Plasma Proteomics of COVID-19 Associated Cardiovascular Complications: Implications for Pathophysiology and Therapeutics

Abstract

Cardiovascular complications are common in COVID-19 and strongly associated with disease severity and mortality. However, the mechanisms driving cardiac injury and failure in COVID-19 are largely unknown. We performed plasma proteomics on 80 COVID-19 patients and controls, grouped according to disease severity and cardiac involvement. Findings were validated in 305 independent COVID-19 patients and investigated in an animal model. Here we show that senescence-associated secretory proteins, markers of biological aging, strongly associate with disease severity and cardiac involvement even in age-matched cohorts. FSTL3, an indicator of Activin/TGFβ signaling, was the most significantly upregulated protein associated with the heart failure biomarker, NTproBNP (β = 0.4;padj=4.6x10− 7), while ADAMTS13, a vWF-cleaving protease whose loss-of-function causes microvascular thrombosis, was the most downregulated protein associated with myocardial injury (β=-0.4;padj=8x10− 7). Mendelian randomization supported a causal role for ADAMTS13 in myocardial injury. These data provide important new insights into the pathophysiology of COVID-19 cardiovascular complications with therapeutic implications.

Progress of the COVID-19 vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape

“…B.1.351 is 6.5-fold more resistant than wild-type pseudovirus to neutralization by sera from individuals vaccinated with BNT162b2 (ref. 49 ). A significant reduction in the neutralization of B.1.351 by sera from humans or non-human primates vaccinated with mRNA-1273 was also observed 43 .…”

Genome-wide analysis of protein–protein interactions and involvement of viral proteins in SARS-CoV-2 replication

“…Vaccines developed using different strategies were authorized by many countries to contain the infection of SARS-CoV-2. However, there are growing concerns about safety like antibody-dependent enhancement (ADE), the duration of the effective anti-SARS-CoV-2 immune response, and the effectiveness against the mutant viruses [ 4 – 6 ]. Thus, the anti-SARS-CoV-2 specific drugs are urgently needed, and more drug targets on this deadly virus are waiting to be uncovered.…”

Proteomic Analyses Unveil Actionable Disease Pathways in COVID-19

“…These factors could affect the identification of a broader range of proteins involved in microthrombi formation and myocardial injury in COVID-19. Indeed, Roh et al 1 found that ADAMTS13 had a significant yet weak negative association with cardiac troponins, a finding that was reproduced in the independent cohort. However, to overcome the limitations from residual confounding and reverse causation, Roh et al 1 conducted an automated 2-sample mendelian randomization to genetically estimate ADAMTS13 protein levels using locus-wide significant Protein Quantitative Trait Loci (pQTLs).…”

“…In this issue of JACC: Basic to Translational Science , Roh et al 1 conducted a matched case-control study examining the plasma proteome of 80 patients with different severities of COVID-19 disease, including those hospitalized (but not in intensive care units) and individuals requiring intensive care with different degrees of cardiac involvement along with non–COVID-19 controls. A series of unsupervised enriched principal component analyses revealed that protein profiles related to innate cellular inflammation, senescence, and RNA processing had the highest biological relevance and distinguished between those with and without COVID-19.…”