The clinical syndrome associated with infection of the Coronavirus Disease 2019 (COVID-19) is
notable for its variable clinical expression. Infection and transmission of the virus by
asymptomatic individuals have been noted and represent one end of the clinical spectrum,
while multi-organ failure, particularly pulmonary failure, and death represent the most
severe end of the clinical spectrum. In a recent study published from the investigator's
institution about the first 393 patients with COVID-19, 77.1% had a fever, a mechanism driven
by IL-1. This suggests that there may be an excess release of IL-1 present.
Cytokine storm syndrome (CSS) has been observed in patients with COVID-19 and has been
proposed to contribute to the acute pulmonary failure that occurs. In distinct clinical
settings, macrophage activation syndrome, elevated levels of pro-inflammatory cytokines,
including IL-1, IL-6, and others, as well as elevations in laboratory indicators, including
ferritin, CRP, d-dimer, and lymphopenia, have been observed. IL-1 production is induced in
response to inflammatory stimuli and mediates various physiologic responses including
inflammatory and immunological responses. Anakinra, a recombinant IL-1 receptor antagonist,
has shown promise in treating CSS. It inhibits both IL-1-alpha and IL-1-beta. It is an FDA
approved medication used in rheumatoid arthritis (RA) and Cryopyrin-Associated Periodic
Syndromes (CAPS). Anakinra's ability to inhibit both IL-1 subtypes and short half-life makes
it favorable to some experts. In the investigator's case-series, using anakinra in patients
with COVID-19 showed promising in preventing the need for mechanical ventilation, and
mortality subsequently.
This study will determine the efficacy of anakinra, an interleukin (IL) -1 receptor blocker,
in reducing the need for mechanical ventilation and/or 28-day mortality among patients with
COVID-19 who have features of CSS and severe respiratory failure. The investigators will test
the hypothesis that the proportion of subjects with COVID-19, features of CSS, and severe
respiratory failure (World Health Organization (WHO) category 4 or 5) alive and without
having required mechanical ventilation at day 28 from randomization will be 18% higher among
those that receive anakinra compared to those that receive a placebo. A secondary hypothesis
is that the number of subjects alive at 60-days will be higher amongst those who receive
anakinra compared to those who receive a placebo.