- SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed.
- So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus.
- This research demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise.
- The transmission is confirmed by comprehensive virological and pathological investigations.
- SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, and (3) neonatal viremia following placental infection.
A research article published in the Nature deals with the neonate which is studied clinically, through imaging. The neonate presented with neurological manifestations is similar to those described in adult patients.
Case Study
A 23-year-old, gravida 1, para 0 was admitted in the university hospital in March 2020 at 35+2 weeks of gestation with fever (38.6 °C) and severe cough and abundant expectoration since 2 days before hospitalisation.
Real-time polymerase chain reaction (RT-PCR) was performed as described in the “Methods” below: 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 × 109/L), lymphopenia (0.54 × 109/L), prolonged APTT (60 s), transaminitis (AST 81 IU/L; ALT 41 IU/L), elevated C-reactive protein (37 mg/L) and ferritin (431 μg/L) were observed upon hospital admission.
Three days after admission a category III-fetal heart rate tracing was observed and therefore category II-cesarean section (i.e., fetal compromise; not immediately life-threatening,https://www.rcog.org.uk/globalassets/documents/guidelines/goodpractice11classificationofurgency.pdf) 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, during cesarean section and tested positive for both the E and S genes of SARS-CoV-2.
Delayed cord clamping was not performed as its effect on SARS-CoV-2 transmission is unknown.
The woman remained hospitalized for surveillance of her clinical conditions and finally she was discharged in good conditions, 6 days after delivery.
Various tests performed
A male neonate was delivered (gestational age 35+5 weeks; birth weight 2540 g).
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 procedure. Blood culture was negative for bacteria or fungi.
Nasopharyngeal and rectal swabs were first collected after having cleaned the baby at 1 h 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.
Routine blood tests (including troponin, liver and kidney function) were repeated on the second day of life and resulted normal. Feeding was provided exclusively using formula milk.
Poor feeding, axial hypertonia and opisthotonos
On the third day of life, the neonate suddenly presented with irritability, poor feeding, axial hypertonia and opisthotonos: cerebrospinal fluid (CSF) was negative for SARS-CoV-2, bacteria, fungi, enteroviruses, herpes simplex virus 1 and 2, showed normal glycorrhachia albeit with 300 leukocytes/mm3 and slightly raised proteins (1.49 g/L).
Blood was taken at the same time and the culture was sterile. Cerebral ultrasound and EEG were also normal. There were no signs suspected for metabolic diseases.
Symptoms improved slowly over 3 days and a second CSF sample was normal on the fifth day of life, but mild hypotonia and feeding difficulty persisted.
Neonate did not receive antivirus
Magnetic resonance imaging at 11 days of life showed bilateral gliosis of the deep white periventricular and subcortical matter, with slightly left predominance .
The neonate did not receive antivirals or any other specific treatment, gradually recovered and was finally discharged from hospital after 18 days.
Follow-up at almost 2 months of life showed a further improved neurological examination (improved hypertonia, normal motricity) and magnetic resonance imaging (reduced white matter injury); growth and rest of clinical exam were normal.
Virology and pathology
RT-PCR on the placenta was positive for both SARS-CoV-2 genes. All RT-PCR results were obtained in different maternal and neonatal specimens: viral load was much higher in placental tissue, than in amniotic fluid and maternal or neonatal blood.
Placental histological examination was performed as described in “Methods” below and revealed diffuse peri-villous fibrin deposition with infarction and acute and chronic intervillositis.
An intense cytoplasmic positivity of peri-villous trophoblastic cells was diffusely observed performing immunostaining with antibody against SARS-CoV-2 N-protein.
No other pathogen agent was detected on special stains and immunohistochemistry.
A classification for the case definition of SARS-CoV-2
A classification for the case definition of SARS-CoV-2 infection in pregnant women, fetuses and neonates has recently been released and we suggest to follow it to characterize cases of potential perinatal SARS-CoV-2 transmission.
According to this classification system, a neonatal congenital infection is considered proven if the virus is detected in the amniotic fluid collected prior to the rupture of membranes or in blood drawn early in life, so our case fully qualifies as congenitally transmitted SARS-CoV-2 infection, while the aforementioned cases would be classified as only possible or even unlikely.
Both “E” and “S” gene of SARS-CoV-2 were found in each and every specimen, thus they were considered all positive, according to the European Centre for Disease Control recommendations (https://www.ecdc.europa.eu/en/all-topics-z/coronavirus/threats-and-outbreaks/covid-19/laboratory-support/questions).
Of note, the viral load is much higher in the placental tissue than in amniotic fluid or maternal blood: this suggests the presence of the virus in placental cells, which is consistent with findings of inflammation seen at the histological examination.
Finally, the RT-PCR curves of neonatal nasopharyngeal swabs at 3 and 18 day of life are higher than that at the first day (while the baby was in full isolation in a negative pressure room): this is also another confirmation that we observed an actual neonatal infection, rather than a contamination.
Suggestions from the findings
Thus, these findings suggest that:
(1) maternal viremia occurred and the virus reached the placenta as demonstrated by immunohistochemistry;
(2) the virus is causing a significant inflammatory reaction as demonstrated by the very high viral load, the histological examination and the immunohistochemistry;
(3) neonatal viremia occurred following placental infection.
These findings are also consistent with a case study describing the presence of virions in placental tissue, although this did not report neither placental inflammation, nor fetal/neonatal infection.
In conclusion, transplacental transmission may cause placental inflammation and neonatal viremia. Neurological symptoms due to cerebral vasculitis may also be associated.
Did you subscribe to our daily newsletter?
It’s Free! Click here to Subscribe!
Source: Nature
