key: cord-0790035-jcpube4u
authors: Zheng, Hua; Tan, Juan; Ma, Ke; Meng, Weihua
title: Changes in RT‐PCR test results and symptoms during the menstrual cycle of female individuals infected with SARS‐CoV‐2: Report of two cases
date: 2020-07-14
journal: J Med Virol
DOI: 10.1002/jmv.26275
sha: c4793ada9237f6f0749c1e74e5eb302e0df64439
doc_id: 790035
cord_uid: jcpube4u

The implications of the menstrual cycle for disease susceptibility, development, and severity of acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection are largely unknown. Here, we describe two women infected with SARS‐CoV‐2 whose real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) test results and symptoms changed during the menstrual cycle. The first patient developed a fever on the first day of her menstrual period, and again on the first day of her next menstrual period after hospital discharge. RT‐PCR test results were positive during the first menstrual period before admission, but turned negative during hospitalization, and then were positive again during the second menstrual period after hospital discharge. Another one also developed a fever again on the first day of her menstrual period after hospital discharge. RT‐PCR test results were negative before admission and during hospitalization, but turned positive during the first menstrual period after hospital discharge. The cases indicate sex hormones may play an important role in SARS‐CoV‐2 infection. For women with history of exposure to SARS‐CoV‐2, the management protocol should include assessment of the menstrual status.

The 2019 novel coronavirus infection , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a major global health threat since December 2019. [1] [2] [3] [4] As of 27 June 2020, the pandemic had registered 9 473 214 cases and 484 249 deaths worldwide. 5 A population level observational study by Sun et al 6 revealed that a sharp increase of COVID-19 was reported among people aged between 30 and 50 years, and 40% of the patients were female, indicates women of childbearing age are at high risk of infection.

Growing evidence indicate that female immunity changes over the menstrual cycle. 7 dinner with her relative on 12 January 2020. Five days later, her relative had a fever and was confirmed to be infected with SARS-CoV-2. The woman had no fever or any other gastrointestinal or respiratory symptoms until 28 January 2020, the first day of her menstrual period ( Figure 1A ). At first, she had only a slight and intermittent fever. However, the next day afternoon, she developed high fever, tiredness, and lack of appetite. Because of the possibility of infection with SARS-CoV-2, she was prescribed ibuprofen, oseltamivir (75 mg every 12 hours orally), arbidol (0.2 g every 8 hours orally), and moxifloxacin (0.4 g every day orally) by a community physician. Lopinavir and ritonavir tablets (200 mg/50 mg every 12 hours orally) were added to her antiviral regimen 2 days later. Her symptoms did not improve, which prompted her to come to the emergency department on 2 February 2020. Although chest auscultation was normal, chest computerized tomography (CT) scans showed bilateral lower lobe infiltrates (Figure 2A ). Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test for nucleic acid of SARS-CoV-2 on an oropharyngeal swab was performed as described in a previous study. 2 The same technician and brand of test kit (Novel Coronavirus PCR Fluorescence Diagnostic Kit, BioGerm Medical Biotechnology), which was recommended by the Chinese Center for Disease Control and Prevention, was used in this report.

The result of RT-PCR test was positive. The patient was asked to selfquarantine at home because of the limited number of hospital beds in Wuhan at that time. Her temperature dropped to normal 1 day later, the last day of her menstrual period.

On 4 February 2020, the patient was hospitalized with COVID-19.

