SARS-CoV-2 Infection in the Third Trimester Is Not an Independent Risk Factor for Immature Immune Function in Preterm Infants

Abstract

Background: Immature immunologic function is the primary reason that premature infants are prone to infection after birth. The outbreak of coronavirus infected disease 2019 (COVID-19) has led to an increase in the incidence of preterm birth, representing a new survival risk for preterm infants.Objectives: From February 2020 to May 2020, 57 premature infants of gestational age (GA) less than 37 weeks (28 +3 -36 +5wks ) born to 48 mothers were hospitalized in Zhongnan Hospital of Wuhan University, Wuhan China. Among them, 14 premature infants were delivered by 13 mothers infected with severe acute respiratory syndrome (SARS-CoV-2) in the third trimester.Methods: Due to the epidemic of COVID-19 in Wuhan and the policy of lockdown, all pregnant women underwent examination for SARS-CoV-2 nucleic acid, serum antibody and lung computer tomography (CT) before delivery. After birth, new-borns’ peripheral blood was collected, and immune cells counts and cytokine concentrations were assessed. Subjects’ clinical data were recorded and analysed.Results: Absolute lymphocyte count (ALC) and CD4 cells of preterm infants increased with GA. CD3, CD4, CD8, CD19, CD16-56 cell counts were positively correlated with ALC. Concentrations of IL-2, IL-4, IFN-γ and TNF-α were in the normal reference range and were not correlated with GA and birth weight (BW). Median IL-6 level in preterm infants was 14.71 pg/ml (IQR 6.47-46.14 pg/ml), which was 5.07-fold higher than the reference intervals, 3.9 pg/ml (IQR, 1.79-14.28 pg/ml), and the ratio of IL-6/IL-10 was 3.77. IL-10 was positively correlated with IL-2, IL-4 and IL-6. Immune cell counts, cytokine levels and clinical prognosis of premature infants born to mothers with SARS-CoV-2 were not different from those without maternal SARS-CoV-2 infection.Conclusions: Immune function in preterm infants was characterized by increased CD4 cells with GA and a positive correlation between high levels of IL-6 and IL-10. Maternal infection with SARS-CoV-2 is not an independent perinatal risk factor for premature infants with immature immune function.Trial Registration: The present study was registered as a clinical study in the Chinese Clinical Trial Registry (ChiCTR-ORC-16008872).Funding Statement: This work was supported by a grant from the Chinese National Natural Science Fund 81170005 and 81670007.Declaration of Interests: No conflict of interest.Ethics Approval Statement: The Institutional Review Board of Zhongnan Hospital of Wuhan University approved this study (approval no. 2015019). All guardians signed informed consents.