Sarilumab Administration in COVID-19 Patients: Literature Review and Considerations

Abstract

Two years have passed since WHO declared a pandemic state for SARS-CoV-2 infection. COVID-19 pathogenesis consists of a first viral phase responsible for early symptoms followed by an inflammatory phase, cytokine-mediated, responsible for late-onset manifestations up to ARDS. The dysregulated immune response has an outstanding role in the progression of pulmonary damage in COVID-19. IL-6, through the induction of pro-inflammatory chemokines and cytokines, plays a key role in the development and maintenance of inflammation, acting as a pioneer of the hyperinflammatory condition and cytokine storm in severe COVID-19. Therefore, drugs targeting both IL-6 and IL-6 receptors have been evaluated in order to blunt the abnormal SARS-CoV-2-induced cytokine release. Sarilumab, a high-affinity anti-IL-6 receptor antibody, may represent a promising weapon to treat the fearsome hyperinflammatory phase by improving the outcome of patients with moderate-to-severe COVID-19 pneumonia. Further prospective and well-designed clinical studies with larger sample sizes and long-term follow-up are needed to assess the efficacy and the safety of this therapeutic approach to achieve improved outcomes in COVID-19.

Keywords: COVID-19; IL-6; IL-6R; cytokines; sarilumab.

Figure 1

The potential role of IL-6 receptor antagonization by sarilumab in SARS-CoV-2-induced cytokine release syndrome (CRS)-like syndrome. After SARS-CoV-2 infection, immune cells release cytokines, including IL-6. IL-6 can either attach to its respective membrane-bound receptor (mIL-6R) or soluble receptor (sIL-6R), which activates JAK/STAT pathways. The different signaling modalities, including cis-signaling, trans-signaling, and trans-presentation are reported. Abbreviations: gp130, glycoprotein 130; IL-6, interleukin-6; JAK, Janus family tyrosine kinase; mIL-6R, membrane-bound interleukin-6 receptor; sIL-6R, soluble interleukin-6 receptor; STAT, signal transducer and activator of transcription; P, phosphoryl group. Illustrations use elements from Servier Medical Art (https://smart.servier.com/, accessed on 10 April 2022).