Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8 + T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

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.

BackgroundThe 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. MethodsWe 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,

Background Data on the characteristics of COVID-19 patients disaggregated by race/ethnicity remain limited. We evaluated the sociodemographic and clinical characteristics of patients across racial/ethnic groups and assessed their associations with COVID-19 outcomes. Methods This retrospective cohort study examined 629,953 patients tested for SARS-CoV-2 in a large health system spanning California, Oregon, and Washington between March 1 and December 31, 2020. Sociodemographic and clinical characteristics were obtained from electronic health records. Odds of SARS-CoV-2 infection, COVID-19 hospitalization, and in-hospital death were assessed with multivariate logistic regression. Results 570,298 patients with known race/ethnicity were tested for SARS-CoV-2, of whom 27.8% were non-White minorities. 54,645 individuals tested positive, with minorities representing 50.1%. Hispanics represented 34.3% of infections but only 13.4% of tests. While generally younger than White patients, Hispanics had higher rates of diabetes but fewer other comorbidities. 8,536 patients were hospitalized and 1,246 died, of whom 56.1% and 54.4% were non-White, respectively. Racial/ethnic distributions of outcomes across the health system tracked with state-level statistics. Increased odds of testing positive and hospitalization were associated with all minority races/ethnicities. Hispanic patients also exhibited increased morbidity, and Hispanic race/ethnicity was associated with in-hospital mortality (OR: 1.39 [95% CI: 1.14-1.70]). Conclusion Major healthcare disparities were evident, especially among Hispanics who tested positive at a higher rate, required excess hospitalization and mechanical ventilation, and had higher odds of in-hospital mortality despite younger age. Targeted, culturally-responsive interventions and equitable vaccine development and distribution are needed to address the increased risk of poorer COVID-19 outcomes among minority populations.

Background: COVID-19 infection in pregnant people has previously been shown to increase the risk for poor maternal-fetal outcomes. Despite this, there has been a lag in COVID-19 vaccination in pregnant people due to concerns over the potential effects of the vaccine on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and booster on maternal COVID-19 breakthrough infections and birth outcomes. Methods: This was a retrospective multicenter cohort study on the impact of COVID-19 vaccination on maternal-fetal outcomes for people that delivered (n=86,833) at Providence St. Joseph Health across Alaska, California, Montana, Oregon, New Mexico, Texas, and Washington from January 26, 2021 through July 11, 2022. Cohorts were defined by vaccination status at time of delivery: unvaccinated (n=48,492), unvaccinated propensity score matched (n=26,790), vaccinated (n=26,792; two doses of mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech), and/or boosted (n=7,616). The primary outcome was maternal COVID-19 infection. COVID-19 vaccination status at delivery, COVID-19 infection-related health care, preterm birth, stillbirth, very low birth weight, and small for gestational age were evaluated as secondary outcomes. Findings: Vaccinated pregnant people were significantly less likely to have a maternal COVID-19 infection than unvaccinated matched (p<0.0001) pregnant people. During a maternal COVID-19 infection, vaccinated pregnant people had similar rates of hospitalization (p=0.23), but lower rates of supplemental oxygen (p<0.05) or vasopressor (p<0.05) use than those in an unvaccinated matched cohort. Compared to an unvaccinated matched cohort, vaccinated people had significantly lower stillbirth rate (p<0.01) as well as no difference in rate of preterm birth (p=0.35), small for gestational age (p=0.79), or rate of very low birth weight (>1,500 g; 0.31). People who were vaccinated who had not received boosters had significantly lower rates of maternal COVID-19 infections (p<0.0001), COVID-19 related hospitalization (p<0.05), preterm birth (p<0.05), stillbirth (p<0.01), small for gestational age (p<0.05), and very low birth weight (p<0.01), compared to vaccinated people that did not receive a third booster shot five months after completing the initial vaccination series. Interpretation: COVID-19 vaccination protects against adverse maternal-fetal outcomes with booster shots conferring additional protection against COVID-19 infection. It is therefore important for pregnant people to have high priority status for vaccination, and for them to stay current with their COVID-19 vaccination schedule. Funding: This study was funded by the National Institute for Child Health & Human Development and the William O. and K. Carole Ellison Foundation.