International Journal of Infectious Diseases 95 (2020) 376–383 Contents lists available at ScienceDirect International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid Coronavirus disease 2019 in pregnancy a,1 b,1 c,1 b a a Xu Qiancheng , Shen Jian , Pan Lingling , Huang Lei , Jiang Xiaogan , Lu Weihua , d d a b, e,f, Yang Gang , Li Shirong , Wang Zhen , Xiong GuoPing *, Zha Lei **, the sixth batch of Anhui medical team aiding Wuhan for COVID-19 a Department of Critical Care Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), No. 2, West Road of Zheshan, Jinghu District, Wuhu, Anhui, 241000 China b Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Jiang,an District, Wuhan, Hubei, 430014 China c Department of Cardiology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), No. 2, West Road of Zheshan, Jinghu District, Wuhu, Anhui, 241000 China d Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Wuhu, No. 265, Jiuhua Road, Jinghu District, Wuhu, Anhui, 241000 China e Department of Biological Sciences, Xi’an Jiaotong-Liverpool University, No. 111, Ren’ai Road, Dushu Lake Higher Education Town, Suzhou Industrial Park, Suzhou, 215123 China f Emergency and Critical Care Unit, Conch Hospital, Wuhu, Anhui, 241000 China A R T I C L E I N F O A B S T R A C T Article history: Objectives: This study aimed to compare clinical courses and outcomes between pregnant and Received 30 March 2020 reproductive-aged non-pregnant women with COVID-19, and to assess the vertical transmission Received in revised form 21 April 2020 potential of COVID-19 in pregnancy. Accepted 22 April 2020 Methods: Medical records of pregnant and reproductive-aged non-pregnant women hospitalized with COVID-19 from January 15 to March 15, 2020 were retrospectively reviewed. The severity of disease, virus Keywords: clearance time, and length of hospital stay were measured as the primary objective, while the vertical COVID-19 transmission potential of COVID-19 was also assessed. clinical feature Results: Eighty-two patients (28 pregnant women, 54 reproductive-aged non-pregnant women) with infection fi pregnancy laboratory-con rmed COVID-19 were enrolled in this study. Univariate regression indicated no SARS-CoV-2 association between pregnancy and severity of disease (OR 0.73, 95% CI 0.08–5.15; p = 0.76), virus virus clearance time (HR 1.16, 95% CI 0.65–2.01; p = 0.62), and length of hospital stay (HR 1.10, 95% CI 0.66–1.84; p = 0.71). Of the pregnant women, 22 delivered 23 live births, either by cesarean section (17, 60.7%) or vaginal delivery (5, 17.9%), and no neonate was infected with SARS-CoV-2. Conclusions: Pregnant women have comparable clinical courses and outcomes with reproductive-aged non-pregnant women when infected with SARS-CoV-2. No evidence supported vertical transmission of COVID-19 in the late stage of pregnancy, including vaginal delivery. © 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc- nd/4.0/). 1. Introduction On March 11, 2020, coronavirus disease 2019 (COVID-19), caused by the emerging severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) (Zhu et al., 2020), was * Corresponding author. Department of Obstetrics and Gynecology, The Central announced as a pandemic by the World Health Organization Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and (Cucinotta and Vanelli, 2020). At at the writing, there were 191 127 Technology, 26 Shengli Street, Jiang,an District, Wuhan, Hubei, 430014, China. Tel.: fi +86 027-65692987 / +86 15207195765. con rmed cases reported globally, with a mortality rate of 4.08% ’ ** Corresponding author. Department of Biological Sciences, Xi an Jiaotong- (WHO, 2020). Epidemiological studies indicated that people of any Liverpool University, No. 111, Ren’ai Road, Dushu Lake Higher Education Town, age were at risk of infection, and the severity was associated with Suzhou Industrial Park, Suzhou, 215123, China. Tel: +86 18155396100. age and comorbidities (Wu and McGoogan, 2020). For example, E-mail addresses: [email protected] (X. GuoPing), [email protected] cancer patients infected with SARS-CoV-2 have shown a higher risk (Z. Lei). 