Heterogeneous immunological recovery trajectories revealed in post-acute COVID-19

The immunological picture of how different patients recover from COVID-19, and how those recovery trajectories are influenced by infection severity, remain unclear. We investigated 140 COVID-19 patients from diagnosis to convalescence using clinical data, viral load assessments, and multi-omic analyses of blood plasma and circulating immune cells. Immune-phenotype dynamics resolved four recovery trajectories. One trajectory signals a return to pre-infection healthy baseline, while the other three are characterized by differing fractions of persistent cytotoxic and proliferative T cells, distinct B cell maturation processes, and memory-like innate immunity. We resolve a small panel of plasma proteins that, when measured at diagnosis, can predict patient survival and recovery-trajectory commitment. Our study offers novel insights into post-acute immunological outcomes of COVID-19 that likely influence long-term adverse sequelae.

Characteristics and Factors Associated with COVID-19 Infection, Hospitalization, and Mortality Across Race and Ethnicity

BackgroundData 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. MethodsThis 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. Results570,298 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]). ConclusionMajor 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. Key pointsRacial/ethnic disparities are evident in the disaggregated characteristics of COVID-19 patients. Minority patients experience increased odds of SARS-CoV-2 infection and COVID-19 hospitalization. Hospitalized Hispanic patients presented with more severe illness, experienced increased morbidity, and faced increased mortality.

Plasma levels of soluble ACE2 are associated with sex, Metabolic Syndrome, and its biomarkers in a large cohort, pointing to a possible mechanism for increased severity in COVID-19

We examined the associations between plasma concentrations of soluble ACE2 and biomarkers of Metabolic Syndrome in a large (N=2,051) sample of individuals who participated in a commercial wellness program and who underwent deep molecular phenotyping. sACE2 levels were significantly higher in men, compared to women, and in individuals with Metabolic Syndrome, compared to controls. sACE2 levels showed reliable associations with all individuals components of Metabolic Syndrome, including obesity, hypertension, insulin resistance, hyperlipidemia, and as well as markers of liver damage. This profile of associations was statistically significantly stronger in men, compared to women, and points to preexisting cardiometabolic conditions as possible risk factors for increased severity of symptoms in some COVID-19 patients through increased expression of ACE2 in the liver.