The SARS-CoV-2 pandemic continues to spread worldwide, following its first emergence in December 2019. The virus induces coronavirus disease (COVID-19) that might be asymptomatic or mild in the majority of patients; however, 20% of infected patients are prone to develop severe to serious diseases with fatal consequences (1). Old age, gender, asthma, hypertension, and other cardiovascular diseases are among the risk factors of COVID-19 (2–4).

Vaccination is the most successful way to prevent the spread of many life-threatening infectious diseases. Thanks to vaccines, millions of lives are saved annually against more than 20 infectious diseases. Some countries have implemented local legislations for COVID-19 obligatory vaccination for access to private and governmental public sectors, making it mandatory for travelers prior to entry into such countries. Despite the significant number of vaccinated individuals worldwide, many people around the world are reluctant to get vaccinated against COVID-19. This fact could be due to the widespread rumors regarding the panic from the side effects that have led to a lack of trust in COVID-19 vaccines.

Starting from December 2020, many SARS-CoV-2 vaccines have been released for emergency use, including spike- gene RNA–vaccines encapsulated in lipid nanoparticles, such as BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna); chimpanzee adenovirus vector vaccine harboring SARS-CoV-2 S gene (ChAdOx1- AstraZeneca), human adenovirus 26 (Ad26.COV2.S-Johnson & Johnson/Janssen), and inactivated SARS-CoV-2 vaccines (Sinopharm and Sinovac). Saudi Arabia approved BNT162b2 then ChAdOx1 for use in the vaccination protocol on 10 December 2020, and 18 February 2021, respectively. Both vaccines have proven to be safe and efficacious as evidenced by the results of clinical trials (5, 6). There is a need of up to 14 billion doses of COVID-19 vaccines to cover 70% of global coverage (7). This fact results in the recommendation of the WHO to temporary halt of giving the second dose of COVID-19 vaccine, with the aim of covering more unvaccinated people worldwide (8).

Pain, redness, swelling, fever, tiredness, headache, muscle pain, chills, and nausea are among the common side effects of the vaccines (9). Most of such side effects disappear within 2 days after vaccination (9). Other rare side effects, including vesicolous-bullous skin (10), herpes simplex or varicella zoster reactivation (11–13), nephrotic syndrome and acute kidney injury (14) were also reported. Meanwhile, serious post-vaccinal reactions, including intravascular thrombosis and thrombocytopenia are associated with both ChAdOx1 and the BNT162b2 vaccines; however, the frequency was 5-fold higher in ChAdOx1 than in BNT162b2 (15). It was found that the ChAdOx1 vaccine but not BNT162b2 enhances the production of anti-platelet factor 4 antibodies (15, 16). Accordingly, some countries in Europe suspended the use of the ChAdOx1 vaccine. However, KSA and other European countries decided to continue using the vaccine according to the WHO recommendation that benefits of using ChAdOx1 vaccine outweigh its risks (17).

On the other hand, anaphylaxis reaction has been reported among BNT162b2 vaccinees in an approximate rate of 1:200,000. Such reaction was most probably induced by the polyethylene glycol (PEG 2000 Da) (18). Interestingly ChAdOx1 vaccine contains polysorbate 80, a derivative of the PEG, which is used in a similar concentration in many vaccines including DTaP, HB vaccine, HPV, and influenza vaccines (19). The relatively lower molecular weight of the polysorbate 80 (1310 Da) in comparison to PEG (2000 Da) and the fact that polysorbate 80 is being used in many vaccines, monoclonal antibodies, and most of the injectable biological reagents for many decades alleviates its role as a possible trigger of anaphylaxis (18, 19).

SARS-CoV-2 vaccines are successful in reducing the severity of the disease, hospitalization, and mortality (20). The safety of SARS-CoV-2 vaccines has been successfully and carefully monitored prior to their authorization. However, the tracking of side effects that were not detected during clinical trials is still needed. The current study aimed to screen the incidence of local, systemic, and allergic reactions following SARS-CoV-2 vaccination. We also intended to screen possible factors that may affect the incidence and severity of post-vaccinal reactions, including previous COVID-19 infection, age, sex, and other immunocompromising conditions.

In this study, the majority of respondents were 20–30 years old for both BNT162b2 and ChAdOx1. Considerable adverse side effects among respondents under 50 years of age, were reported. Previous studies support our findings as they showed that a higher rate of post-vaccinal side effects occurred among young subjects (23–25).

Subjects who suffered from chronic diseases are assumed to possess a weakened responsiveness to immunogens and hence are assumed to experience reduced side effects following vaccines (26, 27). In this study, chronic diseases were found to show significant correlation to the development of post-vaccinal adverse effects. However, no published information is available regarding these clusters of patients and their responsiveness or side effects following different COVID-19 vaccinations.

Subjects who previously experienced COVID-19 infection were reported to develop more severe side effects after vaccination (28). However, in our study, we did not find a considerable correlation between previous SARS-CoV-2 infection and the severity of post-vaccinal side effects.

