Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: A single-center cohort study

Abstract

Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-β (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO₂ ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia.

Keywords: COVID-19; SARS-CoV-2; immunomodulation; pneumonia; tocilizumab.

Figure 1

Patient status according to the 6‐point ordinal scale at different times following the administration of the first dose of TCZ (day 0). ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation; TCZ, tocilizumab

Figure 2

Evolution of vital signs following the administration of the first TCZ dose: (A) axillary temperature; (B) respiratory rate; (C) heart rate; and (D) SpO₂/FiO₂ ratio. *P < .05; **P < .01; ***P < .0001 (statistical test for repeated measures was used). SpO₂/FiO₂, pulse oximetry oxygen saturation/fraction of inspired oxygen; TCZ, tocilizumab

Figure 3

Evolution of laboratory values following the administration of the first TCZ dose: (A) lymphocyte count; (B) LDH level; (C) CRP level; and (D) D‐dimer level. *P < .05; **P < .01; ***P < .0001 (statistical test for repeated measures was used). CRP, C‐reactive protein; LDH, lactate dehydrogenase; TCZ, tocilizumab

Figure 4

Median variations (Δ) with 95% confidence intervals for vital signs and laboratory values between days 0 and 3 after the administration of the first TCZ dose in patients with and without clinical improvement at day 7: (A) axillary temperature; (B) respiratory rate; (C) heart rate; (D) SpO₂/FiO₂ ratio; (E) lymphocyte count; (F) LDH level; (G) CRP level; and (H) D‐dimer level. CRP, C‐reactive protein; LDH, lactate dehydrogenase; SpO₂/FiO_2, pulse oximetry oxygen saturation/fraction of inspired oxygen; TCZ, tocilizumab

Figure 5

Impact of patient status according to the 6‐point ordinal scale at day 0 on the clinical outcome by day 7 after the administration of the first tocilizumab dose. ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation