To the Editor
The
coronavirus
disease 2019 (COVID‑19) caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) appears milder in children but little is
known about neonates and about the chains of infections after
delivery.1-3 When in early March 2020 a midwife in our
large maternity and perinatal center returned from vacation in Ischgl,
Austria, she triggered a COVID-19 outbreak affecting 36 midwives, nurses
and doctors. We reported previously on the successful containment of
this outbreak and characterized the clinical symptoms and immunoglobulin
development in staff members exposed to SARS-CoV-2.4-5
Here, we present the data of all deliveries with varying degrees of
unprotected parental contact with SARS-CoV-2-infected personnel during
the first, precontainment, week of the outbreak. Of the 66 families
concerned, 61 consented to a prospective study (University of Regensburg
institutional review board ID 20-1791-10) involving serial symptom
interview, serial SARS-CoV-2 screening in throat rinsing fluid (parents)
and feces (infants), and serum IgA and IgG antibody studies (parents and
infants) 4-5 weeks postpartum. 18 families had extensive unprotected
contact with infected staff lasting >15 minutes at
<1.5 meters distance (Robert Koch Institute [RKI] risk
category I). These families had their first SARS-CoV-2 test in the first
week after delivery; they were quarantined for ≥2 weeks after discharge
home and received weekly study visits. The remaining 43 less exposed
families received only two visits.
We tested for SARS-CoV-2 by real-time reverse transcriptase–polymerase
chain reaction (RT-PCR) for N2 and E gene, Xpert© Xpress SARS-CoV-2,
Cepheid, and for serum IgA and IgG antibodies (EUROIMMUN AG, Lübeck,
Germany) as previously published.5 In addition, to
verify the antibody responses we performed a second antibody assay in
serum and breast milk, which uses a recombinant protein representing the
nucleocapsid antigen for determination of all kind of antibodies against
SARS-CoV-2 following the manufacturer’s instructions (Elecsys
anti-SARS-CoV-2, Roche Diagnostics, Penzberg, Germany). According to the
manufacturer’s recommendations for both antibody assays from EUROIMMUN
and Roche Diagnostics, a cutoff index of < 1.0 was considered
non-reactive (negative for anti-SARS-CoV-2 antibodies) and a value ≥ 1.0
reactive (positive).
One or both parents from 16 families reported symptoms suggestive of a
SARS-CoV-2 infection within 2 weeks postpartum (Table 1). Three of their
infants (all spontaneous births) displayed nonspecific signs of
infection similar to late-onset sepsis, including fever, dyspnea and
compromised circulation leading to admission to our neonatal intensive
care unit, at day of life 5 (ID 3), 10 (ID 7) and 26 (ID 1), resolving
within few days (Figure). Blood cultures and tests for non SARS-CoV-2
viruses remained negative. Although families with symptoms did not
differ in baseline characteristics from those without (n=45), risk
category I families tended to be at higher symptom risk (Table 1).
Five of the 16 families reporting mild COVID-19-compatible symptoms
actually contracted COVID-19 based on the RT-PCR and antibody evidence
(Figure). Two of the three symptomatic neonates were RT-PCR positive and
one asymptomatic neonate. Surprisingly, neither the 3 neonates tested
positive for SARS-CoV-2 nor the uninfected newborns had elevated or even
borderline antibodies. All antibody results obtained by the EUROIMMUN
assay were confirmed by the Roche Diagnostics assay. Of the symptoms
prospectively recorded in adults only anosmia appeared COVID-19-specific
(Figure). Only one mother (ID 3) produced IgG-positive breast milk. Two
neonates, one asymptomatic and one symptomatic (ID 4 and 7,
respectively), excreted virus in feces for weeks (Figure).
Differences in neonatal disease onset timing, between day of life 5 and
26, reflect different chains of intra-family infection. Due to our
unique study setting, antepartum infections can be excluded. Albeit we
cannot exclude completely the risk of vertical infection via breastmilk,
much more likely is postnatal infection through horizontal transmission.
While separation of the newborn from the COVID-19 suspected or proven
mother would theoretically lower infection risk as e.g. suggested by
China consensus guidelines6 we kept our practice from
before the outbreak supporting skin-to-skin care, rooming-in, and
breastfeeding for infants born to mothers with COVID-19 in line with the
recommendations from the WHO.7 The important hygiene
changes from the time before the COVID-19 outbreak and now are the
various protection measures around the mother infant dyad, including
screening of all pregnant women admitted to the maternity hospital and
isolation until SARS-CoV-2 test is negative, surgical face masks for all
personnel and patients, proper personal protective equipment when
working with patients under investigation for SARS-CoV-2 or for
confirmed cases as explained in detail elsewhere.8
The outbreak coincided with the seasonal flu peak ultimately responsible
for most recorded symptoms. Indeed the coincidence blurred initial
pandemic awareness, with some staff and parents already wearing surgical
face masks for seasonal flu protection.
Together, like their parents, newborns can contract COVID-19 in the
first weeks postpartum and their symptoms may show similarities with
late onset sepsis. In adults, anosmia may differentiate mild COVID-19
from common flu.