Immune-related adverse events of biological immunotherapies used in COVID-19

Abstract

The use of biological immunotherapeutic drugs is one of the options currently being evaluated and employed to manage COVID-19, specifically monoclonal antibodies, which have shown benefit by regulating the excessive immune response seen in patients with severe infection, known as a cytokine storm. Tocilizumab has received particular importance for this clinical application, as has sarilumab. Both drugs share a substantial similarity in terms of pharmacodynamics, being inhibitors of the interleukin six receptor (IL-6Rα). Furthermore, sotrovimab, a neutralizing anti-SARS CoV-2 antibody, has gained the attention of the scientific community since it has recently been authorized under certain circumstances, positioning itself as a new therapeutic alternative in development. However, despite their clinical benefit, biological immunotherapies have the potential to generate life-threatening immune-related adverse events. Therefore it is essential to review their incidence, mechanism, and risk factors. This review aims to provide a comprehensive understanding of the safety of the biological immunotherapeutic drugs currently recommended for the treatment of COVID-19, provide a review of the known immune-mediated adverse events and explore the potential immune-related mechanisms of other adverse reactions.

Lung microbiome and origins of the respiratory diseases

“…Thus, some of biological immunotherapies, mainly monoclonal antibodies, have been evaluated aiming at regulating the excessive immune response seen in SARS-CoV-2 patients with severe infection. The two classes of IL-6 inhibitors, the monoclonal antibodies against the IL-6 receptor, including sarilumab, tocilizumab, clazakizumab, olokizumab and the anti-IL-6 monoclonal antibody siltuximab, were investigated in various clinical trials and no clear beneficial were found ( Baracaldo-Santamaría et al, 2022 ). In addition, it was reported that the treatment with these antibodies caused acute pneumonitis, idiopathic pulmonary fibrosis, and exacerbation of rheumatoid arthritis-associated interstitial lung disease in a fraction of patients.…”

Treatment of the cytokine storm in COVID-19: review of clinical pharmacology

“…Tocilizumab is a recombinant human monoclonal antibody, while sarilumab is a recombinant human IgG1 antibody. Both therapies function through the same mechanism of action, which involves targeting the IL-6 receptor protein responsible for immune systeminduced inflammation and inhibiting the IL-6 signaling pathway [117].…”

“…Furthermore, a study conducted by Soin et al comparing the tocilizumab group to the standard care group in terms of COVID-19 development on day 14 revealed additional adverse reactions associated with tocilizumab. These adverse reactions encompassed anaphylactic reactions, anaphylactic shock, renal failure, pulmonary fibrosis, drug-induced liver injury, pancreatitis, pancytopenia, serious infections, and hypersensitivity reactions [117,128].…”

Role of SARS-CoV-2-induced cytokine storm in multi-organ failure: Molecular pathways and potential therapeutic options

“…Other adverse effects include interstitial lung disease [342] , hepatic disorders [343] , and immunogenicity to the drug [344] . Common adverse events of siltuximab are pruritus, hypertension, nausea, vomiting, fatigue, and neutropenia [345] , [346] . Hyperlipidemia, cellulitis, and more severe events like urinary retention, polycythemia, leukopenia, lymphopenia, and hypersensitivity reactions were reported with the administration of siltuximab [345] , [346] , [347] .…”

“…Common adverse events of siltuximab are pruritus, hypertension, nausea, vomiting, fatigue, and neutropenia [345] , [346] . Hyperlipidemia, cellulitis, and more severe events like urinary retention, polycythemia, leukopenia, lymphopenia, and hypersensitivity reactions were reported with the administration of siltuximab [345] , [346] , [347] . Increased risk of infections and cancer, hematologic effects, headache, joint pains, anaphylaxis, skin conditions, abdominal pains, and diarrhea are mentioned as adverse effects of anakinra [348] , [349] .…”