Successful treatment of a critical COVID-19 patient with tocilizumab.

Dear editor,

Interleukin (IL)-6 has been suggested as one critical mediator in acute respiratory distress syndrome (ARDS) due to severe COVID-19. Given that antiviral agents with a confirmed therapeutic effect for COVID-19 remains lacking, anti-IL-6 antibody might confer an anti-inflammatory effect and improve clinical outcome.

A 44-year-old, previously healthy lady presented to the emergency department on 27 March 2020 due to fever, chills, and dry cough for a week. Physical examination revealed a body temperature of 37.7 °C and a respiration rate of 18/min with an oxygen saturation of 100% under nasal cannula with an oxygen flow at 3 L/min. She was soon diagnosed with COVID-19 using real-time reverse transcription-polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 from an oropharyngeal swab. Chest radiography was normal on day 1 and demonstrated poorly defined opacities in the left lower lung on day 4 (Fig. 1 a). On day 6, she remained febrile and dyspnea progressed. A complete blood count revealed a leukocyte count of 6930 cells/μL, a neutrophil-lymphocyte count ratio (NLCR) of 19, and a procalcitonin level of 0.04 ng/mL.

Figure 1

Chest radiographs and clinical course. a) A new pulmonary consolidation at the left lower lobe was noted on hospital day 4. b) The change of body temperatures, clinical laboratory tests, and fraction of inspired oxygen on mechanic ventilation before and after treatment with tocilizumab. Medications are shown at the top of the figure. BT: body temperatures; FiO2: fraction of inspired oxygen; hs-CRP: high sensitivity C-reactive protein; LDH: lactate dehydrogenase; MV: mechanic ventilation; NLCR: neutrophil-lymphocyte count ratio. c) On hospital day 10, bilateral multiple patches of consolidation and diffuse interstitial opacities were noted. d) On hospital day 29, marked resolution of bilateral consolidation was noted.

On hospital day 7, she developed respiratory failure requiring mechanical ventilation (detailed clinical course in Fig. 1b). On hospital day 10, chest radiography revealed multiple ground-grass opacities and bilateral patchy consolidations (Fig. 1c). Her arterial blood gas analysis showed an oxygen tension (PaO2) of 85.2 mm Hg under a fraction of inspired oxygen of 70% and a positive end-expiratory pressure of 10 cmH2O.

On hospital day 11, she was infused with 400 mg tocilizumab (a monoclonal antibody against IL-6 receptor). Two days later, her fever subsided and dyspnea improved along with improvement in laboratory data (Fig. 1b). Microbiological study of blood and sputum for common pathogens, and serological tests for Legionella pneumophila, Streptococcus pneumoniae and influenza virus were all negative.

On hospital day 29, her chest radiography revealed marked resolution of bilateral consolidation (Fig. 1d), and she was extubated. Results of RT-PCR testing for SARS-CoV-2 for three consecutive oropharyngeal and sputum samples, with each collected over 24 h apart, were negative. She was completely symptom-free on hospital day 32.

A recent systematic review and meta-analysis of six studies comprising 1302 COVID-19 patients indicated that the mean IL-6 concentration were 2.9-fold higher in complicated cases (95% confidence interval [CI], 1.17–7.19) than that in uncomplicated cases, implying that tocilizumab, an IL-6 receptor antibody, may be an efficacious treatment. Our report is consistent with an earlier French report where patients were treated successfully with two courses of tocilizumab. In addition, a retrospective study reported that 19 of 21 severe COVID-19 patients receiving tocilizumab experienced clinical improvements in respiratory function, rapid defervescence, and successful discharge without serious adverse events.

In conclusion, tocilizumab might improve the outcome for COVID-19 patient and is well-tolerated. Ongoing clinical trials, like TOCIBRAS, COVIRL002, TOC-COVID and COV-AID, are warrant to confirm the therapeutic efficacy of the tocilizumab in COVID-19 patients.

Authors' contributions

Manuscript writing and figure: Shih-Ming Tsao, Jann-Yuan Wang.

Study design: Yuan-Ti Lee, Yi-Wen Huang.

Data collection: Shih-Ming Tsao, Chien-Feng Li, Ming-Chang Hsieh, Yao-Tung Wang.

Data analysis and interpretation: Kuei-Chuan Chan, Hui-Hsien Pan, Yuan-Ti Lee.

Manuscript revision: Jann-Yuan Wang, Yuan-Ti Lee, Yi-Wen Huang.

Declaration of competing interest

The authors have no conflicts of interest relevant to this article.