Keywords
COVID-19 - vaccine - adverse effects - BNT162b2 - CoronaVac
Introduction
The coronavirus 2019 (COVID-19) pandemic has gravely affected the whole world and
caused the death of millions of people. There is currently no definitive treatment
for the disease, and the best method to prevent its spread is vaccination. Vaccine
studies for the COVID-19 disease were started promptly, and approved vaccines have
been started to be administered across the world.[1]
[2] An ideal vaccine is the one that has the least side-effect profile and high efficacy.
However, the rapid development of vaccines has led to hesitations in society concerning
the safety of their application.[3]
[4]
Vaccine studies in the world have been implemented under five different main platforms:
live attenuated, mRNA-based, DNA-based, inactivated, and viral vector–based. Among
these, the mRNA-based “BNT162b2” developed by Pfizer/BioNTech company is one of the
first approved vaccines and administered in many countries. Phase 4 studies of this
vaccine continue after approval.[5] In Turkey, two types of vaccines are currently administered: the “BNT162b2” and
the “CoronaVac” vaccine developed by Sinovac Biotech.[6] BNT162b2 is a genetic mRNA-based vaccine that creates an immune response by injecting
the genetic code encoding the spike protein of the genome of the severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) virus into the human body in lipid nanoparticles.[7] CoronaVac is an inactive viral vaccine. In both these vaccines, two doses are administered
at an interval of 28 days.[8]
Allergic reactions related to the content of COVID-19 vaccines are the most reported
side effects. In addition, it has been reported that vaccines developed for COVID-19
can cause serious complications, such as myocarditis, thrombocytopenia, and cerebral
venous thrombosis.[5]
[9]
[10]
[11] Although studies have been conducted to investigate the efficacy of COVID-19 vaccines,
there is not sufficient research on their side effects. There are also limited studies
on patient presentations to the emergency department due to vaccine side effects and
the approach to the management of these patients. Therefore, in this study, we aimed
to determine the symptoms of patients who presented to the emergency department with
adverse reactions after COVID-19 vaccination. We investigated whether these symptoms
were seen more frequently depending on the type and dose of the vaccine administered.
Methods
Study Design and Setting
This prospective observational study was conducted in the emergency department of
a tertiary hospital over a 6-month period from May 1, 2021, through November 1, 2021.
Prior to the study, ethical approval was obtained from the local ethics committee,
and permission was granted by the Turkish Ministry of Health. The study was performed
in accordance with the tenets of the Declaration of Helsinki. Informed consent was
obtained from all participants. The study followed the Strengthening the Reporting
of Observational Studies in Epidemiology (STROBE) reporting guidelines for cross-sectional
studies.[12]
Selection of Participants
Patients who presented to the emergency department with vaccine-related complications
after COVID-19 vaccination were included in the study. Patients who did not agree
to participate in the study, those with a respiratory tract infection before vaccination,
and those who were determined to have symptoms related to other diseases were excluded
from the study. At the time of presentations, the patients' symptoms and vital signs
(mean arterial pressure [MAP], heart rate, body temperature, and oxygen saturation
[SpO2]) were determined. In addition, the demographic characteristics of the patients,
the type and dose of vaccine administered, and the time from vaccination to the onset
of symptoms were recorded in prepared forms.
In Turkey, everyone over the age of 18 years was included in the vaccination program
at the time of the study. Currently, two types of vaccines are administered. The BNT162b2
is available in six doses in a 0.3-mL vial. One vial is administered to six patients
in an equally divided dose. The CoronaVac is administered as a single dose in a 0.5-mL
vial. Individuals are free to choose either vaccine but the type administered as the
second dose must be the same as the first dose.
Statistical Analysis
Data analysis was performed using the Statistical Package for the Social Sciences
for Windows, version 17 (SPSS Inc, Chicago, IL, United States). Data were expressed
as mean ± standard deviation for continuous variables, and frequencies and proportions
for categorical variables. Student's t-test was used to analyze the mean differences between the groups. Categorical data
were analyzed using Pearson's chi-square test.
Results
A total of 206 patients were evaluated for the study. Sixteen patients with respiratory
tract infections before vaccination and eight patients with symptoms related to other
diseases were excluded from the study. Finally, the study included 182 patients who
presented to the emergency department with symptoms after COVID-19 vaccination over
a 6-month period. The BNT162b2 vaccine had been administered to 166 (91.2%) of these
patients and the CoronaVac vaccine to the remaining 16 (8.8%) patients. Considering
the age and gender distribution in all cases, the rate of women was higher (57.7%),
and 45.5% of the patients were aged 18 to 40 years. The vast majority of the patients
(70.3%) did not have a history of COVID-19 infection, and the rate of presentation
was higher after the second dose (61%). The time of onset of vaccine-related symptoms
was mostly within 1 to 12 hours (39%). In addition, the majority of patients (97.8%)
were discharged from the emergency department ([Table 1]).
