The immunologic status of newborns born to SARS-CoV-2-infected mothers in Wuhan, China

Abstract

Background: Immunologic dysfunction due to coronavirus disease 2019 (COVID-19) is closely related to clinical prognosis, and the inflammatory response of pregnant women may affect the directional differentiation and function of fetal immune cells.

Objective: We sought to analyze the immune status of newborns from mothers with COVID-19 in the third trimester.

Methods: Along with collecting the clinical data from 51 newborns and their respective mothers, we recorded the immunophenotypes and cytokine and immunoglobulin levels of the newborns.

Results: None of the 51 newborns showed fever or respiratory distress during hospitalization. Detection of severe acute respiratory syndrome coronavirus 2 nucleic acid in pharyngeal swabs was negative. Except for the low level of CD16-CD56 cells, the count and proportion of lymphocytes, CD3, CD4, CD8, and CD19 were all in the normal range. Moreover, the serum IgG and IgM levels were within the normal range, whereas IL-6 showed increased levels. There was no correlation between maternal COVID-19 duration and the lymphocyte subsets or cytokine levels (IFN-γ, IL-2, IL-4, IL-6, IL-10, and TNF-α). There was a positive correlation between IL-6 and IL-10 levels and CD16-CD56 cells. One (1.96%) infant with an extremely elevated IL-6 concentration developed necrotizing enterocolitis in the third week after birth, and the remaining 50 infants did not show abnormal symptoms through the end of the follow-up period.

Conclusions: COVID-19 in the third trimester did not significantly affect the cellular and humoral immunity of the fetus, and there was no evidence that the differentiation of lymphocyte subsets was seriously unbalanced.

Keywords: COVID-19; Newborn; lymphocyte subsets and cytokines; pregnant women; third-trimester.

Fig 1

Maternal disease duration may not affect the number or percentage of immune cells in newborns. The data showed the correlations between maternal disease duration and white cells, lymphocytes, CD3 counts, CD3 counts as a percent of lymphocytes (CD3%), CD4 counts, CD4 counts as a percent of lymphocytes (CD4%), CD8 counts, CD19 counts, and CD16-CD56 counts. ns, Not significant.

Fig 2

Preexisting maternal COVID-19–specific clinical symptoms may not affect lymphocyte subsets of newborns. We compared white cells, lymphocytes, CD3 counts, CD3 counts as a percent of lymphocytes (CD3%), CD4 counts, CD4 counts as a percent of lymphocytes (CD4%), CD8 counts, CD8 counts as a percent of lymphocytes (CD8%), and the CD4/CD8 ratio in the None, Within 1 w, and Over 1 w groups. Data are presented as the mean ± SD. ns, Not significant.

Fig 3

Neonatal CD19 cell and IgG levels were not affected by maternal COVID-19; the IgG concentration was independent of the CD19 cell count. Number and percentages of CD19 cells (A) and IgG concentration (B) in the None, Within 1 w, and Over 1 w groups. Data are presented as the mean ± SD. ns, Not significant.

Fig 4

Effect of maternal SARS-CoV-2 infection on CD16-CD56 cells and cytokines in newborns. A, Numbers and percentages of CD16-CD56 cells and CD16-CD56 cells as a percent of lymphocytes (CD16-CD56 cells%) in None, Within 1 w, and Over 1 w groups. B, Concentration of IFN-γ, IL-2, IL-4, IL-6, IL-10, and TNF-α in the None, Within 1 w, and Over 1 w groups. Data are presented as the mean ± SD. ns, Not significant.

Fig 5

A significant relationship was found between IL-6 and IL-10. The data present the concentrations of IL-6, IL-10, and IFN-γ and the number of CD16-CD56 cells. There were significant positive correlations between IL-6 and IL-10, IL 455 -6 and CD16-CD56 cell counts, IL-10 and IFN-γ, and IL-10 and CD16-CD56 cell counts.

Fig E1

Chest radiographs were performed on the day or the next day of admission, which showed no pneumonia changes. A, The chest computed tomography examination of 1 case with 2 consecutive suspected positive results of pharyngeal swab nucleic acid after birth. B, The chest x-ray picture of neonate born to SARS-CoV-2–infected mother.