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Outcome of universal screening of neonates for COVID-19 from asymptomatic mothers

      Dear Editor,
      Pandemic SARS-CoV-2 is the third Coronavirus to cause severe respiratory illness in humans. Little is known about the effects on pregnant women and the question of whether vertical transmission can occur remains unanswered and controversial.
      Universal screening of pregnant women has been described in the literature however to date universal screening of newborns has not. Here we report our unusual findings of the results of a universal screening programme of asymptomatic and healthy mothers together with their newborns .
      Our Trust, with a delivery rate of 7300 births per year, introduced universal nasopharyngeal screening using RT-PCR of all in-patients, including newborn babies on 27th April 2020.
      Between 27th April and 21st May, 481 infants were delivered and 418 were screened with maternal consent. Nine (2.2%) infants born to asymptomatic mothers screened positive for SARS-CoV-2 all within the first 24 h, three within the first three hours. Of these nine, eight mothers tested negative (Table 1). Only one infant (Case 5) was symptomatic - requiring oxygen for two hours and high flow humidified nasal cannulae for 22 hours. Chest X-ray showed streaky hila bilaterally and hazy consolidation in both lower lobes.
      Table 1Characteristics of infants swabbing positive for SARS-CoV-2 under the universal screening programme.
      NumberSexGestational age at birth (Weeks)Birthweight (gms)Mode of deliveryAge at 1st test (hh:mm)ResultCTAge at 2nd test (days)ResultMaternal 1st testMaternal 2nd test
      Case 1M42+24420EMCS09:21+ve29N/D+veN/D
      Case 2F41+52950SVD06:15+ve303-ve-ve-ve
      Case 3M38+43185ELCS02:15+ve317-ve-ve-ve
      Case 4F41+63020EMCS09:39+ve314-ve-ve-ve
      Case 5M39+13460ELCS04:39+ve292-ve-ve-ve
      Case 6M32403240SVD02:31+ve315-ve-ve-ve
      Case 7M39+13685ELCS02:09+ve29N/D-veN/D
      Case 8F36+42815EMCS not in labour10.20+ve302-ve-veN/D
      Case 9F37+42635SVD5.14+ve301-ve-veN/D
      CT – Cycle Threshold, SVD-Spontaneous Vaginal Delivery, ELCS-Elective Caesarean Section, EMCS: Emergency Caesarean Section N/D- not done.
      This is the first description of a universal screening programme for term and near term neonates. The finding of eight positive infants whose mothers tested negative for SARS-CoV-2 infection has never been described. Four possible explanations for this finding exist.
      Firstly all positive tests were contaminated. However all samples were taken on different days by different staff, all of whom were wearing appropriate PPE and none of whom became ill which makes this explanation very unlikely.
      Secondly the mothers’ results were false negatives. RT-PCR results are influenced by test technique and by clinical severity and duration of symptoms. All the mothers in our cohort were asymptomatic and the sensitivity of the test may have been insufficient to detect the small quantity of viral RNA that these mothers may have had at the time of the test. However, three of the infants were tested within three hours, two following elective Caesarean birth. If these mothers were false negatives these positive neonatal results raise the possibility of vertical transmission due to the short time interval for possible postnatal transmission.
      Thirdly all eight could be false positive results. The quoted specificity of the test is 100% with a cycle threshold of 35 cycles. All eight infants had cycle thresholds of 29–31 which, although within the manufacturer's quoted specificity, are towards the higher end. Internal validation of the test gave a 100% positive predictive value to 35 cycles suggesting that all eight are valid results.
      Fourthly these asymptomatic mothers could have been positive previously and, while no longer shedding viral RNA in the nasopharynx, had shed RNA or RNA fragments into the amniotic fluids which were still within the infant nasopharynx on the first day of life but cleared by the second test. This would explain the high cycle thresholds on the neonatal swabs and could be addressed by maternal/infant serology testing but this was not available at the time.
      Vertical transmission of SARS-CoV-2 has not been proven. To date case series and reports have focussed on infants born to symptomatic positive mothers. Rose et al.
      • Rose D.
      • Piersigilli F.
      • Ronchetti M.
      • Santisi A.
      • Bersani I.
      • et al.
      Novel Coronavirus disease (COVID-19) in newborns and infants; what we know so far.
      reviewed eight case series with a total of 69 pregnant women delivering 70 infants. Only four of 63 tested infants had positive throat swabs. The largest series to date is the UK Obstetric Surveillance System

      Knight M., Bunch K., Vousden N., et al. Characteristics and outcomes of pregnant women hospitalised with confirmed SARS-CoV-2 infection in the UK: a national cohort study using the UK Obstetric Surveillance System (UKOSS), 2020. https://www.npeu.ox.ac.uk/downloads/files/ukoss/annual-reports/UKOSS%20COVID-19%20Paper%20pre-print%20draft%2011-05-20.pdf(accessed 19/05/2020).

      national cohort study. In this series of 427 pregnant women hospitalised with SARS-CoV-2, 247 gave birth or suffered pregnancy loss. 12 infants tested positive; six of those within the first twelve hours. No description of infection control techniques practised by the mothers is given.
      There are several reports of placental infection in symptomatic COVID-19 positive women.
      • Baud D.
      • Greub G.
      • Favre G.
      • et al.
      Second-trimester miscarriage in a pregnant woman with SARS-CoV-2 infection.

