Abstract

Background: Vaccine acceptance in countries throughout the world is primarily explained by personal protection. However, the distress regarding side effects and due to myths, and misconceptions become a hurdle for vaccination drives. Therefore, we aimed at conducting a systematic review of adverse effects following COVID-19 vaccination. Methods: A systematic review was conducted using databases - PubMed, PubMed Central (PMC), and WHO Global Research COVID-19 databases by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used the Medical Subject Headings (MeSH) terms COVID-19 vaccines and adverse effects. All papers from January 2020 to June 2021 are considered for review and only peer-reviewed full-text articles in English languages were included. Results: Of the total 24 studies included in the final analysis, 10 (41%) were cross-sectional studies, and 9 (37%) were case reports. Out of 24 studies, 7 are from European countries, 4 each from India and USA. The most common side effects reported were pain at the injection site, fever, fatigue, and headache. Incidence and severity of adverse effects were more after receiving mRNA-based COVID-19 vaccines when compared to other COVID-19 Vaccines. Conclusion: The majority of adverse effects were local, which included pain at the site of injection, swelling, and redness, and limited systemic reactions including fever, fatigue, and headache were observed. Our results suggest that COVID-19 vaccines were safe and tolerant. Further clinical studies regarding long-term effects and in-depth analysis must be performed to improve the understanding of COVID-19 vaccine adverse effects.

1. Introduction

Coronavirus Disease-19 (COVID-19) is continuing to have a devastating impact on the healthcare of global countries and since the emergence of the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), it has been mutating incessantly. The emerging variants are more transmissible and potentially virulent making it hard to control the spread of infection ^{1, 2}. The situation became more adverse during the second wave in India, where the scarcity of resources contributed to a further increase in mortality ³. To allay the impact of this current pandemic, the development of an effective and efficient vaccine has become a prime necessity, in addition to maintaining social distancing and compliance with face masks ⁴.

However, vaccine acceptance in most countries is primarily affected by the people’s perception of the side effects. This is majorly attributed to the myths and misconceptions among people that resulted in hurdles for vaccination drives ^{5, 6}. Trust in vaccines and the company’s manufacturing them are also the key determinants of the success of any vaccination campaign.

We therefore aimed to conduct a detailed and updated systematic review of adverse effects following COVID-19 vaccination to guide the clinical care and practice of COVID-19 disease.

2. Methodology

A systematic review was performed using PubMed, PubMed Central (PMC), and WHO Global Research COVID-19 Databases by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used the Medical Subject Headings (MeSH) terms COVID-19 vaccines and adverse effects.

All papers from January 2020 to June 2021 are considered for review and only peer-reviewed full-text articles in English were included. Pre-prints, Abstracts papers, grey literature, duplicate articles, and articles other than English language articles were excluded. The screening and depiction of records using PRISMA guidelines were represented in [Figure 1].

3. Results

A total of 24 studies were included in the final results after careful screening using PRISMA guidelines [Figure 1]. Among 24 studies, 10 (41%) were cross-sectional studies, 9 (37%) were case reports, 3 (12%) were case series, and 1 (4%) each were cohort and retrospective studies [Figure 2]. Of the studies included, a total of 9,30,301 participants were involved in the final analysis. A detailed description of 24 studies [7-30] is represented in [Table 1]. Out of the 24 studies, 7 were from European countries, and 4 each were from India and USA.ChAdOx1 nCoV-19 vaccine was used in eleven (11) studies, and the Pfizer BioNTech (BNT162b2) COVID-19 vaccine was used in nine (9) studies. In six (6) studies, healthcare workers were the study population and among eight (8) studies, the female study population was dominant. Among case reports, most of the adverse events were reported in women and older age people. The severe adverse effects were meager in number among the observational studies. The majority of the study participants experienced at least one adverse effect following COVID-19 vaccination. The most common side effects reported were pain at the injection site, fever, fatigue, and headache. Incidence and severity of adverse effects were more after receiving mRNA-based COVID-19 vaccines as compared to other COVID-19 vaccines.

4. Discussion

The present study systematically reviewed various reports available globally concerning the vaccine side effects among individuals after receiving COVID-19 vaccines. Although most of the studies have reported mild adverse reactions only, some studies have shown severe reactions due to COVID-19 vaccination that were life-threatening. The common side effects that were reported in most of the study subjects included injection site pain, fever, fatigue, headache, and muscle ache, among others. However, in a study by Reddy S et al, a 42-year-old patient developed postural orthostatic tachycardia syndrome in association with the mRNA vaccine ¹⁰. In a few cases, Bell's palsy and Guillain barre syndrome were also observed and thus causing life-threatening adverse reactions ^{26, 30}. Vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) is also one of the major adverse effects associated with COVID-19 vaccines ³¹. A few patients also developed systemic adverse reactions like axillary and pectoral lymphadenopathy, generalized blisters, and thromboembolism. The hospital admission rates were less than 1% but as high as 91% of study subjects have shown one of the following adverse reactions after receiving the COVID-19 vaccine.

Although there are several therapeutic strategies to combat COVID-19, vaccines are the key to controlling and reducing the global burden of COVID-19 disease ^{32, 33, 34}. Currently, there are 10 approved COVID-19 vaccines by the World Health Organization (WHO), the list includes Spike vax (Moderna), and Ad26.COV2.S (Janssen), BNT162b2 (Pfizer/BioNTech), Covishield (Oxford/ AstraZeneca formulation), Covaxin, Covilo, CoronaVac, Nuvaxovid, COVOVAX, and Vaxzevria ³⁵. The Vaccination proved that it reduces the severity of the COVID-19 disease and prevents or decreases hospitalization ³⁶. Post COVID-19 complications and severity of COVID-19 were reported less among vaccinated people than in unvaccinated people ^{37, 38, 39, 40}.

The COVID-19 vaccines have been playing a key role in combating the SARS-CoV-2 pandemic. Almost all COVID-19 vaccines are found reasonably effective against emerging SARS-CoV-2 variants and provided the necessary immunity that essentially minimized the severity of infection, hospital admissions, and Intensive Care (ICU) treatments. A booster dose appears to be needed to combat the emerging variants. Nevertheless, vaccine equity should be maintained by ensuring equal distribution of vaccines which further prevents the emergence of new variants. The hesitancy to take COVID-19 vaccines must be handled by educating the public regarding the safety and efficacy of currently available COVID-19 vaccines.

5. Conclusion

The majority of adverse effects were local, which included pain at the site of injection, swelling, and redness, and limited systemic reactions including fever, fatigue, and headache were observed. Adverse effects were more common after the 1st dose of vaccination and were milder. mRNA vaccines led to more local reactions and fewer systemic side effects when compared to other vaccines. Therefore, our analysis suggests that COVID-19 vaccines were safe and tolerant, and further clinical studies regarding long-term effects and in-depth analysis must be performed to get a clear understanding of COVID-19 vaccine adverse effects.

References