COVID-19 during pregnancy causes ‘distinct’ immune changes in mothers, babies
SARS-CoV-2 infection during pregnancy may trigger prenatal immune activation that can lead to adverse maternal and neonatal outcomes, according to a study published in Cell Reports Medicine.
“We know that pregnancy increases maternal risk for COVID-19, but relatively little is known about the long-term consequences of in utero exposure for infants,” author Jae Jung, PhD, Betsy B. deWindt Endowed Chair in Cancer Biology at the Cleveland Clinic Lerner Research Institute, said in a hospital press release.
“It is an area needing further study since generally there is evidence that maternal immune activation in pregnancy is linked to potential long-term neurodevelopmental disorders in early childhood and young adulthood, including autism spectrum disorder and schizophrenia,” said Jung, who also directs the Lerner Institute’s Infection Biology Program.
The study involved 93 mothers (median age, 33 years; 47.3 Latina) who had tested positive for SARS-CoV-2 infection via nasopharyngeal RT-PCR testing (n = 90) or serology (n = 3) at any point during gestation between April 15, 2020, and March 1, 2021, and 45 of the infants who were born and exposed to the virus.
The women and infants were part of the COVID-19 Outcomes in Mother-Infant Pairs Study, a prospective observational cohort of mother-infant pairs diagnosed with SARS-CoV-2 infection in pregnancy in the United States and Brazil. The researchers also included 18 gestational age-matched healthy pregnant women as controls.
The study collected maternal blood specimens at the time closest to initial laboratory-confirmed diagnosis of infection (n = 79), including nine asymptomatic, 46 mild, four moderate, six severe and 14 critical cases, and at labor and delivery (n = 49). Cord blood was collected when possible (n = 32), and blood was taken from all infants at age 1 day as well.
The researchers isolated sera from these blood specimens and subjected them to high-throughput next-generation sequencing-based proteomics multiplexing to detect more than 1,400 cytokines and serum proteins.
After comparing blood specimens from different time points throughout pregnancy and delivery, the researchers found that COVID-19 dysregulates maternal immune response, as indicated by different immune signatures between mothers with asymptomatic and severe disease.
The pregnant women with severe COVID-19 exhibited significantly more inflammation and elevated levels of the interferon lambda 1 (IFNL1) protein and the receptor it binds with, IFNLR1, which the researchers said plays a critical role in protecting against viruses.
“This increase in interferon lambda signaling may help explain why we see relatively little direct transmission of COVID-19 between mother and baby during the period right before or after birth — what we call vertical transmission,” author Suan-Sin (Jolin) Foo, PhD, a research associate in Jung’s lab, said in the press release. “More research will be necessary to determine if increased expression of IFNL1 and IFNLR1 does in fact block vertical transmission.”
At delivery, the women exhibited dysregulated levels of several cytokines associated with pregnancy complications, including MMP7, MDK, ESM1, BGN and CD209.
Among infants, prenatal exposure induced the expression of cytokines related to T cells, which are a type of immune cell involved in recognizing and attacking specific antigens, including IL33, NFATC3 and CCL21.
Most of the births were healthy, the researchers said, though they noted a high incidence of some complications including preeclampsia and fetal growth restriction. The researchers said that further studies will be necessary to understand the extent to which the observed immune changes are related to these clinical outcomes.
“Our findings show that COVID-19 infection during pregnancy leads to distinct immune alterations in mothers and babies, highlighting how important it will be for long-term follow-up after pregnancy to catch and hopefully prevent any unforeseen long-term health conditions related to prenatal infection,” said Jung.