COVID-19 prevention tools have evolved, and so has the virus itself, leading to mild disease in more than 80% of infected individuals. However, this still leaves a substantial population susceptible to severe COVID-19 disease progression.

Older individuals or those with comorbidities are more likely to experience a dysregulated host immune response and excessive inflammation, which may devolve to acute respiratory distress syndrome and multiorgan failure.

The recombinant IL-1 receptor antagonist anakinra has successfully combated pathogeneses consistent with COVID-19 hyperinflammation. A new study, published in JAMA Network Open, assessed the efficacy and safety of anakinra versus standard of care in reducing severe COVID-19 pneumonia and hyperinflammation.

The Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to COVID-19 (ANA-COVID-GEAS) study was a multicenter, randomized, open-label, 2-group, phase 2/3 clinical trial. The trial was decentralized and conducted in 12 hospitals across Spain.

Enrolled participants were adults, aged 18 years and older, with confirmed severe COVID-19 pneumonia “defined as a positive polymerase chain reaction test for SARS-CoV-2 in nasopharyngeal specimens, pulmonary infiltrates compatible with pneumonia on chest imaging, and hyperinflammation.”

Participants were randomly assigned 1:1 to either standard of care (SoC) or SoC plus anakinra. SoC included hydroxychloroquine, lopinavir-ritonavir, and/or azithromycin. The study patients were monitored during hospital stay and then followed up for 28 days after randomization, or until death, loss to follow-up, or study withdrawal.

The anakinra cohort were dosed intravenously, 100 mg 4 times a day, for a maximum of 15 days. Anakinra may have been discontinued before 15 days for the following reasons: need for hospital beds, persistence of elevated inflammatory markers, persistence of pneumonic condensation on radiologic images, or the need for oxygen therapy (these latter patients were transferred home under hospitalization at home protocols).

Data were collected from April-October 2021. The primary study outcome was the proportion of patients not requiring mechanical ventilation (invasive or noninvasive) at 15 days after initiating anakinra treatment.

A total of 179 patients were included in the study, a population that averaged 69.9% male and 60.5 years of age. These severe COVID-19 pneumonia patients were randomly assigned to the anakinra group (n = 92) or the SoC group (n = 87).

Up to day 15, the proportion of patients not requiring mechanical ventilation was not significantly different between the 2 groups. Overall, 77.1% (n = 64) of anakinra recipients and 85.9% (n = 67) of the SoC cohort required mechanical ventilation, and anakinra did not affect the time to mechanical ventilation. There was also no significant difference between the 2 groups in the proportion of patients not requiring invasive mechanical ventilation up to day 15.

This study found that anakinra did not prevent the need for mechanical ventilation nor reduce the risk of mortality in hospitalized patients with severe COVID-19 pneumonia, compared to standard of care. “Although the primary and key secondary outcomes were not met,” the study authors concluded, “anakinra may have a role as an early treatment for patients with less-severe disease and inflammation.”

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