Functional and Immunological Features of Covid-19 Associated Atypical Thyroiditis

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.

Author Correction: Features of fragile people with SARS-CoV-2 infection in isolation in a COVID-19 hotel in Rome, Italy.

Correction to: European Review for Medical and Pharmacological Sciences 2022; 26 (7): 2631-2638-DOI: 10.26355/eurrev_202204_28501-PMID: 35442479, published online on 15 April 2022. After publication, at the request of the Italian Ministry of Health, the authors asked to insert the following statement in the Acknowledgments section: "This research was funded by the Italian Ministry of Health (RC 2022)". There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/28501.

Features of fragile people with SARS-CoV-2 infection in isolation in a COVID-19 hotel in Rome, Italy.

OBJECTIVE: Temporary COVID-19 hotels have been established in Italy to assist the homeless people that test positive for SARS-CoV-2 and require isolation. This observational study aimed to investigate the characteristics of the subjects who were isolated at the Casa tra Noi COVID-19 hotel in Rome between October 2020 and May 2021 and to estimate the duration of SARS-CoV-2 positivity according to their main socio-demographic, behavioural and clinical features. SUBJECTS AND METHODS: Socio-demographic data, clinical history, and anamnestic data of guests were collected by the clinicians reviewing the medical documentation and face-to-face interviewing. Nasopharyngeal swabs were performed every 7 days and the presence of SARS-CoV-2 was assessed by RT-PCR. Median duration of SARS-CoV-2 positivity according to socio-demographic, behavioral factors and clinical condition was calculated. RESULTS: The 196 guests (161 males, 82.1%) had a median age of 41 years (IQR: 30-53), and were mostly African (87, 44.4%). Only asymptomatic/paucisymptomatic infections were observed. Almost half of the individuals (84, 42.9%) were affected by at least one co-morbidity, the frequency of which was higher among women (57.1% vs. 39.8%, p=0.06). The date of the negative SARS-CoV-2 molecular test was known for 144 guests (73.5%). Among these, the median duration of positivity was 21 days (IQR: 14-26) and did not significantly vary with age, country of origin, smoking status, alcohol or drug abuse. Among the co-morbidities, only infectious diseases significantly modified the duration of positivity, which increased from 21 to 34 days (p=0.013). CONCLUSIONS: Hotel guests were frequently affected by physical/mental co-morbidities. Duration of SARS-CoV-2 positivity was significantly prolonged only in individuals affected by an infectious disease.

Thyroid dysfunction in CoViD-19 moderate-to-critical patients: An endocrine complication due to SARS-CoV-2

Background and Aim: CoViD-19 has different clinical manifestations. The aim of this cross-sectional study was to assess thyroid function in CoViD-19 hospitalised patients in relation to the severity of disease. Methods: We assessed 174 CoViD-19 patients hospitalised between March to December 2020 in a High Care Internal Medicine Unit with serum TSH concentration at admission. We excluded those with history of thyroid disease or treated with drugs modifying thyroid function. We evaluated baseline TSH, fT3, fT4 and the severity of disease using PaO2/FiO2, respiratory rate, blood oxygen saturation, type of respiratory support and inflammatory markers. Results: 20% of patients had low TSH (<0.422 mUI/L), 9.9% had thyroiditis (TSH<0.28 mIU/L and/or fT4>17 ng/L). fT3 was assessed in 53 patients and 60% had low fT3 (<2.0 ng/L). Moreover, lower fT3 values were related to higher mortality (p=0.03), hypoalbuminemia (p<0.01) and higher D-dimer (p<0.01). Lower baseline serum TSH concentrations were related to lymphocytopenia (p<0.01) and hypoalbuminemia (p=0.01), and associated with greater need of respiratory support during hospitalisation: the median values were 1.41, 1.38, 1.20 and 0.65 mIU/L in patients who did not need any support, those with only oxygen support, non-invasive ventilation and invasive ventilation respectively (p=0.02). Conclusions: Moderate-to-critical CoViD-19 patients can develop thyroid dysfunctions related to several biomarkers of disease. Baseline serum TSH seems to be related to the severity of respiratory failure developed during hospitalisation.

Evolution of thyroid function in patients with covid-19 related atypical thyroiditis

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.