Wednesday, July 15, 2020

The world's first mother-to-child transmission of SARS-CoV-2 is confirmed: from France, the newborn has neurological symptoms

Reporter : He Liping
Publisher : The Paper, via ScienceNet
Direct translation
 

The latest research shows that mothers who test positive for SARS-CoV-2 (novel coronavirus) may transmit the virus to their babies through the placenta. A research group from France reported relevant evidence through a case study, proving that a local academic journal, Nature Communications, published the above-mentioned research online on July 14, local time, entitled "Transplacental transmission of SARS -CoV-2 infection".

The study was completed by multiple departments of Paris Saclay University Hospitals. The corresponding author is Daniele De Luca, Director of Pediatric and Neonatal Intensive Care Medicine at Antoine Béclère Hospital in Paris.

SARS-CoV-2 is mainly transmitted by droplets, but there are also speculations that there are other transmission routes. Previous studies have discussed the possibility of vertical transmission of mothers and infants during the perinatal period, but it is not clear whether it occurred through transplacental or transcervical routes or environmental exposure.

The authors point out that clarifying whether and how SARS-CoV-2 reaches the fetus is of great significance for preventing neonatal infections, optimizing pregnancy management, and ultimately better understanding the biology of SARS-CoV-2. In this paper, they provide a comprehensive case study demonstrating that SARS-CoV-2 is transmitted through the placenta and that the newborn has the neurological clinical symptoms associated with SARS-CoV-2 infection.

Woman pregnant 35 weeks + 5 days cesarean section baby boy

The details of the paper show that a 23-year-old pregnant woman was admitted to the hospital in March 2020. At that time, the pregnancy was 35 weeks + 2 days. She had fever (38.6°C), severe cough, and excessive phlegm 2 days before admission. Blood tests, nasopharyngeal swabs and vaginal swabs confirmed the presence of SARS-CoV-2 ‘E’ and ‘S’ genes (encoding viral envelope and spike protein, respectively). Before the diagnosis of COVID-19, there were no abnormalities in pregnancy, and ultrasound and routine examinations were normal. Thrombocytopenia, lymphopenia, prolonged APTT, elevated transaminases; increased C-reactive protein and ferritin were observed on admission. A class III fetal heart rate was observed 3 days after admission, so the research team performed a cesarean section on the pregnant woman under complete isolation and general anesthesia, and the amniotic membrane was intact. During the cesarean section, the research team collected clear amniotic fluid before rupture of the membrane and detected that the SARS-CoV-2 ‘E’ and ‘S’ genes were positive. The woman continued to be hospitalized and was discharged 6 days after delivery.

This patient gave birth to a baby boy (gestational age 35 weeks + 5 days; birth weight 2540 grams). Newborn 1 minute Apgar score is 4 (heart rate=1, breathing ability=1, skin color=, muscle tone=1, remaining items are zero), 5 minute Apgar score is 2 (skin color=1, muscle tone =1, zero remaining items), 10 minutes Apga score is 7 (heart rate = 2, breathing ability = 2, skin color = 2, muscle tone = 1).

The newborn was eventually transferred to a negative pressure room in the NICU in complete isolation. Umbilical cord blood gas analysis showed normal pH and normal lactic acid content. The neonate did not receive any sedative or analgesic medication and was monitored in accordance with NICU’s routine post-resuscitation care program: At NICU admission, the Sarnat score, point-of-care echocardiography, and pulmonary ultrasound were normal. Vital sign parameters were normal. After 6 hours of extubation, blood was taken before extubation for capillary blood gas analysis (1.5 hours after birth) and routine blood tests were normal.

Before extubation (1 hour after caesarean section), the research team collected nasopharyngeal swabs and rectal swabs of the baby, and then collected them again after 3 days and 18 days, and detected the presence of ‘E’ and ‘S’ genes. Newborn blood and bronchoalveolar perfusion tests were also positive.

The newborn was fed with formula milk only.

Newborn has related symptoms 3 days after birth and has not received special treatment

It is worth noting that on the third day after birth, the newborn suddenly developed irritability, poor feeding, hypertonic spasm and angulation. Neonatal cerebrospinal fluid (CSF) was negative for SARS-CoV-2, bacteria, fungi, enteroviruses, herpes simplex virus type 1, and herpes simplex virus type 2. Newborn symptoms improved slowly within 3 days, and the second cerebrospinal fluid sample on day 5 was normal, but mild hypotonia and feeding difficulties persisted. MRI imaging 11 days after birth showed bilateral periventricular and subcortical hyperplasia.

However, the newborn did not receive antiviral drugs or any other special treatment, and gradually recovered, and was eventually discharged after 18 days. Follow-up nearly 2 months after birth showed that neurological examination (improved muscle tone, normal blood pressure) and magnetic resonance imaging (reduced white matter damage reduction) showed further improvement; growth and other clinical examinations were normal.

The study also carried out virological and pathological analysis. RT-PCR showed that placental tissue was positive for SARS-CoV-2 ‘E’ and ‘S’ genes, and the viral load in placental tissue was much higher than that in amniotic fluid and maternal or newborn blood.

Histological examination of the placenta revealed diffuse fibrin deposits around the villi and acute and chronic intervillitis. Immunostaining with anti-SARS-CoV-2 N protein antibody showed that the cytoplasm of trophoblast cells around the villi was strongly positive. Special staining and immunohistochemistry did not detect other pathogens.

"Observed a true neonatal infection, not pollution"

The research team once again emphasized in the discussion that it should be noted that the viral load in placental tissue is much higher than that in amniotic fluid or maternal blood, which indicates the presence of virus in placental cells, which is different from the histological examination. The inflammation results were consistent. In addition, the RT-PCR curves of nasopharyngeal swabs on days 3 and 18 of the newborn were higher than those on day 1 after birth, and the baby was completely isolated in a negative pressure room.

The authors believe that this is another reason for confirmation, "We observed a real neonatal infection, not pollution."

The paper points out that these findings suggest that: first, maternal viremia occurs, and immunohistochemistry shows that the virus reaches the placenta; second, high viral load, tissue examination, and immunohistochemistry show that the virus causes obvious inflammation; third, placental infection Afterwards, neonatal viremia appeared.

The authors point out that this finding is also consistent with another case study describing the presence of viral particles in placental tissue, although that study did not report placental inflammation or fetal/newborn infection.

The placenta showed signs of acute and chronic intervillous inflammation, consistent with the severe systemic inflammation of the mother caused by SARS-CoV-2 infection. The RT-PCR test on placental tissue was positive for SARS-CoV-2, and both maternal and neonatal blood samples were positive, so it was clearly transmitted through the placenta. Interestingly, previous studies have shown that the placenta of women infected with SARS-CoV-1 exhibits a similar pathological manifestation of intervillary inflammation and fibrin deposition between the villi.

In addition, current research basically believes that angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2, and it is highly expressed in placental tissue. Animal data shows that the expression of ACE2 in fetal/newborn tissues changes with time, peaking at the end of pregnancy and the first few days after birth.

The authors believe that the combination of these data and their findings can confirm that in the last few weeks of pregnancy, SARS-CoV-2 may indeed be transmitted through the placenta. Of course, they cannot rule out possible transmission and fetal effects in early pregnancy, because there is no definitive literature.

Overall, the authors have demonstrated that SARS-CoV-2 infection may be transmitted through the placenta during the last weeks of pregnancy, and transmission through the placenta can cause placental inflammation and neonatal viremia. Neuroimaging revealed white matter damage, which may be caused by vascular inflammation caused by SARS-CoV-2 infection. A similar situation was found in adult patients.

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