ABSTRACT
Although many potent drugs have been used for cytokine storm, mortality is high for patients with coronavirus disease-2019 (COVID-19), which is followed up in the intensive care unit. Interferons (IFNs) are the major cytokines of the antiviral defense system released from many cell types. However, IFN-γ plays a key role in both primary and secondary cytokine storms. If the cytokine storm is not treated urgently, it will be fatal; therefore, it should be treated immediately. Anakinra, an interleukin-1 (IL-1) antagonist, tocilizumab, an IL-6 antagonist, and Janus kinase (JAK) inhibitors are successfully used in cytokine storm caused by COVID-19. However, sometimes, despite these treatments, the patient's clinical course does not improve. Emapalumab (Eb) is the human immunoglobulin G1 monoclonal antibody and is a potent and noncompetitive antagonist of IFN-γ. Eb can be life saving for cytokine storm caused by COVID-19, which is resistant to anakinra, tocilizumab, and JAK inhibitors.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , COVID-19 Drug Treatment , Cytokine Release Syndrome/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Neutralizing/pharmacology , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , COVID-19/epidemiology , COVID-19/immunology , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/immunology , Disease Progression , Drug Resistance, Viral , Humans , Interferon-gamma/antagonists & inhibitors , Interferon-gamma/immunology , Interleukin 1 Receptor Antagonist Protein/pharmacology , Interleukins/antagonists & inhibitors , Interleukins/immunology , Janus Kinase Inhibitors/pharmacology , RecurrenceABSTRACT
The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as 'cytokine storm'. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.