Background
Coronovirus disease 2019 (COVID-19) infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus was officially declared a pandemic by the World Health Organization in March 2020. According to a search of PubMed for the term COVID-19 on May 5, 2021, thus far, there have been more than 130,000 papers on COVID-19 published in the medical literature. Since the previous comments on thyroid function in COVID-19 in Clinical Thyroidology (1,2) the number of papers on this topic has increased from a handful to 120 (PubMed search for the term COVID-19, thyroid disease on May 5, 2021), including a systematic review (3). One of these articles, the article by Campi et al. reviewed here (4), is a prospective study of thyroid function in patients hospitalized with COVID-19 infection at a single center in Milan, Italy.

Methods
The study included 144 consecutive patients with COVID-19 infection and associated pneumonia (97 men and 47 women; mean [±SD] age, 68.1±14.67 years [range, 26–96]) admitted to a single center in intensive or subintensive care units between March and May 2020 because of respiratory insufficiency of variable severity. SARS-Cov-2 infection was confirmed in all patients by RT-PCR testing on a nasopharyngeal swab. Those with previous thyroid dysfunction or who were taking interfering drugs were excluded. There was no control group. Different from previous reports, serum concentrations of thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (Tg), and anti-Tg autoantibodies (TgAbs) were measured at baseline and every 3 to 7 days thereafter. Serum C-reactive protein (CRP), cortisol, and interleukin-6 (IL-6) were also assayed. The overall mortality rate was 25% (36 of 144). The mean length of hospital stay was 21 days (range, 2–108). Serum Tg and TgAb concentrations were retrospectively measured in the subset of serum with reduced/suppressed TSH levels in order to diagnose or exclude destructive thyroiditis.

Results
Most patients had a normal TSH concentration at admission; most of these patients also had normal FT4 and FT3 levels. Low TSH concentrations were found either at admission or during hospitalization in 39% of patients, which was associated with low FT3 levels in half of these cases. Serum FT4 and Tg levels were normal, and TgAb was negative. Serum TSH and FT3 levels were invariably restored to normal at the time of discharge in survivors, whereas they were permanently low in most deceased cases. Only serum FT3 concentrations predicted mortality. Serum cortisol, CRP, and IL-6 concentrations were higher in patients with low TSH and FT3 concentrations.

Almost half of the COVID-19 patients who were not taking interfering drugs had normal thyroid function tests both at admission and during follow-up. In this series, the transient finding of low TSH with normal FT4 and low FT3 levels inversely correlated with CRP, cortisol, and IL-6 levels and were associated with normal Tg concentrations and without clinical signs of a destructive thyroiditis.

Longitudinal evaluations during the hospital stay showed that TSH suppression was transient in all the survivors, with 5 days (range, 2–9) as the median time to normalization. Serum Tg concentrations were invariably normal in the absence of TgAb interference in all 39 patients with low TSH, either at admission or during follow-up (median Tg, 7.6 µg/L, range: 3–70.3 µg/L).

Conclusions
The study suggests that cytokine release associated with COVID-19 infection causes slight transient central and peripheral thyroid function alterations, as characterized by reduced TSH with normal FT4 and low-normal FT3 levels. Serum thyroid function assessment during acute COVID-19 infection is not recommended. Clinical and biochemical monitoring after discharge/improvement are appropriate, as subacute thyroiditis may complicate the recovery.