Thrombosis Occurrence in COVID-19 Compared With Other Infectious Causes of ARDS: A Contemporary Cohort.

Thrombosis occurrence in coronavirus disease 2019 (COVID-19) has been mostly compared to historical cohorts of patients with other respiratory infections. We retrospectively evaluated the thrombotic events that occurred in a contemporary cohort of patients hospitalized between March and July 2020 for acute respiratory distress syndrome (ARDS) according to the Berlin Definition and compared those with positive and negative real-time polymerase chain reaction results for wild-type severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using descriptive analysis. The association between COVID-19 and thrombotic risk was evaluated using logistic regression. 264 COVID-19-positive (56.8% male, 59.0 years [IQR 48.6-69.7], Padua score on admission 3.0 [2.0-3.0]) and 88 COVID-19-negative patients (58.0% male, 63.7 years [51.2-73.5], Padua score 3.0 [2.0-5.0]) were included. 10.2% of non-COVID-19 and 8.7% of COVID-19 patients presented ≥ 1 clinically relevant thrombotic event confirmed by imaging exam. After adjustment for sex, Padua score, intensive care unit stay, thromboprophylaxis, and hospitalization length, the odds ratio for thrombosis in COVID-19 was 0.69 (95% CI, 0.30-1.64). We, therefore, conclude that infection-induced ARDS carries an inherent thrombotic risk, which was comparable between patients with COVID-19 and other respiratory infections in our contemporary cohort.

Immunouniverse of SARS-CoV-2.

SARS-CoV-2 virus has become a global health problem that has caused millions of deaths worldwide. The infection can present with multiple clinical features ranging from asymptomatic or mildly symptomatic patients to patients with severe or critical illness that can even lead to death. Although the immune system plays an important role in pathogen control, SARS-CoV-2 can drive dysregulation of this response and trigger severe immunopathology. Exploring the mechanisms of the immune response involved in host defense against SARS-CoV-2 allows us to understand its immunopathogenesis and possibly detect features that can be used as potential therapies to eliminate the virus. The main objective of this review on SARS-CoV-2 is to highlight the interaction between the virus and the immune response. We explore the function and action of the immune system, the expression of molecules at the site of infection that cause hyperinflammation and hypercoagulation disorders, the factors leading to the development of pneumonia and subsequent severe acute respiratory distress syndrome which is the leading cause of death in patients with 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.

The dual FXa/thrombin inhibitor SATI prevents fibrin and platelet deposition in hypercoagulant rats.

INTRODUCTION: Systemic hypercoagulation is often a severe complication of infective and inflammatory diseases, which overcome the hemostatic balance and lead to multiple thrombotic occlusions in the microvasculature and organ damage and is related to high mortality rates. SATI is a potent dual inhibitor of FXa and thrombin with antithrombotic efficacy in venous and arterial thrombosis models. In this study, the antithrombotic efficacy of SATI was investigated in a microthrombosis model in rats with an induced hypercoagulant state. MATERIALS AND METHODS: The hypercoagulant state was generated by infusion of TF in sixty rats (12 groups, consisting of 5 rats each). SATI was administered in two different doses by constant infusion and its antithrombotic efficacy was investigated using two different approaches: 1) measuring 125I-fibrin deposition in various organs and 2) continuous whole-body imaging of 111In-platelet biodistribution in anesthetized animals. RESULTS: After start of the TF infusion in rats with radioactively-labeled fibrinogen, the radioactivity was accumulated in liver, spleen, kidney, and mostly in the lung as a consequence of fibrin generation. SATI efficiently reduced the pulmonary deposition of fibrin in a dose- and time-dependent manner. In the SATI groups the splenic and renal radioactivity was enhanced at later time points probably as consequence of the clearance of 125I-fibrin(ogen). Imaging of rats that received 111In-platelets prior to systemic TF administration showed retention of the radioactivity mainly in the lungs in the control group. SATI efficiently blocked the platelet accumulation in the lungs and increased platelet recruitment by the spleen. CONCLUSIONS: SATI is a promising candidate for prevention of microcirculatory disturbances by inhibiting fibrin deposition and platelet accumulation in the lungs and thereby conferring organ protection. Both methods used in this study are suitable for investigating the antithrombotic efficacy of new drugs in microthrombosis. Continuous imaging of 111In-platelets allowed for follow-up of thrombus formation in living animals without the need for tissue harvesting.