any medication that were taken, doctor’s
visits due to side-effects, and admission to the hospital. A thorough list of potential side-
effects, covering the most common symptoms reported by previous studies, was provided
in the questionnaire. Moreover, an open section was also provided for reporting other
unlisted symptoms which might have been experienced by the respondents.
Vaccines 2022, 10, 223 4 of 14

Participants who made appointments to get vaccinated and notified the survey team
were followed up. The survey’s link was sent to the participants through WhatsApp
and/or e-mail. All participants were asked to respond to the survey; thus, the survey
team members contacted those who did not respond weekly to identify and verify their
responses. Only those who had received the first dose of Oxford/AstraZeneca vaccine and
submitted the required questionnaires during the follow-up period were included in the
final analysis. Out of 485 eligible participants, 41 (8.5%) individuals were lost to follow-up
during the study period. Therefore, 437 HCWs were included in the final analysis.

2.4. Data Analysis


The data were exported from Google Forms (Mountain View, CA, USA) into Microsoft
Excel (Redmond, WA, USA) and then exported into the Statistical Package for Social
Sciences (SPSS) software version 21.0 (IBM, Inc., Armonk, NY, USA) for statistical analysis.
For descriptive analysis, frequency and proportion were used to express the distribution of
categorical variables while mean ± standard deviation (SD) or median (interquartile range,
IQR) were used to present quantitative variables. Before analysis, all quantitative variables
were assessed for normality by Shapiro–Wilk test. Pearson’s chi-square (χ2 ) test or Fisher’s
exact test was used where appropriate to examine the association between reporting
COVID-19 post-vaccination side-effects as the dependent variable and the independent
variables (demographic and health background characteristics). Likewise, Mann–Whitney
U and Kruskal–Wallis tests were used to assess the number of COVID-19 post-vaccination
side-effects reported by the studied HCWs as an ordinal dependent variable according to
the independent variables.
Moreover, multivariate logistic regression analysis was also used to investigate the
factors associated with reporting of side-effects following the Oxford/AstraZeneca COVID-
19 vaccine, which was coded as a dummy dependent variable (yes = 1 and no = 0). In
addition, multivariate ordinal logistic regression analysis was performed to assess the
factors associated with the number of side-effects following the vaccine. All variables
that showed associations with p ≤ 0.25 in the univariate analyses were included in the
multivariate logistic regression models [30]. Odds ratios (ORs) with a 95% confidence
interval (CI) were computed for different analyses. Statistical significance was defined
as a p-value of less than 0.05. Where applicable, p-values were adjusted for multiple
comparisons using the sequential Bonferroni correction (Bonferroni–Holm) method [31].

3. Results
3.1. General Characteristics of Participants
A total of 437 HCWs who were vaccinated with the first dose of the Oxford/AstraZeneca
COVID-19 vaccine participated in the study. The mean ± SD age of the participants was
33.6 ± 7.3 years; around two-thirds (64.8%, n = 283) of them were females, and 35.2% were
males. Nurses were the dominant HCW group at 38.2% (n = 167), followed by medical record
professionals (14.0%, n = 61). The participants were from three governorates, namely, Jazan,
Sabia, and Abu Arish, with the majority (86.5%, 378/437) living in Jazan city. Participants
who had been previously diagnosed with COVID-19 made up 12.6% (n = 55), most of whom
were females (80.0%, 44/55). Only three participants (0.7) had a history of chronic disease,
both diabetes mellitus (DM) and hypertension. Table 1 shows the general demographic and
health characteristics of the participants.

3.2. Reported COVID-19 Vaccine Side-Effects


The results of this study showed that 57.2% (250/437) of the HCWs who participated
in this study reported at least one COVID-19 post-vaccination side-effect. The median (IQR)
number of the reported side-effects was 3.0 (2, 4). Figure 1 shows that most HCWs reported
four side-effects (32.4%, 81/250), and 24% reported three side-effects, while six side-effects
were reported by only 1.6%.
Vaccines 2022, 10, 223 5 of 14

Table 1. General demographic and health characteristics of the participants (n = 437).

Characteristics n (%)
Age group (years) 20–30 169 (38.7)
31–40 202 (46.2)
41–50 50 (11.4)
>50 16 (3.7)
Nationality Saudi 187 (42.8)
Non-Saudi 250 (57.2)
Gender Females 283 (64.8)
Males 154 (35.2)
Marital Status Married 250 (57.2)
Single 187 (42.8)
Residence Jazan 378 (86.5)
Sabia 29 (6.6)
Abu Arish 30 (6.9)
Occupation Nurse 167 (38.2)
Medical record professional 61 (14.0)
Administrative professional 52 (11.9)
Workers (such as cleaning staff,
45 (10.3)
drivers, storekeepers)
Physician 39 (8.9)
Technician—medical 37 (8.5)
Security 18 (4.1)
Technician—nonmedical 16 (3.7)
Pharmacist 2 (0.5)
Diagnosed previously with
Yes 55 (12.6)
COVID-19
No 382 (87.4)
Vaccines 2022, 10, x FOR PEER REVIEWHistory of chronic diseases DM and hypertension 3 (0.7) 6 of 1
No 434 (99.3)

Figure1.1.Total
Figure Total number
number of COVID-19
of COVID-19 vaccine
vaccine side-effects
side-effects reported
reported among
among the the participants.
participants.

