Aruna subramanian driver#

A better understanding of how the inflammatory state in severe COVID-19 compares with that of other critical illnesses would not only provide insight into pathophysiology, but could inform study design for trials of immunosuppressive treatments for COVID-19 going forward.

If the inflammatory response in severe COVID-19 is no different than that in ARDS or sepsis, testing of immune modulators in unselected COVID-19 patients may likewise fail, or lead to inconclusive or contradictory results. This is an important comparison, as large-scale randomized controlled trials of immune modulators (e.g., anti–IL-1β, activated protein C, steroids) have failed to demonstrate clear benefit in ARDS and sepsis ( 9). While it is clear that COVID-19 is a highly inflamed state (similar to other viral respiratory infections including H5N1 influenza, SARS-CoV, and MERS-CoV) ( 6– 8), it is unknown if inflammatory cytokine levels differ in patients with severe COVID-19 compared with critically ill patients with sepsis or acute respiratory distress syndrome (ARDS) due to other causes.

Aruna subramanian driver#

These data have sparked interest in “cytokine storm” as a major driver of illness severity in COVID-19, and multiple clinical trials are underway to test the efficacy of immunosuppressive therapies, including IL-6 antagonists ( 5). Numerous studies have established that levels of inflammatory biomarkers are elevated in COVID-19 patients, and higher levels of inflammatory cytokines are consistently associated with more severe disease and worse outcomes ( 1– 4). Funding was received from NHLBI K23 HL125663 (AJR) The Bill and Melinda Gates Foundation OPP1113682 (AJR and CAB) Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687 NIH/NIAID U19AI057229-16 Stanford Maternal Child Health Research Institute and Chan Zuckerberg Biohub (CAB). Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies use of these therapies in unselected patients with COVID-19 may be unwarranted.įUNDING. Levels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. There were no statistically significant differences in baseline levels of IL-1β, IL-1RA, IL-6, IL-8, IL-18, and TNF-α between patients with COVID-19 and critically ill controls with ARDS or sepsis.ĬONCLUSION. Fifteen hospitalized COVID-19 patients, 9 of whom were critically ill, were compared with critically ill patients with ARDS ( n = 12) or sepsis ( n = 16).

Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1β, IL-1RA, IL-6, IL-8, IL-18, and TNF-α) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis. We used a Luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. It is unknown, however, how these levels compare with those observed in critically ill patients with acute respiratory distress syndrome (ARDS) or sepsis due to other causes. Elevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients.