COVID-19 and Thyroid Function: A Bi-Directional Two-Sample Mendelian Randomization Study.

Area of Science:

• Endocrinology
• Infectious Diseases
• Genetics

Background:

• Thyroid dysfunction is observed in COVID-19 patients, but the causal relationship remains unclear.
• Investigating a bidirectional link between COVID-19 and thyroid health is crucial for understanding disease mechanisms and patient outcomes.

Purpose of the Study:

• To examine the bidirectional causal relationship between genetic liability to COVID-19 phenotypes and thyroid dysfunction traits.
• To determine if SARS-CoV-2 infection or its severity influences thyroid dysfunction, or vice versa.

Main Methods:

• Utilized a two-sample Mendelian randomization (MR) approach with summary statistics from large genome-wide association studies.
• Analyzed host genetic liability for SARS-CoV-2 infection, hospitalized, and severe COVID-19 against hyperthyroidism, hypothyroidism, autoimmune thyroid disease, and thyroid hormone levels (TSH, fT4).
• Employed inverse-variance weighted (IVW) as the primary MR method, with weighted median, contamination mixture, MR-Egger, and MR-PRESSO for sensitivity analyses.

Main Results:

• Host genetic susceptibility to SARS-CoV-2 infection showed a causal association with an increased risk of hypothyroidism (OR=1.335, p=2.4×10⁻⁵).
• Sensitivity analyses confirmed this association, with consistent causal estimates across different MR methods.
• No significant causal associations were found between genetic liability to hospitalized or severe COVID-19 and thyroid dysfunction, nor in the reverse direction (thyroid dysfunction influencing COVID-19 risk).

Conclusions:

• This study provides evidence supporting a causal role of the host response to SARS-CoV-2 infection in increasing the risk of hypothyroidism.
• Long-term follow-up studies are recommended to confirm the observed increased risk of hypothyroidism post-SARS-CoV-2 infection.