Abstract

INTRODUCTION
Covid-19 is associated with elevated proinflammatory cytokines that are associated with increased severity and mortality. There is controversy about the true role of cytokine storm (CS) in the pathophysiology of COVID-19.

METHODS
Prospective, observational, longitudinal study of 91 hospitalized patients with different severity. It included Viral phase(1-9 days from clinical onset), early inflammatory (10-16 days), and late (>17 days). Clinical data, immune cell counts, proinflammatory cytokine levels (TNF-a,IL-1ß,IL-8,IL-6,INF-?,IL-17A andG-CSF), serum inflammatory markers (CRP,PCT,D-dimer,ferritin) and tissue damage markers (LDH and cfDNA) were included.

RESULTS
TNF- a, IL-8,IL-6 and G-CSF, were elevated in the most severe patients. IL-6, IL-8 and G-CSF were already elevated in the first admission sample in those who died. Only IL-6 remained elevated in all 3 phases of the disease in deceased patients. IL-1ß, INF-? and IL-17A were not related to severity. We found increased levels of cytokines from the viral phase to the early inflammatory phase, significant in moderate Covid-19, but stable in severe and decreasing in critically ill patients. Only IL-6 showed increasing levels in the evolution of critically ill patients. IL-6 correlated with the tissue damage markers studied and with length of stay, especially in critical patients (r=0.598).

CONCLUSIONS

Only IL-6, TNF-a,IL-8 and G-CSF were associated with severity.
IL-6 was the cytokine that best expressed hyperactivation of the innate immune response and cellular damage in critically ill.
There was no significant and sustained increase in cytokines in late inflammation, as would be expected in major CS.