SARS-CoV-2 vertical maternal/neonatal transmission

A recent report from Wuhan strongly suggested vertical transmission of SARS-CoV-2 from mothers to newborns (see covid vertical transmission jamaped2020 in dropbox, or doi:10.1001/jamapediatrics.2020.0878)

Details:

-- 33 neonates born to mothers with COVID-19, of whom 3 were likely SARS-CoV-2 infected. The 3 cases:

    --40 weeks gestation, delivered by C-section because of meconium stained amniotic fluid and confirmed maternal COVID pneumonia. On day 2 of life the infant had lethargy and fever, unremarkable physical exam, was sent to the NICU. Chest x-ray showed pneumonia and pro-calcitonin was positive. nasopharyngeal and anal swabs were positive for SARS-CoV-2 on days 2 and 4 but negative on day 6

    --40 weeks/4 days gestation. C-section because of confirmed maternal COVID pneumonia. Neonate had lethargy, vomiting and fever. Normal physical. Had leukocytosis, lymphocytopenia, elevated CK-MB. Chest x-ray showed pneumonia. Nasopharyngeal and anal swabs were positive for SARS-CoV-2 on days 2 and 4 but negative on day 6

    --31 weeks/2 days gestation. C-section because of fetal distress and confirmed maternal COVID pneumonia. Infant resuscitated, with Apgars of 3, 4 and 5. Neonatal resp distress syndrome (RDS) and pneumonia were confirmed on x-ray, resolving on day 14 of life with treatment with noninvasive ventilation, caffeine, and antibiotics. Also likely sepsis with Enterobacter-positive blood cultures, which improved with antibiotics. Nasopharyngeal and anal swabs were positive for SARS-CoV-2 on days 2 and 4 but negative on day 7

Results:

--of the 33 newborns, comparing those without (30 newborns) vs with (3 newborns)  SARS-CoV-2:

    --male: 53% vs 100% (though 100% of the small sample: 3 of 3)

    --small for gestational age (SGA):7% vs 33%

    --fever: 0 vs 67%

    --pneumonia: 0 vs 100%

    --RDS: 10% vs 33%; similar numbers for shortness of breath, cyanosis and feeding intolerance

    --labs:

        --WBC 9800 vs 19200

        --lymphocyte count: 4300 vs 2600

        --CK-MB: 13 vs 31

    --treatment:

        --mechanical ventilation: 0 vs 33% (1 infant)

        --NICU stay: 0 vs 4 days

Commentary:

-- one reason I bring this up is that several earlier reports (all small) had questioned the existence of vertical transmission of COVID from mothers to their newborns. For example an earlier analysis of 10 neonates from mothers with COVID found that 4 were full-term and 6 were premature, two were SGA and one was LGA, and 6 had significant neonatal complications. However none of these neonates had COVID, raising the suggestion that there may have been adverse COVID effects on newborns that were not directly related to their getting SARS-CoV-2 infection (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036645/pdf/tp-09-01-51.pdf )

COVID-negative infants with COVID-positive mothers did quite well overall

-- In this study the 3 infants (of a total of 33 born from COVID-positive symptomatic mothers) very likely had COVID infections, seemed to do less well in terms of their hospital course, but ultimately did well; the symptoms of the sickest one may well be related to prematurity and sepsis as opposed to SARS-CoV-2 infection: there were strict infection controls during the delivery and after, so it is likely that the source of the infection was maternal.

   -- though, there were really few infants evaluated: so hard to draw strong conclusions about the overall clinical course of SARS-CoV-2 infected children from the 3 evaluated. the lab tests in these infants were consistent with a true SARS-CoV-2 infection, though ascribing infection to PCR-positivity is also potentially a logical leap (??colonization and not infection)

-- there is no information on whether vaginal vs C-section is preferred: Chinese recommendations now are to do whatever is indicated for the delivery, and that it does not seem that the type of delivery matters (see covid pregnant women intljgynob2020, or doi:10.1002/ijgo.13146). There is reference in a New York guideline that the virus is not present in vaginal samples, but i have not found any substantiation of that in the medical literature.  Early studies have suggested that there is no transmission in stool samples, but there have subsequently been cases of culturable virus found in the stool, suggesting but not confirming transmissability (given the logical leap that in-vitro cultures are translatable to human transmission). And we do not know for sure if stool virus viability implicates a mechanism for vaginal colonization???? (for example, we do know that there is pretty frequent vaginal fecal contamination: often female urinary tract infections involve fecal flora). for now, it certainly makes sense at this time to be extra diligent with all secretions in a SARS-CoV-2 positive person, in the absence of more definitive data

-- and, a recent lancet article of 9 women who had C-sections found no SARS-CoV-2 in amniotic fluid, cord blood, throat swab, or breast milk samples, with multiple test done over 9 days and tested with both the CDC and Chinese RT-PCR kits; though there was no testing of maternal vaginal samples (see covid vertical transmission none lancet2020 in dropbox, or doi.org/10.1016/ S0140-6736(20)30360-3). though, again, a very small study

-- and, of course, we cannot determine at this point if there are neonatal complications of SARS-CoV-2 infections at different stages of the pregnancy. does first semester infection during fetal organogenesis lead to gross or subtle changes later??

so, there really are not enough cases in the literature to argue strongly about the clinical characteristics of the effects of SARS-CoV-2 in newborns. maybe the newborns will have stormier courses?? time and more data will tell.  But the above 3 cases do pretty strongly suggest that the virus can pass from mothers to newborns. 

--but based on this, one could argue prudence: that pregnant women should be screened (not sure when or how often), and if positive, they should have the usual quarantine and more aggressive surveillance (perhaps largely telephonic), and their infants should be assessed for SARS-CoV-2 infection and also quarantined (even if this is just SARS-CoV-2 carriage)

--and, as with all things (pretty much) COVID, we are accumulating information at a pretty amazing rate, though it is still difficult in these early stages of infection to know for sure what larger/longer studies will find.  and this article is a case-in-point, given the several prior ones not showing vertical transmission...

geoff​

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