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CME / ABIM MOC / CE

Does Interferon Treatment Affect the Thyroid in Patients With COVID-19?

  • Authors: News Author: Nancy A. Melville; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 12/3/2021
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 12/3/2022
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Target Audience and Goal Statement

This activity is intended for infectious disease clinicians, diabetologists/endocrinologists, family medicine/primary care clinicians, internists, family medicine clinicians, nurses, pharmacists, and other members of the healthcare team for patients with COVID-19.

The goal of this activity is to describe the impact of short-term interferon (IFN) β-1b on incident thyroid dysfunction and autoimmunity among COVID-19 survivors, according to a prospective series of consecutive adults without known thyroid disorder who were admitted to Queen Mary Hospital for COVID-19 from July 2020 to January 2021 and who had thyroid function tests and antithyroid antibodies measured both on admission and at 3 months.

Upon completion of this activity, participants will:

  • Describe the impact of short-term IFN therapy on incident thyroid dysfunction and autoimmunity among COVID-19 survivors, according to a prospective study
  • Identify clinical implications of the impact of short-term IFN therapy on incident thyroid dysfunction and autoimmunity among COVID-19 survivors, according to a prospective study
  • Outline implications for the healthcare team


Disclosures

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Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


News Author

  • Nancy A. Melville

    Freelance writer
    Medscape

    Disclosures

    Disclosure: Nancy A. Melville has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Editor/CE Reviewer

  • Esther Nyarko, PharmD

    Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Esther Nyarko, PharmD, has disclosed no relevant financial relationships.

CME Reviewer/Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

None of the nonfaculty planners for this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.


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CME / ABIM MOC / CE

Does Interferon Treatment Affect the Thyroid in Patients With COVID-19?

Authors: News Author: Nancy A. Melville; CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CME / ABIM MOC / CE Released: 12/3/2021

Valid for credit through: 12/3/2022

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Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to COVID-19 vaccines may be provided in this activity to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

Some studies have shown that interferon (IFN) treatment in COVID-19 may shorten duration of viral shedding, alleviate symptoms, and reduce cytokine responses, mortality, and intensive care unit (ICU) admission; however, long-term IFN treatment in multiple sclerosis may cause incident thyroid dysfunction and autoimmunity.

Study Synopsis and Perspective

Treatment of COVID-19 with IFN β-1b even for just a few days -- a much shorter period than is commonly used for maintenance in multiple sclerosis (MS), for example -- is associated with potentially important adverse effects on thyroid function, according to research presented at the virtual 90th Annual Meeting of the American Thyroid Association.[1]

"Our study is the first to report on the impact of [IFN] treatment on the thyroid in the context of COVID-19," first author David T.W. Lui, MBBS, of the department of medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, told Medscape Medical News.

"If short courses of [IFN] treatment become a standard therapy for COVID-19, the modest changes detected thus far may indicate a phenomenon of clinical importance," he noted.

"As for now, our findings suggest that clinicians monitor the thyroid function and antithyroid antibodies [(ATAs)] among [IFN]-treated COVID-19 survivors and call for further follow-up studies regarding the clinical significance of these changes," added Lui.

The study, also published in Frontiers in Endocrinology,[2] involved 226 patients in Hong Kong who were treated for COVID-19 and had no known prior thyroid disorders.

Among those patients who received treatment with IFN, there were significant increases in ATAs, including anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) at 3 months compared with baseline whereas no similar increases were observed among those patients not receiving IFN treatment.

In a multivariate analysis, treatment with IFN was found to be independently associated with more than 5 times greater odds of having a significant increase in anti-TPO titers at 3 months vs no IFN treatment (adjusted odds ratio [aOR] = 5.73 [95% CI: 1.46, 22.5]; P = .031).

"Interferon treatment for COVID-19, even for a short duration of a few days, could induce significant, though modest, increases in [ATA] titers," Lui reiterated.

Previous studies evaluating the effects of IFN on thyroid function in patients with MS have shown that up to 33% of patients developed thyroid dysfunction and 20% developed thyroid autoimmunity, particularly during the first year of treatment, Lui and coauthors noted in their study.

Although the patients in the current study did not become symptomatic, the changes nevertheless could be indicative of further dysfunction and are important enough to warrant follow-up, Lui noted.

"Despite a modest magnitude of anti-TPO titer elevation among patients who developed incident anti-TPO positivity, further follow-up is warranted for potential subsequent thyroid dysfunction as the occurrence of anti-TPO can precede thyroid dysfunction," he noted.

Experience in Multiple Sclerosis Raises Thyroid Concerns

Interferon, a potent antiviral and anti-inflammatory agent, is well-established in the treatment of MS, often used over months or years as a maintenance therapy, and the drug has been repurposed in the age of COVID-19, where it has shown benefit as a much shorter-term, higher-dose treatment of just a few days, with benefits observed especially when initiated in the initial stages of infection.

With increasing reports of thyroid effects after COVID-19, in general, and known previous reports of incident thyroid dysfunction also associated with the use of interferon in MS, Lui and colleagues sought to evaluate whether IFN treatment for COVID-19 affected thyroid function.

The study's 226 patients were treated at Queen Mary Hospital, in Hong Kong, for COVID-19 between July 2020 and January 2021. They were a median age of 55 years, and about half were men.

A large majority (68.6%) of the COVID-19 cases were mild, 27% were moderate, and 4.4% were severe.

Among the patients, 135 (59.7%) received treatment with IFN for a median duration of 5 (range, 1-15) days at a dose of 16 million IU/d, and 16.4% required dexamethasone.

Of note, patients treated with IFN had a higher SARS-CoV-2 viral load and more lymphopenia upon admission, and as ribavirin was given in combination with IFN, the IFN-treated patients were more likely to also be treated with that drug.

