The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome

Abstract

Background Although 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. Methods Thirty-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. Results At 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. Conclusion We 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.

The cytokine storm in COVID-19: Further advances in our understanding the role of specific chemokines involved

“…al [ 9 ] CCL15 Lucas et. al [ 9 ] CCL10 Yao et al [ 54 ] CCL19 Balnis et al [ 60 ] CCL20 Chua et al ; Huang et al ; Gruber et al, Blot et al [ 7 , 21 , 50 , 65 ] CCL21 Lucas et. al [ 9 ] CCL22 Lucas et.…”

“…The idea that CXCL10 and CCL2 should be regarded as “dominant” in the chemokine immune signature stems from the number of studies consistently reporting their crucial role in the onset of the cytokine storm of COVID-19 and from their relevance in determining specific features of this condition. Indeed, among the several chemokines which have been evaluated and found to be involved in COVID-19, CXCL10 and CCL2 were found to be the most up-regulated ones as compared to controls, showing different degrees of correlation with the viral load as well as with several peculiar symptoms (asthenia, dyspnea, anosmia) [ 5 , [7] , [8] , [9] , [10] , [11] , [21] , [22] , [23] , 29 , 36 , 37 , [44] , [45] , [46] , 49 , 54 , [65] , [66] , [67] ]. Most importantly, CXCL10 and CCL2 were identified to be rather good markers of disease severity since their circulating levels progressively increase in patients with moderate, mild and severe clinical manifestations.…”

Correction to: The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome

“…Following publication of the original article [ 1 ], the authors identified an error in the author group. The investigators of the Lymphonie study group weren’t tagged as collaborators.…”

“…The collaborators’ names are included in the ‘Acknowledgements’ section and listed below. The author group has been updated above and the original article [ 1 ] has been corrected.…”

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 Patients

“…Early from the start of the pandemic caused by SARS-CoV-2, it was realized that patients with severe or critical illness present with profound immune dysregulation with the main features of lymphopenia, hyper-production of proinflammatory cytokines, hyper-ferritinemia and pro-inflammatory/anti-inflammatory imbalance (1)(2)(3)(4). An important question arising regarding the transition from severe COVID-19 pneumonia to critical illness and acute respiratory distress syndrome (ARDS) was whether this was identical in all patients, or whether different immune endotypes can be described in the severely ill patients (5).…”