COVID-19 ARDS MANAGEMENT IN AN INTENSIVE CARE WARD USING ANTI-CD6 MONOCLONAL ANTIBODY: A CASE SERIES

Background: Covid-19 ARDS is a common presentation in the emergency ward and needs quick assessment and treatment. Material and Methods: This case series was aggregated from patients admitted to the emergency ward, with a diagnosis of mild to moderate ARDS with impending cytokine release syndrome (CRS). Results: These 10 patients were treated with antiCD6 monoclonal antibody, Itolizumab as it had been given emergency use approval for critically ill patients on CRS. Of the 10 patients, 8 received Itolizumab on day 2 while 2 received it on day 1. Nine out of ten patients recovered and were discharged, while one patient died. Patients' progress was monitored by daily evaluation of patients' CRP and cytokine (IL-6) levels, LDH, and clinical and radiological assessment. All 10 patients were observed for oxygen delivery parameters including days of ventilation support, and total oxygen delivery. Conclusion: The administration of antiCD6 monoclonal antibody, itolizumab early has shown to reduce the duration of ventilation support to 5.4 days, total oxygen requirements to 12 days, and hospital stay to 13.3 days. [ FROM AUTHOR] Copyright of Journal of Cardiovascular Disease Research (Journal of Cardiovascular Disease Research) is the property of Journal of Cardiovascular Disease Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Comparison of the efficacy of tocilizumab and itolizumab for the treatment of severe COVID-19: a retrospective cohort study

Introduction: Itolizumab, a CD6 inhibitor has been found to be effective in COVID-19 in some studies [1] but there is no randomised controlled trial at present to prove its effectiveness. Method(s): The study population was adults (> 18 years) with severe COVID-19 pneumonia admitted in the ICU who received either tocilizumab or itolizumab in their course of stay in ICU. The primary outcome of the study was a clinical improvement (CI). The secondary outcomes were time for clinical improvement, improvement in PO2/ FiO2 ratio, best PO2/ FiO2 ratio, need for mechanical ventilation (MV) after administration of study drugs, time to discharge and survival days. Result(s): 126 patients were included in the study;92 received tocilizumab, and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was statistically non-significant. The time to CI was also non-significant between the tocilizumab and itolizumab groups (median 12 vs 11 days). The number of days required to achieve the improvement of 100 in the PO2/ FiO2 ratio was significantly less with itolizumab as compared to tocilizumab. (6 vs 8 days, p value = 0.028). The best PO2/ FiO2 ratio achieved was also significantly better with itolizumab as compared to tocilizumab (315 vs 250, p value = 0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab as compared to tocilizumab (14.7 vs 3.26%). The estimated median time for CI was 12 days and 11 days in the tocilizumab and itolizumab groups, respectively and was non-significant (log-rank p value = 0.262) (Fig. 1). Conclusion(s): The clinical improvement and survival rates with itolizumab are similar to tocilizumab. Better oxygenation can be achieved with itolizumab and can be a substitute for tocilizumab in managing severe COVID-19 infection.

REcovery and SURvival of patients with moderate to severe acute REspiratory distress syndrome (ARDS) due to COVID-19: a multicenter, single-arm, Phase IV itolizumab Trial: RESURRECT.

BACKGROUND: Itolizumab, an anti-CD6 monoclonal antibody, down-regulates COVID-19-mediated inflammation and the acute effects of cytokine release syndrome. This study aimed to evaluate the safety and efficacy of itolizumab in hospitalized COVID-19 patients with PaO2/FiO2 ratio (PFR) ≤200 requiring oxygen therapy. RESEARCH DESIGN AND METHODS: This multicenter, single-arm, Phase 4 study enrolled 300 hospitalized adults with SARS-CoV-2 infection, PFR ≤200, oxygen saturation ≤94%, and ≥1 elevated inflammatory markers from 17 COVID-19 specific tertiary Indian hospitals. Patients received 1.6 mg/kg of itolizumab infusion, were assessed for 1 month, and followed-up to Day 90. Primary outcome measures included incidence of severe acute infusion-related reactions (IRRs) (≥Grade-3) and mortality rate at 1 month. RESULTS: Incidence of severe acute IRRs was 1.3% and mortality rate at 1 month was 6.7% (n = 20/300). Mortality rate at Day 90 was 8.0% (n = 24/300). By Day 7, most patients had stable/improved SpO2 without increasing FiO2 and by Day 30, 91.7% patients were off oxygen therapy. Overall, 63 and 10 patients, respectively, reported 123 and 11 treatment-emergent adverse events up to Days 30 and 90. No deaths were attributable to itolizumab. Patient-reported outcomes showed gradual and significant improvement for all five dimensions on EQ-5D-5L. CONCLUSION: Itolizumab demonstrated acceptable safety with a favorable prognosis in hospitalized COVID-19 patients. CLINICAL TRIAL REGISTRATION: CTRI/2020/09/027941 (Clinical Trials Registry of India).

