Abstract： Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has mutated multiple times since the first report in December 2019 and is still spreading globally. A variant of SARS-CoV-2, Omicron, was prevalent in Shanghai from March to May 2022. Based on published data and the experience in the management of neonatal COVID-19 cases and infants of mothers with COVID-19 during the pandemic in Shanghai, it is suggested that neonates are infected with SARS-CoV-2 mainly through postnatal horizontal transmission, but rarely through vertical transmission. The risk of SARS-CoV-2 infection in infants born to mothers with COVID-19 is low if quarantine measures are appropriately implemented. Even if they are infected, the risk of severe neonatal COVID-19 is low, but long-term neurological prognosis needs to be followed closely. Human milk feeding without contact is advocated for infants of infected mothers. During the COVID-19 pandemic, attention should also be paid to indirect effect on neonatal health due to possible inadequate medical resources.