Plasma Proteomics of COVID-19–Associated Cardiovascular Complications

Roh, Jason D.; Kitchen, Robert; Guseh, James S.; McNeill, Jenna; Aïd, Malika; Martinot, Amanda J.; Yu, Andy; Platt, Colin; Rhee, James; Weber, Brittany; Trager, Lena; Hastings, Margaret H.; Ducat, Sarah; Xia, Peng; Castro, Claire; Singh, Abhilasha; Atlason, Bjarni; Churchill, Timothy W.; Carli, Marcelo F. Di; Ellinor, Patrick T.; Barouch, Dan H.; Ho, Jennifer E.; Rosenzweig, Anthony

doi:10.1016/j.jacbts.2022.01.013

Cited by 24 publications

(21 citation statements)

References 62 publications

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“…Similar with findings from CPASSOC, we found shared genes between COVID-19 and cancers that are related to hematologic systems ( ABO ), immune function ( MUC1, PLEKHM1 ), and cell proliferation ( KANSL1 - AS1 ). The multiple genes identified in blood vessel or heart tissues indicate a biological mechanism through the cardiovascular system, which corroborates well with the established knowledge as both COVID-19 and cancer are associated with a number of cardiovascular complications 49,57 . In addition, we identified shared regulatory features in the nervous system, especially for COVID-19 severity.…”

Section: Discussionsupporting

confidence: 87%

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis

Zhao

Xiao

et al. 2022

Preprint

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Background: Little is known regarding the long-term adverse effects of COVID-19 on female-specific cancers due to the restricted length of observational time, nor the shared genetic influences underlying these conditions. Methods: Leveraging summary statistics from the hitherto largest genome-wide association studies conducted in each trait, we performed a comprehensive genome-wide cross-trait analysis to investigate the shared genetic architecture and the putative genetic associations between COVID-19 with three main female-specific cancers: breast cancer (BC), epithelial ovarian cancer (EOC), and endometrial cancer (EC). Three phenotypes were selected to represent COVID-19 susceptibility (SARS-CoV-2 infection) and severity (COVID-19 hospitalization, COVID-19 critical illness). Results: For COVID-19 susceptibility, we found no evidence of a genetic correlation with any of the female-specific cancers. For COVID-19 severity, we identified a significant genome-wide genetic correlation with EC for both hospitalization (r_g=0.19, P=0.01) and critical illness (r_g=0.29, P=3.00*10-4). Mendelian randomization demonstrated no valid association of COVID-19 with any cancer of interest, except for suggestive associations of genetically predicted hospitalization (ORIVW=1.09, 95%CI=1.01-1.18, P=0.04) and critical illness (ORIVW=1.06, 95%CI=1.00-1.11, P=0.04) with EC risk, none withstanding multiple correction. No reverse association was found. Cross-trait meta-analysis identified multiple pleiotropic SNPs between COVID-19 and female-specific cancers, including 20 for BC, 15 for EOC, and 5 for EC. Transcriptome-wide association studies revealed shared genes, mostly enriched in the hematologic, cardiovascular, and nervous systems. Conclusions: Our genetic analysis highlights an intrinsic link underlying female-specific cancers and COVID-19 - while COVID-19 is not likely to elevate the immediate risk of the examined female-specific cancers, it appears to share mechanistic pathways with these conditions. These findings may provide implications for future therapeutic strategies and public health actions.

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Section: Discussionsupporting

confidence: 87%

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis

Zhao

Xiao

et al. 2022

Preprint

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“…We also compared our platelet proteomic findings to three recently reported studies on changes in the plasma/serum proteome in COVID-19 patients [42][43][44]. Using a threshold setting of the protein being detected in two out of the three published studies in plasma/serum, we found a subset of the proteins that were highly enriched in platelets from COVID-19 patients.…”

Section: Discussionmentioning

confidence: 82%

“…The plasma protein S100A8/A9 did not pass our selection criteria of being elevated in two out of three proteomic studies [42][43][44], however several studies have reported raised plasma S100A8/A9 in COVID-19 patients and plasma levels correlated to poor outcome [64][65][66][67]. S100A8/A9 can induce platelet procoagulant responses and promote platelet/neutrophil interaction by enhancing P-selectin levels [66].…”

Section: Discussionmentioning

confidence: 99%

“…We explored whether plasma or serum proteins reported to be affected by COVID-19 were also affected in platelets [42][43][44]. To explore the effect that a COVID-mediated change in platelet proteins may have on platelet function, we integrated proteomic results with GO pathway annotations.…”