In this study, the female gender was also associated with development of moderate and severe post-vaccinal adverse effects, showing a positive correlation of gender to the severity of the post-vaccinal side effects. This finding also agrees with other findings and confirms that the development of post-vaccinal side effects were significantly higher in females than in males (23, 24, 29). However, it disagrees with a recent study (30) that reported that males developed more severe post-vaccinal reactions in comparison to females.

In general, ChAdOx1 showed a highly significant increase in the severity and duration of systemic post-vaccinal reactions than BNT162b2. Meanwhile, the side effects of BNT162b2 after the second dose were more severe than that reported after the first dose of the vaccine. In this respect, our findings agree with other studies that reported similar findings (24, 31, 32).

The most common side effect was local pain after vaccine injection: 80.27% and 85.85% for BNT162b2 and ChAdOx1, respectively. This finding agrees with the data of phase 2/3 clincal trial that reported 88% pain at the site of injection following vaccination with ChAdOx1 (25), in individuals 18–55 of age and it reached >80% in individuals (≥16 years old) vaccinated with BNT162b2 (23). Similarly, the detected fatigue, muscle and joint pain following BNT162b2 and ChAdOx1 vaccinations matched what was reported previously (23, 25).

In the USA, many neurological side effects were reported (33, 34). In the current study, signs of transient central nervous system affections ranged from 14.1 to 29.5% of the reported side effects. They included impaired concentration, insomnia, and dizziness. These affections were reported in a significantly higher frequency in ChAdOx1 as compared to BNT162b2. Similarly, their frequencies were higher after the second dose of BNT162b2, in comparison to those after the first dose. Meanwhile, rare solitary neurological signs, including anxiety, depression, sleepiness, mood disturbance, numbness of face, pain in the ear, and tinnitus were also detected in the current study. Our finding agrees with previous reports of rare reports of tremor, diplopia, dysphonia, seizures, tinnitus, herpes reactivation, facial palsy, transverse myelitis, and acute disseminated encephalomyelitis detected in the USA following COVID-19 vaccination (33, 34).

Palpitation was not previously reported among the side effects of COVID-19 vaccination; however, a case report of postural orthostatic tachycardia syndrome was recently reported following BNT162b2 vaccination (35). Interestingly, in the current study, palpitation was reported with high frequency after COVID-19 vaccination: 7.42% and 17.14% for BNT162b2 and ChAdOx1, respectively. Similarly, the signs were reported more frequently in vaccinees after the second dose (13.22%) in comparison to the first dose (4.17%) for BNT162b2. In addition, chest pain and breathlessness were also reported in this study with ChAdOx1 and to a lower frequency among BNT162b2 vaccinees. In April 2021, the Vaccine Adverse Event Reporting System (VAERS) detected more than 1,000 cases reporting myocarditis and pericarditis following mRNA vaccination (36). Palpitation was also reported in another study in Saudi Arabia in 7(0.4%) subjects following vaccination with ChAdOx1 (30) and in South Korea in 28.3% and 4.3% of ChAdOx1 and NT162b2 vaccinees, respectively (37).

Diarrhea and abdominal pain were recorded in respondents vaccinated with ChAdOx1. The percentages of such side effects were significantly higher than those reported for BNT162b2. The latter showed a higher frequency of complaints after the second dose in comparison to the first dose. A meta-analysis study reported similar side effects for both BNT162b2 and ChAdOx1 (38).

Menstrual disturbance, including excessive hemorrhage and irregular menstrual cycle were reported after the administration of BNT162b2 (643 cases) and ChAdOx1 (315 cases) (39). In contrast, in this study, irregular menstrual cycle was reported in 18 cases vaccinated with BNT162b2 (0.69%) and only 7 cases (0.45%) vaccinated with ChAdOx1.Thrombocytopenia and underlying platelets disorders, or possible hormonal disturbance may explain excessive menstrual bleeding. More investigations are needed to determine the link between COVID-19 vaccination and the menstrual irregularities (40, 41).

In conclusion, both vaccines induce transient side effects that ranged from mild to severe. ChAdOx1 induced more severe side effects than BNT162b2. The latter vaccine induces more severe adverse effects after the second dose of the vaccine. High frequency of palpitation was reported following vaccination. All the reported side effects are tolerable. Women are more prone to developing more severe side effects and for longer durations. Palpitation is among the common systemic side effects that appear following vaccination of both vaccines.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.

The studies involving human participants were reviewed and approved by Taif University Ethical Committee with approval No. 42-169 on 3/05/2021.

ASA, ANA, MA, and DA collected, curated, analyzed the data, and wrote the first draft of the manuscript. AA-M conceptualized the study, verified the results, and critically revise the manuscript. All authors reviewed and edited revisions of the manuscript.

This work was funded by Taif University Deanship of Scientific Research (Project No. 1-441-41).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.