key: cord-0803419-tybeo7vy
authors: Cao, Dongmei; Yin, Heng; Chen, Jun; Tang, Fei; Peng, Min; Li, Ruobing; Xie, Hui; Wei, Xiaoying; Zhao, Yun; Sun, Guoqiang
title: Clinical analysis of ten pregnant women with COVID-19 in Wuhan, China: A retrospective study
date: 2020-04-23
journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
DOI: 10.1016/j.ijid.2020.04.047
sha: 7e89812bfd92b2a7e22d8596bc9f907dbfdf1997
doc_id: 803419
cord_uid: tybeo7vy

Abstract Background COVID-19 is spreading globally. This study aims to evaluate the clinical characteristics and outcomes of pregnant women confirmed with COVID-19 to provide reference for clinical work. Methods The clinical features and outcomes of 10 pregnant women confirmed with COVID-19 at Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, a tertiary- care teaching hospital in Hubei province, Wuhan, China from January 23 to February 23, 2020 were retrospectively analyzed. Results All the 10 observed pregnant women including 9 singletons and 1 twin were native people in Wuhan. All of them were diagnosed mild COVID-19, and none one of the patients developed severe COVID-19 or died. Among the 10 patients, two patients underwent vaginal delivery, two patients underwent intrapartum cesarean section, and the remaining six patients underwent elective cesarean section. All of 10 patients showed lung abnormalities by pulmonary CT images after delivery. Their eleven newborns were recorded and no neonatal asphyxia was observed. Conclusions Pulmonary CT screening on admission may be necessary to reduce the risk of nosocomial transmission of COVID-19 during the outbreak period. And COVID-19 is not an indication of cesarean section.

Since December 2019, the outbreak of the 2019 novel coronavirus disease (COVID- 19) infection has progressed to a pandemic in China, especially in Wuhan [1] . At the beginning, a series of unknown viral pneumonia cases were found in Wuhan, the capital city of Hubei province, and spread rapidly throughout China and other countries, including Thailand, Republic of Korea, Japan, United States, Philippines, Viet Nam [2] . Further investigation revealed a novel coronavirus, termed 2019-nCoVat first and subsequently SARS-CoV-2 [3] , and COVID-19 was the term agreed internationally for the name of the acute respiratory disease syndrome caused by the pathogen ultimately. As of April 5, 2020, according to data released by the National Health Commission of China, the cumulative number of confirmed cases in mainland China has reached 81708, including 77078 cured cases, 3331 death cases, and 88 suspected cases [4] . A recent study by Huang and colleagues [5] focused on the epidemiological, clinical characteristics, treatment and clinical outcomes of nonpregnant patients with laboratory-confirmed COVID-19. However, there are some reports on pregnant women with COVID-19 infection at present [6] [7] [8] [9] . In order to address the clinical features of pregnant women with confirmed COVID-19, we retrospectively reviewed clinical records, laboratory findings and chest CT scan of 10 pregnant women with laboratory-confirmed COVID-19 (tested positive on maternal throat swab), who were admitted to Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 23th to February23th, 2020.

J o u r n a l P r e -p r o o f

During the out-breaking of COVID-19, the hospitals were divided into designated hospitals for COVID-19 and other non-designated hospitals [12] . Our birth center is a big center handling about 30,000 deliveries per year in the last three years. It belongs to a non-designated hospital, so non-COVID-19 pregnant women can delivery in our center. If the confirmed cases and suspected cases were in labor, they were allowed to deliver their babies in an isolation suite. After delivery, the confirmed cases were transferred to designated hospitals for further treatment and the suspected cases continued to be observed in our isolation suite. Additionally, if the cases were not timely diagnosed for COVID-19 on admission, they could be transferred to an isolation suite anytime for observation based on symptoms such as fever and/or cough, chest CT scan, and laboratory findings. The delivered babies were transferred to an isolation suite of NICU. 

Statistical analysis was carried out using SPSS, version 19.0. Continuous variables were directly expressed as a range. Categorical variables were expressed as number (n).

