Early in the pandemic, Yale researchers demonstrated that SARS-CoV-2, the virus responsible for COVID-19, could infect the placenta during acute maternal illness — a condition known as COVID-19 placentitis that was linked in some cases to inflammation and pregnancy complications.
For a new study, the researchers asked a critical follow-up question: Does the virus remain in placental tissue after the mother recovers? Writing in the journal JAMA Network Open, they report that the answer is no, offering important reassurance for clinicians and patients alike.
“Our study reassures pregnant patients that if they become infected with COVID during their pregnancy, the placenta won’t become a reservoir for the virus,” said Harvey Kliman, a research scientist in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine (YSM) and senior author of the study.
What you need to know
What is long COVID?
Long COVID is a chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months. The serious illness can lead to chronic health issues ranging from fatigue and brain fog to shortness of breath and headaches.
Why is the placenta a magnet for SARS-CoV-2?
The placenta is a magnet for SARS-CoV-2 because it’s covered with ACE2, the receptor for the spike protein of the virus.
What happens to SARS-CoV-2 in the placenta once it’s infected?
Although SARS-CoV-2 infects the placenta during pregnancy, the placenta is able to clear the virus, eliminating the placenta as a persistent reservoir for future persistent long COVID infections.
The findings offer important insight into what is known as long COVID, a chronic condition that occurs after SARS-CoV-2 infection and is present for at least three months. The serious illness can lead to a range of health issues, from fatigue and brain fog to shortness of breath and headaches. But it has been unclear whether long COVID can happen in the placenta, which is known to be a magnet for SARS-CoV-2 because it is covered with ACE2, the receptor for the spike protein of the virus.
“We knew that the SARS-CoV-2 virus specifically homed onto the placenta because of the fact that it is covered with the ACE2 receptor,” said Shelli Farhadian, associate professor of medicine (infectious diseases) at YSM, associate professor of epidemiology at the Yale School of Public Health, and first author of the study. “What we didn’t know is if the virus stayed in the placenta once it was infected.”
To answer that question, the researchers analyzed placentas collected at delivery from women who had recovered from COVID-19 40 to 212 days earlier, spanning pregnancies that ended in stillbirth and those resulting in healthy births. Specifically, they studied placenta from three groups of patients: women who were pregnant before 2020, meaning they couldn’t have been exposed to COVID-19; women infected with the virus prior to the availability of vaccines who were infected and had a pregnancy loss due to the infection; and women who had recovered from COVID-19.
They then used two methods to determine which placenta had virus in them. For the first method, called immunohistochemistry, researchers used an antibody against the item of interest (in this case, the SARS-CoV-2 virus) and performed a procedure to see where the antibody attached and hence where the virus was in the tissues. The second method, called in situ hybridization, uses a genetic probe to latch onto the virus instead of an antibody, which is then visualized much like the immunohistochemistry method.
Using these sensitive techniques to detect viral protein and RNA, the researchers found no evidence of persistent virus in any of the samples, even in cases of fetal or neonatal loss. However, they did observe structural and inflammatory changes in some placentas, suggesting the immune response triggered during infection can outlast the virus itself.
The findings, researchers say, suggest that although SARS-CoV-2 infects the placenta during pregnancy, the placenta is able to clear the virus, eliminating the placenta as a persistent reservoir for future persistent long COVID infections.
“Pregnant women should take reasonable precautions to stay healthy during their pregnancy, but if they do contract COVID-19, they don’t need to worry that the virus will linger in their placenta for a long time,” Kliman said. “Of course, it’s still important to be followed closely by your doctor if you do acquire this infection during your pregnancy.”
Farhadian added: “This helps clarify an important aspect of COVID-19 in pregnancy and suggests that ongoing placental effects after recovery are unlikely to be driven by persistent virus.”
Going forward, the researchers will continue to collect and study placentas from patients who become COVID-19 positive while pregnant to confirm their initial results.
This work was supported by the National Institutes of Health.