Comparative study of tocilizumab versus itolizumab in coronavirus disease 2019-infected patients: a randomized controlled trial

Objective We aimed to compare the effect of tocilizumab and itolizumab in terms of PaO2/FiO2 ratio (P/F ratio), interleukin 6 (IL-6) level, serum ferritin, C-reactive protein, and a reduction in mortality. Our primary objective was to compare P/F ratio at various time intervals: baseline (before administering the drug), 12 h after drug administration, once a day for the next 7 days, and on the 14th day. Our secondary objective was to evaluate serum level of biomarkers like IL-6, ferritin, and C-reactive protein before start of drug infusion and following drug infusion at 72 h and on 7th day. Patients and methods A total of 50 patients, age between 18 and 60 years, having moderate Acute Respiratory distress syndrome (ARDS) following coronavirus disease 2019 infection were recruited. Patients of group I received a single dose of injection of tocilizumab 8 mg/kg intravenously (i.v.) via infusion over 1–2 h. Group II patients received premedication with hydrocortisone 100 mg and pheniramine 30 mg and a single dose of injection itolizumab 1.6 mg/kg dissolved in 250 ml of 0.9% normal saline infusion over 5–6 h. Results We observed significantly higher P/F ratio in the itolizumab group (239.18±97.31) than in the tocilizumab group (104.87±75.25) on the 3rd day following drug administration (P<0.001). Similarly, the IL-6 level was lower in the itolizumab group (72±100) in comparison with the tocilizumab group (682±1360), and the differences were statistically significant (P<0.05). We identified adverse effects of the drugs in 10 patients who have received itolizumab. Conclusion We observed an increasing trend in P/F ratio on the 3rd day following itolizumab administration in comparison with tocilizumab, and the difference was statistically significant (P<0.001).

Pharmacological treatment of COVID-19: an opinion paper.

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.

Comparison of the Efficacy of Tocilizumab and Itolizumab for the Treatment of Severe Covid-19: A Retrospective Cohort Study

Aim and background: Alcohol intoxication can complicate detection and timely management of poisoning. Case report: A 52-year-old male was found unconscious at home following heavy alcohol drinking. He presented in emergency department in the gasping state, with hypoglycemia and un-recordable BP. He had tension pneumothorax which was managed accordingly and put into mechanical ventilation, resuscitated with fluids and dextrose. However, in view of persistent hemodynamic instability needing triple inotropes, refractory hypoxemia with cyanosis on a mechanical ventilator and dark brown colored blood co-oximetry was done which showed severe methemoglobinemia. Patient was treated with intravenous methylene blue which led to a dramatic recovery. The inciting event came out to be the ingestion of paintthinner liquid under the influence of alcohol. Conclusion: We report a case of severe methemoglobinemia due to paint-thinner ingestion. High index of suspicion and timely management with methylene blue can save patients of severe methemoglobinemia.

Immunomodulator Therapy in Severe COVID-19 Pneumonia with Respiratory Failure During the Second Wave of the Pandemic: A Retrospective Analysis

