Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms.

Introduction: Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart failure (HF). DCM is a frequent complication in oncologic patients receiving Doxorubicin (Dox). Dox is a highly cardiotoxic drug, whereas its damaging spectrum affects most of the organs by multiple pathogenic cascades. Experimentally reproduced DCM/HF through Dox administrations has shed light on the pathogenic drivers of cardiotoxicity. Growth hormone (GH) releasing peptide 6 (GHRP-6) is a GH secretagogue with expanding and promising cardioprotective pharmacological properties. Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats. Methods: Myocardial changes were sequentially evaluated by transthoracic echocardiography. Autopsy was conducted at the end of the administration period when ventricular dilation was established. Semiquantitative histopathologic study included heart and other internal organs samples. Myocardial tissue fragments were also addressed for electron microscopy study, and characterization of the transcriptional expression ratio between Bcl-2 and Bax. Serum samples were destined for REDOX system balance assessment. Results and discussion: GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function. GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality. Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity. These evidences contribute to pave potential avenues for the clinical use of GHRP-6 in Dox-treated subjects.

Carcinogenic effect of human tumor-derived cell-free filtrates in nude mice.

Cancer remains a worldwide cause of morbidity and mortality. Investigational research efforts have included the administration of tumor-derived extracts to healthy animals. Having previously demonstrated that the administration of non-transmissible, human cancer-derived homogenates induced malignant tumors in mice, here, we examined the consequences of administering 50 or 100 µg of protein of crude homogenates from mammary carcinoma, pancreatic adenocarcinoma, and melanoma samples in 6 inoculations per week during 2 months. The concurrent control mice received homogenates of healthy donor-skin cosmetic surgery fragments. Mammary carcinoma homogenate administration did not provoke the deterioration or mortality of the animals. Multiple foci of lung adenocarcinomas with a broad expression of malignity histomarkers coexisting with small cell-like carcinomas were found. Disseminated cells, positive to classic epithelial markers, were detected in lymphoid nodes. The administration of pancreatic tumor and melanoma homogenates progressively deteriorated animal health. Pancreatic tumor induced poorly differentiated lung adenocarcinomas and pancreatic islet hyperplasia. Melanoma affected lungs with solid pseudopapillary adenocarcinomas. Giant atypical hepatocytes were also observed. The kidney exhibited dispersed foci of neoplastic cells within a desmoplastic matrix. Nuclear overlapping with hyperchromatic nuclei, mitotic figures, and prominent nuclear atypia was identified in epidermal cells. None of these changes were ever detected in the control mice. Furthermore, the incubation of zebrafish embryos with breast tumor homogenates induced the expression of c-Myc and HER-2 as tumor markers, contrasting to embryos exposed to healthy tissue-derived material. This study confirms and extends our hypothesis that tumor homogenates contain and may act as vectors for "malignancy drivers," which ultimately implement a carcinogenesis process in otherwise healthy mice.

Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial.

Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 µg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. Clinical Trial Registration: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

Pharmacodynamic of Recombinant Human Interferon Alpha-2b Nasal Drops and Effective Prophylaxis Against SARS-COV-2 Infection.

The recombinant human interferon alpha-2b (IFN-α2b) nasal drop formulation (Nasalferon) was studied as prophylaxis for SARS-CoV-2. Healthy volunteers between 19 and 80 years of age received 0.5 million international units of IFN in one drop (0.05 mL ) in each nostril, twice a day, for 10 consecutive days. The nondetection of SARS-CoV-2 by real-time polymerase chain reaction was the primary outcome variable. Several IFN-α biomarkers, including intranasal gene expression and innate immune effector activity, were increased in participants who received intranasal IFN-α2b. The study included 2,930 international travelers and 5,728 persons who were their close contacts. The subjects were treated with Nasalferon in January 2021, and 9,162 untreated travelers were included as controls. COVID-19 rate in treated subjects was significantly lower than in untreated subjects (0.05% vs. 4.84%). The proportion of travelers with COVID-19 decreased from 60.9% to 2.2% between December 2020 and February 2021. Furthermore, 1,719 tourism workers also received Nasalferon, and no cases of SARS-CoV-2 infection were detected, whereas 39 COVID-19 cases (10.6%) were reported in 367 untreated subjects. The main adverse events associated with the use of intranasal IFN-α2b were nasal congestion, headache, and rhinorrhea. Our prophylactic health interventions study demonstrates that the daily administration of Nasalferon for 10 days decreases the risk of developing COVID-19 in healthy volunteers. [Figure: see text].

