INTRODUCTION
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally was rapid, and so was the development of the COVID-19 vaccines. SARS-CoV-2 was discovered to be the causative agent for the unusual pneumonia cases that were first reported in Wuhan City, Hubei Province of China.[ 1 ] An imported case from Italy was recorded in Nigeria on the 27th February 2020, this marked the beginning of the outbreak in the country.[ 2 ] Due to the virus's rapid spread across international boundaries, the World Health Organisation (WHO) declared the situation a global pandemic on 11 March 2020.[ 3 ] To halt the spread of the virus, laws restricting social gatherings were enacted and enforced in most countries, leading to total or partial lockdowns of its citizens. This had effects on the socioeconomic and psychological wellbeing of citizens.[ 4 ] To address the new threat, scientists across the globe searched for old drugs that could be repurposed for treating the disease and vigorously pursued the development of new ones.[ 5 ] This effort went on simultaneously with the race for vaccine development,[ 5 ] and thanks to nanotechnology, candidate vaccines became available within a year of identifying the virus and were pre-qualified for emergency use by the WHO, having passed the third phase of clinical trials and approved by the United States Food and Drug Administration, and European regulatory agencies.[ 6 ]
In the past, vaccine development took several years or even decades to be available due to the rigorous scrutiny of various regulatory agencies in certifying its safety. For instance, it took 26 years to develop the human papillomavirus vaccine and 25 years to secure one for rotavirus.[ 7 , 8 ] The perception that the new vaccine was rushed comes with concern about vaccine safety due to fear of side effects, thus resulting in vaccine hesitancy.[ 9-11 ]
Vaccines generally are known to cause side effects that range from mild to severe forms.[ 12 ] The mild side effects signify that the body's immune system is responding to the vaccine and are not a cause for alarm as they always go away within a few days, unlike severe side effects that are unexpected, last more than 3 days, and require medical intervention.[ 12 ] Side effects are monitored and reported as adverse events following immunisation (AEFI) in the immunisation program. AEFI could result from defects in vaccine quality or the administering device provided by the manufacturer, vaccine product-related, immunisation anxiety-related, co-incidental and immunisation error-related.[ 13 ] Some side effects commonly reported after vaccination include fever, vomiting, pain and swelling at the injection site and seizure. Several side effects have been reported in the case of the COVID-19 vaccine. These adverse events ranged from mild to severe, some of which include fever, myalgia, headache, fatigue, chills and shivers, nausea, diarrhea, etc.[ 14 ]
Health workers and other frontline workers were the focus of COVID-19 vaccines at the onset of vaccinations in most countries, including Nigeria, due to the peculiarity of their work. This makes them a group of interest when considering the prevalence and severity of adverse events following COVID-19 vaccinations. Currently, only a few studies are available on this topic. In a study among health workers in the Czech Republic, 89.8% reported pain at the injection site, 62.2% reported having fatigue, 45.6% reported headache and 21.7% reported fever.[ 15 ]
Nigeria took its first delivery of the COVID-19 vaccines from the international COVID-19 Vaccines Global Access scheme on the 2nd March 2021. Health workers, first responders and other citizens who expressed interest by registering on the National Primary Health Care Development Agency (NPHCDA) electronic platform were the focus of the initial vaccination exercise. Evidence has shown that there exist ethnic and racial disparities in how individuals react to drugs.[ 16 ] Most of the clinical trials for COVID-19 vaccine trials were carried out in western and Asian countries;[ 17-21 ] therefore, it becomes imperative to determine the adverse events among COVID-19 vaccine recipients in Nigeria and their severity. This study determined the prevalence and severity of the various adverse events following COVID-19 vaccination reported by healthcare workers in tertiary health facilities in Nigeria. We believe findings from the study will contribute to the body of evidence on COVID-19 vaccine safety as this area is still evolving and assure the general public on the safety of the vaccine.
MATERIALS AND METHODS
Study design
This descriptive, cross-sectional study was conducted in Nigeria between November 2021 and April 2022.
Study location
Nigeria is one of the countries in sub-Saharan Africa, with a projected population of 218 million based on the 2006 population census at a growth rate of 2.41%.[ 22 ] The health system is structured into three primary, secondary and tertiary levels, each providing preventive and curative services to the populace. There are 36 teaching hospitals, 22 Federal Medical Centers, and 13 specialist hospitals nationwide. The health workforce in these facilities comprises doctors, nurses/midwives, pharmacists, physiotherapists, medical laboratory scientists, radiographers, medical record officers and others. This study was conducted in six tertiary health facilities spread across the six geopolitical zones in the country.
