COVID-19 linked to chronic villitis and placental lesions in pregnancy

COVID-19 linked to chronic villitis and placental lesions in pregnancy | Image Credit: © oz - © oz - stock.adobe.com.

Chronic villitis is the most specific histopathologic finding linked to COVID-19 infection, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Stillbirth, preterm birth, and preeclampsia risks are increased from COVID-19 infection during pregnancy. Vertical transmission and viral infection of the placenta are rare in these cases, reported in 0%, 3%, in 7%, respectively.

According to investigators, “the pathophysiological mechanism for these outcomes is unclear” because of this rarity. Vascular malperfusion (FVM) and maternal vascular malperfusion (MVM) have been indicated as the main pathologic findings in pregnant women infected with GDM.²

Placental chronic inflammation often manifests as chronic villitis (CV).¹ An infection or villitis of unknown etiology (VUE) may lead to CV, with regulation achievable from immune checkpoint inhibitors on T cells. Therefore, investigators conducted a retrospective cohort study to assess the immune signature of COVID-19 villitis.

Participants included pregnant patients with COVID-19 infection confirmed by a nasopharyngeal polymerase chain reaction (PCR) assay from March 2020 to September 2021. Those delivering at a non-study institution or with a multifetal gestation were excluded from the analysis.

These participants were compared with a historic control group and a time-matched control group. Singleton placentas obtained from an institutional biobank between March 2017 and February 2017 comprised the historic control group, while singletons selected based on delivery date during the same timeframe as COVID-19-affected patients comprised the time-matched control group.

Electronic medical records were evaluated for maternal demographic data, pregnancy outcomes, neonatal outcomes, and COVID-19 infection data. At least 2 records of newly elevated blood pressure over 140/90 mm Hg indicated preeclampsia, and small for gestational age (GA) was based on birth weight under the tenth percentile.

The hospital conducted placental examinations based on Amsterdam criteria. A single perinatal pathologist reviewed all cases. Adjustment for GA was performed through logistic regression modeling.

There were 272 patients infected with COVID-19 included in the analysis. These patients were often younger than historic controls and more likely to deliver vaginally and present with pregestational diabetes. Preeclampsia was also reported more often in COVID-19 patients than historic controls.

When compared to time-matched controls, COVID-19 patients had reduced rates of preterm birth, preeclampsia, and small for GA delivery. CV and severe CV were more common in COVID-19 patients vs time-matched controls, with odds ratios (ORs) of 1.56 and 2.36, respectively.

These associations remained when controlling for GA, with adjusted ORs (aORs) of 1.52 and 2.12, respectively. Several histopathologic findings were also more common in COVID-19 patients when compared to historic controls. These included acute chorioamnionitis, CV, and FVM as the most common findings.

Other common findings included MVM, FVM, CV, and severe CV with aORs of 2.76, 2.53, 2.81, and 5.25, respectively. Most placental lesions did not differ based on the severity of COVID-19 or the timing of infection. However, patients with moderate-critical disease were more likely to report cesarean delivery than those with asymptomatic disease.

These results indicated increased rates of histopathologic lesions in the placenta of patients with COVID-19 infections, with villitis being the most specific placental injury. Investigators recommended further studies comparing the pathophysiological mechanisms of COVID-19 placentitis to VUE to “identify a common therapeutic target for both conditions.”

References

1. Gabby LC, Jones CK, McIntyre BB, et al. Chronic villitis as a distinctive feature of placental injury in maternal SARS-CoV-2 infection. Am J Obstet Gynecol. 2025;232:123.e1-12. doi:10.1016/j.ajog.2024.04.002
2. Shanes ED, Mithal LB, Otero S, Azad HA, Miller ES, Goldstein JA. Placental Pathology in COVID-19. Am J Clin Pathol. 2020;154(1):23-32. doi:10.1093/ajcp/aqaa089