The Nucleocapsid Protein of SARS-CoV-2, Combined with ODN-39M, Is a Potential Component for an Intranasal Bivalent Vaccine with Broader Functionality.

Despite the rapid development of vaccines against COVID-19, they have important limitations, such as safety issues, the scope of their efficacy, and the induction of mucosal immunity. The present study proposes a potential component for a new generation of vaccines. The recombinant nucleocapsid (N) protein from the SARS-CoV-2 Delta variant was combined with the ODN-39M, a synthetic 39 mer unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN), used as an adjuvant. The evaluation of its immunogenicity in Balb/C mice revealed that only administration by intranasal route induced a systemic cross-reactive, cell-mediated immunity (CMI). In turn, this combination was able to induce anti-N IgA in the lungs, which, along with the specific IgG in sera and CMI in the spleen, was cross-reactive against the nucleocapsid protein of SARS-CoV-1. Furthermore, the nasal administration of the N + ODN-39M preparation, combined with RBD Delta protein, enhanced the local and systemic immune response against RBD, with a neutralizing capacity. Results make the N + ODN-39M preparation a suitable component for a future intranasal vaccine with broader functionality against Sarbecoviruses.

Preparing for the Next Pandemic: Increased Expression of Interferon-Stimulated Genes After Local Administration of Nasalferon or HeberNasvac.

HeberNasvac, a therapeutic vaccine for chronic hepatitis B, is able to safely stimulate multiple Toll-like receptors, increasing antigen presentation in vitro and in a phase II clinical trial (Profira) in elderly volunteers who were household contacts of respiratory infection patients. Thus, a new indication as a postexposure prophylaxis or early therapy for respiratory infections has been proposed. In this study, we evaluated the expression of several interferon-stimulated genes (ISGs) after mucosal administration of HeberNasvac and compared this effect with the nasal delivery of interferon alpha 2b (Nasalferon). Molecular studies of blood samples of 50 subjects from the Profira clinical trial who were locally treated with HeberNasvac or Nasalferon and concurrent untreated individuals were compared based on their relative mRNA expression of OAS1, ISG15, ISG20, STAT1, STAT3, and DRB1-HLA II genes. In most cases, the gene expression induced by HeberNasvac was similar in profile and intensity to the expression induced by Nasalferon and significantly superior to that observed in untreated controls. The immune stimulatory effect of HeberNasvac on ISGs paved the way for its future use as an innate immunity stimulator in elderly persons and immunocompromised subjects or as part of Mambisa, a nasal vaccine to prevent severe acute respiratory syndrome coronavirus 2 infection.

Contribution of human recombinant Interferon-Alpha 2b treatment in symptomatic and asymptomatic patients with SARS-CoV-2 virus infection / Contribución del tratamiento con Interferón-Alpha 2b humano recombinante en pacientes sintomáticos y asintomáticos con infección por el virus SARS-CoV2

