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Severe COVID-19 in pregnancy has a distinct serum profile, including greater complement activation and dysregulation
Marie Altendahl1, Thalia Mok1, Christine Jang1
1Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Insights
Severe Coronavirus Disease 2019 (COVID-19) in pregnancy alters protein and lipid profiles, indicating increased inflammation and complement activation. These multi-omic changes may predict adverse pregnancy outcomes.
Area of Science:
- Immunology
- Metabolomics
- Proteomics
Background:
- Pregnancy involves significant physiological changes impacting immune, cardiovascular, and respiratory systems.
- Coronavirus Disease 2019 (COVID-19) in pregnancy increases the risk of severe morbidity.
- The impact of COVID-19 severity on protein and metabolite expression during pregnancy is not well understood.
Purpose of the Study:
- To investigate the pathophysiology of diverse clinical outcomes in pregnant patients with COVID-19.
- To utilize multi-omics profiling to understand COVID-19's effects on pregnant individuals.
- To identify molecular signatures associated with different COVID-19 severity levels in pregnancy.
Main Methods:
- Prospective cohort study involving 30 pregnant patients.
- Categorization of participants by COVID-19 severity: control, asymptomatic, mild/moderate, and severe.
- Maternal serum analysis using liquid chromatography-mass spectrometry (LC-MS) for multi-omics profiling (proteins, lipids, electrolytes, metabolites).
- Statistical analysis including linear regression and Reactome pathway enrichment analysis.
Main Results:
- Severe COVID-19 in pregnancy showed distinct proteomic and lipidomic profiles.
- These profiles were significantly enriched for pathways related to complement and antibody activity (FDR < 0.05).
- Mild/moderate, post-infection COVID-19 did not show significant alterations in serum analytes compared to controls.
Conclusions:
- Severe COVID-19 during pregnancy is associated with heightened inflammation and complement activation.
- Dysregulation of serum lipids is observed in severe cases.
- Altered multi-omic profiles offer insights into severe COVID-19 pathophysiology in pregnancy and potential biomarkers for adverse outcomes.
Background:
Pregnancies complicated by Coronavirus Disease 2019 (COVID-19) are at an increased risk of severe morbidity due to physiologic changes in immunologic, cardiovascular, and respiratory function. There is little is known about how severity of COVID-19 changes protein and metabolite expression in pregnancy.
Objective:
This study aims to investigate the pathophysiology behind various clinical trajectories in pregnant patients diagnosed with COVID-19 using multi-omics profiling.
Study Design:
This is a prospective cohort study of 30 pregnant patients at a single tertiary care center. Participants were categorized by severity of COVID-19 disease (control, asymptomatic, mild/moderate, or severe). Maternal serum samples underwent LC-MS-based multiomics analysis for profiling of proteins, lipids, electrolytes, and metabolites. Linear regression models were used to assess how disease severity related to analyte levels. Reactome pathway enrichment analysis was conducted on differential analytes.
Results:
Of 30 participants, 25 had confirmed diagnosis of COVID-19 (6 asymptomatic (one post-infection), 13 mild/moderate (all post-infection), 6 severe), and 5 participants were controls. Severe COVID-19 was associated with distinct profiles demonstrating significant proteomic and lipidomic signatures which were enriched for annotations related to complement and antibody activity. (FDR < 0.05). Downregulated analytes were not significantly enriched but consisted of annotation terms related to lipoprotein activity (FDR > 0.2). Post-infection mild/moderate COVID-19 did not have significantly altered serum protein, metabolite, or lipid metabolite levels compared to controls.
Conclusions:
Pregnancies with severe COVID-19 demonstrate greater inflammation and complement activation and dysregulation of serum lipids. This altered multiomic expression provides insight into the pathophysiology of severe COVID-19 in pregnancy and may serve as potential indicators for adverse pregnancy outcomes.