All the 10 pregnant women were native people in Wuhan, who had a history of epidemiological exposure to COVID-19. The age of the pregnant women ranged from normal body temperature during hospitalization. Other symptoms such as an upper respiratory tract infection were not clinically significant too, only one patient had an occasional cough and at the same time felt slight chest tightness. All of them were diagnosed mild COVID-19, and none of them developed severe COVID-19 with severe respiratory distress, or required mechanical ventilation, or died during the treatment period in designated hospitals or home quarantine period. All cases were followed up by telephone until reported fully recovered. During the observation period, no patients had myalgia, chill, sore throat, diarrhea or chest pain. ( Table 2) Data from laboratory tests showed that only one of ten patients had lymphopenia (<1.0× 10 9 /L) on admission. After delivery, six patients exhibited lymphopenia and six patients had slight elevated concentrations of C-reactive protein (>4 mg/L). The concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lactate dehydrogenase, D-dimer and complement were normal during hospitalization in our hospital.

All of the ten patients showed lung abnormalities by chest CT images, six patients underwent CT scan before delivery on admission (one was normal, five were abnormal), and all patients underwent CT scan for postpartum fever after delivery. All of the enrolled patients showed lung abnormalities by pulmonary CT images, six patients underwent CT before delivery and one of them was normal in CT result. All of the patients were reexamined by chest CT scan 3-4 days after the first CT examination during hospitalization period in our hospital J o u r n a l P r e -p r o o f From the chest CT images, six cases showed aggravation, one case showed no change and three cases showed dissipation (Table 3) .

Four newborns were premature, two of them had a birthweight lower than 2500 g. All eleven live births had a 1-min Apgar score of 8-9 and a 5-min Apgar score of 10 ( Table 3) . 11 newborns (including twins) underwent throat swab test for COVID-19 after birth and the results were negative. From birth to February 25, 2020, which was a 14-day period, no neonatal death or neonatal asphyxia was observed, and no one presented with fever, cough, or diarrhea. (Table 4) The chest CT images [5, 13, 14] , including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV and SARS-CoV-2. The pandemic of SARS, MERS and COVID-19 demonstrate that coronaviruses are a significant public health threat causing significant loss of life [15, 16] . When the SARS-CoV and MERS-CoV infected pregnant women, poor obstetric outcomes can be resulted, including maternal morbidity and death [17] [18] [19] [20] , but there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present COVID-19 epidemic [17] . The COVID-19 has at least 70% similarity in genetic sequence to SARS-CoV [21] . However, the effect of COVID-19 on pregnant women remains unknown at present. Due to the normal maternal physiologic changes and immune suppression during the pregnant period, these women are particularly susceptible to respiratory pathogens. During the Asian flu epidemic in 1957-1958, 10% of mortality occurred in pregnant women, and the fatality rate of pregnant women was twice as high as that of infected women who were non-pregnant [22] . A case-control study [18] on the effect of SARS among pregnant women and nonpregnant women revealed that maternal mortality rate, renal failure, disseminated intravascular coagulopathy (DIC), the intensive care unit (ICU) admission rate were J o u r n a l P r e -p r o o f higher in pregnant SARS patients. Huang C et al [5] reported that the COVID-19 infection of non-pregnant people caused clusters of severe respiratory illness similar to SARS, of which common symptoms were fever (98%), cough (76%), and myalgia or fatigue (44%), less common symptoms were sputum production (28%), headache (8%), haemoptysis (5%), and diarrhoea (3%), and the complications were acute respiratory distress syndrome (29%), RNA anaemia (15%), acute cardiac injury (12%) and secondary infection (10%) . However, in our study, none of the ten pregnant women developed or died of severe COVID-19 pneumonia but only showed similar clinical symptoms to non-pregnant adult patients such as fever and cough, whereas others common symptoms such as myalgia, sore throat and dyspnea were not observed. This is probably due to the fact our hospital is not a designated hospital for COVID-19 and lacks serious patients with typical symptoms, only a small number of cases were enrolled in our observation and the patients' length of stay was short.

Therefore, we should also be alert to the possibility that the disease course and prognosis of COVID-19 could follow the same trend as SARS in pregnant women.

In our study, ten pregnant women were tested positive for COVID-19, while only one patient had lymphopenia on admission, and six cases exhibited lymphopenia after delivery. Three cases did not have any discomfort. In contrast, all patients showed lung abnormalities in chest CT images. However, among them five patients showed pleural effusion, which was different from the topical images like patch, strip, or GGO [10] . The produce of pleural effusion probably due to postpartum physiological changes in pregnant women. Therefore, non-specific manifestations such as pleural effusion should also be attached with great attention in diagnosis of COVID-19 infection if there is postpartum fever. In Wuhan where the incidence of COVID-19 is exceptionally high, it is necessary to do pulmonary CT screening on admission, which will help to detect asymptomatic infection and latent period patients, thus reducing the transmission of virus between people and nosocomial infection.