Overall, those patients treated with IFN showed a tendency toward having more abnormal function tests upon reassessment after 3 months (8.1% vs 2.2%; P = .08).

Further Evaluation of Patients Who Had Full Details on Antithyroid Antibodies

In a further evaluation of 179 patients who had full details on ATAs, persons who were treated with IFN (65.4%) showed significant increases in median anti-TPO levels, from 29.21 U at baseline to 34.3 U (P < .001) at the 3-month reassessment.

Likewise, the IFN-treated patients had median increases in anti-Tg titers, from 8.23 U at baseline to 9.14 U at reassessment (P = .001).

There were meanwhile no similar significant changes in those measures among patients not treated with IFN.

Of the 179 patients, 143 were negative for anti-TPO at baseline, and 22 of these patients had significant interval increases in anti-TPO titers, defined as > 12 U, after 3 months.

Eight of these patients fully switched from being anti-TPO negative to positive, nearly all of whom (n = 7) were IFN-treated, with just one being interferon-naive.

There were no significant differences in disease severity, viral load, or lymphopenia between patients who did and did not have significant increases in anti-TPO titers, Lui noted.

Aside from IFN treatment, other factors found in the multivariate analysis to be independently predictive of higher odds of having a significant increase in anti-TPO titers at 3 months included baseline C-reactive protein (CRP) levels (aOR = 1.59 [95% CI: 1.04, 2.44]; P = .012) and higher baseline anti-TPO titers (aOR = 4.41 [95% CI: 1.85, 10.5]; P = .001).

Evaluate Other COVID-19 Treatments for Thyroid Dysfunction?

Of note, the IFN-dosing regimen used in the study of 16 million IU/d contrasts with the usual lower regimen of 8 million IU every other day as a chronic therapy in MS.

"Intriguingly, even with such a short duration of [IFN] therapy, we still observed a 5.6% rate of incident anti-TPO positivity at 3 months, which correlated with a higher chance of abnormal thyroid function tests during convalescence," Lui and coauthors added.

Amid ongoing efforts to disentangle the links between COVID-19 and thyroid dysfunction, the findings suggest importance in also considering COVID treatment, Lui noted.

"The thyroid risk has not been evaluated for other COVID treatments," he said.

The authors have reported no relevant financial relationships.

Study Highlights

  • Participants were 226 consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to January 2021 who had TFTs and ATAs measured on admission and at 3 months.
  • Median age was 55 years; 49.6% were men: 135 were IFN-treated.
  • IFN-treated vs IFN-naive patients tended to have more abnormal TFTs at follow-up (8.1% vs 2.2%, P = .08).
  • Among 179 patients with complete ATA reassessment, the IFN-treated (65.4%) but not IFN-naive group had significant increases in titers of anti-TPO, from 29.21 (IQR, 14.97-67.14) U at baseline to 34.3 (IQR, 18.82-94.65) U; P < .001 at follow-up, and anti-Tg, from 8.23 (IQR, 5.4-18.44) U to 9.14 (IQR, 6.83-17.17) U; P = .001.
  • IFN treatment was independently associated with changes in anti-TPO titer (P = .001).
  • In multivariate analysis, IFN treatment vs no IFN treatment was independently associated with increased anti-TPO titers at 3 months (aOR = 5.73 [95% CI: 1.46, 22.5]; P = .031).
  • Of 143 patients negative for anti-TPO at baseline, 8 became anti-TPO positive when retested (7 IFN-treated; 1 IFN-naive).
  • Patients who did and did not have significant increases in anti-TPO titers had no significant differences in disease severity, viral load, or lymphopenia.
  • Incident anti-TPO positivity was more likely to be associated with abnormal TFTs upon reassessment (P = .025).
  • In addition to IFN therapy, other independent predictors of significant increase in anti-TPO titers at 3 months were baseline CRP (aOR = 1.59 [95% CI: 1.04, 2.44]; P = .012) and higher baseline anti-TPO titers (aOR = 4.41 [95% CI: 1.85, 10.5]; P = .001).
  • The investigators concluded that IFN for COVID-19, even when used short-term, was associated with modest increases in ATA titers, and a trend of more incident anti-TPO positivity and abnormal TFTs during convalescence.
  • They suggest that clinicians should monitor TFTs and ATAs among IFN-treated COVID-19 survivors and that further follow-up studies are needed regarding the clinical significance of these changes, particularly if short courses of IFN become a standard therapy for COVID-19.
  • They noted that the IFN regimen used in this study (16 million IU/d for a few days) contrasts with 8 million IU every other day used for chronic MS therapy.
  • Risks for thyroid dysfunction have not been evaluated for other COVID treatments.
  • Study limitations include relatively small sample, missing follow-up data regarding ATAs, and lack of thyroid imaging.
  • Most IFN-treated patients also received ribavirin, and none received ribavirin monotherapy, hindering determination of whether IFN alone or the IFN-ribavirin combination accounted for increased ATA titers.
  • As only 1 of the 62 interferon-naive patients had incident anti-TPO positivity, there is no convincing evidence of COVID-19 triggering autoimmunity, which was suggested by existing case reports.
  • Nonetheless, SARS-CoV-2 infection may cause destructive thyroiditis and development of autoimmunity a few months later, and the present cohort had relatively short follow-up duration.
  • Longer follow-up is therefore needed.

Clinical Implications

  • Interferon for COVID-19, even when used short-term, was associated with modest increases in ATA titers.
  • Further follow-up studies are needed regarding the clinical significance of these changes.
  • Implications for the Healthcare Team: Clinicians should monitor TFTs and ATAs among IFN-treated COVID-19 survivors.

 

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