Safety of intravenous anakinra in COVID-19 with evidence of hyperinflammation, a case series

Abstract

Objectives Anakinra is a selective IL-1 inhibitor, which has been used in the context of secondary haemophagocytic lymphohistiocytosis. Although usually given in the s.c. form, previous anecdotal reports have emphasized its utility when given i.v. Our aim is to report our experience on the beneficial effects of anakinra i.v. in patients with SARS-CoV-2 and evidence of hyperinflammation. Methods We report four patients with severe COVID-19 infection requiring intensive care admission and ventilatory support. Results All four patients showed evidence of deterioration, with hyperferritinaemia and increasing oxygen requirements and with superadded bacterial infections. Upon commencement of anakinra i.v., there was subsequent improvement in the patients clinically, with reduction in ventilatory support and inotropic support, and biochemically, with rapid improvement in inflammatory markers. Conclusion Anakinra is safe to use i.v. in patients with COVID-19 and evidence of superadded bacterial infection. Although its utility has not been confirmed in a randomized trial, current research in the COVID-19 pandemic aims to establish the utility of immunosuppression, including IL-1 blockade, on the outcomes of patients with moderate to severe disease. Our case series supports its use in patients with severe, life-threatening COVID-19 and evidence of hyperinflammation.

Current evidence on the use of anakinra in COVID-19

“…Case series of COVID-19 patients who received anakinra after clinical deterioration, mechanical ventilation, and late after symptoms onset showed controversial results as is shown in Table 2 [47] , [48] , [49] . In a case series by Dimopoulos et al, anakinra administration in severe COVID-19 patients who were mostly intubated improved respiratory function.…”

The COVID-19 Treatment Landscape: A South African Perspective on a Race Against Time

“…The pro-inflammatory effects of IL-1 are mitigated by the binding of IL-1 receptor agonists such as anakinra to the IL-1 receptor (123). Preliminary results indicate control of inflammation in a few severe COVID-19 cases (124)(125)(126)(127)(128), notably reducing mortality and the need for mechanical ventilation (129)(130)(131)(132)(133). As of 12 January 2021, 28 clinical trials registered on clinicaltrials.gov were recruiting patients for the use of anakinra to treat severe to critical COVID-19 patients.…”

Therapeutic role of immunomodulators during the COVID-19 pandemic– a narrative review

“…Data seem to consistently show the ability of anakinra to alleviate hyperinflammation in critical COVID-19 cases, with reported effects on CD4 count [ 136 ], fever, ferritin plasma levels, as well as other clinical parameters [ 142 , 143 ] and inflammatory markers [ 144 , 145 ]. This was observed even in patients with evidence of superadded bacterial infection [ 146 ]. Anakinra addition to standard of care could also improve survival and decrease the need for mechanical ventilation and oxygen supplementation in severe COVID-19 cases [ 143 , 144 , 147 ].…”