Belgian twins born with the Gamma variant of SARS-CoV-2: Transplacental versus intrapartum transmission?

Dear Editor,

We would like to take this opportunity to present a 'triple' case of interest: that of a 32-year-old woman (gravida 3, para 2) admitted to a tertiary hospital in Brussels, Belgium, and her twins (bi-chorionic bi-amniotic). She had no relevant past medical history except for gestational diabetes treated with diet alone, when she presented at 30 weeks and 5 days' gestation with preterm prelabor rupture of membranes. The 27-week ultrasonography had showed growth at the 44th and 25th percentile and normal doppler signals.

She reported nausea, postprandial vomiting, weakness and myalgia in the week prior to her admission. A diagnosis of Coronavirus Disease 2019 (COVID-19) was confirmed by a reverse transcription polymerase chain reaction (RT-PCR) test on a nasopharyngeal swab. She delivered two babies with vaginal partus under epidural analgesia without complication. The first born, a 1400 g-male, had Apgar scores of 8, 9 and 10 at respectively 1, 5 and 10 min. The second born was a 1020 g-female, suffered peripartum asphyxia with apgar scores of 1, 4 and 6 at respectively 1, 5 and 10 min, requiring intubation. No skin-to-skin contact with the babies was allowed. Adequate personal protective equipment was used by the healthcare workers during partus. Both twins were admitted to the department of neonatology for respiratory support in the context of prematurity, and then did well. The twins were tested 4 h after birth; both tests came back positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and were repeated thereafter.

Two days after delivery, the mother developed dyspnea and desaturation requiring supplemental oxygen at a flow rate of 2 L/min. A CT scan of the thorax was suggestive of COVID-19 pneumonia and excluded pulmonary embolism. She was started on dexamethasone and prophylactic low-molecular-weight heparin as per local protocol.

SARS-CoV-2 strains from the mother and both neonates were identified as the B.1.1.28.1. or 'Gamma P.1′ lineage. Swab and biopsy samples from both placentas were also positive for SARS-CoV-2 with RT-PCR. All viral loads are plotted in the Fig. 1 . Immunoglobulins targeting SARS-CoV-2 nucleocapsid protein were detected in the mother’s, but not in the neonates’ blood at 3–6 days post-partum. Both placentas were sent for histopathological examination. This revealed intervillous deposits of fibrin, micro-infarcts and deciduitis. The immunohistochemistry test for SARS-CoV-2 was positive.

Fig. 1

SARS-CoV-2 peripartum viral loads in the mother and her twins: Viral loads from the different samples are depicted in the figure. The mother’s respiratory SARS-CoV-2 viral load at delivery was 6,3 log copies/mL and the placental tissue 7,2 log copies/mL. The neonates’ viral loads at birth were respectively 3,7 and 4,0 log copies/mL for the boy and the girl respectively, peaked at 9,2 and 8,5 log copies /mL at day 2 post-partum and decreased thereafter.

With these clinical and laboratory findings, we became interested in establishing the moment of infection (transplacental or intrapartum), which may become an important aspect of congenital infections as we learn more about SARS-CoV-2. According to Shah et al. our findings would classify the twins as cases of 'possible congenital infection in live born neonates' or as 'confirmed neonatal infection acquired intrapartum' [1]. The kinetics of the viral load in the babies over time would rather suggest an intrapartum infection. Indeed, the viral replication increased after the twins' births. Moreover, the high viral loads in placental tissues support a very recent infection in the mother, which may not have had the time to crossover to the fetuses in utero. However, a very late transplacental infection cannot be completely excluded.

In conclusion, the transmission of SARS-CoV-2 in our twins definitely took place in the peripartum period, and probably during partus. This raises the question of whether vaginal delivery should be contra-indicated in COVID-19 positive mothers, despite reports of low risks of peripartum infections [2], [3] and the mild clinical course of most neonatal COVID-19-infections [4], [5]. If SARS-CoV-2 infections in neonates turn out to be associated with adverse outcomes, future guidelines could focus on pre-partum screening of vaginal secretions of COVID-19 positive mothers, in order to infer the risk of COVID-19 transmission during a vaginal delivery.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.