Real-world evidence of the incidence of endocrine-related disorders following COVID-19 vaccination and SARS-CoV-2 infection

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need for the rollout of vaccination programme to reduce virus transmission and alleviate disease severity. Although COVID-19 vaccinations have proven effective against infection, hospitalisation and severe diseases, concerns have emerged regarding the incidence of adverse events, including endocrine-related disorders following vaccination. Moreover, the expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor, has been discovered in the endocrine system, raising concerns about developing endocrine-related disorders following SARS-CoV-2 infection. Population-based epidemiological studies are imperative for evaluating the safety of COVID-19 vaccines, understanding the impact of SARS-CoV-2 infection, and formulating the benefit-risk profile of COVID-19 vaccines in relation to endocrine health.

To address these knowledge gaps, COVID-19 vaccination and infection records from the Department of Health (DH) and electronic medical records (EMRs) from the Hong Kong Hospital Authority (HA) were used to investigate the incidence of endocrine-related disorders, focusing mainly on diabetes mellitus, thyroid dysfunction, and major osteoporosis fracture, following COVID-19 vaccination and SARS-CoV-2 infection.

The first study evaluated the risk of new-onset diabetes following COVID-19 vaccination and SARS-CoV-2 infection, employing a cohort study design. The findings indicated an increased risk of incident diabetes following SARS-CoV-2 infection (Hazard Ratio [HR]=1.23, P < 0.001), even with the prevailing Omicron variants, albeit at a lower risk. No increase in the risk of incident diabetes was observed following COVID-19 vaccination. Instead, fully vaccinated individuals might suppress the risk of incident diabetes following SARS-CoV-2 infection. The second study assessed the risk of thyroid dysfunction in individuals vaccinated with BNT162b2 or CoronaVac. Thyroid dysfunction includes the initiation of anti-thyroid drugs or levothyroxine, hyperthyroidism, hypothyroidism, Graves' disease, and thyroiditis. Using a self-controlled case series (SCCS) design, this study found no elevated risk of thyroid dysfunction during the post-vaccination period, indicating the safety of COVID-19 vaccines for thyroid health. The third study explored the risk of incident thyroid dysfunction in the post-acute phase (the period beyond 30 days after the first positive COVID-19 test) of COVID-19. This population-based cohort study provided important reassuring data that COVID-19 is unlikely to be associated with persistent effects on thyroid function. The fourth study investigated the incidence of major osteoporotic fractures following SARS-CoV-2 infection in individuals aged 50 and older. This study found an increased risk of major osteoporotic fractures (HR=1.22, P < 0.001) and falls (HR=1.28, P < 0.001) that persisted after infection and in the following months, underscoring the lasting impact of COVID-19 on bone health in older adults.

This thesis provides real-world evidence that COVID-19 vaccines do not increase the risk of major endocrine-related disorders, supporting the safety profile of BNT162b2 or CoronaVac vaccines. Furthermore, our findings emphasize the critical role of getting fully vaccinated in protecting against incident diabetes following SARS-CoV-2 infection. Along with the noted increased risk of incident major osteoporotic fractures after SARS-CoV-2 infection, future surveillance studies are essential to ascertain the long-term risk of endocrine-related disorders following infection.