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March 10, 2021
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Thyroid disease does not influence COVID-19 progression

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The risk for testing positive for COVID-19 or developing more severe disease does not differ between adults treated for hypothyroidism or hyperthyroidism and euthyroid controls, according to a Danish database analysis.

Angiotensin-converting enzyme 2, or ACE2, has been established as the COVID-19 receptor for host-cell entry, and tissue distribution of ACE2 is influenced by serum concentrations of thyroid hormones, Thomas H. Brix, MD, PhD, of the department of endocrinology at Odense University Hospital, Denmark, and colleagues wrote in correspondence published in The Lancet Diabetes & Endocrinology. Additionally, adults with hypothyroidism and hyperthyroidism have an increased burden of cardiovascular and psychiatric comorbidities, which are also reported among patients with severe COVID-19, and susceptibility to infection and course of infection might be negatively affected by thyroid dysfunction.

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“Whether these pathophysiological observations in patients with thyroid disease translate into increased risk of acquiring or a worse prognosis of SARS-CoV-2 infection is unknown,” the researchers wrote.

In a population-based, case-control study, Brix and colleagues analyzed data from all adults in Denmark who tested negative for SARS-CoV-2 (n = 2,400,609) or positive for SARS-CoV-2 (n = 28,078) between Feb. 27 and Sept. 30, 2020. Patients prescribed levothyroxine were defined as having hypothyroidism; patients prescribed antithyroid drugs were defined as having hyperthyroidism. Researchers calculated ORs for testing positive for SARS-CoV-2, comparing users of levothyroxine or antithyroid drugs with euthyroid adults. Positive COVID-19 cases were matched 1:10 with COVID-19-negative controls by age, sex and week of COVID-19 test.

In a separate cohort study, researchers analyzed data from Danish adults who tested positive for SARS-CoV-2 between Feb. 27 and Aug. 31, 2020 (n = 16,502). Researchers estimated adjusted risk ratios and risk differences for mortality, hospital stay beyond 12 hours, ICU admission, use of mechanical ventilation, and dialysis during the 30 days after a positive test.

In the case-control study, 809 (2.9%) of COVID-19-positive patients and 7,994 (2.9%) of matched COVID-19-negative patients were using levothyroxine, whereas 91 (0.3%) COVID-19-positive patients and 936 (0.3%) COVID-19-negative patients were using antithyroid drugs.

Researchers found that patients treated for hypothyroidism or hyperthyroidism did not have an increased risk for contracting COVID-19 infection, with an adjusted OR of 1.03 for those with hypothyroidism (95% CI, 0.95-1.11) and an aOR of 1.03 for those with hyperthyroidism (95% CI, 0.82-1.28).

Among COVID-19-positive patients in the separate cohort study, 572 (3.5%) were using levothyroxine and 75 (0.5%) were using antithyroid drugs. In analyses using propensity score weighting, patients prescribed levothyroxine were more likely to experience hospitalization (RR = 1.19; 95% CI, 1.02-1.4) and dialysis (RR = 2.23; 95% CI, 1.06-4.69) after COVID-19 diagnosis compared with those who were not prescribed levothyroxine. However, results did not persist in supplementary analyses extending follow-up to 60 days and taking different testing strategies into account.

There was no association between current use of antithyroid drugs and adverse outcomes of COVID-19 infection after propensity score weighting.

“These results suggest that receiving treatment for thyroid dysfunction should not affect the clinical management of the patient’s risk of acquiring SARS-CoV-2 infection or the management of patients who already contracted the infection,” the researchers wrote. “The crude analysis shows an excess risk of adverse outcomes of SARS-CoV-2 infection in patients treated for hypothyroidism and hyperthyroidism, but these associations attenuate after adjustment for comorbidity and temporal changes in the Danish SARS-CoV-2 test strategy.”