Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14 (2020) 1429e1430

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Diabetes & Metabolic Syndrome: Clinical Research & Reviews

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Thyroid disease is associated with severe coronavirus disease 2019

(COVID-19) infection
calculated using the Mantel-Haenszel formula with fixed-effects
models. We used the I2 statistic to assess the heterogeneity, value
of <25%, 26e50%, and >50% considered as low, moderate, and
Keywords: high degrees of heterogeneity, respectively. The effect estimate
Coronavirus disease 2019
COVID-19
was reported as odds ratio (OR) along with its 95% confidence inter-
Thyroid disease vals (CIs) for dichotomous variables, respectively. P-value was two-
Endocrine disease tailed, and the statistical significance set at
0.05.
Metabolic disease A total of 17,200 records were obtained through systematic elec-
tronic searches and other ways. After screening titles, abstracts, and
full texts, 8 studies [1e8] with a total of 2169 COVID-19 patients
were included in the meta-analysis. The essential characteristics
Dear Editor, of included studies are summarized in Table 1, whilst the individual
and pooled ORs for thyroid disease predicting severe COVID-19 is
Coronavirus disease 2019 (COVID-19) has caused significant shown in Fig. 1. Our pooled analysis showed a significant associa-
health burden across the world. Identification of factors contrib- tion of thyroid disease with severe COVID-19, with no relevant het-
uting to severe disease is important to enable stratification of erogeneity [OR 2.48 (95% CI 1.32e4.66), p ¼ 0.005, I2 ¼ 0%, fixed-
risk, optimize the reallocation of hospital resources, and guide pub- effect modelling].
lic health recommendations and interventions. Unfortunately, until Based on a contrite meta-analysis of available data, thyroid dis-
now, no study provides clear evidence regarding the link between ease seems to be associated with an enhanced risk of severe COVID-
thyroid disease and COVID-19. This article aims to explore the po- 19 infection. Several reasons can be proposed to explain this result.
tential association between thyroid disease and the severity of First, thyroid hormones were important in the regulation of innate
COVID-19 infection. immune response [9]. Therefore, excess or deficiency of thyroid
A search of the literature was conducted on Google scholar using hormones levels observed in thyroid disease will lead to dysregula-
the keywords “thyroid disease” OR “hyperthyroid” OR “hypothy- tion of innate immune response. Meanwhile, innate immune
roid” OR “clinical characteristics” OR “comorbidities” OR “risk fac- response were thought to be contributed the most in the pathogen-
tors” AND “coronavirus disease 2019” OR “COVID-19”, between esis of COVID-19 as it is the front lines of body defense system to
2019 and present time (July 18th, 2020) with language restricted fight against SARS-CoV-2, the virus responsible for causing
to English only. The title, abstract, and full text of all articles iden- COVID-19 infection. Dysregulation of innate immune response as
tified that matched the search criteria were assessed, and those evidenced by higher levels of neutrophil, increased levels of
reporting the rate of thyroid disease in COVID-19 patients with a CD14þ monocytes and macrophages, decreased levels of NK cells,
clinically validated definition of “severe disease” were included in and increased levels of complement was significantly associated
this meta-analysis. with severe COVID-19 infections [10]. Second, increased levels of
A meta-analysis was performed using Review Manager 5.4 proinflammatory cytokines such as TNF-a and IL-6 was observed
(Cochrane Collaboration) software. Dichotomous variables were in patients with thyroid disease [11,12]. Increased levels of these

Table 1
Characteristics of included studies.

Study Sample size Design Severe patients Non-severe patients

n (%) Age (years) n (%) Age (years)

Almazeedi S et al. [1] 2020 1096 Retrospective cohort 42 (3.8%) 55 (44e66) 1054 (96.2%) 37 (21e53)
Cao M et al. [2] 2020 198 Retrospective cohort 19 (9.6%) 63 (56e80) 179 (90.4%) 48 (33e64)
Liu J et al. [3] 2020 40 Retrospective cohort 13 (32.5%) 59 (49e70) 27 (67.5%) 43 (31e55)
Shabrawishi M et al. [4] 2020 150 Case series 16 (10.6%) 49 (34e65) 134 (89.4%) 46 (30e61)
Siso-Almirall [5]. 2020 322 Case series 56 (17.3%) 68 (53e83) 266 (82.7%) 54 (46e71)
Wang Y et al. [6] 2020 55 Retrospective cohort 2 (3.6%) 62 (62e64) 53 (96.4%) 49 (3e69)
Yan S et al. [7] 2020 168 Retrospective cohort 36 (21.4%) 61 (50.3e68) 132 (78.6%) 49 (34e60)
Zhang J et al. [8] 2020 140 Retrospective cohort 58 (41.4%) 64 (25e87) 82 (58.6%) 51.5 (26e78)

