Transmission

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years who were BCG-vaccinated in childhood as compared to non-BCGvaccinated. Data on the effect of BCG vaccination on COVID-19 disease severity are unavailable (Hamiel 2020). In the adaptive response to any virus, cytotoxic T cells play an important role in regulating responses to viral infections and control of viral replication. Children could benefit from the fact that the cytotoxic effector function of CD8 T cells in viral infection in children may be less detrimental compared to adults. Immune dysregulation with exhaustion of T cells has been reported in adults with COVID-19 infection. Regarding humoral immunity, IgG maternal antibodies are actively transferred to the child via placenta and/or IgA via breast milk. They may not include anti CoV-2 antibodies, if the mother is naïve to CoV-2 or infected late in pregnancy. In mothers with COVID-19 pneumonia serum and throat swabs of their newborns were negative for CoV-2 but virus-specific IgG antibodies were detected (Zeng H 2020). Thus, neonates may benefit from placental transmission of virus-specific antibodies from pre-exposed mothers. As shown in SARS CoV-1 it is likely that in SARS-CoV-2 a newly infected child will mount a significant humoral response with neutralizing IgM (within days) and IgG antibodies (within 1-3 weeks) to one of the immunodominant epitopes, e.g. the crown-like spike proteins giving the coronaviruses their name. Infections with non-SARS COV are very common in children (see above); however, to what extent previous infections with nonSARS coronaviruses may have led to protective cross-reactive antibodies is unclear. Data regarding IgG and IgM seroprevalence and quality of the immune response in children are lacking. No human re-infections with CoV-2 have been demonstrated yet but overall it is not clear whether children mount a durable memory immune response to CoV-2. In summary, differences in the immune system such as more efficient innate and adaptive immunity to COV-2 (associated with better thymic function), cross-reactive immunity to common cold coronaviruses and differences in the ACE2 receptor expression as well as better overall health may be factors leading to a better COVID-19 outcome in children (Consiglio 2020).

Studies on the risk of acquiring SARS-CoV-2 infection in children in comparison to adults have shown contradicting results (Mehta 2020, Gudbjartsson 2020, Bi 2020). The exact role that children play in the transmission of SARSCoV-2 is not yet fully understood. Population based studies performed so far indicate that children might not play a major factor in the spreading of COVID-19 (Gudbjartsson 2020).

Pediatrics | 483

Vertical transmission

Contraction of COVID-19 in a pregnant woman may have an impact on fetal outcome, namely fetal distress, potential preterm birth or respiratory distress if the mother gets very sick. Schwartz reviewed 5 publications from China and was able to identify 38 pregnant women with 39 offspring among whom 30 were tested for COVID-19 and all of them were negative (Schwartz 2020, Chen 2020). Among the 24 infants born to women with COVID-19, 15 (62.5%) had detectable IgG and 6 (25.0%) had detectable IgM; nucleic acid test results were all negative. Among 11 infants tested at birth, all had detectable IgG and 5 had detectable IgM. IgG titers with positive IgM declined more slowly than those without (Gao 2020). In the PRIORITY study (n = 263), adverse outcomes, including preterm birth, NICU admission, and respiratory disease, did not differ between infants born to mothers testing positive for SARS-CoV-2 (n = 184) and those born to mothers testing negative (n = 79), suggesting that infants born to mothers infected with SARS-CoV-2 generally do well in the first 6-8 weeks after birth (Flaherman 2020). Transmission of COVID-19 appears unlikely to occur if correct hygiene precautions are undertaken. In 1481 deliveries at three hospitals in New York City, 116 (8%) mothers tested positive for SARS-CoV-2; 120 neonates were identified and none were positive for SARS-CoV-2 (Salvatore 2020). In another study from New York, 101 newborns of SARS-CoV-2 infected mothers no transmission was observed despite sleeping in the same room and breastfeeding (Dumitriu 2020). Initially it was thought that CoV-2 is not vertically transmitted, but in a more recent analysis of 31 mothers with SARS-CoV2, SARS-CoV-2 genome was detected in one umbilical cord blood, two at-term placentas, one vaginal mucosa and one breast-milk specimen. Three cases of vertical transmission of SARS-CoV-2 have been documented (Fenizia 2020). In a UK national population-based cohort study on SARS-CoV-2 infected pregnant women, twelve (5%) of 265 infants subsequently tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth (Knight 2020). Postpartum acquisition appears to be the most common mode of infection; in a recent review only 4/1141 neonates born to SARS-CoV-2 infected mothers were thought to have a congenital infection (Dhir 2020).

Horizontal transmission

Culture-competent SARS-CoV-2 has been grown from the nasopharynx of symptomatic neonates, children, and adolescents: 12 (52%) of 23 symptomatic SARS-CoV-2–infected children, the youngest being 7 days old. SARS-CoV-2 viral load and shedding patterns of culture-competent virus in the 12 symp-