Among
Among thethe
250250
HCWsHCWswho who
developed COVID-19
developed post-vaccination
COVID-19 side-effects, side-effects,
post-vaccination Figure 2 Fig
shows that pain and redness at the site of injection (80.0%) and fever (73.2%) were
ure 2 shows that pain and redness at the site of injection (80.0%) and fever (73.2%) wer the most
frequently reported side-effects, followed by whole-body pain/fatigue (56.4%) and headache
the most frequently reported side-effects, followed by whole-body pain/fatigue (56.4%
(48.8%). On the other hand, the least frequently reported side-effects were diarrhea at 1.2%,
and headache
shortness (48.8%).
of breath, On the and
chest tightness, other hand, at
vomiting the least
0.8% frequently
each, reported
and backache side-effects
and skin rash at wer
diarrhea
0.4% each. at 1.2%, shortness of breath, chest tightness, and vomiting at 0.8% each, and back
ache and skin rash at 0.4% each.
Among the 250 HCWs who developed COVID-19 post-vaccination side-effects, Fig-
ure 2 shows that pain and redness at the site of injection (80.0%) and fever (73.2%) were
the most frequently reported side-effects, followed by whole-body pain/fatigue (56.4%)
and headache (48.8%). On the other hand, the least frequently reported side-effects were
Vaccines 2022, 10, 223 6 of 14
diarrhea at 1.2%, shortness of breath, chest tightness, and vomiting at 0.8% each, and back-
ache and skin rash at 0.4% each.

Figure2.2.The
Figure Thefrequency
frequency
ofof COVID-19
COVID-19 vaccine
vaccine side-effects
side-effects reported
reported among
among the participants
the participants (n = (n = 250).
250).

Thedistribution
The distributionofof different
different side-effects
side-effects according
according to participants’
to participants’ gender
gender was was inves-
investi-
gated
tigatedamong
amongthe the
HCWs
HCWs whowho
developed COVID-19
developed post-vaccination
COVID-19 side-effects
post-vaccination (Table(Table
side-effects 2).
The
2). results showed
The results that female
showed HCWs HCWs
that female had a significantly higher frequency
had a significantly of side-effects
higher frequency of side-
ofeffects
dizziness (11.9% vs.
of dizziness (11.9% χ2 =
3.3%;vs. 3.3%; χ2 p==5.236;
5.236; 0.022)pand chillsand
= 0.022) (6.2% vs. (6.2%
chills
2 = 5.859; 2
0.0%; χvs. 0.0%; χ =
p5.859;
= 0.015) compared to male HCWs. On the other hand, the male HCWs had
p = 0.015) compared to male HCWs. On the other hand, the male HCWs had a sig- a significantly
higher frequency
nificantly higheroffrequency
whole-body pain/fatiguepain/fatigue
of whole-body (67.8%, 61/90) compared
(67.8%, 61/90) to their female
compared to their
peers (50.0%, 80/160) (χ 2 = 7.403; p = 0.007). Nonetheless, these significant differences were
female peers (50.0%, 80/160) (χ2 = 7.403; p = 0.007). Nonetheless, these significant differ-
not retained
ences were when the Bonferroni–Holm
not retained adjustment was
when the Bonferroni–Holm applied. was applied.
adjustment
Table 2. Distribution of COVID-19 vaccine side-effects reported among the healthcare worker partici-
pants according to gender (n = 250).

Male Female Total


Symptoms χ2 (p)
(n = 90) (n = 160) (n = 250)
Pain or redness at the site
72 (80.0) 128 (80.0) 200 (80.0) 0.001 (0.999)
of injection
Fever 65 (72.2) 118 (73.8) 183 (73.2) 0.069 (0.793)
Whole body pain/fatigue 61 (67.8) 80 (50.0) 141 (56.4) 7.403 (0.007)
Headache 51 (56.7) 71 (44.4) 122 (48.8) 3.483 (0.062)
Cough 13 (14.4) 12 (7.5) 25 (10.0) 3.086 (0.079)
Sore throat 12 (13.3) 10 (6.2) 22 (8.8) 3.601 (0.058)
Dizziness 3 (3.3) 19 (11.9) 22 (8.8) 5.236 (0.022)
Runny nose 6 (6.7) 6 (3.8) 12 (4.8) 1.072 (0.301) †
Chills 0 (0.0) 10 (6.2) 10 (4.0) 5.859 (0.015) †
Joint pain 2 (2.2) 5 (3.1) 7 (2.8) 0.172 (0.587) †
Diarrhea 1 (1.1) 2 (1.2) 3 (1.2) 0.009 (0.735) †
Shortness of breath 0 (0.0) 2 (1.2) 2 (0.8) 1.134 (0.549) †
Chest tightness 0 (0.0) 2 (1.2) 2 (0.8) 1.134 (0.549) †
Vomiting 0 (0.0) 2 (1.2) 2 (0.8) 1.134 (0.549) †
Backache 1 (1.1) 0 (0.0) 1 (0.4) 1.785 (0.630) †
Skin rash 0 (0.0) 1 (0.6) 1 (0.4) 0.565 (0.710) †
χ2 , chi-square test statistic. Significant difference between the two groups (unadjusted p < 0.05). † Fisher’s exact
test statistic.
Vaccines 2022, 10, 223 7 of 14

3.3. Associations of the Reported COVID-19 Vaccine Side-Effects


Table 3 shows the associations of COVID-19 vaccine side-effects with participants’
demographic and health background characteristics. The results showed comparable fre-
quencies (p = 0.758) of HCWs who developed side-effects between female (56.5%, 160/283)
and male (58.4%, 90/154) participants. Similarly, there was no significant difference in the
frequency of side-effects according to participants’ age (p > 0.05). The side-effects were
significantly more frequent among Saudi HCWs (73.8%, 138/187) compared to non-Saudis
(44.8%, 112/250) (p < 0.001). Similarly, participants from the Jazan governorate had a
significantly lower frequency of side-effects (54.2%) than that reported for participants from
the Abu Arish (76.7%) and Sabia (75.9%) governorates (p < 0.05). Interestingly, medical
HCWs had a significantly lower frequency of side-effects than nonmedical HCWs (51.0%
vs. 65.1%; p = 0.003). After Bonferroni–Holm correction, only two variables, nationality
(Saudi) and occupation (medical), showed a significant association with the reporting of
side-effects, while the significance of residence (Jazan) was lost (Table 2).

Table 3. Associations of the reported COVID-19 vaccine side-effects with the participants’ background
characteristics (n = 437).

