Abstract
Introduction/objectives: An interleukin-6 inhibition strategy could be effective in selected COVID-19 patients. The objective is to present our experience of tocilizumab use in patients with severe COVID-19.Methods: Observational retrospective cohort study. Hospitalized patients were evaluated by our multidisciplinary team for eventual use of tocilizumab. Patients with progressive ventilatory impairment and evidence of a hyperinflammatory state despite usual treatment received tocilizumab 8 mg/kg intravenous (maximum dose 800 mg), in addition to standard treatment. The use and time of use of mechanical ventilation (MV), the change of the Alveolar-arterial (A-a) gradient, of the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) and of inflammation laboratory parameters after 72 h of tocilizumab use was evaluated.Results: 29 patients received tocilizumab. 93.1% were men, 37.9% were obese, and 34.5% had hypertension. Of the 20 patients who were not on MV when receiving tocilizumab, 11 required non-invasive MV, for an average of 5 days, and one of them required intubation. A-a gradient, PaO2/FiO2, and inflammation parameters improved significantly. A better lymphocyte count, which improved significantly after tocilizumab use, was significantly associated with less use of MV. Five patients presented positive culture samples after tocilizumab, three being of clinical significance. A lower lymphocyte count was associated with having a positive culture. No other significant adverse events were seen.Conclusion: Our study suggests the utility and shows the safety of tocilizumab use in COVID-19 patients who have respiratory failure and evidence of hyperinflammation. Lymphocyte improvement was a predictor of good response.
Highlights
A better lymphocyte count, which improved significantly after tocilizumab use, was significantly associated with less use of mechanical ventilation (MV)
Patients hospitalized in Clínica Alemana, Santiago, Chile, with a diagnosis of COVID-19, for whom evaluation was requested by our multidisciplinary team for eventual tocilizumab use
Ventilatory Parameters A greater percentage improvement in the A-a gradient was significantly associated with a lower level of D-dimer when receiving tocilizumab, and a greater improvement in PaO2/FiO2 was associated with a higher level of erythrocyte sedimentation rate (ESR) and lower Ddimer at the time of receiving tocilizumab
Summary
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can lead to life-threatening respiratory symptoms [1].The pathogenesis of the disease is complex and not yet fully understood [2, 3], as a consequence of lytic viral infection macrophage activation, and immune cell recruitment to alveoli, a significant increase in the secretion of proinflammatory cytokines occurs, referred to as “cytokine release syndrome” (CRS) [4, 5].Different phases have been proposed in the course of this disease, stage I (mild) of early infection and active viral replication, stage II (moderate) of lung involvement without (IIa) or with hypoxia (IIb), where viral replication and local inflammation can coexist, and stage III (severe), with systemic hyperinflammation [6]. Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can lead to life-threatening respiratory symptoms [1]. The pathogenesis of the disease is complex and not yet fully understood [2, 3], as a consequence of lytic viral infection macrophage activation, and immune cell recruitment to alveoli, a significant increase in the secretion of proinflammatory cytokines occurs, referred to as “cytokine release syndrome” (CRS) [4, 5]. Different phases have been proposed in the course of this disease, stage I (mild) of early infection and active viral replication, stage II (moderate) of lung involvement without (IIa) or with hypoxia (IIb), where viral replication and local inflammation can coexist, and stage III (severe), with systemic hyperinflammation [6]. Tocilizumab is a humanized anti IL-6 receptor antibody approved for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis, and life-threatening cytokine release induced by chimeric-antigen receptor T-cell therapy [14]
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