Table 1
Demographic characteristics of the patients
|
N
|
%
|
|
Gender
|
|
Male
|
77
|
42.3
|
|
Female
|
105
|
57.7
|
|
Age (y)
|
|
18–40
|
81
|
44.5
|
|
41–60
|
78
|
42.9
|
|
> 61
|
23
|
12.6
|
|
Type of vaccine
|
|
BNT162b2
|
166
|
91.2
|
|
CoronaVac
|
16
|
8.8
|
|
Dose of vaccine
|
|
First
|
54
|
29.7
|
|
Second
|
111
|
61
|
|
Third
|
15
|
8.2
|
|
Fourth
|
2
|
1.1
|
|
History of COVID-19
|
|
Present
|
54
|
29.7
|
|
Absent
|
128
|
70.3
|
|
Onset of complaints after vaccination
|
|
< 1 h
|
13
|
7.1
|
|
1–12 h
|
71
|
39
|
|
13–48 h
|
69
|
37.9
|
|
> 48 h
|
29
|
15.9
|
|
Hospitalization
|
|
Present
|
4
|
2.2
|
|
Absent
|
178
|
97.8
|
Abbreviation: COVID-19, coronavirus disease 2019.
When the presentation symptoms of the patients after vaccination were examined, it
was determined that the most common complaint was fatigue (n = 70), followed by muscle/joint pain (n = 52), headache (n = 33), and fever (n = 32) ([Fig. 1]).
Fig. 1 Distribution of symptoms.
Considering the relationship between symptoms and vaccine type, for the patients vaccinated
with BNT162b2, the most common symptom was fatigue (n = 61, 36.7%), followed by joint pain (n = 47, 28.3%) and headache (n = 32, 19.3%). In the CoronaVac vaccine group, the most common symptom was similarly
fatigue (n = 9, 56.3%), followed by muscle/joint pain (n = 5, 31.3%), headache (n = 3, 18.8%), fever (n = 3, 18.8%), and dizziness (n = 3, 18.8%). The rate of dizziness was statistically significantly higher in the
CoronaVac vaccine group than in the BNT162b2 vaccine group (p = 0.008). However, there was no statistically significant difference between the
two groups in relation to the remaining symptoms (p > 0.005). In addition, no relationship was found between the type and dose of vaccine
and whether the patients had a history of COVID-19 infection and onset of symptoms
after vaccination (p > 0.05; [Table 2]).
Table 2
Comparison of variables between the two vaccine groups
|
BNT162b2
n = 166 (%)
|
CoronaVac
n = 16 (%)
|
p-Value
|
|
Gender
|
|
Female/male
|
94 (56.6)/72 (43.4)
|
11 (68.7)/5 (31.3)
|
0.349
|
|
Complaint[a]
|
|
Fatigue
|
61 (36.7)
|
9 (56.3)
|
0.126
|
|
Joint pain
|
47 (28.3)
|
5 (31.3)
|
0.804
|
|
Headache
|
32 (19.3)
|
3 (18.8)
|
0.959
|
|
Fever
|
30 (18.1)
|
3 (18.8)
|
0.946
|
|
Nausea
|
28 (16.9)
|
2 (12.5)
|
0.653
|
|
Allergy
|
14 (8.4)
|
0 (0)
|
0.227
|
|
Chest pain
|
12 (7.2)
|
1 (6.3)
|
0.885
|
|
Sore throat
|
10 (6)
|
0 (0)
|
0.313
|
|
Sweating
|
7 (4.2)
|
0 (0)
|
0.402
|
|
Diarrhea
|
7 (4.2)
|
0 (0)
|
0.402
|
|
Dizziness
|
6 (3.6)
|
3 (18.8)
|
0.008
|
|
Shortness of breath
|
6 (3.6)
|
1 (6.3)
|
0.601
|
|
Cough
|
4 (2.4)
|
0 (0)
|
0.530
|
|
Abdominal pain
|
3 (1.8)
|
0 (0)
|
0.588
|
|
Other[b]
|
4 (2.4)
|
0 (0)
|
0.530
|
|
Onset of complaints after vaccination
|
|
< 1 h
|
11 (6.6)
|
2 (12.5)
|
0.058
|
|
1–12 h
|
67 (40.4)
|
4 (25)
|
|
13–48 h
|
65 (39.2)
|
4 (25)
|
|
> 48 h
|
23 (13.9)
|
6 (37.5)
|
|
Dose of vaccine
|
|
First
|
50 (30.1)
|
4 (25)
|
0.87
|
|
Second
|
101 (60.8)
|
10 (62.5)
|
|
Third
|
13 (7.8)
|
2 (12.5)
|
|
Fourth
|
2 (1.2)
|
0
|
|
History of COVID-19
|
|
Present
|
52 (31.3)
|
4 (25)
|
0.779
|
|
Absent
|
114 (68.7)
|
12 (75)
|
Abbreviation: COVID-19, coronavirus disease 2019.
a Multivariable.
b Includes dry mouth, palpitations, and visual impairment.
