In December 2019, Wuhan City, China, experienced an outbreak of COVID-19 caused by SARS-CoV-2. The World Health Organization declared it a public health emergency. Over 16,000 deaths and 2.8 million new cases occurred in 28 days, with 764 million confirmed cases and 6.9 million fatalities.1,2

Ensure reliable diagnostic laboratory operations, avoid cross-contamination, and follow proper laboratory practices and guidelines. Maintain unidirectional workflow and follow the aseptic technique in each step to prevent cross-contamination and ensure proper handling of biological specimens.3

COVID-19 patients typically experience mild-to-moderate respiratory illness and recover without therapy. Serious diseases are more common in older individuals and those with underlying medical disorders.4

COVID-19 causes respiratory symptoms like fever, coughing, and shortness of breath, potentially leading to pneumonia, severe acute respiratory syndrome, and death.5 Preventing spread involves hand hygiene, covering the nose and mouth, and avoiding close contact with those with fever and cough.6 COVID-19 is a mysterious infection requiring extensive study and collaboration for containment, prevention, and treatment.7 A safe and effective vaccine is crucial for addressing the pandemic.8

Saudi Arabia has experienced 475,500 COVID-19 cases and 7000 fatalities.9 The country has implemented preventive measures, including banning international flights, closing mosques, schools, and universities, and implementing a reliable vaccine program to mitigate the impact of disease.10,11

The Saudi Arabian Food and Drug Authority approved four COVID-19 vaccines, including Pfizer-BioNTech, Oxford-AstraZeneca, Johnson & Johnson, and Moderna, nationwide. The program began in December 2021 and has immunized around 16 million people.12–14 Vaccine campaign targeted high-risk groups, including the elderly and healthcare professionals.15 Saudi Arabia initiates early immunization drive to combat COVID-19.10,16

Saudi Arabia Food and Drug Authority approved four COVID-19 vaccines, but differences in vaccination effectiveness may be due to faster development and mRNA vaccines, a new technology.17–19 Saudi Arabia’s Ministry of Health combines multiple COVID-19 vaccines amid scarcity.20 Accordingly, the study assesses post-vaccination side effects of mixed and matched COVID-19 vaccines in Makkah, Saudi Arabia, focusing on prominent adverse effects.


Study Design and Period

This observational cross-sectional study was conducted between June 29, 2021, and August 11, 2021.

Study Setting

The study was conducted at King Abdullah Medical City Specialist Hospital, ‏Al Ukayshiyyah, and Umm Al-Qura University vaccination centers in Al-Abdiyah, Makkah, Saudi Arabia.

Study Participants

The study included 805 participants aged 12–87 from Saudi Arabia who received COVID-19 vaccinations at King Abdullah Medical City Specialist Hospital, Al Ukayshiyyah, and Umm Al-Qura University. Pregnant, lactating women and serious illness participants were excluded.

Study Sampling

The study involved 805 participants from King Abdullah Medical City Specialist Hospital, Al Ukayshiyyah, and Umm Al-Qura University vaccination centers in Al-Abdiyah, Makkah, Saudi Arabia, with a response rate of 89.4%.

Data Collection

Interview Based Questionnaire

The study used an interview-based questionnaire to gather demographic data, medical history, and post-COVID-19 symptoms. The questionnaire’s face and content validity were independently validated by seven experts.21 The pilot study involved 30 participants, with a Cronbach’s alpha of 0.85. Participants received COVID-19 vaccines, were informed of study purposes, and were given communication methods like Call, WhatsApp, or Telegram. Study participants were contacted via a preferred method to discuss post-COVID-19 vaccine symptoms. Results were shared on the first, seventh, and twenty-eighth days of receiving the first- and second-dose vaccines (Figure 1).

Figure 1 Schematic diagram of the recruitment plan of the study participants.

The study used a census sampling method to reduce bias and ensure qualified data collectors conducted data collection. The independent variable was COVID-19 vaccination, while the dependent variables were visible symptoms associated with the vaccine and other factors.

Assessment of Anthropometric Measurements

A measuring rod attached to a balanced beam scale was used to measure each participant’s height (in centimeters) after receiving the first dose of the COVID-19 vaccination. Participants were asked to stand barefoot with their heads up. A standard scale (Seca) was used to measure weight (kg). Participants were requested to remove their bulky outerwear before stepping on the scale, and weight was recorded to the nearest 0.1 kg. By dividing a person’s weight in kilograms by their height in square meters, the body mass index (BMI) was determined.22

Data Analysis

SPSS for Windows (version 25), a statistical program for social science, was used for data analysis. Descriptive statistics were used to characterize both continuous and categorical data. The significance of the differences between category variables was determined using the chi-square test. The differences between the mean were tested by independent samples t-test. Furthermore, crude and adjusted odds ratio (OR) and 95% confidence interval (CI) for the most visible symptoms among the study participants after the COVID-19 vaccine by gender were calculated using binary logistic regression.

