tetano
Editor, Senior Moderator
Am J Respir Crit Care Med
. 2020 Aug 31.
doi: 10.1164/rccm.202005-1885OC. Online ahead of print.
Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 ARDS
Sophie Hue[SUP] 1 2 [/SUP], Asma Beldi-Ferchiou[SUP] 3 [/SUP], In?s Bendib[SUP] 3 [/SUP], Mathieu Surenaud[SUP] 4 [/SUP], Slim Fourati[SUP] 3 [/SUP], Thomas Frapard[SUP] 3 [/SUP], Simon Rivoal[SUP] 3 [/SUP], Keyvan Razazi[SUP] 5 6 [/SUP], Guillaume Carteaux[SUP] 7 8 [/SUP], Marie-H?l?ne Delfau-Larue[SUP] 3 [/SUP], Armand Mekontso Dessap[SUP] 9 10 [/SUP], Etienne Audureau[SUP] 11 [/SUP], Nicolas de Prost[SUP] 12 13 [/SUP]
Affiliations
Abstract
Rationale: Uncontrolled inflammatory innate response and impaired adaptive immune response are associated with clinical severity in patients with Coronavirus disease 2019 (COVID-19).
Objectives: To compare the immunopathology of COVID-19 acute respiratory distress syndrome (ARDS) to that of non-COVID-19 ARDS, and to identify biomarkers associated with mortality in patients with COVID-19 ARDS.
Methods: Prospective observational monocenter study. Immunocompetent patients diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and ARDS admitted between March 8 and March 30, 2020 were included and compared with patients with non-COVID-19 ARDS. The primary clinical endpoint of the study was mortality at day 28. Flow cytometry analyses and serum cytokines measurements were performed at days 1-2 and 4-6 of ICU admission.
Measurements and main results: As compared with patients with non-COVID-19 ARDS (n=36), those with COVID-19 (n=38) were not significantly different regarding age, gender, and SOFA and SAPS II scores but exhibited a higher day-28 mortality (34% vs 11%, p=0.030). COVID-19 patients showed profound and sustained T CD4+ (p=0.002), CD8+ (p<0.0001) and B (p<0.0001) lymphopenia, higher HLA-DR expression on monocytes (p<0.001) and higher serum concentrations of EGF, GM-CSF, IL-10, CCL2/MCP-1, CCL3/MIP-1a, CXCL10/IP-10, CCL5/RANTES, and CCL20/MIP-3a. After adjusting on age and SOFA, serum CXCL10/IP-10 (p=0.047) and GM-CSF (p=0.050) were higher and naso-pharyngeal RT-PCR cycle threshold values lower (p=0.010) in COVID-19 patients who were dead at day-28.
Conclusions: Profound global lymphopenia and a "chemokine signature" were observed in COVID-19 ARDS. Increased serum concentrations of CXCL10/IP-10 and GM-CSF, together with higher naso-pharyngeal SARS-CoV-2 viral load, were associated with day-28 mortality. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: SARS-CoV-2, COVID-19, ARDS, chemokines, cytokines.
. 2020 Aug 31.
doi: 10.1164/rccm.202005-1885OC. Online ahead of print.
Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 ARDS
Sophie Hue[SUP] 1 2 [/SUP], Asma Beldi-Ferchiou[SUP] 3 [/SUP], In?s Bendib[SUP] 3 [/SUP], Mathieu Surenaud[SUP] 4 [/SUP], Slim Fourati[SUP] 3 [/SUP], Thomas Frapard[SUP] 3 [/SUP], Simon Rivoal[SUP] 3 [/SUP], Keyvan Razazi[SUP] 5 6 [/SUP], Guillaume Carteaux[SUP] 7 8 [/SUP], Marie-H?l?ne Delfau-Larue[SUP] 3 [/SUP], Armand Mekontso Dessap[SUP] 9 10 [/SUP], Etienne Audureau[SUP] 11 [/SUP], Nicolas de Prost[SUP] 12 13 [/SUP]
Affiliations
- PMID: 32866033
- DOI: 10.1164/rccm.202005-1885OC
Abstract
Rationale: Uncontrolled inflammatory innate response and impaired adaptive immune response are associated with clinical severity in patients with Coronavirus disease 2019 (COVID-19).
Objectives: To compare the immunopathology of COVID-19 acute respiratory distress syndrome (ARDS) to that of non-COVID-19 ARDS, and to identify biomarkers associated with mortality in patients with COVID-19 ARDS.
Methods: Prospective observational monocenter study. Immunocompetent patients diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and ARDS admitted between March 8 and March 30, 2020 were included and compared with patients with non-COVID-19 ARDS. The primary clinical endpoint of the study was mortality at day 28. Flow cytometry analyses and serum cytokines measurements were performed at days 1-2 and 4-6 of ICU admission.
Measurements and main results: As compared with patients with non-COVID-19 ARDS (n=36), those with COVID-19 (n=38) were not significantly different regarding age, gender, and SOFA and SAPS II scores but exhibited a higher day-28 mortality (34% vs 11%, p=0.030). COVID-19 patients showed profound and sustained T CD4+ (p=0.002), CD8+ (p<0.0001) and B (p<0.0001) lymphopenia, higher HLA-DR expression on monocytes (p<0.001) and higher serum concentrations of EGF, GM-CSF, IL-10, CCL2/MCP-1, CCL3/MIP-1a, CXCL10/IP-10, CCL5/RANTES, and CCL20/MIP-3a. After adjusting on age and SOFA, serum CXCL10/IP-10 (p=0.047) and GM-CSF (p=0.050) were higher and naso-pharyngeal RT-PCR cycle threshold values lower (p=0.010) in COVID-19 patients who were dead at day-28.
Conclusions: Profound global lymphopenia and a "chemokine signature" were observed in COVID-19 ARDS. Increased serum concentrations of CXCL10/IP-10 and GM-CSF, together with higher naso-pharyngeal SARS-CoV-2 viral load, were associated with day-28 mortality. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: SARS-CoV-2, COVID-19, ARDS, chemokines, cytokines.