key: cord-0958028-cge6w1jr authors: Pietrasanta, Carlo; Ronchi, Andrea; Schena, Federico; Ballerini, Claudia; Testa, Lea; Artieri, Giacomo; Mercadante, Domenica; Mosca, Fabio; Pugni, Lorenza title: SARS‐CoV‐2 infection and neonates: a review of evidence and unresolved questions date: 2020-11-24 journal: Pediatr Allergy Immunol DOI: 10.1111/pai.13349 sha: eaa96ed1d8aab67f5092ac660c81e69172b41304 doc_id: 958028 cord_uid: cge6w1jr SARS‐CoV‐2 infection in the neonatal period poses previously unmet challenges to obstetricians and neonatologists, but several key questions are yet to be answered. Few cases of presumed in utero vertical transmission of the virus from infected mothers to fetuses have been reported, but stronger evidence is needed, from larger datasets with multiple biospecimens rigorously analyzed. Whether acquired before or after birth, SARS‐CoV‐2 infection in neonates can be symptomatic, but our comprehension of neonatal immune response and the subsequent clinical characteristics of COVID‐19 in early life are incomplete. Finally, the pandemic challenged several dogmas regarding the management of mother‐infant dyads, and again more robust data are needed to support the formulation of evidence‐based guidelines. Here, we briefly summarize existing evidence and key unresolved questions about SARS‐CoV‐2 infection and COVID‐19 in the neonatal period. SARS-CoV-2 infection in the neonatal period poses previously unmet challenges to obstetricians and neonatologists, but several key questions are yet to be answered. Few cases of presumed in utero vertical transmission of the virus from infected mothers to fetuses have been reported, but stronger evidence is needed, from larger datasets with multiple biospecimens rigorously analyzed. Whether acquired before or after birth, SARS-CoV-2 infection in neonates can be symptomatic, but our comprehension of neonatal immune response and the subsequent clinical characteristics of COVID-19 in early life are incomplete. Finally, the pandemic challenged several dogmas regarding the management of mother-infant dyads, and again more robust data are needed to support the formulation of evidence-based guidelines. Here, we briefly summarize existing evidence and key unresolved questions about SARS-CoV-2 infection and COVID-19 in the neonatal period. 2019-nCoV, COVID-19, neonate, newborn, pregnancy, prematurity, SARS-CoV-2 undoubtedly confirmed nor ruled out so far. In most described cases, RT-PCR for SARS-CoV-2 tested negative on neonatal (nasal-pharyngeal swab, anal swab, or cord blood) and maternal biospecimens (amniotic fluid, rectal swab, or vaginal swab). In the few cases of reportedly vertical transmission, a definitive diagnosis was hindered by either (a) the lag between birth and testing time, that could not rule out a droplet-or contact-mediated transmission from nursing mothers, (b) a negative re-testing soon later, or 3) no confirmation on neonatal biospecimens other than nasal-pharyngeal swab. 2 Nonetheless, 3 cases of neonates with circulating anti-SARS-CoV-2 IgM antibodies soon after birth were reported, suggesting the possibility of intrauterine acquisition of the virus despite negative RT-PCR testing after birth. Finally, a preliminary report confirmed (by RT-PCR, immunohistochemistry, and electron microscopy) the presence of SARS-CoV-2 in the placental tissue of a COVID-19 mother concomitantly affected by severe preeclampsia. 3 Given these areas of uncertainty, future research will have to focus on the analysis of multiple maternal and neonatal biospecimens simultaneously, to clarify whether and in which situations an intrauterine transmission of SARS-CoV-2 is possible. The majority of SARS-CoV-2-positive pregnant women give birth at term or near term. In a few reported cases of preterm delivery, the At present, most scientific societies agree that the mode of delivery should not be influenced by maternal COVID-19, provided the mother is in good clinical conditions. Indeed, SARS-CoV-2 has not been identified in vaginal secretions so far. 5 Rooming-in practice and breastfeeding are beneficial for mother-infant dyads, and, to date, SARS-CoV-2 transmission through breastmilk has not been demonstrated. Thus, several current recommendations encourage rooming-in practice and breastfeeding with contact and droplet precautions, but are not based on robust data yet to be acquired. 5 Studies on large populations are urged to clarify whether active SARS-CoV-2 can be transmitted through breastmilk, whether the risk of mother-to-neonate transmission is through respiratory droplets or contact, and, more importantly, whether breastfeeding may exert a protective role against neonatal infection, through specific anti-SARS-CoV-2 IgA or indirect mechanisms. Evidence regarding the infectivity and pathogenicity of SARS-CoV-2 in infancy is progressively accumulating, as well as few speculations and little data about the age-specific virus-host interaction. A recent report on 731 children affected by COVID-19 highlighted that 10% of patients below 1 year of age presented severe or critical symptoms, although specific data on neonates were lacking. 6 Based on smaller reports, neonates usually present fever, hyporeactivity, mild respiratory distress, and feeding difficulty. 7 Severe symptoms have been described in few neonates. However, they could not be unambiguously attributed to SARS-CoV-2 infection due to the presence of comorbidities, in particular prematurity. 8 The overall lower susceptibility to COVID-19 of children and neonates has given rise to multiple speculations about the underlying biologic reasons. It is known that SARS- The authors declare no commercial or financial relationships that could be construed as a potential conflict of interest. World Health Organization (WHO) Can SARS-CoV-2 infection be acquired in utero?: More definitive evidence is needed SARS-CoV-2 infection of the placenta. medRxiv COVID-19 in a 26-week preterm neonate Frequently Asked Questions: Breastfeeding and COVID-19 For health care workers Epidemiology of COVID-19 among children in China Novel coronavirus disease (COVID-19) in newborns and infants: what we know so far Neonatal early-onset infection with SARS-CoV-2 in 33 neonates born to mothers With COVID-19 in Wuhan, China The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak The immune system of children: the key to understanding SARS-CoV-2 susceptibility? Lancet Child Adolesc Health Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn SARS-CoV-2 infection and neonates: a review of evidence and unresolved questions