Ethics Considerations

The study protocol, which complies with the Declaration of Helsinki (HAPO-02-K-012-2021-08-713), was approved by the College of Medicine at Umm Al Qura University.

Additionally, permission was obtained from the vaccination facilities at King Abdullah Medical City Specialty Hospital, Al Ukayshiyyah, and Umm Al-Qura University. Participants under 18 further provided informed consent signed by a parent or legal guardian. In addition, written informed consent was obtained from each participant.


Eight hundred and five individuals with a mean age of 25.20 ± 15.5 years who lived in Makah and received the COVID-19 vaccine participated in this study. 33.9% of the study participants were from the King Abdullah Medical City Specialist Hospital vaccination center, 32.9% were from the Al Ukayshiyyah vaccination center, and 33.1% were from the Umm Al-Qura University vaccination center. Only 2.2% (n = 18) of them are allergic to the COVID-19 vaccine. 9.6% of the study participants were smokers. More than two-third of the study participants (75.0%) were Saudi. 14.8% of them were classified as underweight (BMI below 18.5 kg/m2), 13.9% were classified as Overweight (BMI 25.0–29.9 kg/m2), and 13.9% were classified as obese (BMI > 30.0kg/m2). Significant statistical associations were found between males and females in smoking status, age, and body mass index (P-value < 0.05) (Table 1).

Table 1 Characteristics of the Study Population by Gender

The medical history of the study participants showed that only 4.2% use anticoagulant drugs, 2.9% use corticosteroid therapy, and 1.0% use immunosuppressive drugs. No participants use cancer treatments or have a history of AIDs. 6.8% of the study participants suffered from hypertension, 5.8% from respiratory diseases, and 0.7% from cancer.

61.7% (n = 497) and 38.3 (n = 308) of the study participants received one and two doses of COVID-19 vaccine, respectively. 87.1% and 12.9% of the study participant received Pfizer-BioNTech, and Oxford/AstraZeneca COVID-19 vaccines for the first dose, respectively. 29.3%, 8.3%, and 0.6% of the study participants received Pfizer-BioNTech, Oxford/AstraZeneca, and Johnson and Johnson COVID-19 vaccine for the second dose, respectively. 25.3% of the study participants were infected with COVID-19; 23% were infected before the first dose, and only 1.6% were infected after the first dose.

Significant statistical associations were found between males and females in having diabetes mellitus, type of COVID-19 vaccine for the first dose, and type of COVID-19 vaccine for the second dose (P-value < 0.05) (Table 2).

Table 2 Medical History Variables for the Study Population by Gender

Table 3 shows the most visible symptoms among the study population after the COVID-19 vaccine by gender. The results revealed that 24.1% of the study participants experienced swelling, redness, or pain at the injection site after the COVID-19 vaccine, followed by headache (14.5%) and exhaustion (14.2%). In addition, 10.6% experienced an increase in body temperature above 36.5 °C, 9.8% experienced muscle or joint pain, 6.2% of the study participants had dizziness, and 7.7% had insomnia. Only 0.9% of the study participants experienced gastritis, 2.0% experienced nausea, 0.4% experienced loss of consciousness, 1.6% experienced shortness of breath or difficulty breathing, 1.0% experienced ringing in the ear, 1.7 experienced harshnesses, 0.5% experienced blood clots, and 2.4% experienced other symptoms.

Table 3 The Most Visible Symptoms Among the Study Population After the COVID-19 Vaccine by Gender

Symptoms such as diarrhea, epileptic seizures, swollen lymph nodes, irritability, and admission to intensive care were not reported. Significant statistical associations were found between males and females in the symptoms of muscle or joint pain, headache, dizziness, and nausea (P-value < 0.05) (Table 3).

