Vaccines 10 00223 v2
Vaccines 10 00223 v2
Vaccines 10 00223 v2
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/).
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.
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.
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).
Table 3. Associations of the reported COVID-19 vaccine side-effects with the participants’ background
characteristics (n = 437).
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).
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).
Table 7. The onset, duration, and management of COVID-19 vaccine side-effects reported among the
healthcare workers participated in the study (n = 250).
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
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.
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