Short-lived neutralizing activity against SARS-CoV-2 in newborns of immunized mothers

Abstract

Background: Newborns under 6 months of age are at high risk of hospitalization for acute respiratory failure following SARS-CoV-2 infection. Herein, we analyzed neonatal protection against SARS-CoV-2 passively acquired after mother vaccination and/or infection (hybrid immunity).

Methods: We enrolled seventy-eight newborns of immunized mothers against SARS-CoV-2 before or during pregnancy, through vaccination and/or infection. Infants were stratified based on the anamnestic lack (SARS-CoV-2 Vaccinated - SV)/presence (SARS-CoV-2 Infected and Vaccinated - SIV) of COVID-19 maternal infection. SARS-CoV-2-specific Neutralizing Activity (NA) in plasma was assessed by virus neutralization assay (vNTA) against the SARS-CoV-2 Omicron strain at delivery (T0), 3 and 6 months after birth (T3 and T6). Cytokine and chemokine profiles in newborns were also analyzed.

Results: At birth, significantly lower NA was observed in infants of SV compared to that of SIV mothers; NA declined equally in both groups 3 months after delivery. The presence of at least 4 immunizing events in the mother significantly enhances the NA against SARS-CoV-2 in newborns, regardless of the type of immunization (vaccination or hybrid immunity) and of the timing of the last maternal immunization. Finally, cytokines and chemokines plasma levels were high at birth in all newborns, followed by a decline over the subsequent month.

Conclusion: Our findings suggest that, independently of a previous SARS-CoV-2 infection or vaccination, it is reasonable to upgrade the recommendation of a booster dose during pregnancy to a "strongly recommended" status, with a view to conferring protection to newborns in the first months after delivery.

Keywords: SARS‐CoV‐2; hybrid immunity; neutralizing activity; newborns; passive immunity.

FIGURE 1

Timeline of sample collection. T0: One day before vaccination; T1: 25 days after the second dose; T2: 6 months after second dose—administration of the third dose; T3: 3 months after the third dose.

FIGURE 2

Neutralizing activity (NA) at birth newborns from SV or SIV mothers. (A) Plasma neutralizing activity (NA) over time (T0, T3 and T6) against the SARS‐CoV‐2 Omicron variant is shown in all the newborns enrolled. (B) The data of the plasma NA over time (T0, T3 and T6) against the SARS‐CoV‐2 Omicron variant is shown by dividing the newborns born from SV (light blue) and SIV (dark blue) mothers. Mean values ± SEM are reported. Significance was set at p < .05 (Two‐way ANOVA test, p values adjusted for multiple comparisons). *p < .05, **p < .01.

FIGURE 3

NA at birth in newborns from mothers who experienced 4 or more immunizing events. (A) Plasma NA over time (T0 and T3) against the SARS‐CoV‐2 Omicron variant is shown in newborns from mothers who experienced 3 or less immunizing events () or 4 or more immunizing events (). (B) The data of the plasma NA over time (T0 and T3) against the SARS‐CoV‐2 Omicron variant is shown by dividing the newborns born from mothers who experienced immunizing events by 12 months before delivery (early event, white) or from mothers who experienced the immunizing events within 12 months before delivery (late event, dark green). Mean values ± SEM are reported. Significance was set at p < .05 (Two‐way ANOVA test, p values adjusted for multiple comparisons). **p < .01.

FIGURE 4

Cytokine and chemokine profile in newborns at birth, at 3 and 6 months of age. (A) Heatmap of cytokine/chemokine concentration (pg/mL) over time (T0, T3, and T6) in the plasma derived from all the newborns enrolled; mean values ± SEM are reported; significance was set at p < .05 (Two‐way ANOVA test, p values adjusted for multiple comparisons), * vs. T3: *p < .05, **p < .01, ***p < .001; # vs. T6: #p < .05, ##p < .01. Histograms of the significantly modulated cytokines/chemokines are reported. (B) Heatmap of cytokine/chemokine profile at different time points (T0 and T3) is shown by dividing the newborns born from SV (light blue) and SIV (dark blue) mothers; mean values ± SEM are reported; significance was set at p < .05 (Two‐way ANOVA test, p values adjusted for multiple comparisons), * vs. T0: *p < .05, **p < .01, ***p < .001. Histograms of the significantly modulated cytokines/chemokines are reported.