Ethical considerations
Ethical approval (NHREC/01/01/2007-19/07/2021) was obtained from NHREC and from the participating institutions' Health Research and Ethics Committee. Participants were duly informed of the purpose of the study, and verbal informed consent was obtained. All information obtained was treated confidentially.
Study population
All healthcare workers (clinical and non-clinical) who had received either one or two doses of the COVID-19 vaccine were eligible to participate in the study, while nursing mothers and those that were pregnant, ill and those on leave were excluded from the study.
Sample size determination
The minimum sample size for each geopolitical zone was calculated using the fishers formula[ 23 ] for calculating the minimum sample size for a cross-sectional study which is p ’ of the side effects in the general population to be 50% ±5%, and ‘z ’ represents the value of the standard normal variate at 5% type 1 error (P < 0.05) =1.96, and a 5% margin of error.
The minimum sample per region was 384. An adjustment factor of 10% for non-response was made, n = 384/0.9 = 426.
Accordingly, a total of 427 respondents were allocated to each of the geopolitical zones. However, due to vaccine hesitancy, this number could not be attained in two of the participating facilities at the time of the study.
Sampling
Multi-stage sampling technique was used in selecting the study participants as follows:
Stage 1: Selection of participating states
A state was selected from each of the geopolitical zones. This was done using simple random sampling (balloting).
Stage 2: Selection of tertiary health facility (HF)
All tertiary HF in the state were identified, and one was randomly selected by balloting.
Stage 3: Selection of participants
Simple random sampling (table of random numbers method) was used in selecting the study participants from the vaccination registers in the selected HF. Selected individuals were contacted via phone and booked for the interview at a convenient place within the facility after consenting to participate in the study.
Data collection
An interviewer-administered questionnaire was adopted from a previously validated tool.[ 15 ] The questionnaire has sections on socio-demographic characteristics of respondents, co-morbidities (asthma, hypertension, diabetes mellitus, cancer, etc), medication history, adverse events and its severity. The severity of the adverse events was assessed using a Likert scale ranging from 1 to 10, ‘1’ being the lowest and ‘10’ highest.
All the participating sites had research focal persons responsible for recruiting research assistants and sampling. The focal persons' trained research assistants comprising of doctors, nurses and research officers for 2 days at the various sites.
Data analysis
Data were collected electronically using the kobocollect app on android phones and were uploaded to IBM® SPSS version 23 Chicago, Illinois, USA for the data analysis. Age and duration of work experience were summarised using the appropriate measures of central tendency. Quantitative variables were transformed into the categorical variables. The severity of adverse events was categorised into mild (Grades 1–3), moderate (Grades 4–6) and severe (Grades 7–10) during the data analysis. All categorical variables were summarised using frequencies and proportions and presented in tables and charts.
RESULTS
Table 1 shows that a total of 2130 respondents participated in the study, with a mean age of 37.4 ± 9.1 years. The majority, 1233 (57.9%) of the workers, were within the 30–44 years age group and just a little above half, 1101 (51.7%) were females. Bauchi State had the highest proportion of respondents, 442 (20.8%), among the six states involved in the study, while Ebonyi State had the least, 93 (4.4%). Out of all the healthcare workers in this study, nurses/midwives and doctors were the majority, having about 25.0% each. Most 1354 (63.6%) of the respondents had <10 years of working experience, with a median duration of work experience of 6 years.
Table 1:
Sociodemographic variables of respondents (n =2130)
Table 2 shows that only 177 (8.3%) of the respondents had previously suffered from COVID-19 infection, while 300 (14.1%) of them had one form of chronic medical illness or the other. Hypertension was the most common chronic illness reported by the respondents, accounting for 59.0%, followed by diabetes which accounted for 29.0%. Paracetamol 1117 (52.4%), antibiotics 575 (27.0%) and non-steroidal anti-inflammatory drugs 315 (14.8%) were the most commonly used drugs among the respondents. Most 1674 (78.6%) of the respondents already had two doses of the COVID-19 vaccine at the time of data collection, and almost half of the respondents, 1025 (48.1%), reported adverse events following the first dose. Nearly all 1977 (92.8%) respondents were willing to recommend the vaccine to others.