Section: Exploring Platelet Pathway Changes Using Gene Ontology (Go) ...mentioning

confidence: 99%

“…Previous studies have identified multiple plasma or serum proteins associated with COVID-19 [42][43][44]. Platelets are not only able to release their granule content but can also selectively take up proteins from their environment [49].…”

Section: Enhanced Platelet Content Of Covid-19 Plasma Biomarkersmentioning

confidence: 99%

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Alterations in platelet proteome signature and impaired platelet integrin α_IIbβ₃activation in patients with COVID-19

Goudswaard

Williams

Khalil

et al. 2022

Preprint

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Background Patients with coronavirus disease-19 (COVID-19) are at increased risk of thrombosis, which is associated with altered platelet function and coagulopathy, contributing to excess mortality. Objectives We aimed to characterise the mechanism of altered platelet function in COVID-19 patients. Methods The platelet proteome, platelet functional responses and platelet-neutrophil aggregates were compared between patients hospitalised with COVID-19 and healthy control subjects using Tandem Mass Tag (TMT) proteomic analysis, Western blotting and flow cytometry. Results COVID-19 patients showed a different profile of platelet protein expression (858 altered out of 5773 quantified). Levels of COVID-19 plasma markers were enhanced in COVID-19 platelets. Gene ontology (GO) pathway analysis demonstrated that levels of granule secretory proteins were raised, whereas some platelet activation proteins, such as the thrombopoietin receptor and PKCalpha, were lowered. Basally, COVID-19 platelets showed enhanced phosphatidylserine (PS) exposure, with unaltered integrin alphaIIbBeta3 activation and P-selectin expression. Agonist-stimulated integrin alphaIIbBeta3 activation and PS exposure, but not P-selectin expression, were significantly decreased in COVID-19 patients. COVID-19 patients had high levels of platelet-neutrophil aggregates, even under basal conditions, compared to controls. This interaction was disrupted by blocking P-selectin, demonstrating that platelet P-selectin is critical for the interaction. Conclusions Overall, our data suggests the presence of two platelet populations in patients with COVID-19: one with circulating platelets with an altered proteome and reduced functional responses and another with P-selectin expressing neutrophil-associated platelets. Platelet driven thromboinflammation may therefore be one of the key factors enhancing the risk of thrombosis in COVID-19 patients.

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Differentially‐regulated miRNAs in COVID‐19: A systematic review

Ahmad

Gull

Baby

et al. 2023

Reviews in Medical Virology

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for coronavirus disease of 2019 that infected more than 760 million people worldwide with over 6.8 million deaths to date. COVID-19 is one of the most challenging diseases of our times due to the nature of its spread, its effect on multiple organs, and an inability to predict disease prognosis, ranging from being completely asymptomatic to death. Upon infection, SARS-CoV-2 alters the host immune response by changing host-transcriptional machinery. MicroRNAs (miRNAs) are regarded as post-transcriptional regulators of gene expression that can be perturbed by invading viruses. Several in vitro and in vivo studies have reported such dysregulation of host miRNA expression upon SARS-CoV-2 infection. Some of this could occur as an anti-viral response of the host to the viral infection. Viruses themselves can counteract that response by mounting their own pro-viral response that facilitates virus infection, an aspect which may cause pathogenesis. Thus, miRNAs could serve as possible disease biomarkers in infected people. In the current review, we have summarised and analysed the existing data about miRNA dysregulation in patients infected with SARS-CoV-2 to determine their concordance between studies, and identified those that could serve as potential biomarkers during infection, disease progression, and death, even in people with other comorbidities. Having such biomarkers can be vital in not only predicting prognosis, but also the development of novel miRNA-based anti-virals and Abbreviations: 3 0 UTR, 3 0 untranslated regions; 5 0 UTR, 5 0

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Plasma Proteomics of COVID-19–Associated Cardiovascular Complications

Cited by 24 publications

References 62 publications

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis

Alterations in platelet proteome signature and impaired platelet integrin α_IIbβ₃activation in patients with COVID-19

Differentially‐regulated miRNAs in COVID‐19: A systematic review

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Plasma Proteomics of COVID-19–Associated Cardiovascular Complications

Cited by 24 publications

References 62 publications

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis

Alterations in platelet proteome signature and impaired platelet integrin αIIbβ3activation in patients with COVID-19

Differentially‐regulated miRNAs in COVID‐19: A systematic review

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Alterations in platelet proteome signature and impaired platelet integrin α_IIbβ₃activation in patients with COVID-19