Characteristic Reported Side-Effects OR (95% CI) p


Yes (n = 250) No (n = 187)
Age group (years)
20–30 (n = 169) 94 (55.6) 75 (44.4) 1
31–40 (n = 202) 115 (56.9) 87 (43.1) 1.06 (0.70, 1.60) 0.801
41–50 (n = 50) 29 (58.0) 21 (42.0) 1.10 (0.58, 2.09) 0.766
>50 (n = 16) 12 (75.0) 4 (25.0) 2.39 (0.74, 7.72) 0.134
Gender
Female (n = 283) 160 (56.5) 123 (43.5) 0.93 (0.62, 1.38) 0.701
Male (n = 154) 90 (58.4) 64 (41.6) 1
Nationality
Saudi (n = 190) 138 (73.8) 49 (26.2) 3.47 (2.30, 5.23) <0.001 *
Non-Saudi (n = 254) 112 (44.8) 138 (55.2) 1
Marital status
Married (n = 255) 145 (57.2) 105 (42.0) 1.08 (0.74, 1.58) 0.699
Single (n = 189) 105 (56.1) 82 (43.9) 1
Residence
Jazan (n = 378) 205 (54.2) 173 (45.8) 0.36 (0.15, 0.86) 0.017
Sabia (n = 29) 22 (75.9) 7 (24.1) 0.96 (0.29, 3.18) 0.924
Abu Arish (n = 30) 23 (76.7) 7 (23.3) 1
Occupation
Medical (n = 245) 125 (51.0) 120 (49.0) 0.56 (0.38, 0.82) 0.003 *
Nonmedical (n = 192) 125 (65.1) 67 (34.9) 1
Diagnosed previously
with COVID-19
Yes (n = 55) 28 (50.9) 27 (49.1) 0.75 (0.43, 1.32) 0.313
No (n = 382) 222 (58.1) 160 (41.9) 1
OR, odds ratio; CI, confidence interval. Significant association (unadjusted p < 0.05). * Significant association
(using the Bonferroni–Holm correction for multiple comparisons).

Differences in the number of COVID-19 post-vaccination side-effects reported by


the studied HCWs according to independent variables were examined, and the results
are shown in Table 4. A Mann–Whitney U test showed that the number of side-effects
was found to be significantly lower among the medical HCWs (median = 3; IQR = 1, 4)
compared to the nonmedical HCWs (median = 4; IQR = 3, 4) (U = 5874; p < 0.001). On the
other hand, the Kruskal–Wallis test results showed no significant difference in the number
of side-effects according to age groups (H = 4.079; p = 0.245). Similarly, differences in the
number of side-effects according to other variables were not significant (p > 0.05).
Vaccines 2022, 10, 223 8 of 14

Table 4. Number of side-effects reported by the participants following the first dose of COVID-19
vaccine according to the participants’ background characteristics (n = 250).

No. of Reported
Characteristic Statistics p
Side-Effects
Median (IQR)
Age group (years) H = 4.079 0.245
20–30 (n = 94) 3 (2, 4)
31–40 (n = 115) 3 (2, 4)
41–50 (n = 29) 3 (1, 4)
>50 (n = 12) 2 (1, 3)
Gender U = 6366 0.117
Female (n = 90) 3 (2, 4)
Male (n = 160) 3 (2, 4)
Nationality U = 7643 0.878
Saudi (n = 138) 2 (3, 4)
Non-Saudi (n = 112) 2 (3, 4)
Marital status U = 7475 0.802
Married (n = 145) 3 (2, 4)
Single (n = 105) 3 (2, 4)
Residence H = 2.125 0.346
Jazan (n = 205) 3 (2, 4)
Sabia (n = 22) 3 (2, 4)
Abu Arish (n = 23) 4 (3, 4)
Occupation U = 5874 <0.001 *
Medical (n = 125) 3 (1, 4)
Nonmedical (n = 125) 4 (3, 4)
Diagnosed previously
U = 3062 0.896
with COVID-19
Yes (n = 28) 3 (3, 4)
No (n = 222) 3 (2, 4)
IQR, interquartile range; U, Mann–Whitney U statistic; H, Kruskal–Wallis test statistic. Significant difference
(unadjusted p < 0.05). * Significant difference (using the Bonferroni–Holm correction for multiple comparisons).

3.4. Multivariate Analyses of Factors Associated with the Reported COVID-19 Vaccine Side-Effects
Table 5 presents the multivariate logistic regression analysis results for the factors
associated with reporting side-effects following the first dose of the COVID-19 vaccine
among the HCWs studied. All variables that showed associations with p ≤ 0.25 in the
univariate analysis presented in Table 3 were included. The Hosmer–Lemeshow test, used
for the inferential goodness-of-fit test, showed that the model fit the data well (χ2 = 4.909;
p = 0.427). The results revealed that Saudi HCWs had a 3.65-fold increased risk of side-
effects compared to non-Saudi HCWs (adjusted odds ratio (aOR) = 3.65; 95% CI = 2.40, 5.55).
Moreover, HCWs who lived in the Jazan governorate had lower odds of reporting COVID-
19 post-vaccination side-effects than those who lived in Abu Arish or Sabia (aOR = 0.38;
95% CI = 0.15, 0.95). However, the significant association of occupation with side-effects
was not retained in the multivariate analysis (p = 0.067).

Table 5. Multivariate analysis of factors associated with reporting of side-effects following COVID-19
vaccine among the participants (n = 437).

Variable aOR 95% CI p


Nationality (Saudi) 3.65 2.40, 5.55 <0.001 *
Residence (Jazan) 0.38 0.15, 0.95 0.038 *
Occupation (medical) 0.67 0.43, 1.02 0.062
aOR, adjusted odds ratio; CI, confidence interval. * Significant association of COVID-19 vaccine side-effects
(p < 0.05).
Vaccines 2022, 10, 223 9 of 14

Furthermore, Table 6 shows the multivariate ordinal logistic regression analysis results
for the factors influencing the number of COVID-19 vaccine side-effects reported by the
studied HCWs. All variables that showed differences with p ≤ 0.25 in the univariate
analysis presented in Table 4 were included in the model. The model was of good fit and
statistically significant (χ2 = 19.672, p < 0.001). The number of reported side-effects was
found to be significantly influenced by the occupation and gender of HCWs. The results
showed that, holding other variables unchanged, medical HCWs were less likely to report
a higher number of side=effects than their nonmedical peers (aOR = 0.42; 95% CI = 0.26,
0.66; p < 0.001). Similarly, female participants were less likely to report a higher number of
side=effects than male participants (aOR = 0.61; 95% CI = 0.38, 0.97; p = 0.038).

