key: cord-0682389-73q14gy0
authors: Lui, David Tak Wai; Lee, Chi Ho; Chow, Wing Sun; Lee, Alan Chun Hong; Tam, Anthony Raymond; Pang, Polly; Ho, Tip Yin; Fong, Carol Ho Yi; Law, Chun Yiu; Leung, Eunice Ka Hong; To, Kelvin Kai Wang; Tan, Kathryn Choon Beng; Woo, Yu Cho; Lam, Ching Wan; Hung, Ivan Fan Ngai; Lam, Karen Siu Ling
title: Long COVID in Patients with Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?
date: 2021-07-06
journal: Endocr Pract
DOI: 10.1016/j.eprac.2021.06.016
sha: 2e6ec8e703b90cab7deedc6a8f435fd1c5a8a2a3
doc_id: 682389
cord_uid: 73q14gy0

OBJECTIVE: Long COVID (LC) is an emerging global health issue. Fatigue is a common feature. Whether thyroid function and autoimmunity play a role is uncertain. We aimed to evaluate the prevalence and predictors of LC and the potential role of thyroid function and autoimmunity in LC. METHODS: We included consecutive adults without known thyroid disorder, admitted to a major COVID-19 centre for confirmed COVID-19 from July to December 2020 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured on admission and at follow-up. LC was defined by the presence or persistence of symptoms upon follow-up. RESULTS: In total, 204 patients (median age: 55.0 years; 46.6% men) were reassessed at a median of 89 days (IQR: 69–99) after acute COVID-19. Forty-one (20.1%) had LC. Female (adjusted odds ratio [aOR] 2.48, p=0.018) and SARS-CoV-2 PCR cycle threshold value <25 on admission (aOR 2.84, p=0.012) independently predicted the occurrence of LC. Upon follow-up, most abnormal TFTs in acute COVID-19 resolved, and incident thyroid dysfunction was rare. Nonetheless, we observed incident anti-TPO (anti-thyroid peroxidase) positivity. While baseline or follow-up TFTs were not associated with the occurrence of LC, among 172 patients symptomatic in acute COVID-19, symptom resolution was more likely in those with positive anti-TPO upon follow-up (p=0.043). CONCLUSION: LC is common among COVID-19 survivors, with female and those with higher viral load in acute COVID-19 particularly vulnerable. The observation of incident anti-TPO positivity warrants further follow-up for thyroid dysfunction. Whether anti-TPO plays a protective role in LC remains to be elucidated.

continue to experience a range of symptoms after recovery from the acute COVID-19 illness, 2 67 variably described as 'long COVID', 'post-acute sequelae of SARS-CoV-2' and 'post-acute 68 COVID-19 syndrome'. 3 This phenomenon is referred to as 'long COVID' in this paper. Typical 69 presentations include fatigue and dyspnoea. 2 Long COVID can represent (i) residual symptoms 70 that persist after recovery from acute infection; or (ii) new symptoms or syndromes that 71 develop after initial asymptomatic or mild infection. 4 As the population of COVID-19 survivors 72 is growing, long COVID could evolve into a 'pandemic of the pandemic'. 5 It is crucial to identify 73 those prone to develop long COVID for the appropriate allocation of health care resources. 74 75 As acute COVID-19 is associated with multisystem involvement by SARS-CoV-2, 6 it is also 76 increasingly recognized that sequelae may occur in multiple systems after acute COVID-19 77 illness. 2 The hypothalamic-pituitary-thyroid axis has attracted clinical interest in its relevance 78 in acute COVID-19. 7 The volume of literature is growing regarding thyroid dysfunction in acute 79 COVID-19, which mainly includes non-thyroidal illness (NTIS) and thyroiditis. However, 80 relatively few studies addressed the thyroid status in the convalescent phase of COVID-19, 81 J o u r n a l P r e -p r o o f mainly reporting the resolution of thyroid dysfunction. Recently, the potential incident thyroid 82 dysfunction and autoimmunity among 122 COVID-19 patients during convalescence has been 83 described. 8 As manifestations of long COVID include fatigue, and immune dysregulation is one 84 of the postulated mechanisms of long COVID, 9 it would be helpful to investigate whether 85 thyroid function and autoimmunity play a role in long COVID. were evaluated with a standard checklist. Respiratory rate, baseline oxygen saturation by 130 pulse oximetry, and oxygen requirement on admission were captured. Chest x-ray was 131 performed in each patient on admission, and abnormal chest x-ray images were graded as 132 mild (opacities in 1-2 lung zones), moderate (opacities in 3-4 lung zones) and severe (opacities 133 in >4 lung zones). 13 We compared patients who did and did not have symptoms upon follow-up ( Table 2) . We 251 observed female preponderance, higher viral load (represented by Ct value <25) and a higher 252 prevalence of long COVID, predicted by female and higher SARS-CoV-2 viral loads. Importantly, 311

our study was the first to investigate the potential role of thyroid function and autoimmunity 312

in long COVID. We demonstrated that, on follow-up, most thyroid dysfunction in acute COVID-313 19 had recovered spontaneously, and incident thyroid dysfunction was relatively rare. ultrasonography suggestive of thyroiditis. This ultrasonographic finding has raised concern for 370 the need for longer-term monitoring for potential incident thyroid dysfunction. Our study 371 findings were in agreement with that follow-up study that most thyroid dysfunction in acute 372 COVID-19 recovered and that incident thyroid dysfunction was rare. Furthermore, our novel 373 observation of incident anti-TPO positivity post-acute COVID-19 suggested potential 374 perturbation of thyroid autoimmunity after COVID-19, and an additional concern for potential 375 incident thyroid dysfunction as the occurrence of anti-TPO can precede thyroid dysfunction. 31 376 Hence, our data further supported the need for follow-up TFTs. The strengths of our study included the following. Firstly, we described the prevalence and 399 predictors of long COVID predominantly among patients with mild to moderate disease, 400 generalizable to COVID-19 patients at large. Secondly, our study findings were based on 401 structured face-to-face assessments, including blood tests for inflammatory markers and 402 SARS-CoV-2 antibodies and chest x-ray, which allowed a systematic evaluation of residual 403 objective abnormalities post-acute COVID-19, beyond symptoms perceived by patients. 

Characteristics of SARS-CoV-2 and COVID-19

Post-acute COVID-19 syndrome

Challenges in defining Long COVID: Striking 439 differences across literature, Electronic Health Records, and patient-reported 440 information

Postacute covid-19: An overview and approach to classification

Unpacking "long COVID

Extrapulmonary manifestations of COVID-19

Thyroid and COVID-19: a review on 450

Quantitative Detection and Viral Load Analysis of SARS-472

CoV-2 in Infected Patients

To Interpret the SARS-CoV-2 Test

Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment

Temporal profiles of viral load in posterior 480 oropharyngeal saliva samples and serum antibody responses during infection by 481

SARS-CoV-2: an observational cohort study

British Society of Thoracic Imaging Post-COVID-19 CXR Report Codes

Association Between Dabigatran vs Warfarin 487 and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial 488

Different glycaemia-related risk factors for

Attributes and predictors of long COVID 512

Clinical sequelae of COVID-19 survivors in Wuhan, China: a 515 single-centre longitudinal study

Are we facing a crashing wave of neuropsychiatric 518 sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic 519 mechanisms

Concern coronavirus may trigger post-viral fatigue syndromes

Long-COVID: An evolving problem with an 523 extensive impact

Significance of Anti-TPO as an Early 526

Predictive Marker in Thyroid Disease

Abbreviations: TSH, thyroid-stimulating hormone; fT4, free thyroxine; fT3