A total of 105 infected pregnant women and 107 newborns (two twin births) were included from GESNEO-COVID cohort.
Description of SARS-CoV-2 infected women during pregnancy
The median age of pregnant women at delivery was 34.1 (IQR: 28.8–37.1) years. More detailed characteristics are shown in Table 1. More than half (59.6%) were Caucasian and 28.8% of them were from Latin America. No woman was diagnosed during the first trimester, 6.7% of the women were diagnosed during the second trimester of pregnancy and 93.3% during the third trimester. There were 51.9% SARS-CoV-2 RT-PCR positive tests at delivery. Overall, 34.3% of women had some comorbidity: 6.7% were obese, 1.9% presented hypertension, 1.9% asthma, 6.7% gestational diabetes, 10.5% gestational hypothyroidism, 1.9% immunosuppression and 10.5% presented other comorbidities. No pre-eclampsia was reported.
Effects of SARS-CoV-2 infection during pregnancy in pregnant women and delivery outcomes
Two thirds (64.8%) of SARS-CoV-2 infected pregnant women had COVID-19 symptoms. The most common symptoms were fever (36.2%), cough (35.2%), and dyspnoea (19.0%). Less frequent symptoms included myalgia (13.3%), anosmia (12.4%), headache (9.5%), rhinorrhoea (8.6%), vomiting (6.7%), diarrhoea (5.7%) and other symptoms (10.5%).
Chest X-ray was performed in 52 women and 32 (61.5%) of them had signs compatible with pneumonia. Overall, radiological images suggested bilateral pneumonia in 20 women and unilateral pneumonia in 12. All 32 pneumonia cases were diagnosed during the first month of the study (15 May-15 April 2020) (Fig. 1). Five women with severe pneumonia and positive RT-PCR at delivery required admission to the Intensive Care Unit for a median of 10.0 (IQR: 6.5–18.5) days, requiring invasive mechanical ventilation. There was no maternal mortality reported.
In the laboratory analyses increased concentrations of D dimer, higher values of liver enzyme alanine aminotransferase and lower count of lymphocytes were found in women with pneumonia compared with women who did not develop pneumonia (Table 2). Obesity was also associated with a higher risk of pneumonia. Lymphopenia (< 1500 lymphocytes/ml) and a lower gestational age at diagnosis were potential predictors for pneumonia in the multivariable analysis (Fig. 2).
Overall, 46 women (43.8%) received treatment under study for COVID-19. Different treatment options were used and sometimes combined; antiviral treatment: lopinavir/ritonavir (28 women), gamma interferon (4 women) and remdesivir (2 women); anti-malarial: hydroxychloroquine (33 women); antibiotic treatment: ceftriaxone (25 women) and other antibiotics (16 women); immunomodulatory drugs: systemic corticoids (8 women) and tocilizumab (4 women); and other treatments (13 women). 61.5% of women received treatment before delivery and 38.5% received treatment the day of delivery or after, including both women receiving remdesivir. Treatments were safe for both mother and newborns.
Globally, 38 (36.2%) of pregnant women had a caesarean delivery and the indication for caesarean section was severe COVID-19 for 28.9% of them. Pregnant women with pneumonia had a 5-fold increased risk of caesarean sections and premature newborns than those without pneumonia in the univariable analysis (OR:5.0 [2.0;12.2], p-value < 0.001) (Table 3). Pneumonia and lower gestational age at delivery were associated with caesarean section as predictor factors in the multivariable analysis (Fig. 2). The women with pneumonia were 4 times at greater risk than those without pneumonia (OR:4.2[1.47–11.99], p = 0.007) adjusted for gestational age at diagnosis and delivery. All women admitted to the ICU had caesarean sections due to the severity of the disease.
Effects of SARS-CoV-2 during pregnancy in newborns
Overall, 53.3% of newborns were women and median weight at delivery was 3.050 kg (IQR: 2780–3455) with 5.6% of newborns were small for gestational age (Table 4). Median gestational age at delivery was 39.0 (IQR: 37.6–40.0) weeks with a range from 24 to 41 weeks. Apgar score at 1 and 5 min ranged from 1 to 9 with a median of 9.0 (IQR: 9.0–9.0) and 3 to 10 with a median of 10.0 (IQR: 10.0–10.0). Prematurity rate was 20.2%. From all newborns, 16.8% required admission to a neonatal intensive care unit with a median duration of 3.0 (IQR: 1.0–8.0) days. None of the newborns presented any symptom of SARS-CoV-2 infection. The most common complications were due to prematurity. 66.4% of the newborns were breastfed.
An extreme premature newborn (24 week) died at 20 days of life due to prematurity-related complications. Another full-term newborn died during the first 24 h from delivery, due to Sudden infant death Syndrome. Both newborns were born from women with severe pneumonia and admitted at the ICU.
Potential predictors for prematurity were diagnosed during the second trimester of pregnancy, having a positive RT-PCR at delivery, pneumonia during pregnancy and caesarean delivery in the univariable analysis. Having a positive RT-PCR at delivery and COVID-19 pneumonia during pregnancy were predictor factors for prematurity in the multivariable analysis (Fig. 2).
Perinatal transmission of SARS-CoV-2 infection
No vertical transmission was detected. Nasopharyngeal RT-PCR was possible to perform at 24–48 h of life in 101 newborns and repeated at 15 days old. None newborn tested positive at birth and one of the 61 (1.6%) neonates tested at 15 days of life had a positive result with a previous negative result at birth. This case was a full-term newborn whose mother tested positive for SARS-CoV-2 RT-PCR during the 24 h previous to admission. Delivery was by caesarean section due to worsened maternal diseases, and after delivery, the mother was admitted at the ICU with COVID-19 pneumonia. The newborn was discharged after testing negative for SARS-CoV-2 RT-PCR at birth and lived with her asymptomatic grandmother, after the 15 days’ diagnosis the neonate was tested positive for 2 SARS-CoV-2 RT-PCR for 2 weeks and under telephonic follow-up. That child was not breastfed, so this case was considered an intra-family transmission.