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Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 Acute Respiratory Distress Syndrome.
Hue, Sophie; Beldi-Ferchiou, Asma; Bendib, Inés; Surenaud, Mathieu; Fourati, Slim; Frapard, Thomas; Rivoal, Simon; Razazi, Keyvan; Carteaux, Guillaume; Delfau-Larue, Marie-Héléne; Mekontso-Dessap, Armand; Audureau, Etienne; de Prost, Nicolas.
  • Hue S; Département Immunologie-Hématologie Hôpitaux Universitaires Henri Mondor.
  • Beldi-Ferchiou A; INSERM U955 Team 16, Créteil, France.
  • Bendib I; Vaccine Research Institute, Faculté de Médecine, Université Paris Est Créteil, Créteil, France.
  • Surenaud M; Université Paris-Est Créteil Val de Marne, INSERM U955, Créteil, France.
  • Fourati S; Département Immunologie-Hématologie Hôpitaux Universitaires Henri Mondor.
  • Frapard T; Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor.
  • Rivoal S; Université Paris-Est Créteil Val de Marne, INSERM U955, Créteil, France.
  • Razazi K; Groupe de Recherche Clinique CARMAS, Université Paris Est-Créteil, Créteil, France.
  • Carteaux G; Vaccine Research Institute, Faculté de Médecine, Université Paris Est Créteil, Créteil, France.
  • Delfau-Larue MH; Laboratoire de Virologie, Département de Prévention, Diagnostic et Traitement des Infections, Hôpitaux Universitaires Henri Mondor, and.
  • Mekontso-Dessap A; Université Paris-Est Créteil Val de Marne, INSERM U955, Créteil, France.
  • Audureau E; INSERM U955 Team "Virus Hepatology Cancer," Créteil, France; and.
  • de Prost N; Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor.
Am J Respir Crit Care Med ; 202(11): 1509-1519, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-952528
ABSTRACT
Rationale Uncontrolled inflammatory innate response and impaired adaptive immune response are associated with clinical severity in patients with coronavirus disease (COVID-19).

Objectives:

To compare the immunopathology of COVID-19 acute respiratory distress syndrome (ARDS) with 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 severe acute respiratory syndrome coronavirus 2 (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 cytokine 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, sex, and Sequential Organ Failure Assessment and Simplified Acute Physiology Score II scores but exhibited a higher Day-28 mortality (34% vs. 11%, P = 0.030). Patients with COVID-19 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 (epithelial growth factor), GM-CSF, IL-10, CCL2/MCP-1, CCL3/MIP-1a, CXCL10/IP-10, CCL5/RANTES, and CCL20/MIP-3a. After adjusting on age and Sequential Organ Failure Assessment, serum CXCL10/IP-10 (P = 0.047) and GM-CSF (P = 0.050) were higher and nasopharyngeal RT-PCR cycle threshold values lower (P = 0.010) in patients with COVID-19 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 nasopharyngeal SARS-CoV-2 viral load, were associated with Day-28 mortality.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Chemokines / COVID-19 / Immunity, Innate / Antibodies, Viral Type of study: Cohort study / Observational study / Prognostic study Topics: Variants Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: Am J Respir Crit Care Med Journal subject: Critical Care Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Chemokines / COVID-19 / Immunity, Innate / Antibodies, Viral Type of study: Cohort study / Observational study / Prognostic study Topics: Variants Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: Am J Respir Crit Care Med Journal subject: Critical Care Year: 2020 Document Type: Article