Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia

Abstract

Background: Pneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients' mortality.

Methods: 85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care.

Results: Patients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported.

Conclusions: Tocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.

Keywords: COVID-19; Pneumonia; Respiratory failure; Retrospective study; SARS-cov-2; Tocilizumab.

Fig. 1

Kaplan- Meier survival curves for Tocilizumab and control groups. HR = Hazard Ratio; C.I. = Confidence Intervals. Multivariate HR is adjusted for baseline variables (age, gender, comorbidities as diabetes, hypertension and heart disease) and serum PCR at admission.

Fig. 2

Detailed longitudinal follow up for patients whose observation is still ongoing. Green bar = improved clinical condition as described in methods; White bar = stable clinical condition; Red bar = worsened clinical condition as described in methods. Asterisk (*) denote each patient who is submitted to mechanical ventilation at the last follow up. On the left side is reported the clinical condition of each patient ad admission. T = Tocilizumab group; SC = standard care control group; Low SpO2 = Low peripheral capillary oxygen saturation; AA = Ambient Air; LFrs = low flow respiratory support (nasal cannula); HFrs = high flow respiratory support (mask); CPAP = Continuous Positive Airway Pressure. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)