Early Use of Tocilizumab in Patients with Severe Pneumonia Secondary to SARS-CoV-2 Infection and Poor Prognostic Criteria: Impact on Mortality Rate and Intensive Care Unit Admission

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against interleukin-6, stands as an option treatment for COVID-19 patients presenting this inflammatory hyper-response. Methods: We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function and improvement of biochemical and haematological parameters were compared between cohorts. Findings: Most patients were male, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough and dyspnoea. 54·8% of patients from the tocilizumab group needed intubation, while in the control group 85·7% needed it. Treatment with tocilizumab significatively increased interleukin-6 levels, (554·45; CI 95% 186·69, 1032·93; p<0·05) while C-reactive protein mean levels were reduced (-108·19; CI 95% -140·15, -75·33; p<0·05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25·0% vs. 42·9%, p=0·021) and the number of ICU admissions (63·9% vs. 100·0%, p=0·021). 44·1% of patients treated with tocilizumab showed a favourable radiological evolution, when compared to 15·4% of patients from the control group. Interpretation: Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease. Funding Statement: Andalusian Public Foundation for Biosanitary Research in Eastern Andalusia - Alejandro Otero (FIBAO). Declaration of Interests: FMP has assisted to conferences and participated as speaker for Roche, Astra Zeneca, Incyte, and Celgene. MIST reports personal fees from Boehringer Ingelheim International Gmbh. All other authors declare no competing interests. Ethics Approval Statement: The study was classified as EPA-OD by the Spanish Agency of Medicines and Medical Devices (AEMPS) on May 8th 2020 and was approved by the Ethic Committee for Research with medicinal products of the province of Jaen on May 18th 2020.