Distinct Cellular Immune Responses to SARS-CoV-2 in Pregnant Women

Abstract

Pregnant women are at increased risk of adverse outcomes, including preeclampsia and preterm birth, that may result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Pregnancy imprints specific maternal immune responses that can modulate host susceptibility to microbial infection; therefore, recent studies have focused on the humoral response against SARS-CoV-2 in pregnant women. However, the pregnancy-specific cellular immune responses triggered by SARS-CoV-2 infection are poorly understood. In this study, we undertook an extensive in vitro investigation to determine the cellular immune responses to SARS-CoV-2 particles and proteins/peptides in pregnant women. First, we show that SARS-CoV-2 particles do not alter the pregnancy-specific oxidative burst of neutrophils and monocytes. Yet, SARS-CoV-2 particles/proteins shift monocyte activation from the classical to intermediate states in pregnant, but not in nonpregnant, women. Furthermore, SARS-CoV-2 proteins, but not particles or peptide pools, mildly enhance T cell activation during pregnancy. As expected, B cell phenotypes are heavily modulated by SARS-CoV-2 particles in all women; yet, pregnancy itself further modified such responses in these adaptive immune cells. Lastly, we report that pregnancy itself governs cytokine responses in the maternal circulation, of which IFN-β and IL-8 were diminished upon SARS-CoV-2 challenge. Collectively, these findings highlight the differential in vitro responses to SARS-CoV-2 in pregnant and nonpregnant women and shed light on the immune mechanisms implicated in coronavirus disease 2019 during pregnancy.

Pregnancy-specific responses to COVID-19 are revealed by high-throughput proteomics of human plasma

“…Thus, given such deficiencies in peripheral adaptive immunity, pregnant women infected with SARS-CoV-2 may rely more heavily on monocytes, which are also potent contributors to anti-viral host defense 108 . Consistently, monocytes undergo substantial expansion and differentiation in patients with severe COVID-19 [109][110][111] , and we have shown that monocytes from pregnant women appear to undergo accelerated transition and activation in response to SARS-CoV-2 exposure 30 , which is in line with a previous report 39 .…”

“…We demonstrated a pregnancy-specific reduction of unswitched memory-like and transitional-like B-cell subsets 30 , which is in line with a prior study showing that such reduction of B-cells is associated with COVID-19 severity 107 . Thus, given such deficiencies in peripheral adaptive immunity, pregnant women infected with SARS-CoV-2 may rely more heavily on monocytes, which are also potent contributors to anti-viral host defense 108 .…”

“…Moreover, given the demonstrated relationship between pathological maternal T-cell activation and pregnancy complications such as preterm labor 62,63 , it is imperative that maternal adaptive immunity remain under strict control until normal parturition at term [103][104][105][106] . Consistently, we recently undertook an ex vivo evaluation of peripheral cellular immune responses against SARS-CoV-2 particles and proteins in pregnant and non-pregnant women 30 .…”

“…Upon the onset of the COVID-19 pandemic, multiple investigations have sought to uncover the effects of SARS-CoV-2 infection on maternal, fetal/placental, and neonatal immunity [19][20][21][22][23][24][25][26][27][28][29][30][31][32] . Indeed, we and others have characterized the changes in systemic parameters such as cellular immune responses, virus-specific immunoglobulins, and inflammatory mediators in the maternal peripheral blood and/or cord blood to generate a profile of the maternal-fetal immune responses against SARS-CoV-2 infection 26,[33][34][35][36] .…”

Placental Characteristics of a Large Italian Cohort of SARS-CoV-2-Positive Pregnant Women

“…In vitro studies detected different cellular immune reactions to SARS-CoV-2 and cytokine secretion in pregnant women compared to non-pregnant women. Especially IL-8 concentration, which has a chemotactic effect on neutrophils and is increased in SARS-CoV-2-positive women [ 25 ].…”