Aim and background: Severe COVID-19 pneumonia can be lifethreatening with a high mortality, largely due to an uncontrolled systemic hyperinflammatory response, generally referred to as cytokine storm. Tempering the immune response with immunomodulators has been considered as a potential therapeutic option. Except for a few, data on the effectiveness of different immunomodulating drugs are scarce and are limited to a few case reports and retrospective observational-cohort studies. Additionally, in the pandemic due to shortages, various immunomodulators were used with limited data on their effectiveness. This study looks at various immunomodulators used in the 2nd wave of COVID-19, and their impact on outcomes. Materials and methods: Retrospective analysis of 124 patients with severe COVID-19 disease who were treated with immunomodulators. The study population included patients above 18 years of age with confirmed COVID-19 admitted to ICU with severe pneumonia. All patients received standard of care treatment at the time of hospital admission according to the hospital protocols and updated data on treatment of COVID-19. Patients were considered eligible for immunomodulatory treatment if they showed rapidly worsening hypoxia and elevated inflammatory markers, as per standard recommendations. Immunomodulators were administered depending on the availability of specific agents at time of treatment. The immunomodulators used were tocilizumab, itolizumab, bevacizumab, pulse dose steroid with methylprednisolone and baricitinib. Results: 124 patients were treated with immunomodulators, 45 (36.3%) of them survived, and 79 (63.7%) passed away. Mean age in survivors was 48.2, and in non-survivors was 54.8, which was statistically significant. Diabetes and hypertension were the most common comorbidities observed. 97/124 patients (78.2%) received immunomodulator therapy within 48 hours of ICU admission, out of which 41 (42.2%) recovered and 56 (57.7%) passed away. 21/124 (21.8%) patients received immunomodulators after 48 hours of admission, and had a high mortality with only 3 (14.2%) recovering and 18 (85.7%) dead. There was a significant reduction in CRP levels post immunomodulator therapy among survivors compared to nonsurvivors. The mean invasive ventilator days were 4.27 and there was a significant difference among survivors and non-survivors. Among survivors (45) in our study, we found that immunomodulator therapy was seen to avoid mechanical ventilation in severe COVID patients (33) who received immunomodulator therapy early within 48 hours of ICU admission as seen by the improvement on a 7-point ordinal scale. The mean ventilator days for patients who received immunomodulator therapy after intubation were also reduced. Most common adverse events were found with itolizumab administration. Secondary infections were more in non-survivors and secondary bacterial pneumonia was the commonest. Conclusion: Our descriptive study showed that the early administration(<48 hours) of various immunomodulators reduced the need for ventilation and the number of ventilator days, compared to administration after 48 hours. There was an increased incidence of secondary bacterial infections among the non-survivors.

Sudden cardiac death in a case of Crohn's disease with COVID-19: A case report

Rationale: The mechanism of sudden cardiac death in COVID-19 can be multifactorial. Cardiac hypersensitivity to 5-ASA therapy leading to myocarditis has been reported in some cases. Cytokine storm syndrome and idiosyncratic reaction with mesalazine use may lead to sudden cardiac death in COVID-19. Use of immunosuppressants in hospitalized COVID-19 patients should be continued with caution, especially in patients with inflammatory bowel disease. Patient's concern: A 75-year-old man who was tested positive for SARS-CoV-2 was admitted with a history of shortness of breath for the last two days. He was a known case of Crohn's disease treated with mesalazine. Diagnosis: COVID-19 pneumonia with underlying Crohn's disease leading to sudden cardiac death. Intervention: Remdesivir, antibiotics, steroids, low molecular weight heparin, tablet zinc, tab vitamin C, and other supportive treatment were started. Because of increased inflammatory markers, itolizumab was given to the patient on the 2nd day. Outcome: On the 5th day of the intensive care unit, the patient complained of sudden chest pain with respiratory distress leading to bradycardia and asystole and could not be resuscitated. Lessons: Causes for sudden cardiac death in COVID-19 pneumonia patients with Crohn's disease is multifactorial. Although mesalazine may be a safe and effective drug in the management of inflammatory bowel disease, it can induce sytokine strom syndrome and idiosyncratic reactions that could be one of the reasons of sudden cardic death. Therefore, we should be aware of its serious and potentially life-threatening complications, especially in COVID-19 infected patients.

Preliminary safety and efficacy of itolizumab, a novel targeted anti-cd6 therapy, in newly diagnosed severe acute graft-versus-host disease: Interim results from the equate study