      Hosier H., Farhadian S., Morotti R., et al. First case of placental infection with SARS-CoV- 2 medRxivpreprint, 2020. https://doi.org/10.1101/2020.04.30.20083907(accessed 18/05/2020).

      • Penfield C.
      • Brubaker S.
      • Limaye M.
      • et al.
      Detection of SARS-COV-2 in placental and fetal membrane samples.
      • Kirtsman M.
      • Diambomba Y.
      • Poutanen S.
      • et al.
      Probable congenital SARS-CoV-2 in a neonate born to a woman with active SARS-CoV-2 infection.
      Two mid-trimester cases
      • Baud D.
      • Greub G.
      • Favre G.
      • et al.
      Second-trimester miscarriage in a pregnant woman with SARS-CoV-2 infection.
      ,

      Hosier H., Farhadian S., Morotti R., et al. First case of placental infection with SARS-CoV- 2 medRxivpreprint, 2020. https://doi.org/10.1101/2020.04.30.20083907(accessed 18/05/2020).

      are described with pre-viable foetuses where viral RNA was positive from the foetal surface of the placenta but not from the fetuses. Penfield et al.
      • Penfield C.
      • Brubaker S.
      • Limaye M.
      • et al.
      Detection of SARS-COV-2 in placental and fetal membrane samples.
      describe placental and membrane swabs sent on eleven COVID-19 positive patients of which three were positive although no infant tested positive on days one to five of life. Kirtsman et al.
      • Kirtsman M.
      • Diambomba Y.
      • Poutanen S.
      • et al.
      Probable congenital SARS-CoV-2 in a neonate born to a woman with active SARS-CoV-2 infection.
      describe a single case of a 35 week gestation infant born to a COVID-19 positive mother with positive placental and membrane swabs and positive nasopharyngeal swabs immediately after birth and on days two and seven.
      Although viral RNA and DNA has been found in amniotic fluid from a number of different viruses including Zika virus and Ebola, vertical transmission of human coronaviruses was not described in either the SARS or MERS outbreaks
      • Schwartz D.
      • Graham A.
      Potential maternal and infant outcomes from coronavirus 2019-nCoV (SARS-CoV-2) infecting pregnant women: lessons from SARS, MERS, and other human coronavirus infections.
      and viral RNA from these related beta-coronaviruses was not found in amniotic fluid.
      Universal screening of 533 pregnant women in Italy

      Gagliardi L., Danieli R., Suriano G., et al. Universal SARS-CoV-2 testing of pregnant women admitted for delivery in two Italian regions, 2020. doi:10.1016/j.ajog.2020.05.017.

      found three positive for SARS-CoV-2 infection all of whom had uneventful deliveries. Neonatal swabs were not reported. Of 215 women tested under a universal swabbing programme in New York City

      Sutton D., Fuchs K., D'Alton M., Goffman D. Universal screening for SARS-CoV-2 in women admitted for delivery. NEJM, 2020. doi:10.1056/NEJMc2009316.

      33 were positive for SARS-CoV-2 of whom 29 (88%) were asymptomatic. Neonatal outcome was not reported. In a second New York study
      • Breslin N.
      • Baptiste C.
      • Gyamfi-Bannerman C.
      • et al.
      COVID-19 infection among asymptomatic and symptomatic pregnant women: two weeks of confirmed presentations to an affiliated pair of New York city hospitals.
      43 pregnant women tested positive for SARS-CoV-2. 18 well infants were delivered and all subsequently tested negative.
      Universal screening of neonates for SARS-CoV-2 infection has not been described and was introduced in our institution alongside universal screening of all in-patients. We describe the unexpected finding of positive infants with negative mothers. The study is limited by its size and the fact that no confirmatory samples such as placental swabs, amniotic fluid or serology in either mother or baby were obtained due to the nature of the universal screening programme. Nevertheless, the positive swabs in 2% of newborns, all within the first twenty four hours and three within the first three hours of life represent a very interesting finding. This study demonstrates that universal swabbing of all newborns is easy and could add substantially to our understanding

      Author's contributions

      All authors made equal contribution to the conception of the work. KM and SP collected the data. KM drafted the work and performed the original literature search. NG and SP performed additional literature searches and reviewed and edited the manuscript. All authors reviewed and approved the final version of the manuscript

      Disclosure statement

      We declare no competing interests.

      References

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        • Piersigilli F.
        • Ronchetti M.
        • Santisi A.
        • Bersani I.
        • et al.
        Novel Coronavirus disease (COVID-19) in newborns and infants; what we know so far.
        Ital J Pediatr. 2020; https://doi.org/10.1186/s13052-020-0820-x
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        Second-trimester miscarriage in a pregnant woman with SARS-CoV-2 infection.
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        Detection of SARS-COV-2 in placental and fetal membrane samples.
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