key: cord-0792168-w58lw2lp
authors: Davoodi, Lotfollah; Oladi, Ziaeddin; Jafarpour, Hamed; Zakariae, Zakaria; Soleymani, Eissa; Razavi, Alireza
title: A 33-year-old man with COVID-19 presented with subacute thyroiditis: A rare case report
date: 2021-03-22
journal: New Microbes New Infect
DOI: 10.1016/j.nmni.2021.100871
sha: 6655ae1eb8b615340b2202952486d88c5bb523dc
doc_id: 792168
cord_uid: w58lw2lp

We report the first case of the novel coronavirus infectious disease 2019 (COVID-19) presented with subacute thyroiditis (SAT) in Ghaemshar, Mazandaran Province, Iran. In our patient, with the initiation of corticosteroid therapy, the symptoms of SAT gently disappeared with the gradual increase in thyroid-stimulation hormone (TSH) and the gradual elimination of thyrotoxicosis. This case shows that decreased TSH and persistent thyrotoxicosis may make the patient's condition worse. Managing this complication can take several weeks and can be complicated.

In December 2019, unknown pneumonia was reported in Wuhan, China, which belongs to the 12 coronavirus family [1, 2] . The disease is highly contagious, with the pandemic reported in the 13 51 st World Health Organization Status Report on 11 March 2020. The disease was caused by a 14 virus called severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), which was later 15 named coronavirus infectious disease 2019 . COVID-19 covers a wide range of 16 symptoms but until now [3] , reports on subacute thyroiditis (SAT) patients with COVID-19 are 17 limited [4] . Here, we report the first confirmed case of COVID-19 presented with SAT in 18 Ghaemshahr, Mazandaran Province, Iran; the patient, who was admitted to our clinic, ultimately 19 achieved remission and was discharged. The aim of this case report is to improve the 20 comprehension of the disease for clinicians, with a specific emphasis on SAT in COVID-19 21 patients. 22

A 33-year-old man presented to the clinic with fever (38.5 °C), sore throat, body aches, and 24 lethargy for 2 days on September 25, 2020. Throat examination and lung auscultation were 25 normal. Initial laboratory tests on admission to the clinic showed an elevated white blood cell 26 count (2335×10 9 /L), high C-reactive protein level (CRP) (46 mg/L, normal: <10 mg/L), normal 27 hemoglobin level (14.1 g/dL), and thrombocytopenia (142 × 10 3 /mcL). Because of clinical 28 features and COVID-19 pandemic, nasopharyngeal swab was used for sampling, and SARS-29

CoV-2 nucleic acid was detected by reverse transcriptase-PCR (rtPCR), and acetaminophen, 30 naproxen, and diphenhydramine were prescribed. On the sixth day, he presented to Emergency 31 J o u r n a l P r e -p r o o f Room (ER) with fever (39 °C) and chills, sweating, sore throat, and dry cough. Except for the 1 heart rate (HR, over 100 beats/min), all other vital signs were in the normal range. 2 Electrocardiogram (ECG) revealed sinus tachycardia. After admission, a lung CT scan showed 3 bilateral peripheral ground-glass opacification (GGO) (Figure 1 ). Due to GGO and clinical 4 symptoms, nasopharyngeal swabs were used for sampling, and SARS-CoV-2 nucleic acid was 5 detected again by rt-PCR. By controlling the patient's fever with injection acetaminophen, HR 6 decreased to 90 b/min. In laboratory tests, troponin and electrolytes were normal. Interleukin 6 7 and D-dimer were 11 pg/ml (normal:<6 pg/ml) and 156 µg/ml (normal:<1 mcg/ml), respectively. 8

Remdesivir 200 mg on the first day, followed by 100 mg daily with enoxaparin 60 mg started for 9 4 days. On the Eighth day, the general condition of the patient improved, but he complained of a 10 sore throat. On re-examination, we noticed a slight tenderness in the neck in the thyroid area. On 11 thyroid ultrasound, a heterogeneous thyroid gland with bilateral ill-defined hypoechoic areas 12 revealed SAT. No cervical lymphadenopathy was noted. His laboratory tests revealed elevated 13 erythrocyte sedimentation rate (ESR) (84 mm/hr, normal: <15 mm/hr), CRP (37.9 mg/L, normal: 14 <10 mg/L), normal platelet, and leukocyte counts. His thyroid function tests (TFTs) were 15 thyroid-stimulation hormone (TSH) < 0.001 mUI/L, total T4 23.1 mcg/dL (normal range: 4-11 16 mcg/dL), and total T3 236 ng/dL (normal range: 75-195 ng/dL) ( Table 1) . Thyroperoxidase 17 antibody (anti-TPO) and thyrotropin receptor antibody (TRAb) were negative (Table 1 ). In blood 18 culture, after 48 hours of incubation, bacterial culture was negative. Autoimmune thyroiditis, 19

Graves' disease, and infectious thyroiditis were ruled out due to the negativity of TRAb and 20

TPOAb as well as the lack of bacterial growth in blood cultures after 48 hours of incubation. 21

Eventually, given the recent COVID-19 infection, it is suspected that the SAT was caused by 22 COVID-19. The patient has treated with dexamethasone 4 mg every 8 hours for 5 days. He 23 discharged with oral prednisone 25 mg daily with taper prescribed. The patient's follow-up was 24 performed 10 days, one month, and 45 days later with TFTs and also, he had no initial symptoms 25 (Table 1) . 26

