Association of hypothyroidism with outcomes in hospitalized adults with COVID‐19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID‐19 Registry

Abstract

Introduction Coronavirus disease 2019 (COVID‐19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID‐19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID‐19 as well as describe the differences in outcomes between patients with and without pre‐existing hypothyroidism using an observational, multinational registry. Methods In an observational cohort study we enrolled patients 18 years or older, with laboratory‐confirmed severe acute respiratory syndrome coronavirus‐2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID‐19 hospitalization, (2) in‐hospital mortality and (3) hospital‐free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. Results Among the 20,366 adult patients included in the study, pre‐existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59–80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre‐existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in‐hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital‐free days (estimated difference 0.01 days; 95% CI: −0.45, 0.47; p = .97). Pre‐existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. Conclusions In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID‐19. Pre‐existing hypothyroidism in hospitalized patients with COVID‐19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID‐19 on the thyroid gland and its function is needed in the future.

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

“…We saw no significant causal association of genetically determined thyroid-related traits with COVID-19 phenotypes. This finding is consistent with three retrospective studies which reported that pre-existing hyperthyroidism (21) and hypothyroidism (21)(22)(23) were not associated with increased risk of SARS-CoV-2 infection, COVID-19-associated hospitalization, ICU admission and mortality. Although a meta-analysis suggested that individuals with pre-existing thyroid abnormalities and hypothyroidism had poorer COVID-19-related outcomes in terms of severity, ICU admission, hospitalization and mortality (20), the discrepancy might be explained by the different study designs, sample size, and unavailability of covariates in some of the included studies.…”

“…Whether SARS-CoV-2 infection or COVID-19 severity would cause long-term thyroid dysfunction warrants further investigation. In the reverse direction, a meta-analysis (20) and three retrospective studies (21)(22)(23) provided contradictory evidence for the association of pre-existing thyroid disease with risk of COVID-19-related outcomes. It remains unknown if thyroid dysfunction alters the susceptibility to SARS-CoV-2 infection and COVID-19 severity.…”

Association of thyroid dysfunction and COVID-19: A systematic review and meta-analysis

“…Moreover, the low levels of TSH and T3 may be seen as part of an adaptive condition of anti-thyroidal disease syndrome caused by a significant stress situation, especially in extreme or critically ill patients (i.e., systemic virus disease) ( 14 , 21 , 25 ). Additionally, evidence suggests,although, preexisting thyroid disease will not increase risk of COVID infection and complication ( 56 ), COVID could activate subclinical conditions in susceptible population or cause relapse of known condition specially Grave’s disease which is mostly temporary and does not need further management, however, as it can aggregate existing condition specially inducing thyroid storm in hyperthyroidism proper management and regular monitoring of thyroid function in this population is desirable and recommended ( 51 , 57 ). As for follow up in these patients, since in most patients, thyroid dysfunction remit in three month no conclusion is proposed for further follow-up by studies and experts ( 51 ).…”

Analyzing the Outcomes of COVID-19 Infection on Patients With Comorbidities: Insights From Hospital-Based Study

“…These findings underscore the pronounced association of hypothyroidism, ischemic heart disease, and multiple comorbidities with mortality risk in COVID-19 patients. It’s important to note that the VIRUS Study from the COVID-19 registry did not find preexisting hypothyroidism to increase the odds of disease severity and mortality [ 18 ]. The discrepancy in findings may stem from methodological disparities, furthermore, disparities in ethnicity and sample sizes between the two studies contribute to this variance.…”