Outcomes and biomarker analyses among patients with COVID-19 treated with interleukin 6 (IL-6) receptor antagonist sarilumab at a single institution in Italy

Abstract

BackgroundThe inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing.Study descriptionIn this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Among 10 patients whose symptoms improved after sarilumab treatment, rapid decreases in CRP levels corresponded with clinical improvement. Lower levels of IL-6 at baseline as well as lower neutrophil to lymphocyte ratio as compared with patients whose COVID-19 did not improve with treatment were associated with sarilumab-responsive disease.ConclusionsThis observation may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 and that CRP could be a potential biomarker of response to treatment.

Cognitive impact of COVID-19: looking beyond the short term

“…There are also elevated levels of pro-inflammatory cytokines, sometimes marked (a so-called cytokine storm). Convalescent plasma [236] and plasma exchange [237,238] improve survival rates in severe disease, and immunomodulatory therapies such as tocilizumab, a monoclonal antibody against the IL-6 receptor [239], and sarilumab, an IL-6 receptor antagonist [240], may offer protection and are currently undergoing clinical trials. Neutralising antibodies targeting other pro-inflammatory cytokines (IL-1, IL-17) may also offer protection, as too may potential inhibitors of complement system activation.…”

Controlling Cytokine Storm Is Vital in COVID-19

“…In addition, IL-6 blockade with tocilizumab does not impair the viral specific antibody responses despite of a delayed viral clearance driven by a higher initial viral load, indicating the safety of tocilizumab in patients with COVID-19 (82). Sarilumab is another kind of IL-6R blocker that is being investigated in SARS-CoV-2 infection (83, 84), which may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 (85).…”

A comprehensive review on sarilumab in COVID-19

“…In Montesarchio et al [62] retrospective case series of 15 patients with laboratory-confirmed SARS-CoV-2 infection, the oxygen saturation of patients at rest under the ambient air was equal or less than 93%, or they required oxygen therapy or mechanical ventilation. Twelve patients received a single SC injection of 400 mg sarilumab, and three received two doses within 24 hours.…”

“…Timely administration of immunomodulatory drugs in covid-19 is a concern that should be taken into attention; for example, Wang et al [63] showed that early IFN-α 2b therapy reduced in-hospital mortality; whereas, late administration of IFN was associated with increased mortality and delayed recovery. Furthermore, it is important to note that all patients who died in Montesarchio et al [62] study were under invasive or noninvasive mechanical ventilation. Notably, patients who died or those nonresponsive to sarilumab had statistically higher baseline levels of IL-6 compared to those who did well, likely due to an advanced cytokine storm syndrome and suggesting that early intervention with sarilumab could prevent patients with COVID-19 from progressing to intensive care support.…”