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.

Enemas de factor de crecimiento epidérmico para inducir la remisión de la colitis ulcerosa izquierda / Epidermal growth factor enemas for induction of remission in left-sided ulcerative colitis

Introducción: la colitis ulcerosa es una enfermedad inflamatoria crónica de etiología poco conocida, que afecta la mucosa del colon. El efecto positivo del factor de crecimiento epidérmico fue reportado en estudio previo con uso de enema para tratamiento de la manifestación izquierda leve o moderada de la enfermedad. Este antecedente sirvió de base para evaluar la eficacia y perfil de seguridad de una solución viscosa del producto.Métodos: fueron aleatorizados 31 pacientes hacia tres grupos de tratamiento diario durante 14 días. Doce recibieron enemas de 10 mg de factor de crecimiento epidérmico en 100 mL de solución viscosa, mientras nueve fueron tratados con enemas placebo conteniendo solamente solución viscosa. Ambos grupos recibieron además 1,2 g diarios de mesalacina oral. El tercer grupo incluyó 10 pacientes con mesalacina en enemas de 3g / 100 mL. La variable principal de eficacia fue la respuesta clínica al finalizar las dos semanas de tratamiento, definida como la disminución de, al menos tres puntos, el índice basal de actividad de la enfermedad acompañada de mejoría endoscópica o histológica.Resultados: se alcanzó remisión de la enfermedad en todos los pacientes que recibieron factor de crecimiento epidérmico y en seis de los grupos mesalacina enema y placebo. Todas las comparaciones entre grupos mostraron superioridad estadísticamente significativa para el factor de crecimiento epidérmico, único producto que logró la reducción significativa del índice de actividad de la enfermedad y de la presencia e intensidad de los síntomas digestivos en los pacientes luego del tratamiento. Ningún evento adverso fue reportado.Conclusiones: estos resultados son consistentes con las anteriores evidencias moleculares y clínicas que señalan al factor de crecimiento...

Introduction: ulcerative colitis is a little known chronic inflammatory disease in colonic mucosa. The positive effect of epidermal growth factor was shown in a previous report, with enema use for treatment of mild to moderate left-sided manifestation of the disease. This evidence provided the basis for evaluating the efficacy and safety profile of a viscous solution of this product. Methods: thirty-one patients were randomized to three groups for daily medications during 14 days. Twelve received one 10 mg enema of epidermal growth factor dissolved in 100 mL of viscous solution whereas nine were treated with placebo enema; both groups also received 1.2 g of oral mesalamine per day. The other group included ten patients with 3 g / 100 mL of mesalamine enema. Primary end point was clinical responses after two weeks of treatment, defined as a decreased of, at least three points from baseline, the Disease Activity Index and endoscopic or histological evidences of improvement. Results: remission of disease was observed in all patients in the epidermal growth factor group, and six in both, mesalamine enema and placebo group. All the comparisons between groups showed statistically significant superiority for epidermal growth factor, the only product with significant reduction in disease activity index as well as the presence and intensity of digestive symptoms in patients after treatment. None adverse event was reported. Conclusions: the results agree with previous molecular and clinical evidences, indicating that the epidermal growth factor is effective to reduce disease activity and to induce remission. A new study involving more patients should be conducted to confirm the efficacy of the epidermal growth factor enemas

Asociación del virus herpes humano 8 y la hiperplasia linfoide nodular difusa del intestino delgado en la inmunodeficiencia variable común / Association between the human herpesvirus 8 and the diffuse nodular lymphoid hyperplasia of the small intestine in common variable immunodeficiency

La inmunodeficiencia variable común (IDVC) es la inmunodeficiencia primaria más frecuente en el terreno clínico y sus formas de presentación son muy variables. Se describe una paciente con IDVC de adulto con síndrome diarreico crónico, pérdida de peso y linfoadenopatías difusas. Sus características inmunológicas más notables fueron una profunda hipogammaglobulinemia de las 3 clases mayores de inmunoglobulinas y la disminución numérica de las células B (CD19+) y células NK (CD3-CD56+) en sangre periférica. La biopsia del intestino delgado obtenida por panendoscopia asistida por video, reveló hiperplasia linfoide multinodular con atrofia parcial de las vellosidades. La inmunohistoquímica mostró que los nódulos consistían en centros germinales aumentados de tamaño con una distribución de células B (CD20+) y células T (CD3+), similar a la del folículo normal. No se encontró expresión diferencial de cadenas ligeras κ y λ. El método de la reacción en cadena de la polimerasa en tiempo real (QRT-PCR) detectó un número apreciable de copias del genoma del virus del herpes humano tipo 8 (VHH-8) (133 copias/µL de ADN) en el ADN del nódulo intestinal biopsiado. La infección con el VHH-8 puede ser un factor importante en la patogenia de los trastornos linfoproliferativos en pacientes con IDVC.

The common variable immunodeficiency (CVID) is the more frequent primary immunodeficiency in clinical field and its presentation forms are very variable. We describe the case of a women presenting with adult CVID with chronic diarrhea syndrome, weight loss and diffuse lymphadenopathies, where the more marked immunologic features were a deep hypogammaglobulinemia of the three major kinds of immunoglobulins and numerical decrease of B cells (CD19+) and NK cells (CD3-CD56+) in peripheral blood. Biopsy of small intestine obtained by video-assisted panendoscope, showed the presence of a multinodular lymphoid hyperplasia with partial atrophy of hairinesses. Immunohistochemistry showed that nodules were high germinal centers with distribution of B cells (CD20+) and T cells (CD3+), similar to that of normal follicle. There was not differential expression of the K and λ light chains. The real time polymerase chain reaction (QRT-PCR) method detected many copies from the genome of type 8 human herpesvirus (VHH-8) (133 copies/µL of DNA) in biopsy of intestinal nodule DNA. VHH-8 infection may to be a significant factor in pathogenesis of lymphoproliferative disorders in patients presenting with CVID.