Table 6. Results of ordinal logistic regression for the factors associated with the number of reported
side-effects following COVID-19 vaccine (n = 250).

Variable aOR 95% CI p


Age (year) 0.97 0.94, 1.49 0.093
Gender (female) 0.61 0.38, 0.97 0.038 *
Occupation (medical) 0.42 0.26, 0.66 <0.001 *
aOR, adjusted odds ratio; CI, confidence interval. * Significant association (p < 0.05).

3.5. Duration and Management of the Reported COVID-19 Vaccine Side-Effects


Among the HCWs who developed COVID-19 post-vaccination side-effects, 93.6%
(234/250) of the reported side-effects occurred on the day of receiving the vaccine (Day 0).
In comparison, 5.6% and 0.8% of the reported side-effects occurred Day 1 and Day 2 post
vaccination (the second and third post-vaccination days), respectively. The duration of
reported side-effects was 2–3 days for 53.2% (n = 133) and 4–5 days for 26.0% (n = 65),
while the side-effects lasted for more than 7 days for only 2.4% (n = 6) of the subset of
participants who reported side-effects. Moreover, 12.4% (n = 31) of those who developed
side-effects visited a doctor, and medication for post-vaccination side-effects was taken by
66.4% (n = 166). Only one female participant (0.4%) was admitted to the hospital (Table 7).

Table 7. The onset, duration, and management of COVID-19 vaccine side-effects reported among the
healthcare workers participated in the study (n = 250).

Onset and Duration of Male Female Total


χ2 (p)
Side-Effects (n = 90) (n = 160) (n = 250)
Onset 0.172 (0.918)
Day 0 84 (93.3) 150 (93.8) 234 (93.6)
Day 1 5 (5.6) 9 (5.6) 14 (5.6)
Day 2 1 (1.1) 1 (0.6) 2 (0.8)
Duration of symptoms 5.196 (0.268)
One day 8 (8.9) 20 (12.5) 28 (11.2)
2–3 days 46 (51.1) 87 (54.4) 133 (53.2)
4–5 days 30 (33.3) 35 (21.9) 65 (26.0)
6–7 days 4 (4.4) 14 (8.8) 18 (7.2)
More than 7 days 2 (2.2) 4 (2.5) 6 (2.4)
Medication taken for side-effects 62 (68.9) 104 (65.0) 166 (66.4) 0.390 (0.532)
Doctor’s visit due to side-effects 10 (11.1) 21 (13.1) 31 (12.4) 0.215 (0.643)
Hospitalization due to side-effects 0 (0.0) 1 (0.6) 1 (0.4) 0.565 (0.641) †
χ2 , chi-square test statistic; † Fisher’s exact test statistic.

4. Discussion
This study aimed to identify short-term side-effects following the Oxford/AstraZeneca
COVID-19 vaccine among Saudi Arabian HCWs in Jazan region. It is essential to assure
COVID-19 vaccine recipients at this critical stage of the vaccination campaigns by collecting
evidence-based data concerning the vaccines’ side-effects, particularly if they are transient
Vaccines 2022, 10, 223 10 of 14

or temporary. Such evidence can alleviate fears and encourage the completion of the
two-dose vaccination series [32].
The present study showed that 57.2% (250/437) of the studied HCWs reported at least
one side-effect following the administration of the first dose of the Oxford/AstraZeneca
COVID-19 vaccine. This finding is lower than recent findings reported in the Jazan region
among the general population aged between 18 and 70 years who received the same
type of COVID-19 vaccine (66.2%; 255/385) [33]. In a study conducted in Abha, Aseer
Region, southwestern Saudi Arabia among 167 individuals aged 18 years and older who
received the Oxford/AstraZeneca vaccine, 74.3% reported side-effects [29]. In contrast,
a study among 1592 individuals in Dhahran City, northeastern Saudi Arabia, reported a
lower incidence (34.7%) of side-effects following the Oxford/AstraZeneca vaccine [34].
Interestingly, Alghamdi et al. [35] found that adverse events and severity following the
first dose of Oxford/AstraZeneca vaccine were more common in HCWs than non-HCW
participants. Indeed, this difference could be attributed to psychosocial factors, as HCWs
may be more sensitive to side-effects due to their health education than non-HCWs [36].
Moreover, due to their high occupational exposure to COVID-19, the likelihood of a
previous asymptomatic COVID-19 infection among HCWs may lead to a stronger immune
response compared to the general population [35]. Individuals who had been previously
diagnosed with COVID-19 were more likely to report more side-effects after the first
dose of the COVID-19 vaccine [15,37]. However, the present study found no considerable
association between the development of side-effects and previous COVID-19 infection
among the studied HCWs, and this agrees with previous studies in Saudi Arabia [33,38].
On the other hand, recent studies conducted in other countries reported higher fre-
quencies of side-effects following the Oxford/AstraZeneca COVID-19 vaccine among
different population groups. For instance, 97.8% of 197 Jordanian HCWs who received
the first or the second dose of the Oxford/AstraZeneca COVID-19 vaccine reported some
side-effects [39]. Likewise, another study from Poland showed that 96.5% of 705 par-
ticipants reported at least one post-vaccination side-effect [40]. A slightly higher fre-
quency of COVID-19 post-vaccination side-effects among HCWs was also reported in
India (65%, 3556/5396) [41]. These differences could be attributed to different factors,
including the incidence of COVID-19, the time these studies were conducted in relation to
the pandemic waves and stages, and other demographic and health characteristics of the
studied populations.
The side-effects can be local, such as injection site pain or redness, which was the
most frequent side-effect reported by the studied participants, or systemic, including all
remaining side-effects. Of these, fever was the second most frequently reported side-
effect. The most common side-effects in the present study were injection site pain and
redness, fever, fatigue, headaches, cough, sore throat, and dizziness. Less common side-
effects were diarrhea, shortness of breath, chest tightness, vomiting, backache, and skin
rash. These findings are similar to those reported among the general population in Saudi
Arabia [33,38]. In comparison with studies conducted elsewhere, the reported frequencies
of these side-effects were slightly higher than those reported by similar studies among
HCWs in Jordan [39] and India [41]. On the other hand, higher frequencies of these side-
effects were reported among the general population in Poland [40]. The present study
found no severe complications linked to the first dose of the Oxford/AstraZeneca COVID-
19 vaccine, and this agrees with previous studies in Saudi Arabia [29,33]. Nonetheless,
serious adverse events such as severe allergic reaction, cardiac arrest, cerebral venous sinus
thrombosis, and pulmonary embolism associated with the COVID-19 vaccine have been
reported worldwide, including in Saudi Arabia [42,43].
In the current study, 93.3% of the side-effects occurred on the day of vaccination,
and 35.6% (89/250) of the symptoms lasted for more than 3 days, which is consistent
with the findings reported in other similar studies [33,39]. In the current survey, about
two-thirds (66.4%, 166/250) of participants took medication (mainly analgesics) to relieve
the side-effects. Taking analgesics to alleviate the side-effects associated with the COVID-19
Vaccines 2022, 10, 223 11 of 14

