A 23-year-old, gravida 1, para 0 was admitted to our university hospital on March 24th, 2020 at 35+2 weeks of gestation with fever (38.6°C) and severe cough since March 22nd. Real-time polymerase chain reaction (RT-PCR) was performed as described in the online methods: both the E and S genes of SARS-CoV-2 were detected in blood, and in nasopharyngeal and vaginal swabs. Pregnancy was uneventful and all the ultrasound examinations and routine tests were normal until the diagnosis of COVID-19. Thrombocytopenia (54 x 109/L, normal range 140-400), lymphopenia (0.54 x 109/L, normal range 1-3.5), prolonged APTT (60 sec, normal range 28.0-41.9), transaminitis (AST 81 IU/L, normal range 13-37; ALT 41 IU/L, normal range 10-40), elevated C-reactive protein (37 mg/L, normal values <10) and ferritin (431 µg/L, normal range 7-191) were observed upon hospital admission. On March 27th, a category III-fetal heart rate tracing7 (Figure 1) was observed and so category II-cesarean section was performed, with intact amniotic membranes, in full isolation and under general anesthesia due to maternal respiratory symptoms. Clear amniotic fluid was collected prior to rupture of membranes and during cesarean section and tested positive for both the E and S genes of SARS-CoV-2. Delayed cord clamping was not performed. The woman was discharged in good condition six days after delivery.
A male neonate was delivered (gestational age 35+5 weeks; birth weight 2540 grams) with Apgar scores of 4 and 2, at 1 and 5 minutes, and needed active resuscitation according to international guidelines8 and was eventually transferred in full isolation to the neonatal intensive care unit (NICU) in a negative pressure room. Cord blood gas analysis showed normal pH and lactate. Sarnat score, point-of-care echocardiography and lung ultrasound were normal upon NICU admission. Vital parameters were always normal and the baby was extubated after six hours. Before the extubation, blood was drawn for capillary blood gas analysis and routine blood tests which yielded normal values. Moreover, before the extubation, blood and non-bronchoscopic bronchoalveolar lavage fluid were collected for RT-PCR and both were positive for the E and S genes of SARS-CoV-2. Lavage was performed using a standardized procedure9 as detailed in online methods. Nasopharyngeal and rectal swabs were first collected after having cleaned the baby at 1 hour of life, and then repeated at 3 and 18 days of postnatal age: they were tested with RT-PCR and were all positive for the two SARS-CoV-2 genes. Feeding was provided exclusively using formula milk.
On the second day of life, the neonate suddenly presented with irritability, axial hypertonia and opisthotonos: cerebrospinal fluid (CSF) was sterile but with 300 leukocytes/mm3. Blood was taken at the same time: the culture was sterile and routine blood tests gave normal values. Cerebral ultrasound and EEG were also normal. Symptoms improved slowly over three days and a second CSF sample was normal on the fifth day of life, but mild hypotonia and feeding difficulty persisted. Magnetic resonance imaging at 11 days of life showed bilateral gliosis of the deep white periventricular and subcortical matter, with slightly left predominance (Figure 2). The neonate gradually recovered, feeding improved and was finally discharged from hospital after 18 days with an outpatient follow-up.
RT-PCR on the placenta was extremely positive for both SARS-CoV-2 genes. Figure 3 shows all RT-PCR results obtained in different maternal and neonatal specimens. Placental histological examination was performed as described in online methods and revealed diffuse perivillous fibrin deposition with infarction and acute and chronic intervillositis. No pathogen agent was detected on special stains and immunohistochemistry performed. Figure 4 depicts the results of the placental histological examination.