Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study

Abstract

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400–800 mg or > 800 mg), either at the viral (1–7 days post-symptom onset), early inflammatory (8–15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37–4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4–15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400–800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Hyperhemolysis in a patient with sickle cell disease and recent SARS‐CoV‐2 infection, with complex auto‐ and alloantibody work‐up, successfully treated with tocilizumab

“…27 The timecourse for achieving measurable improvement after tocilizumab in COVID-19 has been reported as 5-6 days. 28,29 Alloimmunization is a common problem when transfusing patients with SCD. Only 35.2% of HHS episodes are associated with either a new alloantibody or new autoantibody.…”

Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis

“…Moreover, study methodology varied widely regarding both use of biomarkers as inclusion criteria and timing, indication and dose of re-injection, with restrospective data suggesting a variable treatment effect according to disease severity, timing and dosage of treatment. 11,12 Whether identifying a subset of responders, optimal timing or need for higher doses or re-injection would impact survival remains an important unresolved question.…”

“…Retrospective work has suggested that treatment response is variable depending both on illness severity but also on treatment modalities. 11,12 Fine tuning the subset of patients most likely to benefit from such therapies as well as the ideal timing of administration and dosage can only be achieved by a better understanding of their effect on the immune response.…”

Hyperhemolysis in the Setting of Mixed-Autoimmune Hemolytic Anemia: A Rare Complication of COVID-19

“…Also, increased interleukin-6 (IL-6) levels have been strongly associated with a shorter survival amongst patients suffering from SARS-CoV-2 [ 7 ]. The use of IL-6 inhibitors like tocilizumab has been considered since researchers have noted high concentrations of proinflammatory cytokines, such as IL-6 in severe SARS-CoV-2 infections [ 8 ]. It has also been shown to be effective in patients who develop hyperhemolysis in the setting of SCD [ 9 ].…”