A recent study led by Cleveland Clinic and published in The EMBO Journal has unveiled critical insights into how mild and asymptomatic SARS-CoV-2 infections can influence immune responses in pregnant individuals, potentially leading to serious inflammatory reactions in developing fetuses. The research suggests that vertical transmission of the virus from a pregnant person to their fetus may occur more frequently than previously estimated, and highlights that a pregnant individual’s immune response to infection can affect fetal health even without direct viral transmission.
Traditionally, healthcare providers test newborns for SARS-CoV-2, the virus responsible for COVID-19, through nasal swabs after birth. However, the Cleveland Clinic researchers collected samples from the placenta and fetal compartments—tissues surrounding the fetus while in utero—and found a higher incidence of the virus in these tissues compared to what can be detected through nasal swabs. Notably, even in the absence of a full infection, small viral proteins were found to have crossed the placenta.
The findings aim to enhance the speed and reliability of evidence-based medical care for pregnant individuals during health crises and outbreaks.
Addressing Gaps in Knowledge
As the COVID-19 pandemic began, Dr. Ruth Farrell, an OB/GYN at Cleveland Clinic, recognized the need for tailored strategies to manage SARS-CoV-2 infections in pregnant patients. Many prevention and treatment methods applicable to non-pregnant individuals lacked sufficient data for pregnant patients or were impractical to implement.
“Delays in understanding how to prevent and treat pregnant patients with SARS-CoV-2 infection contributed to significant knowledge gaps and disparities in care,” explained Dr. Farrell, who is also Vice Chair of Research for Cleveland Clinic’s Obstetrics & Gynecology Institute.
Collaborating with clinical colleagues from the Clinical and Translational Science Collaborative (CTSC) of Northern Ohio, including researchers from University Hospitals of Cleveland and MetroHealth Medical Center, Dr. Farrell sought to investigate the effects of SARS-CoV-2 on pregnant patients.
Key Findings
The standard COVID-19 test, which relies on nasal swabs to detect the virus in newborns, identifies infections in only about 2% of infants whose mothers tested positive during pregnancy. However, a detailed examination of surrounding tissues—such as amniotic fluid, chorion, and umbilical cord plasma—revealed that over 26% of study participants had detectable levels of the virus.
Furthermore, approximately 66% of participants exhibited elevated immune and inflammatory responses. While previous research showed increased fetal inflammation in cases of severe maternal infections, this study confirmed similar responses in mild or asymptomatic cases.
Dr. Jolin Foo, a maternal-fetal virologist, emphasized the significance of these findings: “Despite only observing vertical transmission in a quarter of cases, we detected robust immune responses in over two-thirds. This indicates that even in the absence of a full infection, fetuses are affected by maternal viral infections.”
Understanding the Mechanism
Dr. Javier Chen, also a maternal-fetal virologist, noted that the SARS-CoV-2 virus produces a protein called ORF8, which resembles a human immune protein known as immunoglobulin G. This protein is capable of crossing the placenta during fetal development, raising concerns about its potential to provoke inflammation in the fetal compartment.
The research team demonstrated that the viral protein ORF8 does pass through the placenta, binding to immune proteins and activating the complement immune response. While the complement system typically supports fetal development, excessive activation can lead to harmful inflammation. Laboratory studies confirmed that this immune response contributes to the heightened inflammation observed in fetuses of infected mothers.
“Our findings challenge existing definitions of vertical transmission,” Dr. Chen stated. “We have shown that even a small portion of a virus can slip through and affect pregnancy outcomes.”
Dr. Foo expressed hopes that the team’s research would inform healthcare providers, researchers, and policymakers about the nuances of vertical transmission and the importance of long-term care for affected individuals.
“It’s a misconception that uninfected babies born to infected mothers are fine,” she remarked. “Pregnancy is a vulnerable time, and any deviation from the norm can have lasting impacts on the child. We must work closely with these individuals to address their unique healthcare needs during public health emergencies.”
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