Chen H et al [6] observed that all nine pregnant women underwent cesarean delivery (CD), and the indications for CD were severe pre-eclampsia, a history of CD and fetal J o u r n a l P r e -p r o o f distress. In our study, two patients underwent vaginal delivery successfully, two patients underwent intrapartum CD for fetal distress, and the remaining six pregnant women underwent selected CD directly for previous CD history, pre-eclampsia, placenta abruption, twins pregnancy. Although COVID-19 infection is not one of the indications for CD, given the uncertainties of a novel disease, we may be more inclined to choose CD.

Previous studies [18] [19] have shown that pregnant women with SARS is associated with a high incidence of adverse neonatal complications, such as spontaneous miscarriage, preterm delivery, intrauterine growth restriction. Zhu et al [7] studied 9 new babies delivered by COVID-19-confirmed women and found 6 were born premature, 2 were small-for-gestational infants and 1 was large-for-gestational infant and 6 had a pediatric critical illness score less than 90, which indicates that perinatal COVID-19

infection may have adverse effects on newborns. But in our study, only four babies were treated for premature delivery and the other seven babies were observed in an isolated NICU suite. Moreover, we followed up the eleven newborns and found that they did not exhibit respiratory distress, fever, feeding intolerance, vomiting or death up to the present time. The difference of results reported here from other publications may be simply due to the small number or other relative risk factors. Although all ten pregnant women tested COVID-19 positive, 5 of these newborns tested negative. This result is consistent with the latest research [6, 7] and past studies of SARS [18, 20] . These data do not support the possibility of vertical transmission of CoVs infection but the small sample size suggests caution in making this assumption.

There are several limitations in our study. First, the sample size was small, collected from non-designated hospital of COVID-19. Second, we did not take throat swab samples from the two newborns delivered vaginally to exclude the possibility of spreading COVID-19 via vaginal delivery. It should be noted also that the diagnosis of COVID-19 in puerpera were 2 days after natural delivery. Third, the samples such as placenta, amniotic fluid and cord blood were not collected for COVID-19 test. 

No funding is associated with this report.

The study protocol was approved by the Ethics Committee of Maternal and Child Health Hospital of Hubei Province. (Record number: [2020]IEC(XM002)). All parturient women with COVID-19 had signed informed consent to publish.

No funding agencies had role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; review, or approval of the manuscript; or decision to submit the manuscript for publication.

The authors declare that they have no competing interests. Placental abruption

Elective CD Yes Yes -Yes --Yes Yes Yes -8 

A Novel Coronavirus from Patients with Pneumonia in China

The outbreak of COVID-19: An overview

Rapid random access detection of the novel SARScoronavirus-2 (SARS-CoV-2, previously 2019-nCoV) using an open access protocol for the Panther Fusion

National Health Commission of the People's Republic of China. The latest situation of novel coronavirus pneumonia as of 24:00 on 23

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia

Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review. Fetal 10. National Health Commission of the People's Republic of China. The National Health Commission of China

Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases. Interim guidance

Public Announcement on Designated Hospitals for Treatment of Pneumonia Infected by Special Population of COVID-19 in Hubei Province

Determination and application of immunodominant regions of SARS coronavirus spike and mucleocapsid proteins recognized by sera from different animal species

Mers-cov: understanding the latest human coronavirus threat

Epidemic and Emerging Coronaviruses (Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome)

From SARS to MERS, Thrusting Coronaviruses into the Spotlight

Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections

A casecontrolled study comparing clinical course and outcomes of pregnant and nonpregnant women with severe acute respiratory syndrome

WHO. Consensus Document on the Epidemiology of Severe Acute Respiratory Syndrome (SARS)Available online

Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome

The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health -The latest 2019 novel coronavirus outbreak in Wuhan, China

Observations on excess mortality associated with epidemic influenza

All data are publicly available or listed in the results of the paper J o u r n a l P r e -p r o o f Apgar score (1, 5 min) 8,10 9,10 8,10 8,10 9,10 9,10 8,10 9,10 9,10 9