A new Cleveland Clinic-led study published in the EMBO journal shows that mild, asymptomatic SARS-CoV-2 infection can trigger an immune response in pregnant people and cause a severe inflammatory response in the developing fetus. It shows that there is a gender. The findings also suggest that vertical transmission of the virus from a pregnant individual to the fetus is more common than previously estimated. And even without this infection, a pregnant person’s immune response to infection can affect the fetus.
After birth, health care providers typically use nasal swabs to test newborns for SARS-CoV-2 infection, the virus that causes COVID-19. For this study, researchers at the Cleveland Clinic collected samples from the placenta and fetal compartment (the tissue that surrounds the fetus while in the womb) and analyzed them for inflammatory markers and the presence of viruses. They found more examples of the virus in these tissues than would be found in a traditional nasal swab, and found that small proteins of the virus cross the placenta even in the absence of a full-blown infection. Researchers hope this study will help ensure that pregnant people quickly and reliably receive the evidence-based medicine they need in the event of a new outbreak or public health crisis. There is.
When the COVID-19 pandemic first began, Dr. Ruth Farrell, an obstetrician-gynecologist at the Cleveland Clinic and other major medical centers, and her colleagues worked to prevent and manage infections in pregnant patients. I wanted to find the best way. During the pandemic, pregnant people required different medical considerations compared to non-pregnant people. Dr. Farrell points out that many of the prevention and treatment approaches used in non-pregnant patients did not have sufficient data or were not feasible to use in pregnant patients.
“During the early stages of the pandemic, there were significant delays in determining how best to prevent and treat pregnant patients with SARS-CoV-2 infection,” said Dr. Farrell, who also serves as vice chair for research in obstetrics at the Cleveland Clinic. explain. & Gynecological Research Institute.
These delays have created gaps in our understanding of the coronavirus pandemic for pregnant women. These gaps also contribute to disparities that prevent pregnant women from receiving the best care as quickly as possible during the pandemic. ”
Ruth Farrell, Cleveland Clinic
Dr. Farrell is collaborating with clinical colleagues from the Northern Ohio Clinical and Translational Science Collaborative (CTSC), including researchers from Cleveland University Hospitals and MetroHealth Medical Center, to investigate SARS-CoV-2 infection in pregnant patients. We developed a method to examine the impact.
She then collaborated with Cleveland Clinic maternal and child virologist Dr. Jolin (Xuan Xin) Fu and Dr. Javier (Weiqiang) Chen of the Infection Biology Program to understand how the virus affects the immune systems of both mother and child. We found out what the impact was.
When standard-of-care coronavirus tests (nasal swabs at birth) are used to detect the virus in newborns, only about 2% of children whose mothers test positive for the virus during pregnancy become infected. It just gets detected. However, Drs. Chen and Fu observed the surrounding tissue while the newborn was still in the womb. High levels of virus were detected in more than a quarter (26%) of study participants – including amniotic fluid, chorion, and umbilical cord plasma.
The research team also found elevated immune and inflammatory responses, which affected pregnancy in about 66% of study participants. Dr. Fu had previously shown that pregnant women who experienced severe SARS-CoV-2 infection during pregnancy had increased levels of fetal inflammation, but the same was true for asymptomatic or mild infections. Few wondered whether it would have an impact. But even with the answers, the team faced more questions.
“Even though we only saw one-quarter of vertical transmission of complete viral infection, we found strong immune and inflammatory responses in more than two-thirds of cases,” Dr. Hu said. “It was clear that the fetus was affected by the mother’s viral infection even when it wasn’t technically infected. But we didn’t really understand how the fetus became infected.”
Elevated levels of inflammation during pregnancy, during COVID-19 and other situations, can have negative effects on offspring long after birth. Further research could reveal how inflammation affects children in the long term.
Dr. Chen pointed out that the SARS-CoV-2 virus has a protein called ORF8, which is physically similar to a human immune protein called immunoglobulin G, which crosses the placenta from mother to fetus during development. did. He wondered if viral proteins could pass through the placental defenses and cause inflammation in the fetal compartment.
Doctors. Hu and Chen, along with co-lead authors Dr. Tamiris Azamor and Dr. Deborah Familia-Macedo (former and current postdoctoral fellows in Dr. Hu’s lab, respectively), confirmed that the virus-produced ORF8 actually I was able to prove that I passed. to the fetus through the placenta. ORF8 then binds to immune proteins and “turns on” a process called the complementary immune response.
At normal levels, the complement system has a positive effect during pregnancy, helping the fetus develop properly, explains Dr. Familia Macedo. Higher levels of the complement system can cause dangerous inflammation in the developing fetus. Clinical studies have confirmed that this immune response is directly linked to increased levels of inflammation seen in the fetuses of pregnant patients infected with the SARS CoV-2 virus.
“Our findings call into question the currently accepted definition of vertical transmission, or what it means to transmit infection from mother to fetus,” Dr. Chen says. “We showed that only a small portion of the virus can slip through and affect pregnancy.”
Dr. Hu added that she hopes her team’s findings will serve as a guide for further research into vertical transmission and long-term care for health care workers, researchers, and policy makers alike.
“We have shown that the misconception that uninfected babies born to infected mothers are OK is sometimes just a misconception,” she says. “Pregnancy is a very vulnerable nine months and any change from normal can have long-term effects on the baby, so we are working more closely with these people to ensure public health We need to understand their unique medical needs in a crisis and how to make sure they get the care they need.”
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Reference magazines:
Azamor, T. et al. (2024). Transplacental SARS-CoV-2 protein ORF8 binds complement C1q and causes fetal inflammation. EMBO Journal. doi.org/10.1038/s44318-024-00260-9.
