ABSTRACT
Hyperinflammation distinguishes COVID-19 patients who develop a slight disease or none, from those progressing to severe and critical conditions. CIGB-258 is a therapeutic option for the latter group of patients. This drug is an altered peptide ligand (APL) derived from the cellular stress protein 60 (HSP60). In preclinical models, this peptide developed anti-inflammatory effects and increased regulatory T cell (Treg) activity. Results from a phase I clinical trial with rheumatoid arthritis (RA) patients indicated that CIGB-258 was safe and reduced inflammation. The aim of this study was to examine specific biomarkers associated with hyperinflammation, some cytokines linked to the cytokine storm granzyme B and perforin in a cohort of COVID-19 patients treated with this peptide. All critically ill patients were under invasive mechanical ventilation and received the intravenous administration of 1 or 2 mg of CIGB-258 every 12 h. Seriously ill patients were treated with oxygen therapy receiving 1 mg of CIGB-258 every 12 h and all patients recovered from their severe condition. Biomarker levels associated with hyperinflammation, such as interleukin (IL)-6, IL-10, tumor necrosis factor (TNF-α), granzyme B, and perforin, significantly decreased during treatment. Furthermore, we studied the ability of CIGB-258 to induce Tregs in COVID-19 patients and found that Tregs were induced in all patients studied. Altogether, these results support the therapeutic potential of CIGB-258 for diseases associated with hyperinflammation. Clinical trial registry: RPCEC00000313.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19 Drug Treatment , Chaperonin 60/therapeutic use , Cytokine Release Syndrome/drug therapy , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents/chemistry , COVID-19/blood , COVID-19/complications , Chaperonin 60/chemistry , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/complications , Female , Humans , Inflammation/blood , Inflammation/complications , Inflammation/drug therapy , Interleukin-10/blood , Interleukin-6/blood , Male , Middle Aged , SARS-CoV-2/drug effects , T-Lymphocytes, Regulatory/drug effects , Tumor Necrosis Factor-alpha/blood , Young AdultABSTRACT
Severe acute respiratory syndrome-related coronavirus 2 infection has been associated with Guillain-Barré syndrome. We investigated here the potential mechanism underlying the virus-induced damage of the peripheral nervous systems by searching the viral amino acid sequence for peptides common to human autoantigens associated with immune-mediated polyneuropathies. Our results show molecular mimicry between the virus and human heat shock proteins 90 and 60, which are associated with Guillain-Barré syndrome and other autoimmune diseases. Crucially, the shared peptides are embedded in immunoreactive epitopes that have been experimentally validated in the human host.