Unique inflammatory profile is associated with higher SARS-CoV-2 acute respiratory distress syndrome (ARDS) mortality

Abstract

COVID19 pandemic has so far caused over three hundred thousand deaths worldwide, primarily due to complications from SARS-CoV-2-associated acute respiratory distress syndrome (ARDS). While an ARDS-driven hyperinflammatory phenotype is associated with higher mortality in non-COVID patients, there is little information on how cytokines and chemokines expressions correlate with clinical outcomes in COVID19 patients. We prospectively enrolled a cohort of 41 patients with acute respiratory distress syndrome on mechanical ventilation. Patients blood was obtained at enrollment and outcome measures were liberation from mechanical ventilation and hospital-free days. We determined the expression levels of 44 circulating cytokines/chemokines and found 13 of them associated with worse outcomes. After correcting for multiple comparisons/false discovery rate, only one chemokine (CCL19) remained significantly associated with outcomes (p=0.009). Although not described in association with COVID19, this chemokine was previously found elevated in an animal model of SARS-CoV. Moreover, CCL19 seems to be relevant for bronchus-associated lymphoid tissue (BALT) maintenance and for lung immunity to influenza virus. While this finding requires corroboration, CCL19 determination could facilitate early identification COVID19-ARDS patients at higher risk of death and be novel target for immunotherapy in this setting.

Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality

“…In conclusion, our work supports further clinical investigation correlating prognosis by stratifying patients based on the circulating molecules involved in complement activation shown recently (Ma et al, 2021), or characteristic cytokines such as CCL19, implicated in COVID-19 mortality (Balnis et al, 2021). Such non-invasive stratification of patients can be used to test the efficacy drugs identified in our study that reverse the molecular changes for the two patient signatures such as cabazitaxel to treat “classical” patients or talampicillin to treat “CRS” patients.…”

“…shown recently , or characteristic cytokines such as CCL19, implicated in COVID-19 mortality (Balnis et al, 2021). Such non-invasive stratification of patients can be used to test the efficacy drugs identified in our study that reverse the molecular changes for the two patient signatures such as cabazitaxel to treat "classical" patients or talampicillin to treat "CRS" patients .…”

SARS‐CoV2 pneumonia recovery is linked to expansion of innate lymphoid cells type 2 expressing CCR10

“…These findings were confirmed by our manual analysis also revealing a significant increase in the CCR10 MFI in the CD161negILC2 (Fig. 2B), which was inversely correlated with the decline of RAGE, a marker of endothelium lung damage [20] and positively correlated with EGF, a cytokine that promotes epithelial proliferation [21] (Fig. 2C).…”

Correlation of IL-1β Level and Body Temperature to the Severity of Acute Respiratory Distress Syndrome (ARDS) and Mortality in COVID-19 Patients

“…A study on the inflammatory profile associated with higher mortality in COVID-19 patients that involved 41 patients prospectively, showed that plasma IL-1Ra levels and IL-8 levels had a positive correlation with mortality in COVID-19 ARDS patients. However, this study still requires further research (23).The total number of ARDS patients was 37 people, 10 people died, and among the 10 people who died there were 2 people (20%) who experienced an increase in IL-1β and 8 people (80%) who experienced a decrease in IL-1β. There were 27 surviving ARDS patients, of which 12 people (44.4%) had an increase in IL-1β and 15 people (55.6%) experienced a decrease in IL-1β.…”

“…This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License ARDS patients. However, this study still requires further research(23).Another study of IL-1β blockade with canakinumab in COVID-19 patients involved 88 patients in a prospective observational cohort design and showed an improvement in the PaO2/FiO2 ratio in 45 patients from the baseline with a median of 160 to 237 on day 7 of canakinumab therapy. Canakinumab is a monoclonal IgG antibody that specifically targets IL-1β.…”