Abstract
BackgroundAlthough immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis.MethodsThirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared.ResultsAt similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7–22] vs. 4 (0–15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1β, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-β), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation.ConclusionWe identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets.ClinicalTrials.gov: NCT03505281.
Highlights
Immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID19), the most relevant targets remain to be found
We recently reported that COVID-19 patients had lower concentrations of interleukin (IL)-6 compared to non-COVID-19 patients with severe pneumonia [12]
Plasma GM‐CSF, CXCL10 and IL‐10 were independently associated with the duration of mechanical ventilation As the particular severity of COVID-19 patients was represented by a significantly longer duration of Mechanical ventilation (MV), we investigated whether immune response could explain this poor outcome
Summary
Immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID19), the most relevant targets remain to be found. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for pneumonia with peculiar characteristics [1]. Dexamethasone is the only treatment that has proven to be effective in reducing 28-day mortality in severe COVID-19 patients receiving mechanical ventilation in a randomized clinical trial [8]. These data support the existence of a unique dysregulated immune response that could be one of the most promising therapeutic targets to date
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