Long COVID: Italian Researchers Warn That SARS-CoV-2 Induced Thyroid Dysfunction Can Linger On For More Than A Year!
: In the early part of 2022, Thailand Medical News
covered a report by a British lab that there an on uptick in the number of patients being diagnosed with thyroid issues and that it was speculated that the Omicron variants and its sub-lineages could be responsible for these.
Numerous past studies have showed that SARS-CoV-2 infections could indeed affect the thyroid glands and lead to a variety of conditions including thyrotoxicosis.
In July 2020, an Italian team of researchers from Endocrinology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan published a study detailing how SARS-CoV-2 infections can lead to atypical thyroiditis and also possible cause manifestations than can also be seen in Long COVID
The same team recently reported their newer findings at the ATA (American Thyroid Association) 2022 Annual Meeting held on October 21, 2022 in which they warned that 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.
These new findings add to evidence on the complex involvement of the thyroid in COVID-19.
Dr Ilaria Muller, MD, PhD, an assistant professor in endocrinology in the Department of Clinical Sciences and Community Health, University of Milan told fellow physicians during the ATA meeting, "To our knowledge these findings are novel. 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."
According to Dr Muller, the long-term effects of thyroid dysfunction 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.
Dr Muller noted that the nature and implications of the persistent thyroiditis areas are uncertain.
Dr Muller explained, "These areas of thyroiditis are likely a sort of 'immunologic scar' of the previous SARS-CoV-2 infection. We still don't know if there are clinical implications, even if they seem unlikely."
Interestingly, 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.
However, the reasons why some patients develop atypical thyroiditis and others don't are also unclear, with Dr Muller's team investigating further.
Significantly, similar effects have been associated with other severe infections, not just COVID-19.
Dr Muller further explained, "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.”
Many other medical researchers also noted that such thyroiditis areas stemming from other types of infection may persist but go unnoticed.
Some commented during the ATA meeting, "Resolution is the clinical rule, and we generally do not restudy in detail those who clinically recover. However, there is evidence of impaired thyroid reserve in those who recover from viral thyroiditis due to other sources."
Other said, "Thyroid symptoms are often not specific, so 'atypical' cases are common, and resolution with restoring thyroid status to normal is mixed.”
However most say that 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.”
Dr Muller and her study 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.
They found, in their new study 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.
In order 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.
Their new study findings showed that 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.
Alarmingly, 60% of those patients with the areas of thyroiditis had low TSH levels, while 25% had normal TSH levels (P = .034).
Furthermore, 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.
Subsequently, in a longitudinal analysis further following patient’s 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.
It was noted that 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.
Importantly, 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.
All the study participants showed no apparent development of thyroglobulin antibody, thyroid peroxidase antibodies, or TSH receptor antibodies.
However, 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 study findings showed "SARS-CoV-2-specific T cells were enriched within the thyroid compared with the blood, many with a tissue resident phenotype.
The study 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. In particular, SARS-CoV-2 specific tissue-resident memory T lymphocytes have not been described before in the thyroid gland.
The study findings will be published shortly.
Dr Muller’s study team is still conducting long -term follow up studies on SARS-CoV-2 induced thyroid dysfunctions.
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