Introduction  

The novel Coronavirus disease (COVID-19 disease) was documented at the end of December 2019 in Wuhan, China [1-3]. Since its outbreak, the Coronavirus disease has caused considerable harm and challenges to all countries around the globe. By 10 August 2021, there were around 205 million Coronavirus cases and an estimated rate of death of 4.3 million people around the world [4]. Safe and highly efficacious vaccines are needed to control the pandemic. As of March 2021, around seven vaccines are available in different countries. Currently, 60 vaccines are in clinical development stages [5]. Among the widely used vaccines are that produced by Pfizer-BioNTech, Moderna, Johnson and Johnson [6], Oxford–AstraZeneca [7], and Sinopharm [8].

Even though vaccination has its highest potential to control the coronavirus pandemic, some side effects might appear after taking the vaccine. Most of the side effects last for few days. Potential systemic side effects, for the different types of vaccines, include tiredness, headache, muscle pain, chills, and fever. Local side effects at the injection site comprise pain, redness, and swelling [6].

Riad et al. conducted a survey study to investigate the side effects following Pfizer–BioNTech COVID-19 vaccine use. The most frequent side effects were pain at the injection site, fatigue, headache, muscle pain, and chills. The side effects disappeared after three days for 33% of the study participants. The prevalence of the side effects was more in the ≤43-year-old group [9]. Comparable common side effects were reported during clinical trials in China [10, 11]. Side effects after the Sinopharm vaccine, from clinical trials and real-world practice, were comparable to that of other vaccines [12, 13]. Common side effects reported from Saudi Arabia, due to Pfizer-BioNTech COVID-19 vaccines, were in line with what was mentioned above. In addition, rare events that included Bell’s palsy and lymph node swelling were also documented [14]. Reports among the American population likewise demonstrated similar side effects after Pfizer-BioNTech and Moderna COVID-19 vaccines, with rare cases of anaphylaxis [15]. The recorded side effects after the first dose of Pfizer- BioNTech COVID-19 vaccine also included a case of neurological complication (Guillain-Barre Syndrome) [16], and anaphylaxis [12]. Rare events following the Oxford–AstraZeneca vaccine also included thrombotic adverse reactions [17-19]. Reports also proposed a possible association between COVID-19 vaccines and cardiovascular adverse events [20-22].

Prior research suggests that age might be an important determinant for the occurrence of the side effects after vaccination. Older adults were found to have mild to moderate side effects due to the Moderna vaccine [23]. Similarly, a study on the Pfizer-BioNTech COVID-19 vaccine reported that people less than 60 years old had more frequent flu-like symptoms compared to 60 years and older [14]. Another investigation suggests a comparable safety profile between younger and adults, however, lower reactogenicity was observed in older adults, with no occurrence of severe side effects in adults ≥60 years [12]. Reports from a randomized, double-blind, placebo-controlled, phase 2 trial on an adenovirus 5 vector-based vaccine showed that adults aged 18–54 years had increased reactogenicity after a single dose in comparison to adults aged 55 years and older [10]. Comparably, Baden et al. observed that the side effects after the Moderna vaccine were more frequent in the 18 to <65 years old group than the ≥65 years old group [24]. In real-world practice, the Sinopharm vaccine showed side effects that were more frequent in ≤ 49-year-old [13].

Generally, side effects represent a major determinant of vaccination acceptance. With the newly developed vaccines, there is a growing need for more investigations, in real practice, on the side effects of the COVIS-19 vaccine. With this growing need, the current study was performed to investigate the side effects after the first dose of the Oxford–AstraZeneca vaccine among vaccine recipients at King Abdullah bin Abdulaziz University Hospital (KAAUH), Riyadh, Saudi Arabia. A particular emphasis was how age affects the frequency and the severity of the side effects during the three days post-vaccination.

