IgM autoantibodies recognizing ACE2 are associated with severe COVID-19 (preprint)

SARS-CoV-2 infection induces severe disease in a subpopulation of patients, but the underlying mechanisms remain unclear. We demonstrate robust IgM autoantibodies that recognize angiotensin converting enzyme-2 (ACE2) in 18/66 (27%) patients with severe COVID-19, which are rare (2/52; 3.8%) in hospitalized patients who are not ventilated. The antibodies do not undergo class-switching to IgG, suggesting a T-independent antibody response. Purified IgM from anti-ACE2 patients activates complement. Pathological analysis of lung obtained at autopsy shows endothelial cell staining for IgM in blood vessels in some patients. We propose that vascular endothelial ACE2 expression focuses the pathogenic effects of these autoantibodies on blood vessels, and contributes to the angiocentric pathology observed in some severe COVID-19 patients. These findings may have predictive and therapeutic implications.

Patient trajectories and risk factors for severe outcomes among persons hospitalized for COVID-19 in the Maryland/DC region (preprint)

BackgroundRisk factors for poor outcomes from COVID-19 are emerging among US cohorts, but patient trajectories during hospitalization ranging from mild-moderate, severe, and death and the factors associated with these outcomes have been underexplored. MethodsWe performed a cohort analysis of consecutive COVID-19 hospital admissions at 5 Johns Hopkins hospitals in the Baltimore/DC area between March 4 and April 24, 2020. Disease severity and outcomes were classified using the WHO COVID-19 disease severity ordinal scale. Cox proportional-hazards regressions were performed to assess relationships between demographics, clinical features and progression to severe disease or death. Results832 COVID-19 patients were hospitalized; 633 (76.1%) were discharged, 113 (13.6%) died, and 85 (10.2%) remained hospitalized. Among those discharged, 518 (82%) had mild/moderate and 116 (18%) had severe illness. Mortality was statistically significantly associated with increasing age per 10 years (adjusted hazard ratio (aHR) 1.54; 95%CI 1.28-1.84), nursing home residence (aHR 2.13, 95%CI 1.41-3.23), Charlson comorbidity index (1.13; 95% CI 1.02-1.26), respiratory rate (aHR 1.13; 95%CI 1.09-1.17), D-dimer greater than 1mg/dL (aHR 2.79; 95% 1.53-5.09), and detectable troponin (aHR 2.79; 95%CI 1.53-5.09). In patients under 60, only male sex (aHR 1.7;95%CI 1.11-2.58), increasing body mass index (BMI) (aHR1.25 1.14-1.37), Charlson score (aHR 1.27; 1.1-1.46) and respiratory rate (aHR 1.16; 95%CI 1.13-1.2) were associated with severe illness or death. ConclusionsA combination of demographic and clinical features on admission is strongly associated with progression to severe disease or death in a US cohort of COVID-19 patients. Younger patients have distinct risk factors for poor outcomes.