https://doi.org/10.1016/j.dsx.2020.07.044
1871-4021/© 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.
1430 T.I. Hariyanto, A. Kurniawan / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14 (2020) 1429e1430

Fig. 1. Forest plot that demonstrates the association of thyroid disease with severe COVID-19 disease.

cytokines were also observed in patients with severe COVID-19 and Obaid EF, et al. Clinical, radiological, and therapeutic characteristics of patients
with COVID-19 in Saudi Arabia. medRxiv. 2020.
correlates to the development of severe outcomes [13]. Finally,
[5] Siso-Almirall A, Kostov B, Mas-Heredia M, Vilanova-Rotllan S, Sequeira-
some thyroid patients, especially subacute thyroiditis were taking Aymar E, Sans-Corrales M, et al. Prognostic factors in Spanish COVID-19 pa-
corticosteroids as their medications [14]. On the other side, meta- tients: a case series from Barcelona. medRxiv. 2020.
analysis showed that corticosteroid treatment in COVID-19 patients [6] Wang Y, Liu Y, Liu L, Wang X, Luo N, Li L, et al. Clinical outcomes in 55 patients
with severe acute respiratory syndrome coronavirus 2 who were asymptom-
was associated with higher mortality, longer length of hospital stay, atic at hospital admission in Shenzhen, China. J Infect Dis 2020;221(11):
and higher rate of bacterial infections [15]. 1770e4.
Patients with thyroid disease should hence be advised to take [7] Yan S, Song X, Lin F, Zhu H, Wang X, Li M, et al. Clinical characteristics of coro-
navirus disease 2019 in Hainan, China. medRxiv. 2020.
extra precaution to minimize risk exposure to the virus. Physicians [8] Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical character-
should be engaged in close monitoring of thyroid disease patients istics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy;
with suspected COVID-19, for timely detecting signs of disease pro- 2020.
[9] Montesinos MDM, Pellizas CG. Thyroid hormone action on innate immunity.
gression. Finally, the presence of thyroid disease shall be regarded Front Endocrinol 2019;10. 350.
as an important factor in future risk stratification models for [10] McKechnie JL, Blish CA. The innate immune system: fighting on the front lines
COVID-19. or fanning the flames of COVID-19? Cell Host Microbe 2020;27(6):863e9.
[11] Figueroa-Vega N, Alfonso-Pe rez M, Benedicto I, Sanchez-Madrid F, Gonz alez-
Amaro R, Marazuela M. Increased circulating pro-inflammatory cytokines and
Funding Th17 lymphocytes in Hashimoto’s thyroiditis. J Clin Endocrinol Metab
2010;95(2):953e62.
[12] Lv LF, Jia HY, Zhang HF, Hu YX. Expression level and clinical significance of IL-
None.
2, IL-6 and TGF-b in elderly patients with goiter and hyperthyroidism. Eur Rev
Med Pharmacol Sci 2017;21(20):4680e6.
Declaration of competing interest [13] Velavan TP, Meyer CG. Mild versus severe COVID-19: laboratory markers. Int J
Infect Dis 2020 Jun;95:304e7.
[14] Hershman JM. Subacute thyroiditis is treated effectively by a low dose of
The authors declare no conflict of interest regarding this article. prednisolone. Clin Thyroidol 2013;25:43e4.
[15] Yang Z, Liu J, Zhou Y, Zhao X, Zhao Q, Liu J. The effect of corticosteroid treat-
Acknowledgment ment on patients with coronavirus infection: a systematic review and meta-
analysis. J Infect 2020;81(1):e13e20.

None.
Timotius Ivan Hariyantoa, Andree Kurniawanb,*
a
Faculty of Medicine, Pelita Harapan University, Boulevard Jendral
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