Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 Acute Respiratory Distress Syndrome.
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 MainResults:
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.Keywords
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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