CD6 is a co-stimulatory receptor predominantly expressed on T cells that acts as a crucial regulator of T-cell activation and is implicated in the pathogenesis of multiple autoimmune diseases. Activated leukocyte cell adhesion molecule (ALCAM), a CD6 ligand, is expressed on antigen-presenting cells, as well as epithelial and endothelial cells of acute GVHD target organs, including the skin and the GI tract.1,2 Previous studies in patients receiving alloHCT showed that ex vivo depletion of donor CD6-positive T cells lowered the incidence of acute GVHD, providing a rationale for therapeutically targeting CD6 in acute GVHD.3 Itolizumab, a humanized immunoglobulin G1 monoclonal antibody undergoing evaluation as treatment for acute GVHD, binds CD6 and blocks interaction with ALCAM to inhibit T-cell activity and trafficking.4 Dr John Koreth presented interim study results from EQUATE, an ongoing phase 1b/2 study of itolizumab in combination with corticosteroids for newly diagnosed severe acute GVHD (grade 3-4) after first alloHCT.5 The phase 1b portion is an open-label, 3+3 dose-escalation study evaluating doses of 0.4, 0.8, 1.6, and 2.4 mg/kg administered intravenously every 2 weeks through day 57. As of November 13, 2020, 10 patients completed treatment: 4 with 0.4 mg/kg, 3 with 0.8 mg/kg, and 3 with 1.6 mg/kg. All patients received corticosteroids at an initial dose of 1 to 2 mg/kg/day. Their mean age was 48 years (standard deviation, 15.7 years), 90% were male, and 90% were white. The graft source was peripheral blood for 80% and bone marrow for 20%, and 80% had an HLA-matched donor. The mean time to onset of GVHD was 43 days, and 100% of patients had GI involvement. At day 57, the ORR was 50% with 0.4 mg/kg, 100% with 0.8 mg/kg, and 100% with 1.6 mg/kg.5 The median percent corticosteroid dose reduction at day 85 was 93%, 87%, and 91% for the 0.4, 0.8, and 1.6 mg/kg groups, respectively (Figure 6). Itolizumab decreased the CD6 levels on T cells in a dose-dependent manner within 24 hours of the first dose, a reduction that was maintained throughout the treatment period. Across the dosing cohorts, all patients developed at least 1 AE. Most AEs were mild to moderate in severity.5 The most common AEs were hypomagnesemia (n=3) and peripheral edema (n=3). One mild infusion reaction was noted. Six patients had serious AEs, including recurrent GVHD (n=1), sepsis (n=2;1 event was considered a dose-limiting toxicity), fever (n=1), COVID-19 (n=1), and disseminated nocardia (n=1).

Off-label Use of Itolizumab in Patients with COVID-19 ARDS: Our Clinical Experience in a Dedicated COVID Center.

Severe acute respiratory syndrome coronavirus 2 has affected millions of people worldwide. This pandemic requires newer medical management strategies to control the morbidity and mortality associated with the disease. Several approaches, including global targeting of inflammation or neutralizing a single key inflammatory mediator, are being employed to cope with cytokine storms in coronavirus disease-2019 (COVID-19). The role of anti-inflammatory biologics, such as acalabrutinib, tocilizumab, anakinra, and itolizumab can become relevant. Itolizumab is a humanized recombinant immunoglobulin G1 monoclonal antibody. It targets the extracellular, scavenger receptor cysteine-rich (SRCR) distal domain 1 of CD6 and is responsible for priming, activation, and differentiation of T-cells. Itolizumab has been approved by the Drug Controller General of India for the treatment of COVID-19 in India. Here, we shared our clinical experience of 20 patients having moderate acute respiratory distress syndrome (ARDS) due to COVID-19 on treatment with itolizumab. We observed the mortality benefit with single-dose itolizumab (1.6 mg/kg) in patients having moderate COVID-19 ARDS. HOW TO CITE THIS ARTICLE: Kumari P, Kumar A, Sinha C, Kumar A, Singh PK, Arun SK. Off-label Use of Itolizumab in Patients with COVID-19 ARDS: Our Clinical Experience in a Dedicated COVID Center. Indian J Crit Care Med 2021;25(4):467-469.

A two-arm, randomized, controlled, multi-centric, open-label phase-2 study to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19.

