Tocilizumab therapy for severely-ill COVID-19 pneumonia patients: a single-centre retrospective study.

ABSTRACT

Systemic hyperinflammation is a hallmark of severe coronavirus disease-2019 (COVID-19). Tocilizumab (TCZ) (an interleukin-6 receptor blocker) therapy is currently used as an anti-inflammatory intervention alongside corticosteroids to modulate the hyperinflammatory response (cytokine storm) in hospitalized patients with severe COVID-19 to prevent mortality. There is, however, a wide uncertainty about its pros and cons in patients with COVID-19, particularly, its possible immunosuppressive effect is of serious concern for the clinicians. The present study aimed to report response of a cohort of severely-ill hospitalized COVID-19 pneumonia patients who were treated with tocilizumab after the initial corticosteroids therapy failed to improve the patients' clinical condition. This was a single-arm retrospective study of 100 severely-ill COVID-19 pneumonia patients who were admitted to the specialized COVID-19 units of Mayo Hospital, Lahore, Pakistan from March 12, 2020, to May 25, 2021. These COVID-19 patients had progressed to cytokine storm with persistent hypoxia, associated with pneumonia, and markedly elevated serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, and ferritin. All the patients had received two separate doses of intravenous 400 mg (4 mg/kg) tocilizumab with an 8-hour interval alongside standard COVID-19 care which includes corticosteroid, antibiotics, and anticoagulants. Following tocilizumab intervention, 75 (75.0%) patients showed clinical improvement, continued to recover, and were safely discharged from the hospital, while in 25 (25.0%) patients, TCZ failed to prevent clinical deterioration, and patients eventually died in the hospital. Amongst the 25 (25.0%) deaths, 8 (32.0%) patients had a single comorbidity, while 9 (36.0%) had two or more comorbidities. The median IQR age for survivors was 57.0 (50.0, 60.0) years, and non-survivors was 60.0 (55.0, 70.0) years; and the period of hospitalization was 25 (20, 40) days and 20 (14, 34) days, respectively. Tocilizumab treatment improved serum inflammatory biomarker levels including CRP, D-dimer, and ferritin, by almost a similar magnitude in both survivors and non-survivors. Development of secondary infections were reported in 25 (25.0%) patients, including 21% patients with bacterial (Pseudomonas, Klebsiella, Acinetobacter) and 4% with fungal (Aspergillus) infection. The emergence of secondary infection was higher in patients who died (72.0%) as compared to those who survived (28.0%). In conclusion: in low- and middle-income countries in the presence of limited therapeutic options, a timely intervention of TCZ alongside corticosteroids may be a suitable anti-inflammatory therapy for severely-ill hospitalized COVID-19 pneumonia patients to prevent mortality. However, patients must be closely monitored for secondary bacterial/fungal infections. Early diagnosis and management of secondary infection can reduce morbidity and mortality.