COVID-19, SARS-CoV-2 and Pregnancy: Does the Past Predict the Present?
Preliminary evidence indicates no direct evidence for intrauterine transmission of the SARS-CoV-2 virus from pregnant women with COVID-19 to their infants.
The growing spread of COVID-19 has created widespread concern and has become one of the most significant global public health problems in recent years. The etiologic agent, SARS-CoV-2 (initially termed 2019-nCoV for 2019 novel coronavirus) is a coronavirus belonging to the Betacoronavirus genus. Two other members of this genus have caused past outbreaks of human disease: severe acute respiratory syndrome (SARS) caused by SARS-CoV, and the Middle East respiratory syndrome (MERS) caused by MERS-CoV. As of February 26, 2020 there have been 81,109 confirmed cases of COVID-19 including 78,191 cases and 2718 fatalities in China, and 2918 confirmed cases and 44 deaths in 37 other countries. As is the case in many large and expanding epidemics, these numbers likely underestimate the prevalence of disease, with the actual number of infected individuals remaining unknown.
While there has been a quickly expanding knowledge base of the genetic, virologic, epidemiologic, and clinical aspects of this new coronavirus pathogen, an important and unanswered question is whether this virus can be transmitted during pregnancy, a process termed vertical transmission.
A recent analysis of previous outbreaks of SARS and MERS outbreaks reveals that there has never been a confirmed case of maternal-fetal coronavirus transmission. During the SARS outbreak that occurred from 2002 to 2003 there were 12 women reported to be infected while pregnant. Adverse clinical outcomes resulting from SARS-CoV infection among this cohort included 4 of 7 women having miscarriages in the first trimester, and 2 of 5 women in the second and third trimester having a newborn with intrauterine growth restriction (IUGR).
Four of 5 pregnancies resulted in preterm birth—1 spontaneous and 3 induction deliveries were performed for maternal conditions. Three women died during their pregnancy, representing a case fatality rate of 25%. MERS is also associated with adverse obstetrical outcomes. A review of 11 pregnant women with MERS-CoV infections revealed that 10 (91%) had poor obstetrical outcomes that included neonatal intensive care hospitalization, severe maternal respiratory disease, premature delivery and neonatal mortality. Thus, although both SARS and MERS were associated with poor obstetrical outcomes, there were no identified cases of intrauterine transmission of either SARS-CoV or MERS-CoV.
On February 12, 2020 a report was published with details of 9 pregnant women with reverse transcription polymerase chain reaction (rt-PCR) confirmed SARS-CoV-2 infection delivered by cesarean section at the Zhongnan Hospital of Wuhan University in China. The report found no evidence of vertical transmission. The mothers had fever (7), cough (4), myalgia (3), sore throat (2) and malaise (2). Eight mothers had abnormal chest radiographs, 6 had elevation of C-reactive protein, 5 had lymphopenia and 3 had increased aminotransferase levels. All 9 mothers were administered oxygen by nasal cannula and received empiric antibiotic therapy; 6 were administered antiviral therapy. All of the infants were liveborn with no evidence of birth depression or asphyxia and had good 1- and 5-minute Apgar scores.
Four infants were born prematurely, but none were born earlier than 36 weeks of gestation. The presence of SARS-CoV-2 was evaluated in samples of amniotic fluid, umbilical cord blood, neonatal throat swabs and breast milk that were taken in the delivery room from 6 patients. Testing for SARS-CoV-2 utilizing rt-PCR assays were all negative, and there was no evidence for intrauterine viral transmission among these newborns.
A February 25, 2020, report describes 3 pregnant women at the Tongji Hospital of Huazhong University who acquired COVID-19 in Wuhan during the late third trimester. All 3 women had rt-PCR confirmed SARS-CoV-2 infection prior to delivery. All 3 infants were delivered full-term: 2 by cesarean section and 1 by elective vaginal delivery. The Apgar scores of all 3 infants were 8 and 9 at 1 and 5 minutes, respectively. None of the newborns had SARS-CoV-2 infection. Testing of a variety of neonatal specimens including placenta, serum and blood, umbilical cord blood, oropharyngeal swabs, urine, feces, as well as maternal specimens including breast milk and vaginal secretions, were all negative for the novel coronavirus.
During the COVID-19 epidemic, 2 cases of confirmed neonatal infection have occurred thus far. One was an infant diagnosed at 17 days of life having a history of close contact with 2 confirmed cases of SARS-CoV-2 infection (mother and nanny), and the other was a neonate who was found to be infected 36 hours following delivery. In both infants there was no direct evidence for vertical transmission, and because viral testing was delayed, a postpartum neonatal infection acquired through an infected contact could not be eliminated.
Similar to the obstetrical outcomes previously described among pregnant women who developed SARS and MERS, at the present time there is no direct evidence for maternal-fetal transmission of SARS-CoV-2. However, the number of cases investigated so far is small, and the published study had a short investigation, and is restricted to women developing SARS-CoV-2 infection in the third trimester. Additional attention will need to focus on the clinical obstetrical and neonatal outcomes of women who develop COVID-19 during pregnancy. It is important to remember that pregnant women can have greater susceptibility to infectious diseases as a result of the physiological changes that accompany pregnancy. Based upon previous experiences with SARS, MERS, and influenza, pregnant women are at an increased risk for developing severe pneumonia following infection with respiratory pathogens, especially if they have chronic or pregnancy-related co-morbid conditions.
Schwartz is a clinical professor at the Medical College of Georgia and specializes in global maternal health. He is involved with public health and transmission aspects of such emerging infectious diseases as Zika and Ebola viruses as they affect pregnant women and infants. He is a member of Contagion®’s Editorial Advisory Board.