Itolizumab Treatment for Cytokine Release Syndrome in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: Clinical Outcomes, A Retrospective Study.

Background: Hyperinflammation, hypercoagulation and multi-organ dysfunction are life-threatening complications needing immediate attention in moderate-tosevere COVID-19 patients. We present our real world experience with Itolizumab, a repurposed immunomodulatory monoclonal antibody, administered in COVID-19 patients.

Methodology: Data from 25 confirmed moderate-to-severe COVID-19 patients, with high levels of pro-inflammatory markers and pulmonary function worsening on best supportive care and Itolizumab were included in this analysis. Patients requiring invasive mechanical ventilation were excluded. Clinical parameters (oxygen requirement) and laboratory parameters (ferritin, interleukin [IL]-6, C-reactive protein [CRP] and absolute lymphocyte count [ALC]) were studied preand post-treatment. Average total length of stay in hospital and ICU, percentage of patients requiring ICU admission and average time taken for weaning off oxygen for all patients were also reported.

Results: All Patients were in the range of 30-78 years of age, with majority being male (76%). Most prevalent comorbid conditions were diabetes (64%) and hypertension (28%). Median IL-6 value showed a decline by 85.4%. Significant reduction in median CRP (86.96%) and Ferritin (55.61%) was observed post- Itolizumab compared to pre-dose values. Median ALC improved from 1605 cells/ mm3 (pre-dose) to 2462.5 cells/mm3 (post-dose). Average recovery time, defined as time from Itolizumab infusion to discharge was 9.28 ± 4.04 days. Average duration of hospitalization and ICU admission was 14.24 ± 4.15 and 8.27 ± 4.47 days, respectively, with 76% patients recovered and discharged. Median oxygen saturation improved from 88 % (pre-dose) to 96 % (post-dose). All patients were weaned off oxygen within Avg + SD : 6.53 ± 2.09 days post-Itolizumab treatment. One and two point reduction in ordinal scale was observed in 88% and 76% patients, respectively. Three patients (12%) did not show improvement in ordinal sore of which two patients died because of complications due to pre-existing comorbidities. The all-cause mortality of 8%; was considered not related to Itolizumab. One infusion related event reported abated with infusion period extension.

Interpretation And Conclusion: A single dose of Itolizumab accelerated recovery in adult patients with COVID-19 by controlling immune hyperactivation. The clinical improvement was demonstrated by reduction in inflammatory markers, weaning off oxygen, reduced length of hospital stay and improvement of ordinal score. Itolizumab was well tolerated and when administered in the early phase of the inflammatory cascade is an efficient therapeutic option for treatment of cytokine release syndrome in moderate to severe COVID-19 patients.