Dimitris Grammatopoulos ^* anisha paneshar Lawrence S Young Natalia Khovanova

• Warwick Medical School, Faculty of Science, Engineering and Medicine, University of Warwick, Coventry, United Kingdom

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has presented multifaceted health challenges. COVID-19 primarily targets the respiratory system but also affects multiple organs, including the endocrine system. Emerging evidence suggests interactions between thyroid function, the acute phase of COVID-19, and the prolonged symptoms known as post-covid sequalae or long-COVID. Several studies have reported that COVID-19 can induce thyroid dysfunction, leading to conditions such as thyroiditis and alterations in thyroid hormone levels. The mechanisms through which SARS-CoV-2 affects the thyroid include direct viral infection of thyroid cells, leading to viral thyroiditis, causing inflammation and transient or sustained thyroid dysfunction and excessive systemic immune response (cytokine storm). This is associated with elevated levels of cytokines such as IL-6 that disrupt thyroid function and lead to non-thyroidal illness syndrome (NTIS). Medications administered during the acute illness phase such as corticosteroids and antiviral drugs, can also impact thyroid hormone actions. The involvement of thyroid gland in long COVID, or Post-Acute Sequelae of SARS-CoV-2 infection is an area not well-defined, with potential implications for understanding and managing this condition. Persistent low-grade inflammation affecting thyroid function over time can lead to ongoing thyroiditis or exacerbate pre-existing thyroid conditions. Viral infections, including SARS-CoV-2, can trigger or worsen autoimmune thyroid diseases such as Hashimoto's thyroiditis and Graves' disease. Long COVID may disrupt the hypothalamic-pituitary-adrenal (HPA) axis, which can, in turn, affect the hypothalamic-pituitary-thyroid (HPT) axis, leading to abnormal thyroid function. This review systematically captures recent literature, around COVID-19-related thyroid dysfunction in the adult population, the prognostic consequences of thyroid dysfunction during COVID-19 and the effects of thyroid dysfunction on patients with long covid. A comprehensive search of PubMed, EMBASE, databases was conducted. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Study quality was assessed using the Critical Appraisal Skills Programme (CASP). A total of 53 studies, met the inclusion criteria. The review summarises recent findings and provides an update of the current understanding regarding thyroid dysfunction in COVID-19-related spectrum of disorders, underscoring the complex nature of SARS-CoV-2 infection and its far-reaching impacts on human health.