vaccine is common among both HCWs and non-HCW populations in Saudi Arabia [35].
Moreover, only 12.4% of the participants needed to see a physician due to side-effects from
the vaccines, and only one female participant was admitted to the hospital. This strongly
supports the safety of these vaccines.
Regarding associations of post-vaccination side-effects with some demographic and
health variables, the present study found that nationality and residence of the participants
were the significant factors associated with the reporting of side-effects. Saudi HCWs had
3.65 times the odds of reporting side-effects compared to non-Saudi HCWs. This might
be attributed to the perception of vaccine safety or the psychological and immunological
status of the participants. Previous studies found that non-Saudi participants were more
inclined to accept the COVID-19 vaccine [22]. They were also more likely to increase their
physical activity during COVID-19 quarantine and mobility restrictions than their Saudi
counterparts [44]. Moreover, the present study found that HCWs who lived in the Jazan
governorate had lower odds of reporting COVID-19 post-vaccination side-effects than those
who lived in Abu Arish or Sabia. While the explanation for this association is unknown, it
might be attributed to the fact that the majority (86.5%) of the participants involved in this
study were from the Jazan governorate.
Furthermore, the present study showed that medical HCWs (including nurses, physi-
cians, medical technicians, and pharmacists) had lower odds of reporting post-vaccination
side-effects than nonmedical HCWs (including administrative and medical record profes-
sionals, workers, security, and nonmedical technicians). However, this association was not
retained when logistic regression analysis was applied. Interestingly, the present study
demonstrated that medical HCWs were likely to report a higher number of side-effects than
the nonmedical HCWs. These findings could be attributed to the higher level of medical
knowledge about vaccine safety among the medical HCWs that would enhance their ability
to identify and differentiate the symptoms.
The present study found comparable frequencies of reporting side-effects for male
and female participants, in agreement with previous studies [39]. However, this finding
contradicts that reported by Alhazmi et al. [33], who found a higher incidence of side-
effects among female participants than male participants. In contrast, a study among 330
individuals in southwestern Saudi Arabia reported a higher incidence of side-effects in
males than females following Pfizer/BioNTech and Oxford/AstraZeneca vaccination [29].
Interestingly, when ordinal logistic regression analysis was applied in the present study,
the female gender was identified as a significant factor associated with reporting a lower
number of side-effects compared to the male gender. This finding is consistent with recent
studies conducted among 1592 individuals in Dhahran City, northeastern Saudi Arabia [34].
However, the finding is inconsistent with that of other reports from Saudi Arabia [38,45]
and elsewhere [14,15,46], which suggested that female gender was a significant factor
for the development of more severe and a higher number of COVID-19 post-vaccination
adverse events. However, findings on the gender-related differences of COVID-19 vaccine
side-effects are still inconclusive.
Indeed, previous studies have suggested a gender-based difference in reporting ad-
verse events following various viral and bacterial vaccines [47,48]. It is found that females
typically mount stronger inflammatory, antibody, and cell-mediated immune responses to
vaccines when compared with males, and this might explain the sex-based differences in
reactions and immunogenicity toward vaccinations [46]. Furthermore, behavioral, genetic,
and hormonal factors might also underlie the gender-based variation in adverse events
following vaccination [46,48,49]. In addition, a few studies have reported significant associ-
ations between the development of post-vaccination side-effects and age. Studies among
HCWs in Jordan [39], Germany [14], and Slovakia [50] found that young adult participants
had a significantly higher incidence of COVID-19 vaccine side-effects compared to their
older age counterparts, and this has been attributed to the fact that immune responses
gradually weaken with age. Nevertheless, in agreement with some studies conducted in
Saudi Arabia [33] and elsewhere [51], the present study did not find such an association.
Vaccines 2022, 10, 223 12 of 14

Some limitations of the current study should be acknowledged to be considered when


interpreting the findings. First, this study used an online self-administered questionnaire
instead of face-to-face interviews, which may result in reporting bias. However, the
HCWs participants are expected to have adequate knowledge about the vital importance
of the COVID-19 vaccine and its associated adverse events. Second, this study reported
only short-term side-effects, while the vaccines’ intermediate and long-term side-effects
were not studied. Similarly, only side-effects following the first dose of the vaccine were
studied, while the side-effects following the second dose of the vaccine were not evaluated.
Furthermore, the study was also predominated by Oxford/AstraZeneca recipients with
only a few Pfizer/BioNTech recipients. This could have been due to the shortage of the
BioNTech vaccine during the study duration and the relatively small sample size; thus,
further multicenter studies with larger sample sizes are warranted to ascertain the safety
profile of different COVID-19 vaccines approved for use in the country.

