key: cord-0938464-k8r14wi1 authors: Hariyanto, Timotius Ivan; Kurniawan, Andree title: Thyroid disease is associated with severe coronavirus disease 2019 (COVID-19) infection date: 2020-07-29 journal: Diabetes Metab Syndr DOI: 10.1016/j.dsx.2020.07.044 sha: 5a59a09c1c6d8da80c380939dcd06ebde98fd6d0 doc_id: 938464 cord_uid: k8r14wi1 nan Coronavirus disease 2019 (COVID-19) has caused significant health burden across the world. Identification of factors contributing to severe disease is important to enable stratification of risk, optimize the reallocation of hospital resources, and guide public health recommendations and interventions. Unfortunately, until now, no study provides clear evidence regarding the link between thyroid disease and COVID-19. This article aims to explore the potential association between thyroid disease and the severity of COVID-19 infection. A search of the literature was conducted on Google scholar using the keywords "thyroid disease" OR "hyperthyroid" OR "hypothyroid" OR "clinical characteristics" OR "comorbidities" OR "risk factors" AND "coronavirus disease 2019" OR "COVID-19", between 2019 and present time (July 18 th , 2020) with language restricted to English only. The title, abstract, and full text of all articles identified that matched the search criteria were assessed, and those reporting the rate of thyroid disease in COVID-19 patients with a clinically validated definition of "severe disease" were included in this meta-analysis. A meta-analysis was performed using Review Manager 5.4 (Cochrane Collaboration) software. Dichotomous variables were calculated using the Mantel-Haenszel formula with fixed-effects models. We used the I 2 statistic to assess the heterogeneity, value of < 25%, 26-50%, and > 50% considered as low, moderate, and high degrees of heterogeneity, respectively. The effect estimate was reported as odds ratio (OR) along with its 95% confidence intervals (CIs) for dichotomous variables, respectively. P-value was two-tailed, and the statistical significance set at ≤0.05. A total of 17,200 records were obtained through systematic electronic searches and other ways. After screening titles, abstracts, and full texts, 8 studies [1] [2] [3] [4] [5] [6] [7] [8] with a total of 2,169 COVID-19 patients were included in the meta-analysis. The essential characteristics of included studies are summarized in Table 1 , whilst the individual and pooled ORs for thyroid disease predicting severe COVID-19 is shown in Figure 1 Based on a contrite meta-analysis of available data, thyroid disease seems to be associated with an enhanced risk of severe COVID-19 infection. Several reasons can be proposed to explain this result. First, thyroid hormones were important in the regulation of innate immune response. [9] Therefore, excess or deficiency of thyroid hormones levels observed in thyroid disease will lead to dysregulation of innate immune response. Meanwhile, innate immune response were thought to be contributed the most in the pathogenesis of COVID-19 as it is the front lines of body defense system to fight against SARS-CoV-2, the virus responsible for causing COVID-19 infection. Dysregulation of innate immune response as evidenced by higher levels of neutrophil, increased levels of CD14+ monocytes and macrophages, decreased levels of NK cells, and increased levels of complement was significantly associated with severe COVID-19 infections. [10] Second, increased levels of proinflammatory cytokines such as TNF-α and IL-6 was observed in patients with thyroid disease. [11, 12] Increased levels of these cytokines were also observed in patients with severe COVID-19 and correlates to the development of severe outcomes. [13] Finally, some thyroid patients, especially subacute thyroiditis were taking corticosteroids as their medications. [14] On the other side, meta-analysis showed that corticosteroid treatment in COVID-19 patients was associated with higher mortality, longer length of hospital stay, and higher rate of bacterial infections. [15] Patients with thyroid disease should hence be advised to take extra precaution to minimize risk exposure to the virus. Physicians should be engaged in close monitoring of thyroid disease patients with suspected COVID-19, for timely detecting signs of disease progression. Finally, the presence of thyroid disease shall be regarded as an important factor in future risk stratification models for COVID-19. Characteristics, risk factors and outcomes among the first consecutive 1096 patients diagnosed with COVID-19 in Kuwait Clinical features of patients infected with the 2019 novel coronavirus (COVID-19 Low T3 syndrome is a strong predictor of poor outcomes in patients with community-acquired pneumonia Clinical, radiological, and therapeutic characteristics of patients with COVID-19 in Saudi Arabia. medRxiv Prognostic factors in Spanish COVID-19 patients: a case series from Barcelona. medRxiv Clinical outcomes in 55 patients with severe acute respiratory syndrome coronavirus 2 who were asymptomatic at hospital admission in Shenzhen Clinical characteristics of coronavirus disease Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan Thyroid hormone action on innate immunity The innate immune system: fighting on the front lines or fanning the flames of COVID-19? Increased circulating pro-inflammatory cytokines and Th17 lymphocytes in Hashimoto's thyroiditis Expression level and clinical significance of IL-2, IL-6 and TGF-β in elderly patients with goiter and hyperthyroidism Mild versus severe COVID-19: Laboratory markers Subacute thyroiditis is treated effectively by a low dose of prednisolone The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis Figure 1. Forest plot that demonstrates the association of thyroid disease with severe COVID-19 disease The authors declare no conflict of interest regarding this article.