ABSTRACT
Mechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells. Sixteen percent of patients display reduced inflammation yet comparably poor outcomes. Comparison of patients who died to severely ill survivors identifies dynamic immune-cell-derived and tissue-associated proteins associated with survival, including exocrine pancreatic proteases. Using derived tissue-specific and cell-type-specific intracellular death signatures, cellular angiotensin-converting enzyme 2 (ACE2) expression, and our data, we infer whether organ damage resulted from direct or indirect effects of infection. We propose a model in which interactions among myeloid, epithelial, and T cells drive tissue damage. These datasets provide important insights and a rich resource for analysis of mechanisms of severe COVID-19 disease.
ABSTRACT
OBJECTIVE: As severity of outcome in COVID-19 is disproportionately higher among individuals with obesity, smokers, patients with hypertension, kidney disease, chronic pulmonary disease, coronary heart disease (CHD), and/or type 2 diabetes (T2D), serum levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2, were examined in these high-risk groups. METHODS: Associations of ACE2 levels to smokers and patients with hypertension, T2D, obesity, CHD, or COPD were investigated in a single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavík Study (AGES-RS) of the elderly (mean age 75 ± 6 years), using multiple linear regression analysis. RESULTS: Serum levels of ACE2 were higher in smokers and individuals with T2D and/or obesity while they were unaffected in the other patient groups. CONCLUSION: ACE2 levels are higher in some patient groups with comorbidities linked to COVID-19 including obesity and T2D and as such may have an emerging role as a circulating biomarker for severity of outcome in the disease.