Introduction: Subjects with asymptomatic infections are not generally admitted to health care facilities, however, they may benefit from antiviral therapy. Objective: To evaluate the contribution to treatment with combined therapy based on recombinant human interferon alpha 2b + Lopinavir/Ritonavir + Chloroquine versus Lopinavir/Ritonavir + Chloroquine in asymptomatic and symptomatic patients. Material and Methods: An observational study was carried out in patients with a positive diagnosis of COVID-19 from April 1st to July 30th, 2020. From a total of 308 patients treated with interferon + Lopinavir/Ritonavir + Chloroquine, we selected a statistically representative sample of 40 patients using a simple randomization process. As a control group, 27 patients who only received treatment with Lopinavir/Ritonavir + Chloroquine were selected. These patients underwent determinations of anti-SARS-CoV-2 antibodies, determinations of inflammatory markers, and follow-up by RT-PCR to evaluate the time length of negativization. Results: The group treated with interferon had a significantly shorter time to negativization. Patients treated with interferon showed a significant decrease in inflammatory markers at the time of hospital discharge and they had an increase in antibody titers at two and four months after hospital discharge, compared to the group of patients who did not receive interferon. Conclusions: The treatment with exogenous interferon in patients with COVID-19 had a significant contribution to the regulation of the immune response of the patients(AU)

Introducción: Los sujetos con infección asintomática generalmente no son admitidos en centros de asistencia médica, sin embargo, pueden beneficiarse de la terapia antiviral. Objetivo: evaluar la contribución al tratamiento de la terapia combinada basada en interferón alfa 2b recombinante humano + Lopinavir/Ritonavir + Cloroquina contra Lopinavir/Ritonavir + Cloroquina en pacientes asintomáticos y sintomáticos. Material y Métodos: Se realizó un estudio observacional en pacientes con diagnóstico positivo de COVID-19, durante los días del 1 de abril al 30 de julio de 2020. De un total de 308 pacientes tratados con interferón + Lopinavir/Ritonavir + Cloroquina, se seleccionaron mediante un proceso de aleatorización simple, una muestra estadísticamente representativa de 40 pacientes. Como grupo control se seleccionaron 27 pacientes que solo recibieron tratamiento con Lopinavir/Ritonavir + Cloroquina. Estos pacientes se sometieron a determinaciones de anticuerpos anti-SARS-CoV-2, determinaciones de marcadores inflamatorios y seguimiento por RT-PCR para evaluar el tiempo de negativización. Resultados: El grupo tratado con interferón tuvo un tiempo significativamente más corto de negativización. Los pacientes tratados con interferón mostraron una disminución significativa de los marcadores inflamatorios en el momento del alta hospitalaria y tuvieron un incremento de los títulos de anticuerpos a los dos y cuatro meses posteriores al alta hospitalaria, en comparación con el grupo de pacientes que no recibió interferón. Conclusiones: El tratamiento con interferón exógeno en pacientes con COVID-19 tuvo una contribución significativa en la regulación de la respuesta inmune de los pacientes(AU)

Reliability of CNEURO hyssops for sample collection in the SARS-CoV-2 diagnosis / Fiabilidad de los hisopos CNEURO para la recogida de muestras en el diagnóstico del SARS-CoV-2

ABSTRACT Introduction: The detection of SARS-CoV-2 genetic material from nasopharyngeal swab samples by RT-PCR is the most specific and sensitive way to test suspected cases. However, factors such as the sampling process, the type of hyssop used, and the anatomical area from which the sample is collected can distort the result and cause false negatives. Objective: To evaluate the reliability of CNUERO hyssops for sample collection for the SARS-CoV-2 diagnosis versus IMPROSWAB hyssops. Material and Methods: To study the reliability of hyssops developed in Cuba for swabbing for the COVID-19 diagnosis by comparing them to other hyssops successfully used for this task, 2 swabbing samples were obtained from each patient (136). One of these two samples was taken using the hyssops made in Cuba, while the other was taken using another hyssop imported from Germany. The positive detections obtained with the use of both hyssops were compared using the Fisher's exact test. The result of the detection of each hyssop was evaluated and compared using the ROC curve. Results: The use of CNEURO hyssops allowed the detection of 45 out of 59 positive cases, while IMPROSAWAB hyssops detected 52 out of 59 true positive cases. There were no significant differences between positive cases detected with the use of each hyssop. The sensitivity of sample detection using CNEURO hyssops was 76,3 % while the one using IMPROSWAB hyssops was 88,1 %. Hence, there are no significant differences in the detection of cases using these two hyssops. Conclusion: CNEURO hyssops are safe and reliable to be used to take nasopharyngeal samples from COVID-19 patients.