Objective: Efficacy and safety of Itolizumab, an immunomodulatory mAb, in treating moderate-to-severe acute respiratory distress syndrome (ARDS) due to cytokine release in COVID-19 patients was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase-2 study.Methods: Patients were randomized (2:1) to Arm-A (best supportive care [BSC]+Itolizumab) and Arm-B (BSC). Primary outcome of interest was reduction in mortality 30-days after enrollment.Results: Thirty-six patients were screened, five treated as first-dose-sentinels and rest randomized, while four patients were screen-failures. Two patients in Arm-A discontinued prior to receiving one complete infusion and were replaced. At end of 1-month, there were three deaths in Arm-B, and none in Arm-A (p = 0.0296; 95% CI = -0.3 [-0.61, -0.08]). At end of study, more patients in Arm-A had improved SpO2 without increasing FiO2 (p = 0.0296), improved PaO2 (p = 0.0296), and reduction in IL-6 (43 vs 212 pg/ml; p = 0.0296) and tumor necrotic factor-α (9 vs 39 pg/ml; p = 0.0253) levels. Transient lymphopenia (Arm-A: 11 patients) and infusion reactions (7 patients) were commonly reported treatment-related safety events.Conclusion: Itolizumab is a promising, safe and effective immunomodulatory therapy for treatment of ARDS due to cytokine release in COVID-19 patients, with survival and recovery-benefit.

An anti-CD6 antibody for the treatment of COVID-19 patients with cytokine-release syndrome: report of three cases.

In COVID-19, the inflammatory cytokine-release syndrome is associated with the progression of the disease. Itolizumab is a monoclonal antibody that recognizes human CD6 expressed in activated T cells. The antibody has shown to be safe and efficacious in the treatment of moderate to severe psoriasis. Its effect is associated with the reduction of pro-inflammatory cytokines release, including IFN-γ, IL-6 and TNF-α. Here, we report the outcome of three severe and critically ill COVID-19 patients treated with itolizumab as part of an expanded access protocol. Itolizumab was able to reduce IL-6 concentrations in all the patients. Two of the three patients showed respiratory and radiological improvement and were fully recovered. We hypothesize this anti-inflammatory therapy in addition to antiviral and anticoagulant therapy could reduce COVID-19 associated morbidity and mortality.

Treatment of COVID-19 patients with the anti-CD6 antibody itolizumab.

OBJECTIVES: COVID-19 can lead to a hyperinflammatory state. CD6 is a glycoprotein expressed on mature T lymphocytes which is a crucial regulator of the T-cell activation. Itolizumab is a humanised antibody targeting CD6. Nonclinical and clinical data in autoimmune diseases indicate that it lowers multiple cytokines primarily involving the Th1/Th17 pathway. The primary objective of this study was to assess the impact of itolizumab in arresting the lung function deterioration of COVID-19 patients. Secondary objectives included safety, duration of ventilation, 14-day mortality and evaluation of interleukin 6 concentration. METHODS: Patients with confirmed SARS-CoV-2 received itolizumab in combination with other therapies included in the national protocol for COVID-19. RESULTS: Seventy critical, severe or moderate patients were treated with itolizumab in 10 Cuban hospitals. Median age was 68, and 94% had comorbidities. After 72 h, most patients improved the PO2/FiO2 ratio and reduced FiO2 requirements. Ventilation time was 8 days for critical and 1 day for severe cases. Ten patients had related adverse events while 3 subjects developed related serious events. In 30 patients, interleukin 6 decreased in individuals with high level and did not change in those with lower concentration. Fourteen-day lethality rate was 4% and 18% for moderate and severe patients, respectively. The proportion of moderate or severe patients with ventilation or death at day 14 was 9.8%. Time to treatment, neurological manifestations and biomarkers such as NLR were significantly associated with higher lethality. CONCLUSIONS: The opportune administration of itolizumab might interrupt the hyperinflammatory cascade and prevent COVID-19 morbidity and mortality.

An anti-CD6 monoclonal antibody (itolizumab) reduces circulating IL-6 in severe COVID-19 elderly patients.

BACKGROUND: Since the COVID-19 outbreak an unprecedented challenge for healthcare systems around the world has been placed. In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities have been the most risky population. Although most patients present a mild to moderate disease, some have developed severe symptoms. One of the possible mechanisms underlying rapid disease progression is a cytokine storm, in which interleukin (IL) -6 seems to be a major mediator. Itolizumab is a humanized recombinant anti-CD6 monoclonal antibody (MAb), with the ability of reducing serum interferon gamma (INF-γ), tumour necrosis factor alpha (TNFα) and IL-6. Based on these previous results in patients with psoriasis and rheumatoid arthritis, an expanded access clinical trial was approved by the Cuban regulatory agency for COVID-19 critically, severely and moderately ill patients. RESULTS: We show here a short kinetic of IL-6 serum concentration in the first 24 COVID-19 patients treated with itolizumab. Most of patients were elderly with multiple comorbidities. We found that with one itolizumab dose, the circulating IL-6 decreased in critically and severely ill patients, whereas in moderately ill patients the values didn't rise as compared to their low baseline levels. CONCLUSION: These findings suggest that itolizumab could be an attractive therapeutic option to decrease the negative outcome of the cytokine storm in COVID-19 patients. TRIAL REGISTRATION: CECMED IIC RD-EC 179, RPCEC00000311. Registered 4 May 2020 - Retrospectively registered, http://rpcec.sld.cu/ensayos/RPCEC00000311-Sp or http://rpcec.sld.cu/trials/RPCEC00000311-En.

