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.
ABSTRACT
Patients with Covid-19 frequently develop atypical thyroiditis coexisting with non-thyroidal illness syndrome (Muller et al LancetD& E 2020). We analysed thyroid dysfunction: 1) in relation to Covid-19 disease severity;2) observing its evolution over time. Baseline assessment of 179 patients hospitalised in sub-intensive care units for Covid-19 disease, without known history of thyroid dysfunction or amiodarone therapy, with thyroid function and inflammatory markers measured at hospital admission. Thyroidultrasound (thyroid-US) and thyroid autoantibodies measurement were performed in 65 patients after they became SARS-CoV-2 negative, of whom 14 were also studied with radioisotope thyroiduptake (99mTc or I123) since showing focal-hypoechoic-areas. 46 patients were re-evaluated at 6 months of follow-up. Patients on steroid treatment started before hospitalization (N = 62) were excluded due to its lowering effect on TSH. At baseline 11/117 patients (9.4%) had thyrotoxicosis (low TSH and/or high FT4);23/117 (19.7%) had low TSH and required a more intensive oxygen support during hospitalization (P = 0.02). TSH positively correlated with lymphocyte count (P < 0.01). FT3 correlated negatively with length of hospitalization (P = 0.04) and death rate (P = 0.03). Only 7.7% patients had detectable TgAb/TPOAb and none TRAb. Thyroid-US showed focal-hypoechoic-areas in 28% patients, of whom thyroid-uptake was focally-reduced in 57%, diffusely-reduced in 14% and normal in 28%. Importantly, focalhypoechoic-areas were more frequent among patients with baseline low TSH compared with normal TSH (P = 0.03). Furthermore, patients with focal-hypoechoic-areas had higher baseline FT4 (P = 0.02) and IL-6 (P = 0.02) than those without. Thyroid function and inflammatory markers had normalized at 3 months and remained normal thereafter. At 6 months focalhypoechoic-areas persisted in the majority of patients, often reduced in size;thyroid-uptake was repeated in 8 patients and resulted increased in 7 (87.5%). Thyroid dysfunction during moderate-to-severe Covid-19 disease was mild and transient and correlated with increased death rate and length of hospitalization;low TSH correlated with lymphopenia and was associated with increased need of oxygen support during hospitalization. Focal-hypoechoic-areas at thyroid-US persisted up to 6 months in nearly 1/3 of patients and correlated with thyroid and inflammatory parameters at hospital admission, confirming a key role of thyroiditis in Covid-19 related thyroid dysfunction;long-term effects are unknown.