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.

Multicentre oncology clinical trials in primary health care in Cuba: evaluation of programme implementation in Villa Clara Province, 2010-2020.

BACKGROUND: The Center of Molecular Immunology of Cuba has developed a programme for the conducting of multicentre oncology clinical trials in primary healthcare centres since 2009. AIM: To evaluate the ability to conduct oncology clinical trials in primary health care. DESIGN & SETTING: A longitudinal, prospective, analytical study was developed between July 2010 and August 2020 in the Villa Clara province. METHOD: Structure, process, and outcome indicators were evaluated by the methods of a structured interview, direct observation, documentary observation, and databases analysis. The investigators' curricula vitae, the investigator site file, minutes of workshops, the monitoring reports, the clinical trial training records, and databases were employed as sources of information. The following criteria were considered adequate: when the indicator met the standard; and not adequate: when the indicator did not meet the standard. RESULTS: The six structure indicators reached adequate results and showed that the programme has allowed building of capacities to conduct clinical trials in primary care. The eight processes indicators and two outcome indicators were considered adequate too. Trials conducted in primary care showed better indicators of patient recruitment than secondary care. Both scenarios showed similar behaviour for the process indicators: retention, protocol compliance, and safety. Survival and satisfaction with health services were also comparable in both scenarios. CONCLUSION: The evaluation of the programme showed adequate indicators for conducting oncology clinical trials in primary care in Villa Clara and these were comparable to those determined in the secondary care.

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.