SAT is a self-limited thyroid disorder associated with a three-stage clinical course of an initial 28 thyrotoxic phase, hypothyroidism, and return to normal thyroid function within three months [5] . 29

This complication is one of the uncommon causes of thyrotoxicosis and is characterized by a 30 painful tenderness in the thyroid gland by referring the pain to the ear along with symptoms such 31 J o u r n a l P r e -p r o o f as fever, lethargy and anorexia [6] . The exact cause of SAT is not known, but several viruses 1 (such as influenza, Epstein-Barr virus, hepatitis E, cytomegalovirus, mumps, HIV, and 2 chickenpox) have been conjectured to stimulate SAT through inducing direct or indirect damage 3 via the circulation of the viral genome or virus-specific antibodies [7] . It seems that SARS-Cov-2 4 can cause SAT [8] . In the cases we examined, patients with COVID-19 developed SAT after 5 partial recovery (Table 2) [4, [9] [10] [11] [12] [13] . The minimum and maximum interval from the onset of 6 COVID-19 symptoms to the onset of SAT symptoms was 4 [11] to 30 [10] days, respectively 7 (Table 2) . Also, the minimum and maximum interval between the onset of SAT symptoms and 8

SAT recovery was 4 [11] to 10 [4, 12] weeks (Table 2 ). In our case, the interval between the 9 onset of the first symptoms of COVID-19 and the onset of SAT symptoms and the interval 10 between the onset of SAT symptoms and recovery was 10 days and 7 weeks, respectively (Table  11 2). 12

Diagnosis of this complication is usually clinical, which is confirmed by laboratory tests and 13 neck imaging. Increased ESR (greater than 50 mm/hr), elevated CRP, low TSH, and high levels 14 of thyroid hormones and thyroglobulin along with absent/low titers of serum thyroperoxidase 15 and thyroglobulin antibodies confirm the diagnosis of SAT [14] . In imaging techniques, during 16 the acute phase of radionuclide thyroid scan, the amount of tracer uptake is usually reduced or 17 absent at all, while thyroid ultrasound shows bilateral hypoechoic areas with reduced or no 18 vascularization [15] so that in our patient's ultrasound, bilateral hypoechoic areas were 19 diagnosed. In our case due to negative TRAb and anti-TPO as well as negative blood culture 48 20 hours after incubation, autoimmune thyroiditis, Graves' disease, and infectious thyroiditis were 21 ruled out. 22

The incidence of SAT is 12.1 per 100,000 per year and is more prevalent in young women than 23 disease and were studied three months after recovery, four patients (6.6%) were diagnosed with 30 primary hypothyroidism [19] , and thyroid lesions were found in the autopsies of people who died 31 J o u r n a l P r e -p r o o f of SARS [20] . Given that SARS-CoV-2 and SARS-CoV are in the same family, there is a 1 possibility that COVID-19 also has the potential to impair thyroid function [21] . It has been 2 reported that messenger RNA (mRNA) encoding expression for the angiotensin-converting 3 enzyme 2 (ACE-2) receptor in thyroid follicular cells makes them a potential target for SARS-4

CoV-2 entry [22] . Moreover, the inflammatory response may cause local damage and apoptosis 5 of thyroid cells [9] . 6

In a single-center prospective study, low PCR cycle threshold values of SARS-CoV-2 and CRP 7 were independently associated with low TSH (p = 0.030) and low free T3 (fT3) (p = 0.007), 8 respectively. Furthermore, the decrease in fT3 was associated with an increase in COVID-19 9 intensity (p = 0.032). In other words, patients with low fT3 had more adverse results than other 10 patients [23] . A separate study illustrates that a significant number of COVID-19 patients who 11 require intensive care develop thyrotoxicosis and decreased TSH concentrations, in line with the 12 SAT induced by SARS-CoV-2. In our patient, with the initiation of corticosteroid therapy, the 13 symptoms of SAT gently disappeared with the gradual increase in TSH, and the gradual 14 elimination of thyrotoxicosis. Therefore, the diagnosis and treatment of thyroid disorders, 15 including SAT, in patients with COVID-19, especially those in need of intensive care, should not 16 be neglected [24] . Remdesivir is a drug previously consumed to treat Ebola virus infection [25, 17 26 ]. According to the COVID-19 pandemic, in the randomized clinical trials, positive results 18 were obtained from the use of this drug in COVID-19 therapy and finally was approved by the 19 US Food and Drug Administration [27] . However, the use of this drug is associated with some 20 side effects. The most common side effects are nausea and elevated liver transaminases, which 21 have been reported in patients with . To date, no side 22 effects of thyroiditis have been reported with this drug. Therefore, in our patient, the occurrence 23 of SAT due to the use of remdesivir seems unlikely. In patients with COVID-19 who develop 24 SAT, care should be taken in the treatment so that the patient does not develop hypothyroidism 25 later, as reported in an Indian 58-year-old man ( The exact mechanism of SAT production due to COVID-19 does not fully clarify, but it can be 27 controlled and treated using corticosteroids. Although COVID-19 presented with SAT is a rare 28 condition, regardless of gender, we need to be watchful about the SAT potential complications as 29 an important and treatable status for COVID-19 especially in patients with severe conditions. thyrotropin receptor antibody; tT4: total thyroxine; tT3: total tri-iodothyronine, fT4: free thyroxine, fT3: free tri- 

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