Table 2:
Clinical profile of respondents and history of adverse events following immunisation
Figure 1 shows that the commonly reported adverse events following the administration of the first dose of the vaccine were fever 649 (30.5%), pain at the injection site 644 (30.2%), headache 530 (24.9%) and fatigue 493 (23.1%), while the least frequent were lymphadenopathy 65 (3.1%) and urticaria 66 (3.1%). With the second dose of the vaccine, pain at the injection site 216 (10.1%), fever 173 (8.1%) and headache 154 (7.2%) were the commonly reported AEFI, while rash 30 (1.4%), lymphadenopathy 28 (1.3%) and urticaria 27 (1.3%) were the least reported.
Figure 1:
Proportions of reported adverse events following immunisation
Table 3 shows the severity of the commonly reported adverse events among respondents following the first dose of the COVID-19 vaccine. Among the respondents that reported fever, the majority, 341 (52.5%), reported it as moderate, while less than a quarter, 152 (23.4%), reported it as severe. For pain at the injection site, the majority of the respondents, 366 (56.8%), reported it to be moderate, and about a quarter 167 (25.9%), reported it as severe. Similarly, for fatigue, the majority of the respondents, 265 (53.8%), reported it as moderate and a little more than a quarter, 132 (26.8%), had severe effects. Most of the adverse events reported by the respondents were moderate in severity.
Table 3:
The severity of adverse events among respondents following the first dose of the vaccine
Table 4 shows the severity of the commonly reported adverse events among respondents following the second dose of the COVID-19 vaccine. The majority of the respondents 118 (54.6%) who reported pain at the injection site described it as moderate, while less than a quarter, 37 (17.1%), described it as severe. Similarly, for fever, the majority, 91 (52.6%), described it as moderate, and less than a quarter, 40 (23.1%), described it as severe. Overall, most of the respondents described the severity of the adverse events as either mild or moderate.
Table 4:
The severity of adverse events among respondents following the second dose of the vaccine
DISCUSSION
The NPHCDA, in response to the COVID-19 pandemic, began vaccinating Nigerians against the virus in Nigeria on the 5 March 2021. The vaccine brands in use in Nigeria are AstraZeneca, Moderna, Pfizer and Johnsons and Johnsons. Early findings from studies across the globe, including Nigeria, showed serious concerns among the general public about the safety of the available vaccines, hence, promoting vaccine hesitancy. Although the adverse events reported in our study were largely mild to moderate, and very few were severe, the fact that these vaccines are novel and are still undergoing post-marketing surveillance means that adequate systems should be in place for detecting, reporting, and analysing various adverse events that could occur after the administration. Reactions to health products vary from one population to another due to genetic composition and the immune system.[ 16 , 24 , 25 ] Therefore, having data from different parts of the world allows for comparability of the safety profile being reported for the vaccines, improve public confidence, and reduce vaccine hesitancy.
