Side Effects and Immunogenicity Following Administration of The Sputnik V COVID-19 Vaccine Among Health Care Workers; An Observational Study in Iran


 The Sputnik V COVID-19 vaccine, have shown excellent safety and efficacy against COVID-19 in phase 3 of the clinical trial. We provided independent evidence on side effects and immunogenicity following the administration of the Sputnik V COVID-19 in Iran. In this observational study, the healthcare workers who vaccinated with the Sputnik V COVID-19 vaccine within February and April 2021 were evaluated. Among a total of 13435 vaccinated healthcare workers, we received 3236 self-declaration reports of Sputnik V associated adverse events with the mean age 39.32±10.19 years old which 38.8% were men and 61.2% were women. The most common side effect was a pain in the injection site (56.9%), fatigue (50.9%), body pain (43.9%), headache (35.7%), fever (32.9%), joint pain (30.3%), chilling (29.8%) and drowsiness (20.3%). Side effects of the vaccine were significantly more frequent in females and younger individuals. Among a total of 238 participants, more than 90% after the first and second dose of vaccine had a detectable level of SARS-CoV-2 RBD antibody and SARS-CoV-2 neutralizing antibody. Although the overall the rate of adverse effects was higher than the interim results from randomized controlled trials, our findings support the manufacturer’s reports about the high humoral immunogenicity of vaccine against COVID-19.


Introduction
The COVID-19 pandemic has resulted in more than 180,654,652 confirmed cases and more than with an important idea to boost the effectiveness of the vaccine, which successfully completed the first and second clinical trial phases. The vaccine is stored and distributed at -18°C, but storage at 2-8°C, has a favorable temperature profile for global distribution 2 . As of February 2021, twenty-one countries have authorized Sputnik V emergency use and more than one billion doses of the vaccine have been ordered for immediate worldwide distribution. Although based on preliminary results published in the clinical stages of the vaccine trial, Sputnik V manufacturers claim that the vaccine is highly immunogenic and has no side effects, it is necessary to evaluate the possible side effects and measure the immunogenicity of this vaccine. The aim of this study is to determine the humoral immunogenicity and possible side effects of the Sputnik V vaccine in the health care workers of Mazandaran University of Medical Sciences as the first group to receiving COVID-19 vaccines in Iran. This study will provide reassurance information regarding what vaccine recipients might expect after vaccination.

Study design, participants and evaluation of vaccine side effects
This observational (survey-based) and cohort study was performed at the Mazandaran University of Medical Sciences, between February 2021 and April 2021. The Strengthening the Reporting of Observational Studies in Epidemiology guideline (STROBE) was followed 4   were used according to the manufacturer's instructions. The titer of IgG to RBD of SARS-CoV-2 virus was measured on days 21 and day 42 after the first dose vaccination. To detect SARS-CoV-2 neutralizing antibodies, the competitive method based on quantitative inhibition of RBD and ACE2 binding, which has the ability to identify all classes of human antibodies that neutralize SARS-CoV-2 virus performed and the human neutralizing antibody was used as the standard. The titer of neutralizing antibodies was measured on day 42 after the first dose vaccination. The manufacturer-reported sensitivity and specificity were respectively, 97.1% and 100% for the SARS-CoV-2 Anti-RBD IgG kit and the accuracy of the SARS-CoV-2 Neutralizing Ab kit was 99.52%.

Statistical analysis
Data were analyzed using the SPSS package (version 24.0; Windows). Descriptive analyses used frequency and percentage based on the non-missing sample size. Differences between groups were determined by the chi-square test or Fisher's exact test with P < 0.05 considered statistically significant.

Results
During February-April 2021, a total of 13435 healthcare workers affiliated to Mazandaran University of medical sciences vaccinated by Sputnik V COVID-19 vaccine. We received 3236 self-declaration reports of Sputnik V associated adverse events during this period. The mean age of vaccine recipients who submitted for adverse events were 39.32±10.19, and it ranged between 19 and 78 years old with a median of 38 years old; 38.8% were men and 61.2%were women (Table1). infection, however, some systemic side effect such as fever, headache, and joint pain were significantly less common in the participants with previous COVID-19 infection (P<0.05)( Table   3). The onset and duration of vaccine side effects after the first and second dose is illustrated in    The numbers in the bars are in percentage.

The vaccine side effects and the Immunogenicity of the Sputnik V COVID-19 vaccine among high-risk occupational groups in the Razi teaching hospital
Participants in the Razi teaching hospital with average age 37.

Discussion
In this study in Iran, we have investigated side effects and immunogenicity following the administration of the Sputnik V COVID-19 vaccine in healthcare workers. The first evidence of safety and efficacy of the Sputnik V COVID-19 vaccine was obtained from a randomized infection 10,11 . Our study has some drawbacks. The first drawback of this study is due to the survey-based strategy that may lead to self-selection bias when perhaps only the highly motivated participants filled in the questionnaire. However all the studied populations were healthcare workers who have a high level of medical expertise, the self-reporting nature of the collected data, can make information bias and can jeopardize its reliability during clinical evaluation. To the best of our knowledge, this study was the first large sample size observational study dealing with the Sputnik V vaccine side effects, and the first designed study evaluating the vaccine side effects among the Iranian population. In conclusion, side effects of the Sputnik V vaccine are more frequent in female and younger individuals and these adverse effects are frequently started within 24 hours after vaccination and will resolve in less than three days.
Moreover, our findings support interim results from randomized controlled trials showing evidence of high humoral immunogenicity against COVID-19 after receiving the Sputnik V vaccine.