CIGB-814

COVID-19 may predispose patients to thrombotic disease, both in venous and arterial circulation, due to excessive inflammation, endothelial dysfunction, platelet activation, and many other prothrombotic factors such as tissue injury, decrease of natural anticoagulants, and stasis.Despite the use of antiviral, anti-inflammatory drugs, anticoagulant therapy, and even invasive mech. ventilation, many patients progress to a critical stage, characterized by acute respiratory distress syndrome (ARDS) and shock.We describe here two patients, in whom thrombolysis using recombinant streptokinase was used to treat refractory hypoxemia after suspecting pulmonary micro- and macro-thrombotic disease.

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.