5. Conclusions
The present study provides important information on the side-effects following
COVID-19 vaccination among healthcare workers in Saudi Arabia. The findings showed
that most participants reported pain at the injection site, fever, fatigue, and headache.
Moreover, nationality (Saudi) and residence (Jazan) were identified as the significant
factors associated with the reporting of side-effects following the first dose of the Ox-
ford/AstraZeneca COVID-19 vaccine, while gender (female) and occupation (medical)
were significantly associated with reporting a lower number of side-effects. The findings
revealed that all the COVID-19 post-vaccination side-effects were mild to moderate, and
only a small portion of vaccine recipients (12.4%) needed to see a physician, while only
one participant (0.4%) admitted to the hospital due to those side-effects. Therefore, the
current study’s findings support the vaccine’s safety and provide important baseline data
to increase healthcare workers’ and the general community’s awareness of the expected
side-effects following COVID-19 vaccines. This might help convince the vaccine-hesitant
individuals and skeptics to accept the COVID-19 vaccine.

Author Contributions: Conceptualized the study, and conducted the survey and data collection,
M.A.D.; data analysis and writing the manuscript, M.A.D. and H.M.A.-M. All authors have read and
agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: The current study was conducted according to the guidelines
proposed by the Declaration of Helsinki, and the protocol was ethically approved by the research
ethics committee of Jazan University (Ref. No. REC42/1/154). Before the commencement of
data collection, written informed consent was obtained from each participant. This procedure was
approved by the research ethics committee.
Informed Consent Statement: Written informed consent was obtained from all participants involved
in the study.
Data Availability Statement: The data that support the findings of this study are available from the
authors upon reasonable request.
Acknowledgments: The authors would like to thank all participants for their fruitful cooperation
and support.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Cucinotta, D.; Vanelli, M. WHO declares COVID-19 a pandemic. Acta Biomed. Atenei Parm. 2020, 91, 157–160. [CrossRef]
2. Algaissi, A.A.; Alharbi, N.K.; Hassanain, M.; Hashem, A.M. Preparedness and response to COVID-19 in Saudi Arabia: Building
on MERS experience. J. Infect. Public Health 2020, 13, 834–838. [CrossRef] [PubMed]
3. Raja, A.A.T.A.; Alshamsan, A.; Al-jedai, A. Current COVID-19 vaccine candidates: Implications in the Saudi population. Saudi
Pharm. J. 2020, 28, 1743–1748. [CrossRef] [PubMed]
Vaccines 2022, 10, 223 13 of 14

