Mesenchymal Stem Cells in the Treatment of COVID-19, a Promising Future.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells' differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration. MSCs are considered safe for human treatment; their use does not involve ethical issues, as embryonic stem cells do not require genetic manipulation as induced pluripotent stem cells, and after intravenous injection, they are mainly found in the lugs. Therefore, these cells are currently being tested in various preclinical and clinical trials for several diseases, including COVID-19. Several affected COVID-19 patients develop induced acute respiratory distress syndrome (ARDS) associated with an uncontrolled inflammatory response. This condition causes extensive damage to the lungs and may leave serious post-COVID-19 sequelae. As the disease may cause systemic alterations, such as thromboembolism and compromised renal and cardiac function, the intravenous injection of MSCs may be a therapeutic alternative against multiple pathological manifestations. In this work, we reviewed the literature about MSCs biology, focusing on their function in pulmonary regeneration and their use in COVID-19 treatment.

Alteraciones de la coagulación en la COVID-19.

Infection with the SARS-CoV-2 virus and the development of all manifestations of COVID-19, predisposes to arterial and venous thromboembolic disease. The coagulation system can be activated by various viruses, including SARS-CoV-2. Vascular endothelial damage, added to the development of disseminated intravascular coagulation, affects the prognosis and mortality from this disease. Treatment is aimed at the prevention, early detection and timely interventions of all coagulation disorders generated by COVID-19. The recommended anticoagulant is low molecular weight heparin, taking into account creatinine clearance, and if major invasive procedures will be performed, unfractionated heparin is a safe option.

La infección por el virus SARS-CoV-2 y el desarrollo de todas las manifestaciones de COVID-19 predisponen a la enfermedad tromboembólica arterial y venosa. El sistema de coagulación puede ser activado por diversos virus, entre ellos el SARS-CoV-2. El daño endotelial vascular, sumado al desarrollo de coagulación intravascular diseminada, afecta el pronóstico y la mortalidad de esta enfermedad. El tratamiento está dirigido a la prevención, la detección temprana y las intervenciones oportunas de todas las alteraciones de la coagulación generadas por la COVID-19. El anticoagulante recomendado es la heparina de bajo peso molecular, tomando en cuenta el aclaramiento de creatinina, y si se realizarán procedimientos invasivos mayores, la heparina no fraccionada es una opción segura.

Recurrent thrombosis in patients with deep vein thrombosis and/or venous thromboembolism associated with anticardiolipin antibodies.

Anticardiolipin antibodies represent one of the main hypercoagulation states associated with venous thromboembolism. The aim of this work was to evaluate symptomatic recurrent thrombosis in patients with anticardiolipin antibodies and deep vein thrombosis of the lower limbs with or without thromboembolism. Sixty patients who suffered from deep vein thrombosis were observed for a 5-year period, whether they had anticardiolipin antibodies or not. The group was made up of 34 females and 26 males with ages ranging from 13 to 73 years. All were diagnosed with deep vein thrombosis by means of phlebography and were tested for anticardiolipin antibodies by use of the ELISA method. The symptomatic signs of recurrent thrombosis were evaluated during this period. In total, 56.6% of the group were considered above normal for anticardiolipin antibodies, 25% positive, another 31.6% borderline, and 43.4% negative. Patients were tested positive when the anticardiolipin antibody count was >15 units/mL, borderline between 10 and 15 units/mL, and normal when <10 units/mL. The method of relative risk was used for statistical analysis of the results. Four positive patients, 1 borderline, and 1 normal patient had recurrent events of thrombosis. In the statistical analysis the relative risk for recurrent thrombosis in the positive patients was 6.0; CI 95%; 1.2 to 29.5. In conclusion patients with deep vein thrombosis who are positive for anticardiolipin antibodies present a higher risk of recurrent thrombosis.

Anticardiolipin antibodies and risk of thromboembolic disease in young Jamaican women.

BACKGROUND: Anticardiolipin antibodies (aCL) are a heterogeneous group of antiphospholipid antibodies that are associated with arterial and venous thrombosis. We measured aCL in women, aged 15-49 years, to determine if they are an independent risk factor for thromboembolic disease. STUDY DESIGN: Case--control study METHODS: Fifty cases were studied including venous thromboembolism (n=29), stroke and myocardial infarction (n=21), along with 148 age-matched controls. Serum samples were assayed for aCL and anti-beta2 glycoprotein 1 antibodies using the enzyme-linked immunosorbent assay (ELISA). Information on other risk factors was obtained by a standardized questionnaire. RESULTS: aCL were present in 16/50 (32%) of cases compared with 25/148 (17%) of controls (P[?]=[?]0.02). Unadjusted odds ratio (OR) and 95% confidence interval (95% CI) for thromboembolic disease associated with aCL was 2.32 (1.10--4.87). Other risk factors were hypertension, 2.93 (1.20--7.17) and a history of other heart diseases, 12.78 (1.32--123.60). Adjustment for hypertension, diabetes, oral contraceptive use, smoking, alcohol use, varicose veins, a family history of cardiovascular disease and a history of other heart diseases yielded OR (95%CI) 2.99 (1.32--6.80). beta2 glycoprotein 1-dependent aCL were also an independent risk factor, OR 4.56 (1.76--17.83). Subgroup analysis was carried out separately for cases of MI and stroke and for venous thrombosis. Adjusted OR (95% CI) associated with aCL in cases of MI and stroke was 1.76 (0.46--6.73) and 3.32 (1.15--9.54) for venous thromboembolism. CONCLUSION: aCL are a risk factor for thromboembolic disease in young Jamaican women. They confer a strong independent risk for venous thromboembolism.

Anti beta 2 glycoprotein I antibodies: detection and association with thrombosis.

It has been demonstrated that antiphospholipid antibodies (aPL) recognize epitopes formed by anionic phospholipids and protein cofactors. beta 2 glycoprotein I (beta 2GPI) is accepted as the cofactor of anticardiolipin antibodies (aCL). In the present study we explored the presence and clinical associations of anti beta 2GPI antibodies of IgG isotype (a beta 2GPI-IgG), measured by ELISA. We studied sera from 169 patients with aCL and/or lupus anticoagulant (LA), including 52 patients with systemic lupus erythematosus and 49 with primary antiphospholipid syndrome (PAPS). We found 31.9% positive sera for a beta 2GPI-IgG in the whole population and 48.6% in the aCL-IgG(+) group. There was a good correlation between the titre of aCL-IgG and the optical density for a beta 2GPI-IgG (r = 0.69, P < 0.01). The presence of a beta 2GPI-IgG was associated with the presence of aCL-IgG (P < 0.0001) and LA (P < 0.0005). However, none of 23 LA (+) patients without aCL had a beta 2GPI-IgG. We found a statistically significant association between the presence of a beta 2GPI-IgG and a history of venous thromboembolism (VTE) in our patients (P < 0.005). This association was observed in PAPS (P < 0.05) but not in secondary antiphospholipid syndrome (SAPS). Our study confirms that some aPL(+) sera react with beta 2GPI in special experimental conditions. In addition, the presence of these antibodies is associated with a history of VTE.

Lúpus discóide com fenômenos trombembólicos como evidência de sistematizaçäo / Discoid lupus erythematosus with thromboembolic phenomena as evidence of systematization

Os autores relatam caso de paciente com lúpus eritematoso discóide que apresentou fenômenos tombembólicos como evidência de sistematizaçäo. Säo discutidos os achados clínicos, radiológicos e laboratoriais e sua relaçäo com os anticorpos antifosfolípides