Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma

Background Pregnant women are at greater risk of adverse outcomes, including mortality and obstetrical complications, from COVID-19, yet pregnancy-specific alterations underlying such outcomes remain unclear. Methods Plasma from pregnant women and non-pregnant individuals (male and female) with (n=72 pregnant, 52 non-pregnant) and without (n=29 pregnant, 41 non-pregnant) COVID-19 was profiled using the SOMAmer platform measuring 7,288 analytes (6,596 unique proteins). COVID-19 cases were categorized by NIH severity. Results COVID-19 induced plasma proteome alterations with a dose-response to severity; however, these perturbations were dampened during pregnancy. Both pregnant and non-pregnant states showed enrichment of mediators implicated in cytokine storm, endothelial dysfunction, and angiogenesis. Shared and pregnancy-specific changes were identified: pregnant women displayed a tailored response potentially protecting the conceptus from heightened inflammation, whereas non-pregnant individuals showed a stronger anti-infective response. The plasma proteome accurately identified COVID-19 patients, including asymptomatic and mild cases. Conclusion This comprehensive characterization of the plasma proteome in pregnant and non-pregnant COVID-19 patients highlights distinct immune modulation in pregnancy, offering insight into COVID-19 pathogenesis and potential explanations for more severe outcomes observed in pregnant women.