4. FDA US. Comirnaty and Pfizer-BioNTech COVID-19 Vaccine. Maryland: The United States Food and Drug Administration.
2021. Available online: https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-COVID-19
/comirnaty-and-pfizer-biontech-COVID-19-vaccine (accessed on 15 October 2021).
5. WHO. Coronavirus Disease (COVID-19): COVID-19 Vaccines; World Health Organization: Geneva, Switzerland, 2021. Available online:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/COVID-19-vaccines (accessed on 10 November 2021).
6. El-Shitany, N.A.; Harakeh, S.; Badr-Eldin, S.M.; Bagher, A.M.; Eid, B.; Almukadi, H.; Alghamdi, B.S.; Alahmadi, A.A.;
Hassan, N.A.; Sindi, N.; et al. Minor to moderate side effects of Pfizer-Biontech COVID-19 vaccine among Saudi residents: A
retrospective cross-sectional study. Int. J. Gen. Med. 2021, 14, 1389–1401. [CrossRef]
7. Cavaleri, M.; Enzmann, H.; Straus, S.; Cooke, E. The European Medicines Agency’s EU conditional marketing authorisations for
COVID-19 vaccines. Lancet 2021, 397, 355–357. [CrossRef]
8. Mallapaty, S. China’s COVID vaccines have been crucial—now immunity is waning. Nature 2021, 598, 398–399. [CrossRef]
9. Lopez Bernal, J.; Andrews, N.; Gower, C.; Robertson, C.; Stowe, J.; Tessier, E.; Simmons, R.; Cottrell, S.; Roberts, R.;
O’Doherty, M.; et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on COVID-19 related symptoms,
hospital admissions, and mortality in older adults in England: Test negative case-control study. BMJ 2021, 373, n1088. [CrossRef]
10. WHO. COVID-19 Advice for the Public: Getting Vaccinated; World Health Organization: Geneva, Switzerland, 2021. Available online:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/COVID-19-vaccines/advice (accessed on 2 November 2021).
11. Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Pérez Marc, G.; Moreira, E.D.;
Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine. N. Engl. J. Med. 2020, 383, 2603–2615.
[CrossRef]
12. Kaur, R.J.; Dutta, S.; Bhardwaj, P.; Charan, J.; Dhingra, S.; Mitra, P.; Singh, K.; Yadav, D.; Sharma, P.; Misra, S. Adverse events
reported from COVID-19 vaccine trials: A systematic review. Indian J. Clin. Biochem. 2021, 36, 427–439. [CrossRef]
13. Abu-Halaweh, S.; Alqassieh, R.; Suleiman, A.; Al-Sabbagh, M.Q.; AbuHalaweh, M.; AlKhader, D.; Abu-Nejem, R.; Nabulsi, R.;
Al-Tamimi, M.; Alwreikat, M.; et al. Qualitative assessment of early adverse effects of Pfizer-BioNTech and Sinopharm COVID-19
vaccines by telephone interviews. Vaccines 2021, 9, 950. [CrossRef]
14. Klugar, M.; Riad, A.; Mekhemar, M.; Conrad, J.; Buchbender, M.; Howaldt, H.P.; Attia, S. Side effects of mRNA-based and viral
vector-based COVID-19 vaccines among German healthcare workers. Biology 2021, 10, 752. [CrossRef] [PubMed]
15. Menni, C.; Klaser, K.; May, A.; Polidori, L.; Capdevila, J.; Louca, P.; Sudre, C.H.; Nguyen, L.H.; Drew, D.A.; Merino, J.; 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, 939–949. [CrossRef]
16. Saeed, B.Q.; Al-Shahrabi, R.; Alhaj, S.S.; Alkokhardi, Z.M.; Adrees, A.O. Side effects and perceptions following Sinopharm
COVID-19 vaccination. Int. J. Infect. Dis. 2021, 111, 219–226. [CrossRef]
17. Thomas, S.J.; Moreira, E.D.; Kitchin, N., Jr.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Pérez Marc, G.; Polack, F.P.;
Zerbini, C.; et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine through 6 months. N. Engl. J. Med. 2021, 385,
1761–1773. [CrossRef] [PubMed]
18. See, I.; Su, J.R.; Lale, A.; Woo, E.J.; Guh, A.Y.; Shimabukuro, T.T.; Streiff, M.B.; Rao, A.K.; Wheeler, A.P.; Beavers, S.F.; et al. US case
reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021.
JAMA 2021, 325, 2448–2456. [CrossRef] [PubMed]
19. Tobaiqy, M.; MacLure, K.; Elkout, H.; Stewart, D. Thrombotic adverse events reported for Moderna, Pfizer and Oxford-
AstraZeneca COVID-19 vaccines: Comparison of occurrence and clinical outcomes in the eudravigilance database. Vaccines 2021,
9, 1326. [CrossRef]
20. Klein, N.P.; Lewis, N.; Goddard, K.; Fireman, B.; Zerbo, O.; Hanson, K.E.; Donahue, J.G.; Kharbanda, E.O.; Naleway, A.; Nelson,
J.C.; et al. Surveillance for adverse events after COVID-19 mRNA vaccination. JAMA 2021, 326, 1390–1399. [CrossRef]
21. MOH. MOH News. Riyadh: Ministry of Health. 2021. Available online: https://www.moh.gov.sa/en/Ministry/MediaCenter/
News/Pages/News-2021-10-15-001.aspx (accessed on 20 October 2021).
22. Elharake, J.A.; Galal, B.; Alqahtani, S.A.; Kattan, R.F.; Barry, M.A.; Temsah, M.H.; Malik, A.A.; McFadden, S.M.; Yildirim, I.;
Khoshnood, K.; et al. COVID-19 vaccine acceptance among health care workers in the Kingdom of Saudi Arabia. Int. J. Infect. Dis.
2021, 109, 286–293. [CrossRef]
23. MOH. COVID-19 & Vaccine FAQs. Riyadh: Ministry of Health. 2021. Available online: https://www.moh.gov.sa/en/Ministry/
HotTopics/Pages/COVID-19-Vaccine.aspx (accessed on 5 January 2022).
24. Our World in Data. Saudi Arabia: Coronavirus Pandemic Country Profile. 2021. Available online: https://ourworldindata.org/
coronavirus/country/saudi-arabia (accessed on 25 October 2021).
25. Al-Mohaithef, M.; Padhi, B.K. Determinants of COVID-19 vaccine acceptance in Saudi Arabia: A web-based national survey. J.
Multidiscip. Healthc. 2020, 13, 1657–1663. [CrossRef]
26. Barry, M.; Temsah, M.H.; Aljamaan, F.; Saddik, B.; Al-Eyadhy, A.; Alenezi, S.; Alamro, N.; Alhuzaimi, A.N.; Alhaboob, A.;
Alhasan, K.; et al. COVID-19 vaccine uptake among healthcare workers in the fourth country to authorize BNT162b2 during the
first month of rollout. Vaccine 2021, 39, 5762–5768. [CrossRef]
27. Lwanga, S.K.; Lemeshow, S.; World Health Organization. Sample Size Determination in Health Studies: A Practical Manual; World
Health Organization: Geneva, Switzerland, 1991. Available online: https://apps.who.int/iris/handle/10665/40062 (accessed on
15 October 2021).
Vaccines 2022, 10, 223 14 of 14

