First long-term safety analysis of the ChAdOx1-nCoV-19 corona virus vaccine: results from a prospective observational study in priority vaccinated groups in North India

INTRODUCTION: Various vaccines for protection against COVID-19 were provided emergency approval in late 2020 to early 2021. Despite more than 1.5 years of public use, no long-term safety data has been released by any vaccine manufacturer. The main aim of this study is to provide the one-year safety results of the ChAdOx1-nCoV-19/AZD1222 vaccine. Risk factors of development of adverse events of special interest (AESIs) as well as persistent AESIs have been determined. METHODOLOGY: This was a prospective observational study conducted from February 2021 to April 2022 in a tertiary hospital of North India and its two associated centers. Health care workers, other frontline workers, and the elderly vaccinated with the ChAdOx1-nCoV-19 corona virus vaccine constituted the study population. Individuals were contacted telephonically at pre-decided intervals for one year and health issues of significant concern were recorded. Regression analysis was conducted to determine risk factors of AESI occurrence and determinants of persistent AESIs. RESULTS: Of 1650 individuals enrolled, 1520 could be assessed for outcomes of interest. COVID-19 at any time post vaccination occurred in 44.1% participants. Dengue occurred in 8% participants and was of ‘serious’ category (FDA) in 19.7% of those affected. Majority of the AESIs belonged to the MedDRA system organ class (SOC) of musculoskeletal disorders (3.7%) followed by general disorders and administration site conditions (2.1%) and infections (2%). Arthropathy in the form of knee joint involvement was the commonest individual AESI (1.7%). New onset hypertension, thyroid function abnormalities and diabetes occurred respectively in 0.9%, 0.4% and 0.3% participants. Five deaths and eleven ‘serious’ adverse events were reported. Among participants receiving booster dose of the COVID-19 vaccine (n=184), 9.8% developed adverse events of concern, of which urticaria and new onset arthropathy were common. Regression analysis showed females, individuals with pre-vaccination history of COVID-19, diabetes, hypothyroidism and arthropathy had a 1.78-, 1.55-, 1.82-, 2.47- and 3.9-times higher odds of AESI development. Females and individuals with hypothyroidism were also at 1.66- and 2.23-times higher risk of persistent AESIs. Receiving any dose of the ChAdOx1 vaccine after history of COVID-19 in the past was associated with a 1.94-times higher risk of persistence of AESIs in comparison with participants developing COVID-19 after their vaccine dose. Compared to individuals with no history of COVID-19, individuals receiving vaccine after COVID-19 were at 2.85 times higher risk of persistence of AESIs. No association of AESI was observed with any post vaccination COVID-19. CONCLUSION: COVID-19 occurred in close to half of the participants receiving ChAdOx1-nCoV-19 vaccine, over the follow-up period, and mostly within 3 months of complete vaccination. Vigilance is warranted for AESIs such as musculoskeletal disorders and severity of non-COVID-19 infections such as dengue. Individuals receiving COVID-19 vaccine after any natural SARS-CoV-2 infection were at increased risk of development as well as persistence of AESIs. Future studies with larger sample size and involving unvaccinated arm are required to give a concise and comparative data of vaccine safety. Sex- and hormonal differences in the occurrence of atypical adverse events should be explored as potential areas of future research. These data may be helpful in the development of safer and effective vaccines for future outbreaks.