Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar 1;320(3):R250-R257.
doi: 10.1152/ajpregu.00324.2020. Epub 2021 Jan 12.

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

Joseph Balnis  1   2 , Alejandro P Adam  1   3 , Amit Chopra  1 , Hau C Chieng  1 , Lisa A Drake  2 , Nina Martino  2 , Ramon Bossardi Ramos  2 , Paul J Feustel  4 , Katherine A Overmyer  5 , Evgenia Shishkova  6 , Joshua J Coon  5   6 , Harold A Singer  2 , Marc A Judson  1 , Ariel Jaitovich  1   2
Affiliations

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

Joseph Balnis et al. Am J Physiol Regul Integr Comp Physiol. .

Abstract

The COVID19 pandemic has caused more than a million of deaths worldwide, primarily due to complications from COVID19-associated acute respiratory distress syndrome (ARDS). Controversy surrounds the circulating cytokine/chemokine profile of COVID19-associated ARDS, with some groups suggesting that it is similar to patients without COVID19 ARDS and others observing substantial differences. Moreover, although a hyperinflammatory phenotype associates with higher mortality in non-COVID19 ARDS, there is little information on the inflammatory landscape's association with mortality in patients with COVID19 ARDS. Even though the circulating leukocytes' transcriptomic signature has been associated with distinct phenotypes and outcomes in critical illness including ARDS, it is unclear whether the mortality-associated inflammatory mediators from patients with COVID19 are transcriptionally regulated in the leukocyte compartment. Here, we conducted a prospective cohort study of 41 mechanically ventilated patients with COVID19 infection using highly calibrated methods to define the levels of plasma cytokines/chemokines and their gene expressions in circulating leukocytes. Plasma IL1RA and IL8 were found positively associated with mortality, whereas RANTES and EGF negatively associated with that outcome. However, the leukocyte gene expression of these proteins had no statistically significant correlation with mortality. These data suggest a unique inflammatory signature associated with severe COVID19.

Keywords: COVID19; IL1RA; chemokines; cytokines; mortality.

PubMed Disclaimer

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Figure 1.
Figure 1.
Cytokine determinations at the time of enrollment and association with mortality based on multiplex system determination. Volcano plot showing cytokines/chemokines significantly associated with mortality: blue dots, negatively associated; red dots, positively associated. Black dots identify entities not statistically significantly associated with mortality. Threshold of significance was established at a P value of 0.05 before adjustment for false discovery rate. IL-1ra, IL1 receptor antagonist.
Figure 2.
Figure 2.
A–D: cytokines associated with mortality based on ELISA tests performed individually. Bar graphs showing the cytokines/chemokines that were found associated with mortality by ELISA testing. *P < 0.05; **P < 0.01; ***P < 0.001. IL-1ra, IL1 receptor antagonist.
See this image and copyright information in PMC

Update of

References

    1. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al . Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382: 1708–1720, 2020. doi:10.1056/NEJMoa2002032. - DOI - PMC - PubMed
    1. Wilson JG, Simpson LJ, Ferreira A-M, Rustagi A, Roque J, Asuni A, Rananath T, Grant PM, Subramanian A, Rosenberg-Hasson Y, Maecker HT, Holmes SP, Levitt JE, Blish CA, Roers AJ. Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis. JCI Insight 5: e140289, 2020. doi:10.1172/jci.insight.140289. - DOI - PMC - PubMed
    1. Zhao Y, Qin L, Zhang P, Li K, Liang L, Sun J, Xu B, Dai Y, Li X, Zhang C, Peng Y, Feng Y, Li A, Hu Z, Xiang H, Ogg G, Ho L-P, McMichael A, Jin R, Knight JC, Dong T, Zhang Y. Longitudinal COVID-19 profiling associates IL-1ra and IL-10 with disease severity and RANTES with mild disease. JCI Insight 5: e139834, 2020. doi:10.1172/jci.insight.139834. - DOI - PMC - PubMed
    1. Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med 2: 611–620, 2014. doi:10.1016/S2213-2600(14)70097-9. - DOI - PMC - PubMed
    1. Calfee CS, Delucchi KL, Sinha P, Matthay MA, Hackett J, Shankar-Hari M, McDowell C, Laffey JG, O’Kane CM, McAuley DF; Irish Critical Care Trials Group. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med 6: 691–698, 2018. doi:10.1016/S2213-2600(18)30177-2. - DOI - PMC - PubMed

Publication types