According to our findings, about 4 in 10 vaccine recipients reported at least one adverse event after vaccination. This is similar to the findings in the COVID-19 vaccines' phase 2 trials, where about a third of recipients also had adverse events.[ 19 , 20 ] However, higher figures have been reported in other prevalence studies conducted among vaccine recipients across the globe. A study among healthcare workers in Togo, West Africa,[ 26 ] reported an AEFI prevalence of 71.6% among recipients, while in another conducted in Malaysia, the prevalence of adverse events was 87.5%.[ 27 ] Furthermore, other studies in Netherlands and Bangladesh reported a higher prevalence of adverse events compared to our study.[ 28 , 29 ]
This study showed that more recipients reported AEFI after the first dose of the vaccine. This compares to studies in Korea[ 30 ] and Indonesia[ 31 ] where more recipients equally reported adverse events after the first dose of the vaccine. Furthermore, experience from other vaccines that have been in use showed more reports of adverse events with first doses.[ 32 , 33 ] About half (48.1%) of the respondents in our study reported adverse events after the first dose, compared to 20.3% who reported adverse events after the second dose. The prevalence of AEFI after the first dose of the vaccine in our study is higher than the 18.8% obtained in another study in India,[ 34 ] and 33.7% in the United Kingdom.[ 14 ] However, in another study in India, 57% of recipients reported AEFI after the first dose of the vaccine.[ 35 ]
The difference in our study and the previous ones could have resulted from several factors; first, most adverse events after immunisations result from the body's response to antigens introduced; this may vary in individuals depending on age, nutrition status and previous exposure to pathogens with similar antigenic properties.[ 36 , 37 ] Furthermore, ongoing community transmission of COVID-19 infection before the commencement of vaccination may have altered individual responses to the vaccine. Another factor that could be responsible for the difference is the vaccine brands used because different rates have been reported for the various vaccine types[ 38 ] and the fact that Nigeria deployed a mix of vaccine brands could have influenced the low prevalence observed in our study. Furthermore, variation due to ethnic and racial disparity cannot be ruled out as this has been identified as a major factor in how individuals react to health products.[ 16 ]
The AEFI commonly experienced by respondents in this study were fever, pain at the injection site, headache, fatigue and malaise. This compares to the reports among COVID-19 vaccine recipients globally.[27,31,34,39-41] Fever was the most common adverse event reported after the first dose, while pain at the injection site was the most common after the second dose of the vaccine. On the contrary, in similar studies in Indonesia and Malaysia, pain at the injection site was the most frequently reported adverse event following both the first and second doses of the vaccine.[ 27 , 31 ] Fever and pain at the injection site are the common adverse events that often accompany most vaccination processes; both have been reported with other vaccines that have been in use in the past, especially those used in childhood immunisations.[ 42 , 43 ] Among respondents that reported fever, approximately one-third had it following the first dose, in contrast to <10% that had it after the second dose. Furthermore, for pain at the injection site, a third of respondents had it after the first dose, compared to about 10% after the second. Furthermore, in Bangladesh, pain at the injection site (34.3%) and fever (32.6%) were the most frequently reported adverse events, while in Saudi Arabia, pain at the injection site (85.2%) was the predominant adverse event reported.[ 44 ] Fever is a sign of having an excellent response to the antigen introduced and can be considered normal following vaccination, usually beginning within 12 h and resolving within 1–2 days.[ 45 ] Fever has been a commonly reported adverse event in other immunisation programmes and should not be a source of vaccine safety concerns.[ 42 , 46 ] Similarly, injection site pain often results from the body's immune response to the antigen introduced and can sometimes be due to the soreness on the muscle where the vaccine was administered.
In terms of severity of adverse events, very few respondents described their symptoms as severe. About one in three respondents reported severe forms of joint pain, myalgia, chills and lymphadenopathy which were largely amenable to paracetamol. The few that experienced urticaria following the first and second vaccination doses reported predominantly mild events that were not life-threatening. Furthermore, most of the fever events were largely mild to moderate that often resolved with or without interventions, with the severe ones resolving with the administration of paracetamol. This compares with finding in a randomised controlled trial on COVID-19 safety[ 47 ] and shows that the COVID-19 vaccine compares favorably to other vaccines previously used in immunisation programmes. Similarly, few respondents with injection site pain had the severe form and this compares to the findings in Vietnam.[ 48 ] Overall, most of the adverse events reported by our respondents were mostly mild to moderate and did not require significant interventions which further speaks to the safety profile of the vaccine.
A major strength of the current study is that health-care workers can recognise and grade adverse events appropriately and are less likely to have anxiety-related events, thereby reducing the false positivity rate of the outcome (adverse events) and their misclassification. However, the study may be prone to recall bias being a retrospective study. Furthermore, we could not disaggregate the adverse events based on vaccine types due to incomplete records in the registers; in spite of this, we believe this finding represents the general experience of COVID-19 vaccine recipients in Nigeria.
CONCLUSION
The study observed a relatively low prevalence of adverse events following COVID-19 vaccination compared to previous studies. The most prevalent among these adverse events were fever and injection site pain. Even though most were mild to moderate, it is crucial that countries continuously collect data on AEFI and establish causality as a way to improve quality and guarantee vaccine safety.
Financial Support and Sponsorship
Study was funded by the researchers
Conflicts of interest
There are no conflicts of interest.
Acknowledgement
The authors wish to appreciate the support of all members of staff of the Department of Community Medicine and Primary Care of Federal Medical Centre Abeokuta towards the successful completion of this work.
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