RESUMEN Introducción: La detección de material genético del SARS-CoV-2 a partir de muestras de hisopos nasofaríngeos mediante RT-PCR es la forma más específica y sensible de analizar los casos sospechosos. Sin embargo, factores como el proceso de toma de muestra, el tipo de hisopo y el área anatómica de la que se extrae la muestra, pueden distorsionar el resultado y provocar falsos negativos. Objetivo: Evaluar la confiabilidad de hisopos CNUERO para la recolección de muestras en el diagnóstico de SARS-CoV-2 versus hisopos IMPROSWAB. Material y Métodos: Se obtuvieron 2 muestras de exudado de cada paciente (136). Una de estas dos muestras se tomó con hisopos CNEURO, mientras que la otra se tomó con el hisopo IMPROSWAB. Las detecciones positivas entre ambos hisopos se compararon mediante la prueba exacta de Fisher. El resultado de la detección de cada hisopo se evaluó y comparó utilizando la curva ROC. Resultados: El uso de hisopos CNEURO permitió detectar 45 de 59 casos positivos, mientras que los hisopos IMPROSAWAB detectaron 52 de 59 casos verdaderos positivos. Se detectaron diferencias no significativas entre los casos positivos detectados entre hisopos. La sensibilidad de detección de muestras utilizando hisopos CNEURO fue del 76,3 % y del 88,1 % cuando se utilizaron hisopos IMPROSWAB. Por tanto, no se detectaron diferencias significativas en la detección de casos utilizando estos dos hisopos. Conclusión: Los hisopos CNEURO son seguros y fiables para su uso en la toma de muestras nasofaríngeas de pacientes con COVID-19.

El tratamiento con Jusvinza disminuye la hiperinflamación y la hipercoagulación en pacientes críticos con la COVID-19

RESUMEN Introducción: La infección con el SARS-CoV-2 induce un estado protrombótico en los pacientes, atribuible a la combinación de la respuesta hiperinflamatoria y la hipoxia. En Cuba, se usa el fármaco Jusvinza, basado en un péptido inmunomodulador, para el tratamiento de los pacientes con la COVID-19, que presenten signos y síntomas de hiperinflamación. Objetivos: Describir la evolución clínica y las variaciones de biomarcadores asociados con la inflamación y la coagulación, en un grupo de pacientes críticos con la COVID-19, tratados con Jusvinza, en comparación con un grupo de pacientes que no recibieron tratamiento con este péptido. Métodos: Se incluyeron 40 pacientes críticos con la COVID-19; se dividieron en 2 grupos: 20 pacientes tratados con Jusvinza y 20 no fueron tratados con dicho péptido (grupo control). Las características demográficas, comorbilidades, signos vitales, parámetros respiratorios, biomarcadores de la inflamación y de la coagulación se obtuvieron a partir de las historias clínicas de cada paciente. Resultados: El tratamiento con Jusvinza indujo una mejoría clínica en los pacientes, asociada con la disminución de varios biomarcadores de la inflamación y la coagulación. La sobrevida de los pacientes tratados con Jusvinza fue significativamente superior a la sobrevida de los pacientes no tratados con este péptido. Conclusiones: Jusvinza es capaz de controlar la hiperinflamación y la hipercoagulación en pacientes críticos con la COVID-19.

