tetano
Editor, Senior Moderator
J Thromb Haemost
. 2021 Sep 19.
doi: 10.1111/jth.15534. Online ahead of print.
Platelets Contribute to Disease Severity in COVID-19
Tessa J Barrett[SUP] 1 [/SUP], Seda Bilaloglu[SUP] 2 [/SUP], Macintosh Cornwell[SUP] 1 [/SUP], Hannah M Burgess[SUP] 3 [/SUP], Vitor W Virginio[SUP] 1 [/SUP], Kamelia Drenkova[SUP] 1 [/SUP], Homam Ibrahim[SUP] 1 [/SUP], Eugene Yuriditsky[SUP] 1 [/SUP], Yin Aphinyanaphongs[SUP] 2 [/SUP], Mark Lifshitz[SUP] 4 [/SUP], Feng Xia Liang[SUP] 5 [/SUP], Julie Alejo[SUP] 6 [/SUP], Grace Smith[SUP] 6 [/SUP], Stefania Pittaluga[SUP] 6 [/SUP], Amy V Rapkiewicz[SUP] 7 [/SUP], Jun Wang[SUP] 4 [/SUP], Camelia Iancu-Rubin[SUP] 8 [/SUP], Ian Mohr[SUP] 3 [/SUP], Kelly Ruggles[SUP] 1 [/SUP], Kenneth A Stapleford[SUP] 3 [/SUP], Judith Hochman[SUP] 1 [/SUP], Jeffrey S Berger[SUP] 1 9 [/SUP]
Affiliations
Abstract
Objective: Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID-19 patients. Given that platelets are key regulators of thrombosis, inflammation, and immunity they represent prime candidates as mediators of COVID-19-associated pathogenesis. The objective of this study was to understand the contribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the platelet phenotype via phenotypic (activation, aggregation) and transcriptomic characterization.
Approach and results: In a cohort of 3,915 hospitalized COVID-19 patients, we analyzed blood platelet indices collected at hospital admission. Following adjustment for demographics, clinical risk factors, medication, and biomarkers of inflammation and thrombosis, we find platelet count, size, and immaturity are associated with increased critical illness and all-cause mortality. Bone marrow, lung and blood from COVID-19 patients revealed the presence of SARS-CoV-2 virions in megakaryocytes and platelets. Characterization of COVID-19 platelets found them to be hyperreactive (increased aggregation, and expression of P-selectin & CD40) and have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets. In vitro mechanistic studies highlight that the interaction of SARS-CoV-2 with megakaryocytes alters the platelet transcriptome, and its effects are distinct from the coronavirus responsible for the common cold (CoV-OC43).
Conclusions: COVID-19 platelet count, size, and maturity associate with increased critical illness and all-cause mortality. Profiling tissues and blood from COVID-19 patients revealed that SARS-CoV-2 virions enter megakaryocytes and platelets and associate with alterations to the platelet transcriptome and activation profile.
Keywords: COVID-19; Platelets; megakaryocytes; thrombosis.
. 2021 Sep 19.
doi: 10.1111/jth.15534. Online ahead of print.
Platelets Contribute to Disease Severity in COVID-19
Tessa J Barrett[SUP] 1 [/SUP], Seda Bilaloglu[SUP] 2 [/SUP], Macintosh Cornwell[SUP] 1 [/SUP], Hannah M Burgess[SUP] 3 [/SUP], Vitor W Virginio[SUP] 1 [/SUP], Kamelia Drenkova[SUP] 1 [/SUP], Homam Ibrahim[SUP] 1 [/SUP], Eugene Yuriditsky[SUP] 1 [/SUP], Yin Aphinyanaphongs[SUP] 2 [/SUP], Mark Lifshitz[SUP] 4 [/SUP], Feng Xia Liang[SUP] 5 [/SUP], Julie Alejo[SUP] 6 [/SUP], Grace Smith[SUP] 6 [/SUP], Stefania Pittaluga[SUP] 6 [/SUP], Amy V Rapkiewicz[SUP] 7 [/SUP], Jun Wang[SUP] 4 [/SUP], Camelia Iancu-Rubin[SUP] 8 [/SUP], Ian Mohr[SUP] 3 [/SUP], Kelly Ruggles[SUP] 1 [/SUP], Kenneth A Stapleford[SUP] 3 [/SUP], Judith Hochman[SUP] 1 [/SUP], Jeffrey S Berger[SUP] 1 9 [/SUP]
Affiliations
- PMID: 34538015
- DOI: 10.1111/jth.15534
Abstract
Objective: Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID-19 patients. Given that platelets are key regulators of thrombosis, inflammation, and immunity they represent prime candidates as mediators of COVID-19-associated pathogenesis. The objective of this study was to understand the contribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the platelet phenotype via phenotypic (activation, aggregation) and transcriptomic characterization.
Approach and results: In a cohort of 3,915 hospitalized COVID-19 patients, we analyzed blood platelet indices collected at hospital admission. Following adjustment for demographics, clinical risk factors, medication, and biomarkers of inflammation and thrombosis, we find platelet count, size, and immaturity are associated with increased critical illness and all-cause mortality. Bone marrow, lung and blood from COVID-19 patients revealed the presence of SARS-CoV-2 virions in megakaryocytes and platelets. Characterization of COVID-19 platelets found them to be hyperreactive (increased aggregation, and expression of P-selectin & CD40) and have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets. In vitro mechanistic studies highlight that the interaction of SARS-CoV-2 with megakaryocytes alters the platelet transcriptome, and its effects are distinct from the coronavirus responsible for the common cold (CoV-OC43).
Conclusions: COVID-19 platelet count, size, and maturity associate with increased critical illness and all-cause mortality. Profiling tissues and blood from COVID-19 patients revealed that SARS-CoV-2 virions enter megakaryocytes and platelets and associate with alterations to the platelet transcriptome and activation profile.
Keywords: COVID-19; Platelets; megakaryocytes; thrombosis.