Placental pathology of 153 SARS-CoV-2 positive women in relation to alpha, delta & omicron variations - a nested case-control study

Background: Maternal SARS-CoV-2 infection has been reported to coincide with specific placental lesions, yet the extent to which these changes differ between viral variants remains insufficiently explored. This study compares placental histopathology in SARS-CoV-2-positive pregnancies with SARS-CoV-2-negative controls and examines differences between Alpha, Delta, and Omicron variants. Methods: This nested case-control study included placentas from 153 SARS-CoV-2-positive pregnancies from the PREGCO cohort at Hvidovre Hospital, Denmark, and 197 SARS-CoV-2-negative controls from the same institution. Histopathological evaluation followed the Amsterdam consensus, conducted by three senior perinatal/placental pathologists. Controls were matched using propensity scores based on maternal age, smoking status, and referral indication. Variant-specific analyses were performed for Alpha (n = 51), Delta (n = 49), and Omicron (n = 53) infections. Bayesian logistic regression with weakly informative priors estimated odds ratios (ORs) and 95% credible intervals. Results: Compared with matched controls, SARS-CoV-2-positive placentas had higher odds of calcifications and subacute inflammatory chorioamnionitis. Between variants, decidual vasculopathy was more frequent in Delta than Omicron, while acute chorionitis occurred more often in Alpha than Delta. Other histopathological findings did not differ significantly between variants. Conclusion: SARS-CoV-2 infection in pregnancy is associated with specific placental lesions, some of which show variant-related differences. Understanding these patterns may improve targeted monitoring and preparedness for future maternal viral infections.