ABSTRACT Introduction: Infection with SARS-CoV-2 induces a prothrombotic state in patients, by the combination of hyperinflammatory response and hypoxia. In Cuba, the drug called Jusvinza, based on an immunomodulatory peptide, is used for the treatment of patients with COVID-19, who present signs and symptoms of hyperinflammation. Objectives: To describe the clinical course and behavior of various biomarkers associated with the inflammation and coagulation, in a group of critically ill patients with COVID-19 treated with Jusvinza, compared to a group of patients who did not receive treatment with this peptide. Methods: 40 critically ill patients with COVID-19 were included. The patients were divided into 2 groups: 20 patients were treated with Jusvinza and 20 were not treated with this peptide (control group). Demographic characteristics, comorbidities, vital signs, respiratory parameters and inflammation and coagulation biomarkers were obtained from the medical records of each patient. Results: Treatment with Jusvinza induced a clinical improvement in the patients, associated with the decrease of several inflammation and coagulation biomarkers. Patients treated with Jusvinza had a significantly higher survival than patients not treated with this peptide. Conclusions: Jusvinza is able to control hyperinflammation and hypercoagulation in critical ill patients with COVID-19.

Comparison between nasopharyngeal swabs and saliva as reliable specimens for the diagnosis of SARS-CoV-2 / Comparación de la confiabilidad del diagnóstico del SARS-CoV-2 entre muestras de hisopado y saliva

Introduction: The SARS-CoV-2 virus is a positive-strand RNA virus. The virus can also be detected in many different specimens as throat swabs, nasal swabs, sputum, saliva, blood, etc. Objective: The aim of this paper is to compare the reliability of different types of specimen collection, saliva and swabs samples for the detection of SARS-CoV-2. Material and Methods: A sample of 22 COVID-19 positive patients was selected. Paired samples from saliva, nasopharyngeal, oropharyngeal and nasopharyngeal + oropharyngeal swabs were collected on the 7th day after diagnosis. The hyssops and medium employed was IMPROSWAB and IMPROVIRAL NAT Medium, Germany. The sample evaluation was conducted through RT-PCR. The results were compared using Fisher's exact test and ROC curve. The gold standard proposed in this paper was the nasopharyngeal + oropharyngeal swabs specimen. Results: The gold standard method detected 10 true positive cases, of which oropharyngeal swabs, nasopharyngeal swabs and saliva only detected three positive cases. Significant differences (Fisher's exact test p = 0.003) were detected in the comparison between saliva and the gold standart proposed. The ROC curve analysis showed that saliva had an area under the curve of 0.650, with a 30 percent of sensibility. However, the nasopharyngeal and nasopharyngeal + oropharyngeal samples had an area under curve of 0.950 and 1.000, respectively, with a sensibility of 90 percent and 100 percent, respectively. Conclusion: Saliva samples are not a reliable specimen for SARS-CoV-2 RNA detection. In turn, the most reliable specimens are nasopharyngeal and nasopharyngeal + oropharyngeal samples collected by swabbing(AU)

Introducción: El SARS-CoV-2 es un virus ARN positivo. Este virus puede ser detectado en diferentes tipos de secreción como hisopada bucal, nasal, esputo, saliva, sangre, etc. Objetivo: El objetivo de este estudio es comparar la confiabilidad de diferentes tipos de muestras, saliva y exudado, en la detección de SARS-CoV-2. Material y Métodos: Una muestra de 22 pacientes con diagnóstico de Covid-19 fue estudiada. Se tomaron muestras pareadas de saliva y exudado nasofaríngeo y orofaríngeo en cada paciente. Se emplearon los hisopos y medios de la firma alemana IMPROVE®. Los resultados de las determinaciones por RT-PCR se compararon mediante test de Fisher (test de la probabilidad exacta de Fisher) y cada sets de muestras fue evaluada individualmente y luego comparadas por curvas ROC. El estándar de oro propuesto fue el doble hisopado nasofaríngeo/orofaríngeo. Resultados: El método de oro propuesto detectó 10 casos positivos. La coincidencia de detección entre todos los sets de muestras fue de 3 casos (30 por ciento). Se obtuvieron diferencias significativas (Fisher p = 0.003) en la comparación de los casos detectados en saliva vs el estándar de oro. El análisis de curvas ROC mostró un área bajo la curva de 0.650 (30 por ciento de sensibilidad) para la saliva. En el caso del hisopado nasofaríngeo y el estándar de oro mostraron un área bajo la curva de 0.95 y 1.00, respectivamente, con una sensibilidad del 90 (AU) por ciento y 100 por ciento, respectivamente. Conclusiones: La saliva no es una muestra confiable para la detección de SARS-CoV-2. La muestra más confiable para el diagnóstico fue el hisopado nasofaríngeo y el doble hisopado(AU)

