Abstract

COVID-19 infection originated in Wuhan, China in December 2019 and crippled human health globally in no time. The public health emergency required urgent efforts to develop and test the efficacy and safety of vaccines to combat the COVID-19 pandemic. The emergency use approval has been granted to COVID-19 vaccines before the completion of conventional phases of clinical trials. However, there is no comprehensive review of safety data reported from the vaccine trials, which is critical information to inform the policies in order to improve uptake of COVID-19 vaccines and mitigate the risk aversion perceived due to the COVID-vaccine side effects. This study aims to systematically review and synthesize the evidence on the safety data from the published COVID-19 vaccine trials. This study followed PRISMA guidelines. We searched three major electronic databases (PubMed, Embase, and Google Scholar) for published studies between Dec 2019 and 2020. Eligible study designs were randomized trials and pre-and post-intervention evaluations. Descriptive findings of included studies were reported stratified by target population, setting, outcomes, and overall results. From PubMed, Embase, WHO database, and Google Scholar screened titles and abstracts, 11 studies were identified in this review. Most of the reactions reported were mild to moderate whereas a few with severe intensity. All reactions resolved within 3–4 days. The commonly reported local adverse events were pain at the site of injection, swelling, and redness. The systemic reactions included fever, fatigue, myalgia, and headache. Some trials also reported laboratory derangements  like decreased hemoglobin, increased bilirubin, altered SGOT and SGPT. None of these alterations were clinically manifested and were self-limiting. Few clinical trials reported serious adverse events, but they were unrelated to vaccination. This systematic review indicates that COVID-19 vaccines can be safe with no serious adverse events. However, long-term post-marketing surveillance data, particularly in high-risk vulnerable populations (elderly and those with co-morbidities, pregnant women, and children) is warranted to ensure the safety of COVID-19 vaccines.Keywords: COVID-19, COVID-19 vaccine, Clinical trials, Adverse effect following immunization, Adverse drug reactions, VaccinationGo to:

Introduction

The year 2020 will be remembered in modern history as the most challenging year in terms to combat SARS CoV-2, a viral infection causing intense respiratory illness. This pandemic burdened the health professionals globally and led to unprecedented paralysis of health care systems and global economic crisis [1]. Healthcare practitioners, researchers, and policymakers around the globe were thrown a challenge to deliver adequate prevention and treatment modalities to combat the pandemic. From the initial stage of this pandemic, scientists were focused on either repurposing the existing drugs or developing vaccines against COVID-19 [2]. The public and private sectors have united together to develop and test the efficacy and safety candidate vaccines. As of January 20th, 2021, one hundred seventy-three vaccines are in preclinical development and 64 in clinical trials [3]. By January 2021, emergency approval was granted to nine vaccines by regulatory authorities in different parts of the globe [4]. The safety data were published for 11 vaccines as interim reports or clinical trial reports [5–17]. At present, it is very crucial to establish the safety of the COVID-19 vaccines when emergency approval is being granted to these vaccines without completion of all phases of clinical trials. Since vaccines are still being tested in clinical trials, there is no systematic review to our knowledge that reported the profile of COVID-19 vaccines. Therefore, the present study reflects the safety generated from the results of published clinical trials of these vaccines.Go to:

Methods

Methods

We followed PRISMA guidelines to conduct this systematic review [18].

Search Strategy

To identify the clinical trials evaluating COVID-19 vaccines, PubMed/Medline, Embase, WHO database, and Google Scholar were systematically screened for medical literature. The articles published up to Dec 22, 2020, were included. The articles were screened by using the search strategy as “(COVID-19 Vaccine)”.

Study Selection

Randomized and nonrandomized Clinical trials assessing the safety of COVID-19 vaccines were included in the study. Trial protocols, observational studies, reviews, meta-analysis, systematic reviews, and commentaries were excluded. Duplicate studies among the clinical trials and trials with different primary objectives or including other interventions other than COVID-19 vaccines were also excluded.

All studies were reviewed for eligibility by two reviewers (RK, SD). Any disagreements and technical uncertainties were discussed and resolved with the third reviewer (JC).

Data extraction

We extracted the vaccine name, type, manufacturer, study phase, number of participants, and safety data from the included clinical trials. The safety information was compared of various COVID-19 vaccines. The data were extracted by two authors (RK, SD) independently from the selected studies. The data were synthesized, disagreements were discussed, and differences were resolved between review authors (RK, SD, JC) (Fig. 1).