1 These authors contributed equally to this work. of severe events and mortality rate compared with those without https://doi.org/10.1016/j.ijid.2020.04.065 1201-9712/© 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). X. Qiancheng et al. / International Journal of Infectious Diseases 95 (2020) 376–383 377 cancer (Liang et al., 2020), and COVID-19 patients with pre-existing further analysis. The medical records of the included patients of digestive diseases were associated with more complications (Mao reproductive age were reviewed independently by two physicians et al., 2020). The higher vulnerability of these patients is likely to (QC. X and SR. L) to confirm whether the diagnosis of COVID-19 met be caused by a suppressed immune system due to the underlying the criteria according to the guidance published by the National diseases or the side-effects from treatments, including surgery, Health Commission of China. All the confirmed cases were then chemotherapy, and immunosuppressive agents. allocated to the pregnant women group or the reproductive-aged Pregnant women develop a special immunological adaptation, non-pregnant women group for further analysis. which is necessary for maintaining tolerance of the fetal semi- Data extracted from the patient records included age, time from allograft (Weetman, 2010). This state of transient suppressed onset of symptoms to hospital admission, the severity of COVID-19, immunity is modulated by suppressing T cell activity, and hence comorbidities, symptoms at onset, vital signs on admission, predisposes pregnant women to viral infections (Longman and laboratory tests, computed tomography (CT) findings, treatments Johnson, 2007; Pazos et al., 2012). In addition, the physiological (antivirus regimens, antibiotics, corticosteroids, gamma globulin), changes occurring in the respiratory and circulatory systems might virus clearance time, and length of hospital stay (LOS). For the worsen clinical outcomes when infected with a virus during pregnant women, gestational age on admission, the outcome of pregnancy (Rasmussen et al., 2020). pregnancy, and information on neonates (including birthweight, During the 2009 H1N1 influenza pandemic, pregnancy caused a Apgar score, and perinatal complications) were also recorded. higher risk of severe pneumonia, ARDS, mechanical ventilation, and death when compared with reproductive-aged non-pregnant 2.3. Outcomes and definitions women (Jamieson et al., 2009). Similar results were also reported for the severe acute respiratory distress syndrome (SARS) and The outcomes of interest included: severity of COVID-19, LOS, Middle East respiratory distress syndrome (MERS) epidemics, and virus clearance time. The neonates were tested for infection where pregnant patients were more likely to develop organ with SARS-CoV-2. Viral clearance was confirmed by serial RT-PCR, dysfunction and die (Rasmussen and Jamieson, 2020; Schwartz using samples from throat swab, with at least two consecutive and Graham, 2020; Wang et al., 2020a,b). However, in the current negative results taken 24 hours apart considered cleared. Virus COVID-19 outbreak, pregnant women seemingly have had fewer clearance time, in days, was defined as starting at the onset of maternal and neonatal adverse events than were reported for SARS symptoms and ending on the date of the first negative RT-PCR test. and MERS (Qiao, 2020), but whether pregnant women have a The diagnostic criteria for COVID-19 in neonates were the same as comparable clinical course and outcome with non-pregnant for adults, with at least two negative RT-PCR tests from throat women is still unclear. swabs after birth and no evidence of pneumonia being considered To facilitate the understanding of pregnancy in COVID-19, we as free from SARS-CoV-2 infection. The severity of disease was carried out a retrospective observational study to compare the classified as mild (mild symptoms and without pneumonia on clinical courses and outcomes of pregnant and non-pregnant chest imaging), moderate (fever and respiratory symptoms, women, and also summarized the neonatal outcomes, including radiological findings of pneumonia), severe (shortness of breath, the vertical transmission potential of COVID-19. with respiratory rate 30 breaths/minute, or oxygen saturation 93% at rest, or alveolar oxygen partial pressure/faction of 2. Methods inspiration O2 (PaO2/FiO2) 300 mmHg), and critical (respiratory failure requiring mechanical ventilation, or shock, or other organ 2.1. Study design and participants failures that needed intensive care unit admission), according to the Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis This was a single-center, retrospective study performed in The and Treatment (NHFPC, 2020). Central Hospital of Wuhan, one of five designated hospitals for pregnant women with COVID-19 in the epicenter of the SARS-CoV- 2.4. Statistical analysis 2 outbreak in China. We included pregnant women hospitalized with COVID-19 and reproductive-aged (defined as 18–41 years old; Continuous variables were summarized as either means and modified from a previous study (Creanga et al., 2010)) non- standard deviations or medians and interquartile ranges (IQR), as pregnant women infected with SARS-CoV-2 as the comparison, appropriate. Categorical variables were described as frequencies from January 15 to March 15, 2020. COVID-19 was diagnosed and percentages.