Role of non‐thyroidal illness syndrome in predicting adverse outcomes in COVID‐19 patients predominantly of mild‐to‐moderate severity

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Abstract

Objective

Existing studies reported the potential prognostic role of non‐thyroidal illness syndrome (NTIS), characterized by low triiodothyronine (T3) with normal/low thyroid‐stimulating hormone (TSH), mainly in severe COVID‐19. None considered the significant impact of SARS‐CoV‐2 viral load on adverse outcomes. We aimed to clarify the prognostic role of NTIS among predominantly mild‐to‐moderate COVID‐19 patients.

Design

A prospective study of COVID‐19 patients.

Patients and Measurements

Consecutive adults admitted to Queen Mary Hospital for confirmed COVID‐19 from July to December 2020 were prospectively recruited. SARS‐CoV‐2 viral load was represented by cycle threshold (Ct) values from real‐time reverse transcription‐polymerase chain reaction of the respiratory specimen on admission. Serum TSH, free thyroxine and free T3 were measured on admission. The outcome was deterioration in clinical severity, defined as worsening in ≥1 category of clinical severity according to the Chinese National Health Commission guideline.

Results

We recruited 367 patients. At baseline, 75.2% had mild disease, and 27 patients (7.4%) had NTIS. Fifty‐three patients (14.4%) had clinical deterioration. Patients with NTIS were older, had more comorbidities, worse symptomatology, higher SARS‐CoV‐2 viral loads and worse profiles of inflammatory and tissue injury markers. They were more likely to have clinical deterioration ( p < .001). In multivariable stepwise logistic regression analysis, NTIS independently predicted clinical deterioration (adjusted odds ratio 3.19, p = .017), in addition to Ct value <25 ( p < .001), elevated C‐reactive protein ( p = .004), age >50 years ( p = .011) and elevated creatine kinase ( p = .017).

Conclusions

Non‐thyroidal illness syndrome was not uncommon even in mild‐to‐moderate COVID‐19 patients. NTIS on admission could predict clinical deterioration in COVID‐19, independent of SARS‐CoV‐2 viral load, age and markers of inflammation and tissue injury.

Related collections

Most cited references 32

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Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

Zunyou Wu, Jennifer M. McGoogan (2020)

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Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan

Xiaochen Li, Shuyun Xu, Muqing Yu … (2020)

Background In December 2019, COVID-19 outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited. Objective The severity on admission, complications, treatment, and outcomes of COVID-19 patients were evaluated. Methods Patients with COVID-19 admitted to Tongji Hospital from January 26, 2020 to February 5, 2020 were retrospectively enrolled and followed-up until March 3, 2020. Potential risk factors for severe COVID-19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients. Results We identified 269 (49.1%) of 548 patients as severe cases on admission. Elder age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-a), and high LDH level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in COVID-19 patients was 0.9%, markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male, elder age, leukocytosis, high LDH level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19. Conclusions Patients with elder age, hypertension, and high LDH level need careful observation and early intervention to prevent the potential development of severe COVID-19. Severe male patients with heart injury, hyperglycemia, and high-dose corticosteroid use may have high risk of death.

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Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial

Ivan Hung, Kwok-Cheung Lung, Eugene Yuk-Keung Tso … (2020)

Summary Background Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir–ritonavir, and ribavirin for treating patients with COVID-19. Methods This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. Findings Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5–11]) than the control group (12 days [8–15]; hazard ratio 4·37 [95% CI 1·86–10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir–ritonavir because of biochemical hepatitis. No patients died during the study. Interpretation Early triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. Funding The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.

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Author and article information

Contributors

Karen Siu Ling Lam:

ORCID: https://orcid.org/0000-0001-5757-541X

ksllam@hku.hk

Journal

Journal ID (nlm-ta): Clin Endocrinol (Oxf)

Journal ID (iso-abbrev): Clin Endocrinol (Oxf)

Journal ID (doi): 10.1111/(ISSN)1365-2265

Journal ID (publisher-id): CEN

Title: Clinical Endocrinology

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 0300-0664

ISSN (Electronic): 1365-2265

Publication date (Electronic): 12 April 2021

Electronic Location Identifier: 10.1111/cen.14476

Affiliations

[ ¹ ] Department of Medicine The University of Hong Kong Queen Mary Hospital Hong Kong China

[ ² ] Division of Chemical Pathology Queen Mary Hospital Hong Kong China

[ ³ ] Department of Microbiology The University of Hong Kong Queen Mary Hospital Hong Kong China

[ ⁴ ] Department of Pathology The University of Hong Kong Hong Kong China

Author notes

[*] [* ] Correspondence

Karen Siu Ling Lam, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

Email: ksllam@ 123456hku.hk

Author information

Karen Siu Ling Lam https://orcid.org/0000-0001-5757-541X

Article

Publisher ID: CEN14476

DOI: 10.1111/cen.14476

PMC ID: 8250365

PubMed ID: 33813743

SO-VID: 9bd05247-795c-4f01-b9af-c9b0b8391c46

License:

This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

History

Date revision received : 27 March 2021

Date received : 04 March 2021

Date accepted : 31 March 2021

Page count

Figures: 0, Tables: 4, Pages: 9, Words: 14154

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ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: covid‐19,euthyroid sick syndromes,prognosis,sars‐cov‐2,thyroid function tests,thyroid gland

Data availability:

ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: covid‐19, euthyroid sick syndromes, prognosis, sars‐cov‐2, thyroid function tests, thyroid gland