28. Israel, G.D. Determining Sample Size; Technical Report; University of Florida: Gainesville, FL, USA, 1992. Available online:
https://www.tarleton.edu/academicassessment/documents/samplesize.pdf (accessed on 5 January 2022).
29. Adam, M.; Gameraddin, M.; Alelyani, M.; Alshahrani, M.Y.; Gareeballah, A.; Ahmad, I.; Azzawi, A.; Komit, B.; Musa, A.
Evaluation of post-vaccination symptoms of two common COVID-19 vaccines used in Abha, Aseer Region, Kingdom of Saudi
Arabia. Patient Prefer. Adherence 2021, 15, 1963–1970. [CrossRef] [PubMed]
30. Bendel, R.B.; Afifi, A.A. Comparison of stopping rules in forward “stepwise” regression. J. Am. Stat. Assoc. 1977, 72, 46–53.
31. Holm, S. A simple sequentially rejective multiple test procedure. Scand. J. Stat. 1979, 6, 65–70.
32. Gee, J.; Marquez, P.; Su, J.; Calvert, G.M.; Liu, R.; Myers, T.; Nair, N.; Martin, S.; Clark, T.; Markowitz, L.; et al. First month of
COVID-19 vaccine safety monitoring—United States, December 14, 2020-January 13, 2021. Morb. Mortal. Wkly. Rep. 2021, 70,
283–288. [CrossRef]
33. Alhazmi, A.; Alamer, E.; Daws, D.; Hakami, M.; Darraj, M.; Abdelwahab, S.; Maghfuri, A.; Algaissi, A. Evaluation of side effects
associated with COVID-19 vaccines in Saudi Arabia. Vaccines 2021, 9, 674. [CrossRef] [PubMed]
34. Al Bahrani, S.; Albarrak, A.; Alghamdi, O.A.; Alghamdi, M.A.; Hakami, F.H.; Al Abaadi, A.K.; Alkhrashi, S.A.; Alghamdi, M.Y.;
Almershad, M.M.; Alenazi, M.M.; et al. Safety and reactogenicity of the ChAdOx1 (AZD1222) COVID-19 vaccine in Saudi Arabia.
Int. J. Infect. Dis. 2021, 110, 359–362. [CrossRef]
35. Alghamdi, A.A.; Alkazemi, A.; Alissa, A.; Alghamdi, I.; Alwarafi, G.; Waggas, H.A. Adverse events following AstraZeneca
COVID-19 vaccine in Saudi Arabia: A cross-sectional study among healthcare and non-healthcare workers. Intervirology 2021.
[CrossRef]
36. Zaki, N.W.; Sidiq, M.; Qasim, M.; Aranas, B.; Hakamy, A.; Ruwais, N.; Alanezi, H.; Al Saudi, D.A.; Alshahrani, R.B.S.; Al-Thomali,
A.B.A.; et al. Stress and psychological consequences of COVID-19 on health-care workers. J. Nat. Sci. Med. 2020, 3, 299–307.
[CrossRef]
37. Tissot, N.; Brunel, A.S.; Bozon, F.; Rosolen, B.; Chirouze, C.; Bouiller, K. Patients with history of COVID-19 had more side effects
after the first dose of COVID-19 vaccine. Vaccine 2021, 39, 5087–5090. [CrossRef]
38. Alghamdi, A.N.; Alotaibi, M.I.; Alqahtani, A.S.; Al Aboud, D.; Abdel-Moneim, A.S. BNT162b2 and ChAdOx1 SARS-CoV-2
post-vaccination side-effects among Saudi vaccinees. Front. Med. 2021, 8, 760047. [CrossRef]
39. Abu-Hammad, O.; Alduraidi, H.; Abu-Hammad, S.; Alnazzawi, A.; Babkair, H.; Abu-Hammad, A.; Nourwali, I.; Qasem, F.;
Dar-Odeh, N. Side effects reported by Jordanian healthcare workers who received COVID-19 vaccines. Vaccines 2021, 9, 577.
[CrossRef] [PubMed]
40. Andrzejczak-Grzadko, ˛ S.; Czudy, Z.; Donderska, M. Side effects after COVID-19 vaccinations among residents of Poland. Eur.
Rev. Med. Pharmacol. Sci. 2021, 25, 4418–4421. [CrossRef] [PubMed]
41. Jayadevan, R.; Shenoy, R.S.; Anithadevi, T.S. Survey of symptoms following COVID-19 vaccination in India. MedRxiv 2021.
Available online: https://www.medrxiv.org/content/10.1101/2021.02.08.21251366v1.full.pdf (accessed on 20 November 2021).
42. Esba, L.; Al Jeraisy, M. Reported adverse effects following COVID-19 vaccination at a tertiary care hospital, focus on cerebral
venous sinus thrombosis (CVST). Expert Rev. Vaccines 2021, 20, 1037–1042. [CrossRef] [PubMed]
43. Greinacher, A.; Thiele, T.; Warkentin, T.E.; Weisser, K.; Kyrle, P.A.; Eichinger, S. Thrombotic thrombocytopenia after ChAdOx1
nCov-19 vaccination. N. Engl. J. Med. 2021, 384, 2092–2101. [CrossRef]
44. Alfawaz, H.; Amer, O.E.; Aljumah, A.A.; Aldisi, D.A.; Enani, M.A.; Aljohani, N.J.; Alotaibi, N.H.; Alshingetti, N.; Alomar, S.Y.;
Khattak, M.; et al. Effects of home quarantine during COVID-19 lockdown on physical activity and dietary habits of adults in
Saudi Arabia. Sci. Rep. 2021, 11, 5904. [CrossRef] [PubMed]
45. Mohammed, R.A.; Garout, R.M.; Wahid, S.; Ayub, F.; Leen, M.; ZinAlddin, F.; Sultan, I. A survey on the side effects of
Pfizer/BioNTech COVID-19 vaccine among vaccinated adults in Saudi Arabia. Cureus 2021, 13, e19222. [CrossRef]
46. Vassallo, A.; Shajahan, S.; Harris, K.; Hallam, L.; Hockham, C.; Womersley, K.; Woodward, M.; Sheel, M. Sex and gender in
COVID-19 vaccine research: Substantial evidence gaps remain. Front. Glob. Women Health 2021, 2, 761511. [CrossRef]
47. Flanagan, K.L.; Fink, A.L.; Plebanski, M.; Klein, S.L. Sex and gender differences in the outcomes of vaccination over the life course.
Annu. Rev. Cell Dev. Biol. 2017, 33, 577–599. [CrossRef]
48. McCartney, P.R. Sex-based vaccine response in the context of COVID-19. J. Obstet. Gynecol. Neonatal Nurs. 2020, 49, 405–408.
[CrossRef]
49. Harris, T.; Nair, J.; Fediurek, J.; Deeks, S.L. Assessment of sex-specific differences in adverse events following immunization
reporting in Ontario, 2012–2015. Vaccine 2017, 35, 2600–2604. [CrossRef] [PubMed]
50. Riad, A.; Hocková, B.; Kantorová, L.; Slávik, R.; Spurná, L.; Stebel, A.; Havril’ak, M.; Klugar, M. Side effects of mRNA-based
COVID-19 vaccine: Nationwide phase IV study among healthcare workers in Slovakia. Pharmaceuticals 2021, 14, 873. [CrossRef]
[PubMed]
51. Jeon, M.; Kim, J.; Oh, C.E.; Lee, J.Y. Adverse events following immunization associated with the first and second doses of the
ChAdOx1 nCoV-19 vaccine among healthcare workers in Korea. Vaccines 2021, 9, 1096. [CrossRef] [PubMed]

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