Probable congenital SARS-CoV-2 infection in a neonate born to a woman with active SARS-CoV-2 infection

• Neonates born to women with confirmed or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection should have testing of the nasopharynx, placenta and cord blood as soon as possible after birth, after thorough cleaning of the neonate.

• Sample timing, collection methods and types of samples should be documented to help differentiate congenital, intrapartum and postpartum acquisition of SARS-CoV-2 infection in neonates.

A 40-year-old woman (gravida 2, para 1) was admitted to a tertiary hospital in Toronto, Ontario. She had familial neutropenia, gestational diabetes and a history of frequent bacterial infections, including 3 episodes (sinusitis, skin infection and bronchitis) during this pregnancy, which resolved with antibiotic treatment. Details of the maternal course and outcome have been published separately because of her hematologic condition.1

The patient presented with myalgia, decreased appetite, fatigue, dry cough and temperature of 39°C in the preceding 24 hours. A nasopharyngeal swab was positive for suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)gene targets via reverse transcription polymerase chain reaction (RT-PCR) testing (Allplex 2019-nCoV assay, Seegene). There were no fetal concerns during the pregnancy or following admission. The woman did not need any respiratory support at the time of birth. A semiurgent cesarean delivery was done under regional anesthesia, with airborne, droplet and contact precautions, owing to worsening coagulopathy (elevated d-dimer and fibrinogen levels, and elevated activated partial thromboplastin time) and reducing platelet count at 35 weeks and 5 days’ gestation. Artificial rupture of membranes was performed at operation. The amniotic fluid was clear. The male neonate was vigorous and did not require resuscitation. His Apgar scores were 9 at 1 minute and 9 at 5 minutes, and his birth weight was 2.93 kg.

In line with our local protocol, delayed cord clamping was not performed, and the neonate was immediately removed from the operative field, in a sterile fashion, to a resuscitator 2 m away in the same room. Placental swabs (both maternal and fetal sides) were obtained. Placental tissue was sent for PCR and histopathologic examination. Nasopharyngeal swabs were obtained from the neonate on the day of birth, day 2 and day 7, after thorough cleansing of the baby and before contact with the mother.

All 3 of the neonate’s nasopharyngeal swabs were positive for SARS-CoV-2 gene targets via RT-PCR testing; neonatal plasma tested positive on day 4, and stool was positive on day 7. The results of the maternal and neonatal investigations, including SARS-CoV-2 PCR results using the Allplex 2019-nCoV assay, are presented in Appendix 1, Supplemental Table S1 (available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.200821/-/DC1). Detailed results including PCR cycle thresholds for specific PCR targets (envelope, RNA-dependent RNA polymerase and nucleocapsid genes) as an indirect measure of viral load are reported in Appendix 1, Supplemental Table S2.

Each of the 5 random sections of placenta showed multiple areas of infiltration by inflammatory cells and extensive early infarction. The inflammatory infiltrate consisted nearly entirely of CD68-positive macrophages. Only scattered T-cells (CD3), B-cells (CD20) and neutrophils (CD15) were identified on immunohistochemical examination. The inflammatory infiltrate was largely confined to the intervillous space, consistent with chronic histiocytic intervillositis. The histopathologic findings, however, differed from those of more typical cases of chronic histiocytic intervillositis in 2 important features: the widespread early infarction and the clustering of the inflammatory cells around the chorionic villi (Figure 1).

• Download figure
• Open in new tab
• Download powerpoint

Figure 1:

Placental photomicrographs. A) On low-power imaging, broad zones of cellular infiltrates are noted frequently but randomly throughout the section (arrows). The most normal area is present on the right side of the slide (hematoxylin–eosin, original magnification ×2). B) Higher-power view shows infiltration of the intervillous space by chronic inflammatory cells (arrows). The chorionic villi are largely spared from the infiltration but, instead, show extensive early necrosis of the syncytiotrophoblast layer. Early perivillous fibrin deposition is also present (hematoxylin–eosin, original magnification ×20). C) High-power view highlights the early infarction, with extensive smudginess and early fragmentation of the syncytiotrophoblast nuclei (arrows) (hematoxylin–eosin, original magnification ×40). D) Immunostaining for the macrophage marker CD68 shows large numbers of the chronic inflammatory cells in the intervillous space, frequently encircling the chorionic villi (CD68 immunostain, original magnification ×20).

The woman and newborn were transferred to a negative-pressure room on the postnatal ward. The woman attempted breastfeeding with appropriate precautions, including wearing a mask, practising appropriate hand and breast hygiene, and keeping the baby 2 m away from her between feedings. The neonate was noted to be neutropenic and had mild hypothermia (lowest temperature 35.9°C), feeding difficulties and intermittent hypoglycemic episodes (lowest glucose level 1.8 mmol/L), which were managed with administration of dextrose gel and formula supplementation. Repeated episodes of hypoglycemia and feeding difficulties necessitated admission to the neonatal intensive care unit (NICU) at 37 hours of age for intravenous administration of glucose, thermoregulation and support for oral feeding. Treatment with ampicillin and tobramycin was started empirically (routine guideline for neonatal sepsis at our institution), which was discontinued 48 hours later after negative blood culture results. Within 24 hours of admission to the NICU, intravenous glucose treatment had been stopped, and the neonate maintained his temperature in an open cot and exhibited improved oral feeding. No radiologic investigations were needed. He was transferred back to his mother’s room on the postnatal ward and was discharged home with his mother on day 4 after birth.

The neonate returned for routine assessment on day 7. The clinical examination was unremarkable, showing no feeding difficulties, fever or cough. Repeat swabs for SARS-CoV-2 were taken from both the mother and the neonate (results in Appendix 1, Supplemental Table S1). A telephone follow-up on day 30 after birth indicated that the baby was thriving. At the time of writing, continued follow-up was in place through a community physician.