In the BNT162b2 vaccine group, the mean values for the vital signs of the patients
were determined as follows: body temperature, 36.55 ± 0.45°C; heart rate, 96.77 ± 13.68/min;
MAP, 89.69 ± 9.42 mm Hg; and SpO2, 96.22 ± 1.83%. In the CoronaVac vaccine group, the mean vital signs were 36.6 ± 0.37°C
for body temperature, 100.2 ± 22.92 for heart rate, 86.87 ± 12.78 for MAP, and 96.22 ± 9.42
for SpO2. There was no statistically significant difference between the two vaccines in terms
of vital signs (p > 0.05; [Table 3]).
Table 3
Relationship between the type of vaccine and vital signs
|
Vital signs
|
BNT162b2
|
CoronaVac
|
Mean difference (%95 CI)
|
p-Value
|
|
MAP, mean ± SD (mm hg)
|
89.69 ± 9.42
|
86.87 ± 12.78
|
2.81 (−2.22 to 7.85)
|
0.271
|
|
Heart rate, mean ± SD (beats per minute)
|
96.77 ± 13.68
|
100.2 ± 22.92
|
−3.43 (−15.78 to 8.92)
|
0.564
|
|
Body temperature, mean ± SD (°C)
|
36.55 ± 0.45
|
36.60 ± 0.37
|
−0.049 (−0.312 to 0.214)
|
0.713
|
|
Oxygen saturation, mean ± SD (%)
|
96.22 ± 1.83
|
96.22 ± 1.51
|
0.005 (−0.926 to 0.937)
|
0.991
|
Abbreviations: CI, confidence interval; MAP, mean arterial pressure; SD, standard
deviation.
Discussion
Vaccination against COVID-19 is the most important approach in preventing the disease.
However, some individuals have hesitations concerning the safety of COVID-19 vaccines.
Side effects and postvaccination symptoms are the main reasons for avoiding vaccination.[13]
[14] To our knowledge, there is no study comparing the side effects of the BNT162b2 and
CoronaVac vaccines. In general, previous studies indicate no serious side effect associated
with COVID-19 vaccines.[15]
[16]
[17] In a study by Baden et al[18] on the efficacy and safety of an mRNA-based vaccine, only local complications were
observed after vaccination. However, there are also publications reporting serious
complications, such as myocarditis after mRNA vaccination.[11]
[19] In the current study, only four patients required hospitalization, who were all
discharged with full recovery after treatment, and no serious side effects were observed.
In the literature, side effects have been reported to occur at a higher rate after
the administration of mRNA-based vaccines compared with inactivated vaccines.[9]
[10]
[18]
[20] In our study, the majority of the patients (91.2%) had received the BNT162b2 vaccine.
However, when the variables were compared according to the vaccine type, there was
no significant difference between the two vaccine groups. The only significant difference
was observed in relation to the complaint of dizziness, which was at a higher rate
among the patients who had received the CoronaVac vaccine.
In studies investigating symptoms observed after COVID-19 vaccination, the most common
complaint was reported to be headache by Li et al,[21] and fatigue, headache, muscle pain, and injection-site pain by Sadoff et al.[22] Similarly, in the current study, the most common complaint was fatigue in both the
vaccine groups.
The literature contains no study evaluating the relationship between vaccine-related
side effects and a history of COVID-19. In this study, we determined that the majority
of the patients (70.3%) had not contracted COVID-19. It can be suggested that COVID-19
vaccines show more symptoms in those who have not had the disease.
There is also no previous study exploring the relationship between the vaccine dose
administered and the occurrence of symptoms. Previous studies have shown that vaccines
increase humoral and T-cell immunity. Li et al reported that T-cell and humoral immunity
were higher in patients who had received mRNA vaccination.[21] In our study, the rate of patient presentation due to vaccine-related side effects
was higher after the second dose of vaccination, which may be due to type 2 sensitivity
reactions. There is a need for further research on this subject.
Limitations
The main limitation of the study is its observational cross-sectional design. This
study has a small number of participants. Consequently, this limited our ability to
conduct multiple subanalyses and generated wide results. In addition, this study was
conducted on a single center. Another limitation is that this study only included
patients presenting to the emergency department.
Conclusions
We determined that patient presentation to the emergency department due to side effects
after vaccination with BNT162b2 was higher compared with those after vaccination with
CoronaVac. Fatigue was the most common symptom in both vaccine types. The rate of
postvaccination hospitalization was very low, and no serious problems were observed
related to either vaccine; therefore, the BNT162b2 and CoronaVac vaccines can be safely
administered.