Finally, the binary logistic regression was employed to calculate the crude and adjusted OR and 95% CI for the most visible symptoms among the study population after the COVID-19 vaccine by gender (Table 4). The findings showed that, after adjusting for confounding factors, the male participants had lower odds of having swelling, redness, or pain at the injection site, muscle or joint pain, headache, dizziness, and nausea compared to female participants [OR = 0.596, 95% CI = (0.388–0.916)], [OR = 0.272, 95% CI = (0.149–0.495)], [OR = 0.529, 95% CI = (0.338–0.828)], [OR = 0.263, 95% CI = (0.125–0.554)], and [OR = 0.145, 95% CI = (0.31–0.679), P < 0.05 for all], respectively.

Table 4 Crude and Adjusted Odds Ratio and 95% Confidence Interval for the Most Visible Symptoms Among the Study Population After COVID-19 Vaccine by Gender


The COVID-19 pandemic began in 2020; nations prioritize preventative measures for safe and effective vaccinations 10. Vaccine candidates were created concurrently; only a few were granted Emergency Use Authorization (EUA).23

Saudi Arabia initiates early COVID-19 vaccination campaign as part of efforts.23,24 Saudi Arabia’s population’s willingness to receive the COVID-19 vaccine varies due to rapid development and mRNA vaccines, which may factor in the difference.17,18,25,26

Recent publications highlight potential severe post-vaccination side effects due to key variables.24,26

This study assessed short-term adverse effects and symptoms of COVID-19 vaccines in Saudi Arabia, focusing on individuals receiving Pfizer-BioNTech, Oxford/AstraZeneca, and Johnson and Johnson vaccinations. Results showed 60% to 80% of side effects influenced by age, vaccine type, and dose.27,28

The study found frequent side effects and symptoms after COVID-19 vaccines, including fatigue (14.2%), headache (14.5%), and swelling (24.1%). These symptoms occurred on the first, seventh, or twenty-eighth days, mainly for those receiving double dosage.27–30

Menni et al report soreness and local pain as common adverse effects after injections.31 70–80% of Saudi Arabian trial participants experienced injection site pain.32 The study finds younger participants experiencing fatigue and headaches, contrasting previous research, mainly due to their younger ages.31,32 Research shows younger people experience more side effects.27,33

Alhazmi et al study show that 60% of respondents experienced adverse effects from COVID-19 vaccines, including weariness and soreness.29

The study finds that female participants in Makkah, Saudi Arabia, have a higher risk of visible COVID-19 symptoms than males, consistent with previous research.29,31 Adam et al found males more likely to experience adverse effects after COVID-19 vaccination.30 The study suggests lower male percentages may cause increased side effects in females, including injection site reactions, fatigue, headache, muscle pain, chills, and nausea.

The study found that 87.1% and 12.9% of participants received Pfizer-BioNTech and Oxford/AstraZeneca COVID-19 vaccines, respectively. The second dose had a higher risk of systemic side effects.34 Future studies are needed to confirm Saudi Arabian findings.

Mild-to-moderate COVID-19 vaccination side effects were reported.27–29,31,32 The study found non-life-threatening COVID-19 vaccine side effects, with 25.3% infected, 23% infected before, and 1.6% after. Age, sex, serostatus, and comorbidities may influence vaccine half-life.35–37

Concerns about mRNA vaccines spreading COVID-19 are unfounded as they were not created using live COVID-19. Insufficient time for T- and B-lymphocyte production after immunization allows for “breakthrough cases” and potential infection.38,39

Research on COVID-19 vaccine adverse effects may increase public trust in vaccine safety, potentially hastening immunization. Addressing vaccine hesitancy through friendly organizations and government-induced policy measures could shift public disbelief to confidence.40 The study reveals women’s gender decreases vaccine hesitancy, while older age, education, and adherence to prevention increase it.41 The study found no serious health issues and raised awareness of COVID-19 vaccine benefits and safety. It dispelled misconceptions about post-vaccination effects and recommended future studies on booster shots. Long-term health care and strategic financial planning are top priorities in many nations.42

This study evaluates visible symptoms of COVID-19 vaccines in Makkah, Saudi Arabia, following participants for the first, seventh, and 28th days. Although it is the first in Saudi Arabia to discuss side effects and symptoms, its cross-sectional design limits generalizability. Additionally, many participants did not receive the second dose, and the predominant circulating variant of COVID-19 did not report during the study period, potentially affecting vaccine efficacy and severity.


The study assessed COVID-19 vaccine-related symptoms in Makkah, Saudi Arabia, revealing common side effects like pain, edema, redness, fatigue, and headache. Female participants were more likely to experience these symptoms. A larger population study is needed to evaluate vaccine effectiveness and long-term side effects.


The authors report no conflicts of interest in this work.


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