Use of a Humanized Anti-CD6 Monoclonal Antibody (Itolizumab) in Elderly Patients with Moderate COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a recent outbreak of coronavirus disease (COVID-19). In Cuba, the first case of COVID-19 was reported on March 11, 2020. Elderly individuals with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS-CoV-2 infection. During the outbreak, a local transmission event took place in a nursing home in Villa Clara province, Cuba, in which 19 elderly residents tested positive for SARS-CoV-2. METHODS: Based on the increased susceptibility to cytokine release syndrome, inducing respiratory and systemic complications in this population, 19 patients were included in an expanded access clinical trial to receive itolizumab, an anti-CD6 monoclonal antibody. RESULTS: All patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease was favorable, and 18 of the 19 patients (94.7%) were discharged clinically recovered with negative real-time reverse transcription polymerase chain reaction test results at 13 days. After one dose of itolizumab, circulating IL-6 decreased within the first 24-48 h in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminarily assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 patients that did not receive immunomodulatory therapy. The control subjects were well matched regarding age, comorbidities, and severity of the disease. The percentage of itolizumab-treated, moderately ill patients who needed to be admitted to the intensive care unit was only one-third of that of the control group not treated with itolizumab. Additionally, treatment with itolizumab reduced the risk of death 10 times as compared with the control group. CONCLUSION: This study corroborates that the timely use of itolizumab in combination with other antivirals reduces COVID-19 disease worsening and mortality. The humanized antibody itolizumab emerges as a therapeutic alternative for patients with COVID-19. Our results suggest the possible use of itolizumab in patients with cytokine release syndrome from other pathologies.

Are We Jumping the Gun with Itolizumab in India? A Situational Analysis from the Pre-COVID Era.

Itolizumab, an anti-CD6 monoclonal antibody, has been recently approved for the off-label indication of cytokine release syndrome in the background of COVID-19, by the Drug Controller General of India. However, this drug has not been included in the National Clinical Management Protocol for COVID-19 yet. The limited-to-no experience of the Indian health workforce with the drug urged us to conduct a situational analysis in the pre-COVID era to analyse the degree of use of the drug and the indications for which it has been employed.

Itolizumab, an anti-CD6 monoclonal antibody, as a potential treatment for COVID-19 complications.

INTRODUCTION: The globally rampant SARS CoV-2 pandemic requires novel medical strategies to control the severity of disease and death due to complications. Of the 15-20% patients that develop pulmonary symptoms, a sub-set develops an acute respiratory distress syndrome (ARDS) rapidly progressing into a critical condition. Marked elevation of cytokines/chemokines is observed with elevation of additional markers of inflammation, coagulation, and organ damage such as CRP, D-dimer, LDH, Ferritin and Troponin-I. This hyperinflammation leads to worsening of oxygen saturation due to pulmonary infiltration and exudation, organ damage, and dysfunction of coagulation pathway and may lead to multi-organ failure. AREAS COVERED: The role of anti-inflammatory monoclonal antibodies such as Itolizumab, in cytokine storm. EXPERT OPINION: Itolizumab, an anti-CD6 humanized IgG1 mAb, binds to domain-1 of CD-6 that is responsible for priming, activation, and differentiation of T-cells. Itolizumab significantly reduces T-cell proliferation along with substantial downregulation of the production of cytokines/chemokines. Approved for moderate to severe chronic plaque psoriasis in 2013 it is currently being studied for addressing COVID-19 related cytokine storm and its complications. This article reviews its use in COVID-19 infections; its dose, administration protocol, contra-indications, and safety in treating moderate-to-severe ARDS by preventing and treating the cytokine storm and its complications.