On admission, the physical examination revealed body temperature of 97.5°F (36.4°C), blood pressure of 98/61mm Hg, pulse rate of 78 beats per minute, respiratory rate of 20 breaths per minute, and oxygen saturation of 95% on room air. The results of her laboratory testing showed a C-reactive protein count 12.3 mg/L (<1 mg/L indicates low risk of cardiovascular disease; 1-3 mg/L indicates medium risk of cardiovascular disease; >3mg/L indicates high risk of cardiovascular F I G U R E 1 Timeline of changes of RT-PCR test results and symptoms during the menstrual cycle of cases infected with SARS-CoV-2. Case one (A). A, Sixteen days after exposure to SARS-CoV-2, fever occurred on the first day of her menstrual period, and again on the first day of her next menstrual period after hospital discharge. RT-PCR test results were positive during the first menstrual period before admission, turned negative during hospitalization, and then positive again during the second menstrual period, which occurred after hospital discharge. Case two (B). B, Fever occurred two days before her menstrual period, and again on the first day of her next menstrual period after hospital discharge. RT-PCR test results were negative before admission and during hospitalization, but turned positive during the first menstrual period after hospital discharge. RT 

A 44-year-old, previously healthy (gravida 1, para 1, regular menstrual cycle, and no history of hormonal therapies), woman was working as a nurse in a hospital in Wuhan, China. On 24 January, she began to have a slight fever, peaking at 100.4°F (38°C) at night ( Figure 1B) . Because of the possibility of infection with SARS-CoV-2 due to occupational contact history, she was prescribed arbidol (0.2 g every 8 hours orally) by a physician. On 26 January 2020, the first day of her menstrual period, she developed tiredness, muscle soreness, palpitation, and lack of appetite. She continued taking arbidol during the menstrual period, but the symptoms did not improve. On 2 February, the patient went to outpatient department in a hospital.

Chest CT scans showed multiple infiltration in the bilateral lung view Figure 2H ). The patient still had a slight and intermittent fever until 25 February 2020, the day before the last day of her menstrual period. Since then, her temperature had remained normal. The RT-PCR test on oropharyngeal swab was performed on 28 February 2020, the results were negative.

There are reported sex differences in the susceptibility and outcomes of infectious disease. 9,10 A recent epidemiological study of the COVID-19 outbreak shows that SARS-CoV-2 might have a longer incubation period and less pronounced symptoms in women than in men. 11 However, the mechanism underlying these differences remains unclear. Here, we report two women infected with SARS-CoV-2 whose RT-PCR test results and symptoms changed during the menstrual cycle. The first patient developed a fever on the first day of her menstrual period, and again on the first day of her next menstrual period after hospital discharge. RT-PCR test results were positive during the first menstrual period before admission, turned negative during hospitalization, and then positive again during the second menstrual period, which occurred after hospital discharge. Another patient also developed a fever again on the first day of her menstrual period after hospital discharge. RT-PCR test results were negative before admission and during hospitalization, but turned positive during the first menstrual period after hospital discharge. These cases indicate sex hormones may play an important role in SARS-CoV-2 infection.

In female humans, the levels of sex hormones, largely estrogens and progesterone, vary during the menstrual cycle and decrease sharply before menstruation. 12 The dramatic fluctuation in sex hormone levels is associated with changes in immune function and response to respiratory virus infections. 13 In an animal model of influenza A virus infection, estrogen is reported to be a potent antiinflammatory hormone and to reduce adaptive immune responses and protect hosts from influenza A virus-mediated pathogenesis. 14 In summary, our report provides an initial view of the association between the menstrual cycle, symptoms and RT-PCR test results.

Future studies in large cohorts are necessary to address the effect of sex hormones on the clinical course of COVID-19.

A novel coronavirus from patients with pneumonia in China

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

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Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series

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Changes in RT-PCR test results and symptoms during the menstrual cycle of female individuals infected with SARS-CoV-2: Report of two cases

The authors thank the patients for cooperating with the investigation. 

manuscript. This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

The authors declare that there are no conflict of interests.

All authors discussed the results and commented on the manuscript.Specifically, HZ and JT contributed to the conception of the idea and the study design. HZ and JT prepared the data set, performed the analysis, and wrote the manuscript. KM contributed to analysis and interpretation of data. WM provided intellectual inputs for the project and critical comments on the manuscript.

All data generated or analyzed during this study are included in this published article.

Institutional Review Board (IRB) approval for this report was granted through the ethic committee of Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-C20200142). The signed consent has been obtained from the patients in this case report.

http://orcid.org/0000-0003-0134-0990