Elevated antiviral, myeloid and endothelial inflammatory markers in severe COVID-19

Abstract

The mechanisms that underpin COVID-19 disease severity, and determine the outcome of infection, are only beginning to be unraveled. The host inflammatory response contributes to lung injury, but circulating mediators levels fall below those in classical cytokine storms. We analyzed serial plasma samples from 619 patients hospitalized with COVID-19 recruited through the prospective multicenter ISARIC clinical characterization protocol U.K. study and 39 milder community cases not requiring hospitalization. Elevated levels of numerous mediators including angiopoietin-2, CXCL10, and GM-CSF were seen at recruitment in patients who later died. Markers of endothelial injury (angiopoietin-2 and von-Willebrand factor A2) were detected early in some patients, while inflammatory cytokines and markers of lung injury persisted for several weeks in fatal COVID-19 despite decreasing antiviral cytokine levels. Overall, markers of myeloid or endothelial cell activation were associated with severe, progressive, and fatal disease indicating a central role for innate immune activation and vascular inflammation in COVID-19.

Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study

“…However, comparisons to other critically ill populations are under-reported. For example, comparisons of plasma biomarkers of endothelial function have largely focused on COVID-19 alone [ 8 ], comparisons between COVID-19 and healthy controls [ 9 ], and comparisons between patients with increasing severity of COVID-19 [ 10 ]. While these studies have advanced our knowledge, the findings are conflicting and the study designs prevent discriminating differences specific to the host response to severe SARS-CoV-2 infection versus a general signature of critical illness.…”

Chronic Obstructive Pulmonary Disease Patients Have Increased Levels of Plasma Inflammatory Mediators Reported Upregulated in Severe COVID-19

“…Our induced network analysis revealed protein-protein interactions between HGF and OPG mediated by the von Willebrand factor (VWF) suggesting a connection of these markers with the coagulation system (Figure 5). In the study of Thwaites et al, the von-Willebrand factor A2 was elevated in all hospitalized COVID-19 patients and the elevation was higher in severely affected COVID-19 patients (29). Other studies also report the elevation of VWF as risk factor for severe COVID-19 (30).…”

Patients with Asthma and Chronic Obstructive Pulmonary Disease (COPD) have increased levels of plasma inflammatory mediators upregulated in severe COVID-19

“…Our induced network analysis revealed protein-protein interactions between HGF and OPG mediated by the von Willebrand factor (VWF) suggesting a connection of these markers with the coagulation system ( Figure 5 ). In the study of Thwaites et al ., the von-Willebrand factor A2 was elevated in all hospitalized COVID-19 patients and the elevation was highest in severely affected COVID-19 patients [39]. Other studies also support the elevation of VWF as risk factor for severe COVID-19 [40].…”