Thyroid Dysfunction May Linger a Year After Severe COVID-19

 Patients hospitalized with severe COVID-19 and no prior history of thyroid dysfunction show signs of thyroiditis that, although asymptomatic, continue to persist for up to a year after infection, according to research that adds to evidence on the complex involvement of the thyroid in COVID-19.

"To our knowledge these findings are novel," first author Ilaria Muller, MD, PhD, an assistant professor in endocrinology in the Department of Clinical Sciences and Community Health, University of Milan, Italy, told Medscape Medical News.

"Little has been written about the long-term follow-up of thyroid function after severe COVID-19 disease and we have followed patients up to 1 year after infection."

The effects are seen in about 10% to 15% of patients, and "[while] the thyroid dysfunction is transient, ultrasound areas of thyroiditis may persist after 1 year, even if they progressively shrink," said Muller, who presented the findings at the American Thyroid Association (ATA) 2022 Annual Meeting.

Immunological Scars? Clinical Implications Unclear

The nature and implications of the persistent thyroiditis areas are uncertain, Muller noted. "These areas of thyroiditis are likely a sort of 'immunologic scar' of the previous SARS-CoV-2 infection," she explained. "We still don't know if there are clinical implications, even if they seem unlikely."

Of note, increases in autoimmune processes or a higher incidence of thyroid dysfunction after COVID-19 have not been observed, and the shrinkage of the areas of thyroiditis over time is encouraging, she said.

The reasons why some patients develop atypical thyroiditis and others don't are also unclear, with Muller's team investigating further. Importantly, similar effects have been associated with other severe infections, not just COVID-19. "It is well known that in classic subacute thyroiditis due to other viral infections, the areas of thyroiditis persist for months, so this phenomenon might not be unique to COVID-19," she explained.

Commenting on the story, Jeffrey R. Garber, MD, also noted that such thyroiditis areas stemming from other types of infection may persist — but go unnoticed.

"Resolution is the clinical rule, [and] we generally do not restudy in detail those who clinically recover," he told Medscape Medical News. "However, there is evidence of impaired thyroid reserve in those who recover from viral thyroiditis due to other sources."

"Thyroid symptoms are often not specific, so 'atypical' [cases] are common, [and] resolution with restoring thyroid status to normal is mixed," noted Garber, an associate professor of medicine at Harvard Medical School and chief of the Division of Endocrinology at Atrius Health in Boston, Massachusetts.

In terms of clinical practice, while such issues should be kept in mind when evaluating abnormal thyroid tests during severe COVID-19, "it is not a call for routinely checking it in the absence of clinical suspicion," he observed.

Study Details

Muller and her team previously observed that patients hospitalized in intensive care with COVID-19 often had low or suppressed serum thyroid-stimulating hormone (TSH) levels, with and without elevated free thyroxine concentrations, suggestive of thyrotoxicosis.

Upon investigating those cases, they found, as in their previous study reported by Medscape Medical News, that a painless, atypical thyroiditis occurs with nonthyroidal illness syndrome among patients hospitalized with severe COVID-19. The atypical thyroiditis was slightly more common in men and was associated with lymphopenia.

To further investigate those cases and follow patients up to 1 year, the team conducted a longitudinal study of 183 patients hospitalized with severe COVID-19 in Italy. The patients, who had no known prior history of thyroid dysfunction, were assessed for serum thyroid function, autoantibodies, and inflammatory markers.

At baseline, 10% of the patients were found to have thyrotoxicosis, and ultrasound performed within 2 to 3 months post-infection on 65 patients showed that 18 (28%) had areas of thyroiditis.

Importantly, 60% of those patients with the areas of thyroiditis had low TSH levels, while 25% had normal TSH levels (P = .034).

In addition, those showing the presence of thyroiditis on ultrasound at 2 to 3 months were more likely to have elevated serum concentrations of FT4 (P = .018) and higher levels of interleukin-26 (P = .016), compared with those with normal ultrasound readings.

In a longitudinal analysis further following patients post-infection, among 15 patients who were evaluated at 6 months, most, 13 (87%), still had areas of thyroiditis, and 6 of 12 (50%) had thyroiditis areas that, though reduced in size, still persisted even at 12 months.

In terms of thyroid uptake, at 3 months, 14 of 17 patients (82%) had diffused or focal areas of a reduction of uptake. After 6 months, there was a recovery, with a median of 28% of thyroid uptake recovered, however, 67% of patients still had some focal or diffused reduction in thyroid uptake.

Of note, the indications of thyroiditis on imaging persisted even though patients' TSH levels had quickly normalized at the end of infection and remained normal up to 1 year of follow-up.

The patients showed no apparent development of thyroglobulin antibody, thyroid peroxidase antibodies, or TSH receptor antibodies.

A further fine needle aspiration (FNA) analysis of eight patients with atypical thyroiditis at 3 months after infection showed that those patients had tissue resident memory T cells (CD4+/CD8+/CD103+/CD69+) within the thyroid, but not in the blood as expected.

Additional assessments at 8 months after infection showed those tissue resident memory T cells continued to be present on imaging.

The results showed "SARS-CoV-2-specific T cells were enriched within the thyroid compared with the blood, many with a tissue resident phenotype," Muller explained.

The findings are notable in that "such an in-depth characterization of areas of thyroiditis triggered by SARS-CoV-2 infection combining ultrasound, scintigraphy, and immunological phenotyping has not been performed so far," she said.

"In particular, SARS-CoV-2 specific tissue-resident memory T lymphocytes have not been described before in the thyroid gland."

Muller and Garber have reported no relevant financial relationships.

ATA 2022 Annual Meeting. Oral Abstract 12. Presented October 21, 2022.

https://www.medscape.com/viewarticle/983254