Analysis of placental pathology after COVID-19 by timing and severity of infection.

BACKGROUND: COVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology. OBJECTIVE: This study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes. STUDY DESIGN: This was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings. RESULTS: This study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timing or severity of COVID-19. There was a higher frequency of placental features associated with response to infection in the placentas from infections before 20 weeks of gestation than that from infections after 20 weeks of gestation (P=.001). There was no difference in maternal vascular malperfusion by the timing of infection; however, features of severe maternal vascular malperfusion were only found in the placentas of patients with SARS-CoV-2 infection in the second and third trimesters of pregnancy, not in the placentas of patients with COVID-19 in the first trimester of pregnancy. CONCLUSION: Placentas from patients with COVID-19 showed no specific pathologic feature, regardless of the timing or severity of the disease. There was a higher proportion of placentas from patients with COVID-19-positive tests in earlier gestations with evidence of placental infection-associated features. Future studies should focus on understanding how these placental features in SARS-CoV-2 infections go on to affect pregnancy outcomes.

Severe COVID-19 in pregnancy has a distinct serum profile, including greater complement activation and dysregulation of serum lipids.

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.

Perinatal Maternal-Fetal/Neonatal Transmission of COVID-19: A Guide to Safe Maternal and Neonatal Care in the Era of COVID-19 and Physical Distancing.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), is highly contagious and can cause serious respiratory illness and other clinical manifestations. The aim of this review is to summarize the clinical presentation, diagnosis, and outcomes of COVID-19 in pregnant women and neonates, who may be especially vulnerable to the effects of COVID-19, and to discuss what is known about potential maternal-fetal and maternal-neonatal transmission of SARS-CoV-2.