The impact of interferon beta-1b therapy on thyroid function and autoimmunity among COVID-19 survivors

Abstract

Background: Interferon beta-1b (IFN) is an effective COVID-19 treatment. We aimed to evaluate the impact of short-term IFN on incident thyroid dysfunction and autoimmunity among COVID-19 survivors. Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to January 2021 who had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine and anti-thyroid antibodies measured both on admission and at three months. Positive anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) was defined by >100 units. In evaluating patients with negative baseline anti-TPO, we defined a significant increase in anti-TPO titre to be >2 times the SD, i.e. >12 units, on reassessment, compared with that at baseline. Results: 226 patients were included (median age 55.0 years; 49.6% men): 135 were IFN-treated. The median duration of IFN was 5 days (range: 1 – 15 days; 65.9% received 5 days of IFN). There tended to be more abnormal thyroid function tests (TFTs) upon reassessment in IFN-treated patients (8.1% vs 2.2%, p=0.080). Among 179 patients (65.4% IFN-treated) with a complete reassessment of anti-thyroid antibodies, anti-TPO and anti-Tg titres increased upon reassessment in IFN-treated (anti-TPO: from 29.21 units [IQR: 14.97 – 67.14] to 34.30 units [IQR: 18.82 – 94.65], p<0.001; anti-Tg: from 8.23 units [IQR: 5.40 – 18.44] to 9.14 units [IQR: 6.83 – 17.17], p=0.001) but not in IFN-naïve group. Of the 143 patients negative for anti-TPO at baseline, upon reassessment, 22 had a significant interval increase in anti-TPO titre (by >12 units); of these, eight became anti-TPO positive (seven IFN-treated; one IFN-naïve). Incident anti-TPO positivity was more likely to be associated with abnormal TFTs upon reassessment (phi 0.188, p=0.025). IFN treatment (adjusted odds ratio [aOR] 5.73, 95% CI 1.46 – 22.5, p=0.031) independently predicted significant increase in anti-TPO titre, in addition to baseline C-reactive protein levels (aOR 1.59, 95% CI 1.04 – 2.44, p=0.012) and higher baseline anti-TPO titres (aOR 4.41, 95% CI 1.85 – 10.5, p=0.001). Conclusion: IFN for COVID-19 was associated with increases in anti-thyroid antibody titres, incident anti-TPO positivity and thyroid dysfunction during convalescence. Our findings would support close monitoring of COVID-19 survivors' thyroid function and autoimmunity, especially if treated with IFN.