Section 2.3: Congenital and perinatal infections with SARS-CoV-2 (from DOI: 10.1016/j.jcv.2020.104372)
From publication: "SARS-CoV-2: Is it the newest spark in the TORCH?" published as J. Clin. Virol.; 2020 Apr 14 ; 127 104372. DOI: https://doi.org/10.1016/j.jcv.2020.104372
Section 2.3: Congenital and perinatal infections with SARS-CoV-2
To date, the morbidity and mortality described for SARS-CoV-1 and MERS-CoV infections during pregnancy do not appear to be as severe for SARS-CoV-2. Most reviews have concluded there is no conclusive evidence of transplacental transfer of SARS-CoV-2 from mothers with COVID-19 disease. A recent review and summary of COVID-19 cases, chiefly compiled from those published in a series of reports from China, described 38 pregnant women with COVID-19 and their newborns and included information on clinical, laboratory and virologic data. This analysis revealed that, unlike coronavirus infections of pregnant women caused by SARS and MERS, in the 38 pregnant women with COVID-19 there were no maternal deaths. Signs and symptoms of illness were described in some infants born to SARS-CoV-2 infected mothers, including shortness of breath, fever, thrombocytopenia, abnormal liver function tests, tachycardia, vomiting, and pneumothorax; one infant born prematurely (at an estimated gestational age of 34 weeks) died due to refractory shock, multiple organ failure and disseminated intravascular coagulation. Despite evidence of illness in some newborns, it was noted that there had been no virologic evidence of newborn infection, and no confirmed cases of intrauterine transmission of SARS-CoV-2 from mothers.
After this review was published, another analysis of COVID-19 cases examined the outcomes of 55 pregnant women infected with COVID-19, and 46 neonates, reported in the literature and also concluded that there was no definite evidence of vertical transmission. Other reports and small case series have provided similar reassuring observations. However, standing in contrast to these reassuring observations are a series of more recent case reports that seem to document that vertical (in utero) transmission of SARS-CoV-2 can indeed occur. In one study reported from Zhongnan Hospital of Wuhan University in China, six women with mild COVID-19 disease gave birth via Caesarean section to infants using multiple infection control measures, including isolation of their infants immediately following delivery. Notably, two of these six infants had IgM antibodies to SARS-CoV-2 present, although neither infant had symptoms. All of these infants were repeatedly negative when tested for viral RNA upon subsequent testing, leaving only the demonstration of IgM antibody as a marker defining fetal transmission. In a second report from Wuhan hospital, viral nucleic acid testing made for a more compelling case for vertical transmission. This analysis of 33 neonates born to mothers with COVID-19 identified three neonates with SARS-CoV-2 infection. In one infant, chest radiographic image showed pneumonia within 48 h of age, and nasopharyngeal and anal swabs were positive for SARS-CoV-2 RNA on days 2 and 4 of life. A second infant born to a woman with confirmed COVID-19 pneumonia developed lethargy, vomiting, and fever. A chest radiographic image revealed pneumonia, and nasopharyngeal and anal swabs were positive for SARS-CoV-2 on days 2 and 4 of life. The third patient was born at 31 weeks gestation by Cesarean delivery; neonatal respiratory distress syndrome and pneumonia were confirmed by chest radiographic image on admission, and nasopharyngeal and anal swabs were positive for SARS-CoV-2 on days 2 and 4 of life (and negative on day 7). Thus, SARS-CoV-2 was not only transmitted vertically, but caused disease in the infected newborns. A third study also demonstrated a positive IgM serology in a neonate born by Cesarean section to a mother with SARS-CoV-2 pneumonia. The infant was delivered in a negative-pressure isolation room, and her mother wore an N95 mask and did not hold the infant. The positive IgM titer in the newborn, along with an elevated cytokine profile, suggested vertical transmission had occurred, although nucleic acid studies were negative.
Thus, SARS-CoV-2 can likely be transmitted to the fetus pre-natally or to the newborn infant post-natally. Non-congenital routes of perinatal transmission could include aerosol and droplet transmission in the delivery room, or transmission in the birth canal. Another important possible route of post-natal transmission could be through breastfeeding. Studies reported to date do not find any evidence of COVID-19 in breast milk, although more studies are needed. Both intrapartum transmission during vaginal delivery and post-natal acquisition via breast milk are well-described for CMV infection. These modes of transmission may complicate the analysis of whether an infant undergoing assessment for congenital CMV may have acquired infection in utero versus post-natally. Clinicians should learn lessons from these congenital/perinatal CMV infection considerations, and be mindful that these same issues may complicate the question of whether an infant with SARS-CoV-2 acquires infection by a pre-natal versus a post-natal route.
Although the studies performed to date leave us with mixed findings about whether SARS-CoV-2 can be acquired in utero, enough evidence exists of pre-natal acquisition that the transplacental route should be assumed to be a mechanism of transmission unless proven otherwise by future studies. The various studies reported to date are summarized in Table 1 . It is also uncertain what measures should inform guidelines about the separation of a COVID-19 positive mother and her newborn infant, given inconsistent recommendations across expert groups. At this time, the WHO advises that infected mothers can share a room with their infant and breastfeed but should practice "respiratory hygiene", including washing their hands and wearing a mask, acknowledging that a mask might not be available. The CDC advises that facilities should "consider temporarily" separating infected mothers and newborns after "discussing the risks and benefits with the mother and health care team." Mothers may breastfeed while exercising respiratory hygiene, and separated infants must be isolated from other infants. The CDC also makes provisions for room sharing if "it is in accordance with the mother's wishes" or if it is unavoidable due to facility limitations. The American College of Obstetricians and Gynecologists (ACOG) defers to CDC guidelines; in addition, ACOG does not recommend routine COVID-19 testing for pregnant women. The American Academy of Pediatrics, on the other hand, offers more stringent guidelines, including the recommendation that COVID-19 positive mothers be separated from their newborns until they are asymptomatic, and until they have two separate virological determinations demonstrating that they are free of infection. These inconsistencies in expert recommendations underscore the knowledge gaps that exist regarding perinatal transmission of SARS-CoV-2 and highlight high priority areas for future studies.
