ABSTRACT
OBJECTIVE: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic disease (Covid-19) affects thyroid function via multiple mechanisms. We described painless atypical thyroiditis coexisting with non-thyroidal illness syndrome in patients hospitalized for severe Covid-19 disease. We aimed to better characterize it and to follow its evolution over time. METHOD(S): Baseline (at hospital admittance) and longitudinal study of consecutive patients hospitalized for severe Covid-19 disease, without known history of thyroid disfunction, assessing serum thyroid function and autoantibodies, inflammatory markers and thyroid ultrasound scan (US). Patients showing US focal hypoechoic areas suggestive for thyroiditis (thyroiditis-areas) also underwent thyroid 99mTc or I123 uptake scan and thyroid US-guided fine needle aspiration (US-FNA) for lymphocyte and SARS-CoV-2 RNA analysis. RESULT(S): Among 183 patients, thyroid US was performed at the earliest possible time (2-3 months post infection) in 65 (35%) and showed thyroiditis-areas in 18/65 (28%) patients;thyroid 99mTc/I123 uptake was reduced in 14/17 (82%). Thyroiditis-areas were present in 6/10 (60%) patients with baseline low TSH (versus 10/40, 25%, normal TSH, p = 0.034). Patients with thyroiditis-areas also had higher baseline FT4 (p = 0.018) and IL-6 (p = 0.016) compared with normal thyroid US. Thyroid US-FNA showed CD4+CD8+CD103+CD69+ tissue resident memory T-cells, a recently identified lymphocyte lineage that occupies tissues without recirculating, in 7/8 (87%) patients. Preliminary findings using MHC I and II dextramers also identified SARS-CoV-2-specific T-cells, but no viral RNA. Follow-up analysis, conducted in 75/183 (41%) patients, showed thyroid function and inflammatory markers normalized at all time-points and no increase of thyroid autoantibodies positivity. The thyroiditis-areas, often reduced in size, were still present after 6 and 12 months in 13/15 (87%) and 6/12 (50%) patients, respectively. After 9 months the thyroid uptake at 99mTc/I123 scintigraphy was still reduced in 4/6 (67%) patients, even if partially recovered (mean +28%) compared with baseline. CONCLUSION(S): Thyroid dysfunction during moderate-to-severe Covid-19 disease is mild and transient. Thyroiditis-areas occur frequently and may persist after one year, even if reduced in size. The association of thyroiditis-areas with low TSH and high FT4 and IL-6 serum concentrations, and the preliminary finding of intra-thyroid SARS-CoV-2-specific T-cells, support the hypothesis of a direct thyroid gland involvement in SARS-CoV-2 infection.