Materials and Methods

Study design, setting, and participants

A cross-sectional survey was conducted to collect data from individuals (≥ 18 years old) who took the first dose of the Oxford–AstraZeneca COVID-19 vaccine at KAAUH, Riyadh, Saudi Arabia. The target individuals were those who received the first dose of the Oxford–AstraZeneca COVID-19 vaccine at KAAUH from February 28 – March 12, 2021. A convenient sampling technique was used, and the data was collected through a telephone-based survey. During the two-week study period, two of the investigators approached the vaccine recipients on the third day after receiving the vaccine and invited them to take part in the study. The investigators used the hospital telephone number to contact the vaccine recipients.

The appropriate sample size was calculated based on the general rule of having a minimum of five observations per variable, and acceptable sample size would have 10 observations per variable [25]. The survey consisted of 40 variables and hence the required sample size was 400. However, the investigators aimed to collect as many responses as possible from the vaccine recipients during the study period.

Study instrument

A telephone-based survey was used to collect data from the vaccine recipients. The survey was developed based on the previously published literature and the side effects of the vaccines announced on the websites of the World Health Organization and Centers for Disease Control and Prevention. The survey involved two sections. The first section encompassed demographic characteristics which included age, weight, height, gender, ethnicity, co-morbid conditions, and previous exposure to COVID-19 disease. The second section asked about the symptoms experienced in the first three days post-vaccination. A list of ten symptoms was provided which comprised fever, sore through, myalgia, eye muscle pain, loss of smell or taste, shortness of breath, headache, numbness, palpitation, and gastrointestinal symptoms. The participants were also asked to add any additional symptoms that they experienced and they were not mentioned in the list. Furthermore, the participants were requested to rate the severity of each symptom as mild, moderate, or severe. Two additional questions in the second section examined the onset and duration of the side effects, and the use of painkillers to monitor some conditions.

The survey underwent content validity by a physician, a clinical pharmacist, an infection control nurse from KAAUH, and an assistant professor from the College of Pharmacy, Princess Nourah University. Besides, face validity was judged by administering the survey to six vaccine recipients. The survey was piloted on 15 vaccine recipients to test the study feasibility before large-scale data collection. The final data analysis excluded the pilot study results.

Ethical considerations

This study was approved by KAUUH Institutional Review Board (IRB Log #: H-01-R-059). Participants gave their consent in an electronic form before participating in the study. Participants were informed that their participation was voluntary and they could drop out of the study at any time without any effect on their relationship with KAAUH. Additionally, subjects were assured that their identity would be confidential and the recorded information would be kept secure.

Data analysis

Data analysis was performed using Statistical Package for Social Sciences (IBM SPSS – version 24). Descriptive statistics were performed in the form of frequency and percentage. For categorical data, the Chi-square (χ2) test/ Fisher exact test was used, as appropriate, to report any associations between independent and dependent variables. Quantitative data were checked for normal distribution and compared using a t-test. The data was then presented as a mean with standard deviation. A P-value of < 0.05 was considered in this study.

Results and Discussion

Characteristics of the participants

During the study period, 528 vaccine recipients answered the survey. Participants were asked about their age, BMI, previous COVID-19 disease, and comorbidities. The results of this section are presented in (Table 1).

*Chi-square test or Fisher's Exact test were used as appropriate.

** Indicates significantly different characteristics.

Abbreviations: SD, Standard Deviation; BMI, Body Mass Index.

Side effects reported after receiving the first dose of the Oxford–AstraZeneca vaccine

Study participants were asked about the side effects they experienced during the three days post-vaccination. The findings of this part, according to age groups, are illustrated in (Table 2). Amongst all participants, the commonly experienced side effects during the first day were; myalgia (49.8%), fever (42%), and headache (40%). Less frequent side effects involved numbness (8.5%), eye muscle pain (6.3%), palpitations (4.7%), shortness of breath (4.4%), sore throat (4.2%), gastrointestinal symptoms (4.2%), and smell or taste loss (1%). No anaphylaxis or thrombotic events were reported during the study period.

 *Chi-square test or Fisher's Exact test were used as appropriate

 ** Indicates significant difference

The severity of the side effects reported after receiving the first dose of the Oxford–AstraZeneca vaccine (according to the age group)

The survey also investigated the severity of the side effects as perceived by the participants during the three days following vaccination. Responses to this inquiry are shown in (Figure 1).