GeneSet Information

Tier IV GS399756 • Genes upregulated in platelets of ICU COVID-19 patients

DESCRIPTION:

This set includes genes that have increased RNA expression in platelets of ICU patients with COVID-19 disease versus healthy donors. COVID-19 is the disease caused by SARS-CoV2 infection. Genes were selected for an adjusted p-value <0.05 and a log2fold-change >1.0. Genes were converted to HGNC identifiers. Those that could not be unambiguously converted were omitted from the set. Values are log2fold change.

LABEL:

up in ICU COVID-19 platelets

SCORE TYPE:

Effect

DATE ADDED:

2021-04-23

DATE UPDATED:

2021-09-10

SPECIES:

AUTHORS:

Bhanu Kanth Manne, Frederik Denorme, Elizabeth A Middleton, Irina Portier, Jesse W Rowley, Chris Stubben, Aaron C Petrey, Neal D Tolley, Li Guo, Mark Cody, Andrew S Weyrich, Christian C Yost, Matthew T Rondina, Robert A Campbell

TITLE:

Platelet gene expression and function in patients with COVID-19.

JOURNAL:

Blood 09 2020, Vol 136, pp. 1317-1329

ABSTRACT:

There is an urgent need to understand the pathogenesis of coronavirus disease 2019 (COVID-19). In particular, thrombotic complications in patients with COVID-19 are common and contribute to organ failure and mortality. Patients with severe COVID-19 present with hemostatic abnormalities that mimic disseminated intravascular coagulopathy associated with sepsis, with the major difference being increased risk of thrombosis rather than bleeding. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters platelet function to contribute to the pathophysiology of COVID-19 remains unknown. In this study, we report altered platelet gene expression and functional responses in patients infected with SARS-CoV-2. RNA sequencing demonstrated distinct changes in the gene-expression profile of circulating platelets of COVID-19 patients. Pathway analysis revealed differential gene-expression changes in pathways associated with protein ubiquitination, antigen presentation, and mitochondrial dysfunction. The receptor for SARS-CoV-2 binding, angiotensin-converting enzyme 2 (ACE2), was not detected by messenger RNA (mRNA) or protein in platelets. Surprisingly, mRNA from the SARS-CoV-2 N1 gene was detected in platelets from 2 of 25 COVID-19 patients, suggesting that platelets may take-up SARS-COV-2 mRNA independent of ACE2. Resting platelets from COVID-19 patients had increased P-selectin expression basally and upon activation. Circulating platelet-neutrophil, -monocyte, and -T-cell aggregates were all significantly elevated in COVID-19 patients compared with healthy donors. Furthermore, platelets from COVID-19 patients aggregated faster and showed increased spreading on both fibrinogen and collagen. The increase in platelet activation and aggregation could partially be attributed to increased MAPK pathway activation and thromboxane generation. These findings demonstrate that SARS-CoV-2 infection is associated with platelet hyperreactivity, which may contribute to COVID-19 pathophysiology. PUBMED: 32573711
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Annotation Information



Coronavirus Infections (D018352)
Blood Platelets (D001792)
Coronavirus (D017934)
coronavirus infectious disease (EFO:0007224)

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