Background: Patients with severe coronavirus disease 2019 (COVID-19) have elevated levels of acute phase reactants and inflammatory cytokines, including interleukin-6, indicative of cytokine release syndrome (CRS). The interleukin-6 receptor inhibitor tocilizumab is used for the treatment of chimeric antigen receptor T-cell therapyÀinduced CRS. Methods: Patients aged 18 years or older with laboratory-confirmed COVID-19 admitted to the Annunziata Hospital in Cosenza, Italy, through March 7, 2020, who received at least one dose of tocilizumab 162 mg subcutaneously for the treatment of COVID-19Àrelated CRS in addition to standard care were included in this retrospective observational study. The primary observation was the incidence of grade 4 CRS after tocilizumab treatment. Chest computed tomography (CT) scans were evaluated to investigate lung manifestations. Findings: Twelve patients were included; all had fever, cough, and fatigue at presentation, and all had at least one comorbidity (hypertension, six patients; diabetes, five patients; chronic obstructive lung disease, four patients). Seven patients received high-flow nasal cannula oxygen therapy and five received non-invasive mechanical ventilation for lung complications of COVID-19. No incidence of grade 4 CRS was observed within 1 week of tocilizumab administration in all 12 patients (100%) and within 2 days of tocilizumab administration in 5 patients (42%). The predominant pattern on chest CT scans at presentation was ground-glass opacity, air bronchograms, smooth or irregular interlobular or septal thickening, and thickening of the adjacent pleura. Follow-up CT scans 7 to 10 days after tocilizumab treatment showed improvement of lung manifestations in all patients. No adverse events or new safety concerns attributable to tocilizumab were reported. Interpretation: Tocilizumab administered subcutaneously to patients with COVID-19 and CRS is a promising treatment for reduction in disease activity and improvement in lung function. The effect of tocilizumab should be confirmed in a randomised controlled trial.

Introduction The fully-human monoclonal anti-interleukin (IL)-1β antibody canakinumab may inhibit the production of inflammatory mediators in patients with coronavirus disease 2019 (COVID-19) and the hyperinflammatory response potentially leading to acute respiratory distress syndrome. Objectives The goal of our retrospective, observational analysis was to evaluate the safety and efficacy of subcutaneous (s.c.) canakinumab in combination with our standard of care (SOC) treatment of selected patients with COVID-19 with respiratory failure and elevated reactive pro-inflammatory markers. Methods Eight participants received two doses of s.c. canakinumab 150 mg (or 2 mg/kg for participants weighing ≤40 kg) in addition to SOC. 12 patients received only SOC treatment. Results Canakinumab treatment reduced the need for mechanical ventilation and reduced proinflammatory markers, resulting in an amelioration of the final outcome, with respect to the control group who received SOC alone. The treatment was safe and well tolerated; no adverse events were reported. Conclusion The use of canakinumab (300 mg, s.c.) in the early stage of COVID-19 with mild-to-moderate respiratory failure was superior to SOC at preventing clinical deterioration and may warrant further investigation as a treatment option for patients with COVID-19 who experience a hyperinflammatory response in the early stage of the disease.

Oseltamivir is an orally administered antiviral medication that selectively inhibits the influenza neuraminidase enzymes that are essential for viral replication and it is active against both influenza A and B viruses. Oseltamivir is indicated for therapy or post-exposure prevention of influenza A and B. Side effects are uncommon and include mild nausea, gastrointestinal upset, dizziness, and headache. Despite widespread use, oseltamivir has not been associated with clinically apparent liver injury; however, there is growing evidence of possible toxic liver involvement during oseltamivir therapy. To the best of our knowledge, this is the first reported case in Italy linking the development of acute hepatitis and oseltamivir therapy, in a patient suffering from influenza H1N1 infection. We also present a review of the literature on cases of oseltamivir hepatotoxicity, through the consultation of PubMed database, the bibliographical references of various articles and an extensive search using Google. In view of the analyzed results, we suggest that experts should carefully consider the need for inclusion of potential serious liver reactions be added to the oseltamivir product label.

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