The impact of maternal SARS-CoV-2 infection and COVID-19 vaccination on maternal-fetal outcomes.

The rapidly evolving COVID-19 pandemic has resulted in an upsurge of scientific productivity to help address the global health crisis. One area of active research is the impact of COVID-19 on pregnancy. Here, we provide an epidemiological overview about what is known about the effects of maternal SARS-CoV-2 infection and COVID-19 vaccination on maternal-fetal outcomes, and identify gaps in knowledge. Pregnant people are at increased risk for severe COVID-19, and maternal SARS-CoV-2 infection increases the risk of negative maternal-fetal outcomes. Despite this elevated risk, there have been high rates of vaccine hesitancy, heightened by the initial lack of safety and efficacy data for COVID-19 vaccination in pregnancy. In response, retrospective cohort studies were performed to examine the impact of COVID-19 vaccination during pregnancy. Here, we report the vaccine's efficacy during pregnancy and its impact on maternal-fetal outcomes, as well as an overview of initial studies on booster shots in pregnancy. We found that pregnant people are at risk for more severe COVID-19 outcomes, maternal SARS-CoV-2 infection is associated with worse birth outcomes, COVID-19 vaccine hesitancy remains prevalent in the pregnant population, and COVID-19 vaccination and boosters promote better maternal-fetal outcomes. The results should help reduce vaccine hesitancy by alleviating concerns about the safety and efficacy of administering the COVID-19 vaccine during pregnancy. Overall, this review provides an introduction to COVID-19 during pregnancy. It is expected to help consolidate current knowledge, accelerate research of COVID-19 during pregnancy and inform clinical, policy, and research decisions regarding COVID-19 vaccination in pregnant people.

Risk factors for severe COVID-19 differ by age for hospitalized adults.

Risk stratification for hospitalized adults with COVID-19 is essential to inform decisions about individual patients and allocation of resources. So far, risk models for severe COVID outcomes have included age but have not been optimized to best serve the needs of either older or younger adults. Models also need to be updated to reflect improvements in COVID-19 treatments. This retrospective study analyzed data from 6906 hospitalized adults with COVID-19 from a community health system across five states in the western United States. Risk models were developed to predict mechanical ventilation illness or death across one to 56 days of hospitalization, using clinical data available within the first hour after either admission with COVID-19 or a first positive SARS-CoV-2 test. For the seven-day interval, models for age ≥ 18 and < 50 years reached AUROC 0.81 (95% CI 0.71-0.91) and models for age ≥ 50 years reached AUROC 0.82 (95% CI 0.77-0.86). Models revealed differences in the statistical significance and relative predictive value of risk factors between older and younger patients including age, BMI, vital signs, and laboratory results. In addition, for hospitalized patients, sex and chronic comorbidities had lower predictive value than vital signs and laboratory results.

The effect of maternal SARS-CoV-2 infection timing on birth outcomes: a retrospective multicentre cohort study.

BACKGROUND: The impact of maternal SARS-CoV-2 infection remains unclear. In this study, we evaluated the risk of maternal SARS-CoV-2 infection on birth outcomes and how this is modulated by the pregnancy trimester in which the infection occurs. We also developed models to predict gestational age at delivery for people following a SARS-CoV-2 infection during pregnancy. METHODS: We did a retrospective cohort study of the impact of maternal SARS-CoV-2 infection on birth outcomes. We used clinical data from Providence St Joseph Health electronic health records for pregnant people who delivered in the USA at the Providence, Swedish, or Kadlec sites in Alaska, California, Montana, Oregon, or Washington. The SARS-CoV-2 positive cohort included people who had a positive SARS-CoV-2 PCR-based test during pregnancy, subdivided by trimester of infection. No one in this cohort had been vaccinated for COVID-19 at time of infection. The SARS-CoV-2 negative cohort were people with at least one negative SARS-CoV-2 PCR-based test and no positive tests during pregnancy. Cohorts were matched on common covariates impacting birth outcomes, and univariate and multivariate analysis were done to investigate risk factors and predict outcomes. The primary outcome was gestational age at delivery with annotation of preterm birth classification. We trained multiple supervised learning models on 24 features of the SARS-CoV-2 positive cohort to evaluate performance and feature importance for each model and discuss the impact of SARS-CoV-2 infection on gestational age at delivery. FINDINGS: Between March 5, 2020, and July 4, 2021, 73 666 pregnant people delivered, 18 335 of whom had at least one SARS-CoV-2 test during pregnancy before Feb 14, 2021. We observed 882 people infected with SARS-CoV-2 during their pregnancy (first trimester n=85; second trimester n=226; and third trimester n=571) and 19 769 people who have never tested positive for SARS-CoV-2 and received at least one negative SARS-CoV-2 test during their pregnancy. SARS-CoV-2 infection indicated an increased risk of preterm delivery (p<0·05) and stillbirth (p<0·05), accounted for primarily by first and second trimester SARS-CoV-2 infections. Gestational age at SARS-CoV-2 infection was correlated with gestational age at delivery (p<0·01) and had the greatest impact on predicting gestational age at delivery. The people in this study had mild or moderate SARS-CoV-2 infections and acute COVID-19 severity was not correlated with gestational age at delivery (p=0·31). INTERPRETATION: These results suggest that pregnant people would benefit from increased monitoring and enhanced prenatal care after first or second trimester SARS-CoV-2 infection, regardless of acute COVID-19 severity. FUNDING: US National Institutes of Health.

Integrated analysis of plasma and single immune cells uncovers metabolic changes in individuals with COVID-19.

A better understanding of the metabolic alterations in immune cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may elucidate the wide diversity of clinical symptoms experienced by individuals with coronavirus disease 2019 (COVID-19). Here, we report the metabolic changes associated with the peripheral immune response of 198 individuals with COVID-19 through an integrated analysis of plasma metabolite and protein levels as well as single-cell multiomics analyses from serial blood draws collected during the first week after clinical diagnosis. We document the emergence of rare but metabolically dominant T cell subpopulations and find that increasing disease severity correlates with a bifurcation of monocytes into two metabolically distinct subsets. This integrated analysis reveals a robust interplay between plasma metabolites and cell-type-specific metabolic reprogramming networks that is associated with disease severity and could predict survival.

Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.