tetano
Editor, Senior Moderator
Front Immunol
. 2022 Mar 11;13:844701.
doi: 10.3389/fimmu.2022.844701. eCollection 2022.
Disease Severity in Moderate-to-Severe COVID-19 Is Associated With Platelet Hyperreactivity and Innate Immune Activation
Kai Jakobs[SUP] 1 2 [/SUP], Leander Reinshagen[SUP] 1 2 [/SUP], Marianna Puccini[SUP] 1 2 [/SUP], Julian Friebel[SUP] 1 2 3 [/SUP], Anne-Christin Beatrice Wilde[SUP] 4 [/SUP], Ayman Alsheik[SUP] 1 [/SUP], Andi Rroku[SUP] 1 2 [/SUP], Ulf Landmesser[SUP] 1 2 3 [/SUP], Arash Haghikia[SUP] 1 2 3 [/SUP], Nicolle Kränkel[SUP] 1 2 [/SUP], Ursula Rauch-Kröhnert[SUP] 1 2 [/SUP]
Affiliations
Abstract
Background: Hemostasis and inflammation are both dysregulated in patients with moderate-to-severe coronavirus disease 2019 (COVID-19). Yet, both processes can also be disturbed in patients with other respiratory diseases, and the interactions between coagulation, inflammation, and disease severity specific to COVID-19 are still vague.
Methods: Hospitalized patients with acute respiratory symptoms and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-positive (COV[SUP]pos[/SUP]) and SARS-CoV2-negative (COV[SUP]neg[/SUP]) status were included. We assessed adenosine diphosphate (ADP)-, thrombin receptor activator peptide 6 (TRAP)-, and arachidonic acid (AA)-induced platelet reactivity by impedance aggregometry, as well as leukocyte subtype spectrum and platelet-leukocyte aggregates by flow cytometry and inflammatory cytokines by cytometric bead array.
Results: ADP-, TRAP-, and AA-induced platelet reactivity was significantly higher in COV[SUP]pos[/SUP] than in COV[SUP]neg[/SUP] patients. Disease severity, assessed by sequential organ failure assessment (SOFA) score, was higher in COV[SUP]pos[/SUP] than in COV[SUP]neg[/SUP] patients and again higher in deceased COV[SUP]pos[/SUP] patients than in surviving COV[SUP]pos[/SUP]. The SOFA score correlated significantly with the mean platelet volume and TRAP-induced platelet aggregability. A larger percentage of classical and intermediate monocytes, and of CD4[SUP]pos[/SUP] T cells (T[SUB]H[/SUB]) aggregated with platelets in COV[SUP]pos[/SUP] than in COV[SUP]neg[/SUP] patients. Interleukin (IL)-1 receptor antagonist (RA) and IL-6 levels were higher in COV[SUP]pos[/SUP] than in COV[SUP]neg[/SUP] patients and again higher in deceased COV[SUP]pos[/SUP] patients than in surviving COV[SUP]pos[/SUP]. IL-1RA and IL-6 levels correlated with the SOFA score in COV[SUP]pos[/SUP] but not in COV[SUP]neg[/SUP] patients. In both respiratory disease groups, absolute levels of B-cell-platelet aggregates and NK-cell-platelet aggregates were correlated with ex vivo platelet aggegation upon stimulation with AA and ADP, respectively, indicating a universal, but not a COVID-19-specific mechanism.
Conclusion: In moderate-to-severe COVID-19, but not in other respiratory diseases, disease severity was associated with platelet hyperreactivity and a typical inflammatory signature. In addition to a severe inflammatory response, platelet hyperreactivity associated to a worse clinical outcome in patients with COVID-19, pointing to the importance of antithrombotic therapy for reducing disease severity.
Keywords: COVID-19; disease severity; immunothrombosis; inflammation; platelet hyperactivity; platelet-leucocyte aggregates; survival.
. 2022 Mar 11;13:844701.
doi: 10.3389/fimmu.2022.844701. eCollection 2022.
Disease Severity in Moderate-to-Severe COVID-19 Is Associated With Platelet Hyperreactivity and Innate Immune Activation
Kai Jakobs[SUP] 1 2 [/SUP], Leander Reinshagen[SUP] 1 2 [/SUP], Marianna Puccini[SUP] 1 2 [/SUP], Julian Friebel[SUP] 1 2 3 [/SUP], Anne-Christin Beatrice Wilde[SUP] 4 [/SUP], Ayman Alsheik[SUP] 1 [/SUP], Andi Rroku[SUP] 1 2 [/SUP], Ulf Landmesser[SUP] 1 2 3 [/SUP], Arash Haghikia[SUP] 1 2 3 [/SUP], Nicolle Kränkel[SUP] 1 2 [/SUP], Ursula Rauch-Kröhnert[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35359931
- PMCID: PMC8963244
- DOI: 10.3389/fimmu.2022.844701
Abstract
Background: Hemostasis and inflammation are both dysregulated in patients with moderate-to-severe coronavirus disease 2019 (COVID-19). Yet, both processes can also be disturbed in patients with other respiratory diseases, and the interactions between coagulation, inflammation, and disease severity specific to COVID-19 are still vague.
Methods: Hospitalized patients with acute respiratory symptoms and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-positive (COV[SUP]pos[/SUP]) and SARS-CoV2-negative (COV[SUP]neg[/SUP]) status were included. We assessed adenosine diphosphate (ADP)-, thrombin receptor activator peptide 6 (TRAP)-, and arachidonic acid (AA)-induced platelet reactivity by impedance aggregometry, as well as leukocyte subtype spectrum and platelet-leukocyte aggregates by flow cytometry and inflammatory cytokines by cytometric bead array.
Results: ADP-, TRAP-, and AA-induced platelet reactivity was significantly higher in COV[SUP]pos[/SUP] than in COV[SUP]neg[/SUP] patients. Disease severity, assessed by sequential organ failure assessment (SOFA) score, was higher in COV[SUP]pos[/SUP] than in COV[SUP]neg[/SUP] patients and again higher in deceased COV[SUP]pos[/SUP] patients than in surviving COV[SUP]pos[/SUP]. The SOFA score correlated significantly with the mean platelet volume and TRAP-induced platelet aggregability. A larger percentage of classical and intermediate monocytes, and of CD4[SUP]pos[/SUP] T cells (T[SUB]H[/SUB]) aggregated with platelets in COV[SUP]pos[/SUP] than in COV[SUP]neg[/SUP] patients. Interleukin (IL)-1 receptor antagonist (RA) and IL-6 levels were higher in COV[SUP]pos[/SUP] than in COV[SUP]neg[/SUP] patients and again higher in deceased COV[SUP]pos[/SUP] patients than in surviving COV[SUP]pos[/SUP]. IL-1RA and IL-6 levels correlated with the SOFA score in COV[SUP]pos[/SUP] but not in COV[SUP]neg[/SUP] patients. In both respiratory disease groups, absolute levels of B-cell-platelet aggregates and NK-cell-platelet aggregates were correlated with ex vivo platelet aggegation upon stimulation with AA and ADP, respectively, indicating a universal, but not a COVID-19-specific mechanism.
Conclusion: In moderate-to-severe COVID-19, but not in other respiratory diseases, disease severity was associated with platelet hyperreactivity and a typical inflammatory signature. In addition to a severe inflammatory response, platelet hyperreactivity associated to a worse clinical outcome in patients with COVID-19, pointing to the importance of antithrombotic therapy for reducing disease severity.
Keywords: COVID-19; disease severity; immunothrombosis; inflammation; platelet hyperactivity; platelet-leucocyte aggregates; survival.