Clinical outcomes and complications in pregnancies with COVID-19
Participant 5 was diagnosed with SARS-CoV-2 at GA 29w1d. She presented at the antenatal ward at GA 29w6d with reduced fetal movements and vaginal bleeding. The neonate was delivered the same day by emergency caesarean section due to a pathological cardiotocography (CTG) and was born small for gestational age (birth weight 1235 g, Z-score -1.87). APGAR was 8 after 5 minutes and umbilical cord blood with respiratory compensated metabolic acidosis (arterial pH 7.23, Base Excess -10.4 and venous pH 7.33, Base Excess -12.0). Microscopic examination of the placenta showed severe acute and chronic intervillositis with necrosis of the trophoblast (Figure S1). Swabs from the fetal side of the placenta were positive for SARS-CoV-2. The results of the vaginal swabs were inconclusive. The neonate was admitted to NICU for 40 days. The mother had a complicated puerperal period with fever, fatigue, and diarrhea. Yersinia enterocolitica was found in a maternal fecal sample. Bacterial culture from the placenta was negative. SARS-CoV-2 antibodies were not detected in either maternal or in cord blood. Eleven weeks after delivery, anti-cardiolipin antibodies were found associated with an increased risk of arterial and venous thrombosis. The findings could be consistent with intrauterine SARS-CoV-2 infection, but bacterial infection could not be ruled out.
Participant 6 tested positive for SARS-CoV-2 at GA 31w2d. Her partner was tested positive the same day. She presented at the antenatal ward at 32w0d with a reduction in fetal movements but was discharged after a normal CTG. At 32w3d, she presented with contractions. The neonate was delivered shortly after by emergency caesarean section due to a preterminal CTG with APGAR 0 after 5 minutes and arterial pH 6.82, Base Excess -17.5 and venous pH 6.85, Base Excess -17.2. Birth weight was 2000 g and Z-score -0.29. One hour after delivery, the neonate was declared dead after a prolonged neonatal resuscitation attempt. Autopsy of the neonate showed no malformations, but signs of asphyxia from petechiae and meconium aspiration. In addition, there was some histologic evidence of acute thymic involution and adrenal stress-related changes, but no signs of prolonged intrauterine stress or growth restriction. Microscopic examination of the placenta showed severe abnormality with acute and chronic intervillositis and abundant perivillous fibrin deposits comprising 70% of the parenchyma (Figure S2). SARS-CoV-2 was detected in the vaginal swab at delivery and in swabs from both the fetal and maternal side of the placenta. Neonatal swabs were SARS-CoV-2 negative. The mother tested positive for SARS-CoV-2 antibodies while umbilical cord blood tested negative. Blood and urine culture at the time of delivery were negative. The placental findings, potentially linked to intrauterine SARS-CoV-2 infection were likely to have caused the fatal fetal outcome.
Participant 27 was diagnosed with gestational diabetes mellitus at GA 13w0d. She tested positive for SARS-CoV-2 at GA 27w2d and was hospitalized at GA 28w0d due to COVID-19. During the admission, she was diagnosed with three segmental lung embolisms and a secondary pneumonia was suspected. She was treated with Low Molecular Weight Heparins, Remdesivir, antibiotics, and prednisolone. Vaginal swabs analysed for SARS-CoV-2 were negative. She gave birth by an uncomplicated planned caesarean section at GA 38w0d. During admission, no antibodies were detected in maternal blood eight days after the SARS-CoV-2 positive pharyngeal swab, whereas at delivery, 75 days after the initial infection, SARS-CoV-2 antibodies were detectable in both maternal and cord blood samples.
Participant 28 presented at the antenatal ward at GA 24w5d with vaginal bleeding and at GA 25w1d with symptoms of deep vein thrombosis of the femoral vein, which was confirmed by ultrasound. She started treatment with Low Molecular Weight Heparin. The vaginal bleeding was derived from a varicose vein in the left labium minor. Eleven days later (GA 26w5d), she contacted the Emergency Department due to shortness of breath and vomiting. There was no suspicion of pulmonary embolism or severe COVID-19. She tested positive for SARS-CoV-2 by a pharyngeal swab and was admitted for two days. At day one after the positive pharyngeal swab, two vaginal swabs were positive for SARS-CoV-2, but no maternal antibodies were detected. Blood culture and urine culture taken after admission to the hospital with COVID-19 were negative. She gave birth by an uncomplicated planned caesarean section at GA 38w5d. On day 16 and 37 after the positive swab and at delivery (day 84), SARS-CoV-2 antibodies were detected in maternal blood samples. At delivery, antibodies were also detected in cord blood.
Besides the abovementioned four severe cases, a few other complications were found among participants during pregnancy and delivery (table 1).