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Platelet proteome reveals features of cell death, antiviral response and viral replication in covid-19
Monique R O Trugilho1,2, Isaclaudia G Azevedo-Quintanilha3, João S M Gesto4
1Center for Technological Development in Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. monique.trugilho@fiocruz.br.
Insights
Platelets are key players in COVID-19 pathogenesis, showing altered activation, antiviral responses, and cell death. Nonsurvivors exhibited distinct protein changes, highlighting translation pathways and viral presence in platelets.
Area of Science:
- * Hematology
- * Virology
- * Proteomics
Background:
- * Coronavirus disease 2019 (COVID-19) has caused significant global mortality.
- * Hypercoagulation and thrombosis are critical factors in COVID-19 lethality, implicating platelets as a SARS-CoV-2 target.
- * Understanding platelet responses is crucial for deciphering COVID-19 pathogenesis.
Purpose of the Study:
- * To investigate the platelet proteome in COVID-19 patients using label-free shotgun proteomics.
- * To identify platelet responses, including activation, cell death, and antiviral mechanisms.
- * To compare proteomic profiles between COVID-19 survivors and nonsurvivors.
Main Methods:
- * Label-free shotgun proteomics analysis of platelet samples from COVID-19 patients.
- * Identification and classification of exclusively detected proteins (EPs) and differentially expressed proteins (DEPs).
- * Whole-genome sequencing of SARS-CoV-2 within patient platelets.
Main Results:
- * Significant alterations in proteins associated with platelet activation, cell death, and interferon type-I antiviral responses were observed in all patients.
- * Nonsurvivors showed distinct protein expression profiles, particularly in translation-related pathways.
- * SARS-CoV-2 genome was detected in platelets, suggesting viral internalization and processing, with CD147 as a potential entry receptor.
Conclusions:
- * Platelets play a multifaceted role in COVID-19 pathogenesis.
- * Platelet activation, antiviral responses, and protein expression changes correlate with disease severity.
- * Platelet proteomic analysis offers insights into COVID-19 outcomes and potential therapeutic targets.
Abstract:
Coronavirus disease 2019 (COVID-19) has affected over 400 million people worldwide, leading to 6 million deaths. Among the complex symptomatology of COVID-19, hypercoagulation and thrombosis have been described to directly contribute to lethality, pointing out platelets as an important SARS-CoV-2 target. In this work, we explored the platelet proteome of COVID-19 patients through a label-free shotgun proteomics approach to identify platelet responses to infection, as well as validation experiments in a larger patient cohort. Exclusively detected proteins (EPs) and differentially expressed proteins (DEPs) were identified in the proteomic dataset and thus classified into biological processes to map pathways correlated with pathogenesis. Significant changes in the expression of proteins related to platelet activation, cell death, and antiviral response through interferon type-I were found in all patients. Since the outcome of COVID-19 varies highly among individuals, we also performed a cross-comparison of proteins found in survivors and nonsurvivors. Proteins belonging to the translation pathway were strongly highlighted in the nonsurvivor group. Moreover, the SARS-CoV-2 genome was fully sequenced in platelets from five patients, indicating viral internalization and preprocessing, with CD147 as a potential entry route. In summary, platelets play a significant role in COVID-19 pathogenesis via platelet activation, antiviral response, and disease severity.
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