**2.7 Tocilizumab**

Tocilizumab is an Interleukin-6 (IL-6) Receptor inhibiting monoclonal antibody. Studies have shown that infection with the SARS virus leads to a cytokine storm with the release of inflammatory cytokines like IL-6, Tumor Necrosis Factor- α (TNF –α), and IL-12 [49]. Further research done on MERS-CoV showed IL-6, IL-1β, and IL-8 were elevated in these patients. In patients with confirmed COVID-19 infection who were admitted to ICU, levels of IL-2, IL-6, IL-7, IL-10, granulocyte-colony stimulating factor (G-CSF), interferon-γ-inducible protein (IP10), monocyte chemoattractant protein (MCP1), macrophage inflammatory protein 1 alpha (MIP1A), and TNF-α levels were found to be high, suggesting possible cytokine storm [50]. The first trial involving tocilizumab was performed in China in February 2020. The National Institute for Infectious disease had recommended tocilizumab in moderate to severe infections and IL-6 levels >40 pg/mL (or D-dimer levels >1000 ng/mL). However, it is not recommended by the CDC. In an RCT published in JAMA, in moderate-to-severe pneumonia, tocilizumab did not reduce the WHO Clinical Progression Scale scores. The proportion of patients with non-invasive or invasive ventilation or death at day 14 was 36% with usual care and 24% with tocilizumab. There were no differences in 28 days mortality. This meant tocilizumab could decrease the requirement for mechanical and non-invasive ventilation or death by day 14 but not mortality by day 28 [51, 52]. An RCT published by NEJM in October 2020, which included patients fulfilling at least two of the following: fever, pulmonary infiltrates, or the need for oxygen therapy to maintain oxygen saturation more than 92%, concluded that tocilizumab was not effective in preventing intubation or death in moderately ill hospitalized patients with Covid-19 [53]. Sarilumab, another IL-6 receptor antagonist was being tested in a multicentre trial for hospitalized patients with severe COVID-19 [54]. It was concluded that at 28 days, clinical improvement and mortality in severe COVID-19 were not significantly different between sarilumab and standard of care [55]. Preliminary results from the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) were released in a non-peer-reviewed report. REMAP-CAP is the largest trial to date investigating the use of IL-6 inhibitors in COVID-19. In February 2021, after reviewing the evidence from REMAP-CAP and other trials, the NIH Panel revised the recommendations on the use of tocilizumab and sarilumab, stating there was insufficient data to recommend either for or against the use of these drugs. But given the REMAP-CAP trial, some members suggested administering a single dose of tocilizumab (8 mg/kg of actual body weight, max 800 mg) in addition to dexamethasone in the ICU patients having high oxygen requirements/invasive and non-invasive mechanical ventilation and exhibiting rapid progression of respiratory failure [56]. The number of patients receiving sarilumab in the REMAP-CAP trial was too low to assess the efficacy.