Péptido inmunomodulador CIGB-258 para el tratamiento de pacientes graves y críticos con la COVID-19 / An immunomodulatory peptide CIGB-258 for the treatment of critical and severe COVID-19 patients

Introducción: El CIGB-258 es un péptido inmunomodulador con propiedades antiinflamatorias. Objetivos: Establecer la frecuencia de dosis y el tiempo de tratamiento con el péptido CIGB-258, para pacientes críticos con COVID-19. Además, definir los criterios de uso y el esquema terapéutico del péptido, para pacientes graves con COVID-19. Métodos: Se incluyeron 9 pacientes críticos y 3 pacientes graves. Las evaluaciones clínicas, radiológicas y de laboratorio se registraron de acuerdo al protocolo establecido. Se obtuvieron muestras de suero antes y después del tratamiento con la CIGB-258, para la determinación de los biomarcadores de la inflamación. Resultados: Se estableció el protocolo de actuación con el péptido CIGB-258, el cual consiste en la administración intravenosa de 1 mg del péptido cada 12 horas a los pacientes críticos. La dosis debe aumentarse a 2 mg cada 12 horas, para los pacientes que no muestren mejoría clínica y radiológica en 24 horas. Después de la extubación, los pacientes deben recibir 1 mg de CIGB-258 al día, durante otros tres días. Los pacientes graves deben recibir 1 mg de CIGB-258 cada 12 horas, hasta que resuelvan su condición clínica. Conclusiones: CIGB-258 mostró un buen perfil de seguridad. El protocolo de actuación establecido contribuyó a que todos los pacientes críticos se recuperaran de la dificultad respiratoria y fueran extubados. Los pacientes graves mejoraron considerablemente. Los niveles de los biomarcadores asociados con hiperinflamación y las citocinas disminuyeron significativamente durante el tratamiento(AU)

Introduction: CIGB-258 is an immunomodulatory peptide with anti-inflammatory properties. Objectives: To establish the therapeutic schedule with CIGB-258 peptide for COVID-19 critically ill patients. In addition, to define the criteria for use and schedule of this peptide for COVID-19 seriously ill patients. Methods: 9 critically ill patients and 3 seriously ill patients were included in this study. Clinical, radiological and laboratory evaluations were recorded according to the established protocol. Serum samples were obtained before and after treatment with CIGB-258, for the determination of the inflammation biomarkers. Results: The therapeutic protocol was established with the CIGB-258 peptide, which consists of intravenous administration of 1 mg of peptide every 12 hours for critically ill patients. The dose should be increased to 2 mg every 12 hours, for patients who do not show clinical and radiological improvement in 24 hours. After extubation, patients should receive 1 mg of CIGB-258 daily, for another three days. Seriously ill patients should receive 1 mg of CIGB-258 every 12 hours, until their clinical condition resolves. Conclusions: CIGB-258 showed an excellent safety profile. The established therapeutic protocol contributed to all critically ill patients recovering from respiratory distress and being extubated. Seriously ill patients improved considerably. The levels of the biomarkers associated with hyperinflammation and cytokines decreased significantly during treatment(AU)