Rapid and Impressive Response to a Combined Treatment with Single-Dose Tocilizumab and NIV in a Patient with COVID-19 Pneumonia/ARDS

Abstract

Treatment of acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia (CARDS) represents a clinical challenge, requiring often invasive mechanical ventilation (IMV). Since the pathogenesis of CARDS it probably involves a direct viral attack to pulmonary and endothelium cells, and immune-mediated inflammation with dysfunctional coagulation, it was suggested to interfere with interleukin-6 (IL-6) activity by using the IL-6 receptor monoclonal antibody tocilizumab (TCZ). We reported the case of a 54-year-old 100 kg male COVID-19 patient (BMI 29) with severe respiratory insufficiency featuring dyspnea and hypoxia (SpO2 89% on room; PaO2 53 mmHg). Despite treatment with antiviral and non-invasive ventilation (NIV), after 24 h there was a progressive worsening of clinical conditions with higher fever (40 °C), increased dyspnea, and hypoxia (PaO2/FiO2 or P/F ratio of 150). The patient was at the limit to be sedated and intubated for IMV. He was treated with tocilizumab (8 mg/Kg i.v., single shot 800 mg) and NIV in the prone positioning. After only 96 h, the clinical, laboratory, and imaging findings showed incredible improvement. There was an important gain in oxygenation (P/F 300), a decrease of C-reactive protein values, and a decrease of the fever. Both the neutrophil-to-lymphocyte ratio (NLR) and the derived NLR ratio dropped down to 44%. Chest imaging confirmed the favorable response. This case suggested that for CARDS management efforts are needed for reducing its underlying inflammatory processes. Through a multiprofessional approach, the combination of IL-6-targeting therapies with calibrated ventilatory strategies may represent a winning strategy for improving outcomes.

A two-arm, randomized, controlled, multi-centric, open-label Phase-2 study to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19

“…Tocilizumab, an IL-6 inhibitor, used in rheumatoid arthritis, has been repurposed for use in COVID-19, and has also received emergency use authorization in India. However, it remains limited by the fact that it blocks only IL-6, has no T-cell mediated immunomodulation, and has a short duration of action due to its downstream point of action [30,[63][64][65][66][67][68]. Itolizumab has a broad immunological window being a CD6 inhibitor and is an option in the treatment of cytokine release syndrome in COVID-19 patients.…”

Recent Developments on Therapeutic and Diagnostic Approaches for COVID-19

“…The suppression of pro-inflammatory signaling pathways by monoclonal antibodies (tocilizumab, sirukumab, olokizumab, clazakizumab, etc.) as well as other inhibitors of inflammatory pathways (like baricitinib and ruxolitinib, which also inhibits clathrin-mediated endocytosis and therefore suppresses penetration of viruses into cells preventing infection) may be (and in some cases were) beneficiary on the advanced stages of COVID-19 (110)(111)(112)(113). Dapsone, colchicine, and olanzapine were also suggested for the prevention of COVID-19associated ARDS (114).…”

Clinical Management of COVID-19: A Review of Pharmacological Treatment Options

“…Similarly to anakinra and corticosteroids, TCZ has been employed as supportive therapy in COVID-19 to manage symptoms of hyper-inflammation and other immune responses. Several published case series and reports observed remarkable clinical responses following the use of TCZ in COVID-19 patients, including the clinical resolution of septic shock, reduction in the markers of inflammation, enhanced negative conversion, and reduced need for invasive mechanical ventilation [128][129][130][131][132][133][134][135][136][137][138][139].…”

“…Remarkable clinical improvement was observed only 4 days after TCZ administration. [130] TCZ; case report 36-year-old severe COVID-19 patient whose symptoms did not improve with HCQ and antiviral drugs. A single-dose TCZ was infused.…”