Specific Clinical and Immunological Changes Following Mesenchymal Stem Cell Transplantation in COVID-19-induced Acute Respiratory Distress Syndrome Patients: A Phase-I Clinical Trial.

Acute respiratory distress syndrome (ARDS) is a systemic inflammation resulting from immune system overactivity. ARDS is also a fatal complication of COVID-19. Mesenchymal stem cells (MSCs) have immune modulatory properties. This study evaluated the safety and efficacy of three times transplantation of umbilical cord-derived MSCs (UC-MSCs) in terms of specific immunological and clinical changes in mild-to-moderate COVID-19-induced ARDS patients. In this single-center, open-label, phase 1 clinical trial, 20 patients diagnosed with COVID-19 and mild-to-moderate ARDS were included and were divided into two groups: a control group receiving standard care and an intervention group receiving UC-MSC in addition to standard care. Three consecutive intravenous transplants of UC-MSC (1×  cells/kg body weight per each transplant) were performed in the intervention group on days 1, 3, and 5. The biological assay was investigated four times (days 0, 5, 10, and 17). UC-MSCs improved the patients' clinical and paraclinical parameters, including leukocytosis, lymphopenia, thrombocytopenia, and liver enzyme abnormalities compared to the control group. They also decreased pro-inflammatory lymphocytes (TH1 and TH17) and increased anti-inflammatory T lymphocytes. Cell therapy also reduced the mean fluorescence intensity (MFI) in overactivated CD8+ T cells.  These findings show that three UC-MSC injections could regulate a hyperactivated immune system in COVID-19-induced ARDS patients by decreasing the inflammatory T lymphocyte subset and can improve the patient's hematological condition and liver function. However, more studies are needed in this area.

The Role of Biochemical and Respiratory Markers in the Mortality of Patients With SARS-CoV-2 Infection in a Mexican Population.

BACKGROUND: The SARS-CoV-2 pandemic has challenged the traditional perspectives of health care. The objective of our study was to analyze the association of different hematological biomarkers and respiratory assistance with the disease's severity and mortality in COVID-19. MATERIALS AND METHODS: A single reference center, cross-sectional, retrospective, descriptive and analytical, observational study was carried out on 362 SARS-CoV-2 positive adults from April to October 2020. RESULTS: The mean age of the population was 55.92±13.12 years. A distribution by gender of n=227 (63.0%) men and n=135 women (37.0%) was found. Mortality occurred in 14% of the studied population. Comorbidities associated were hypertension n=128 (35.0%) and diabetes n=112 (31.0%). Of the 362 patients, 64 required advanced ventilatory support when taken to the intensive care unit, of these 39 (60.9%) died and only 25 (39.1%) survived (p<0.0001). On the other hand, biochemical indicators such as CRP, D-dimer, DHL, lymphocytes, leukocytes, neutrophils, and the neutrophil/lymphocyte ratio, showed a significant difference (p<0.0001) at admission and during the stay in the intensive care unit. CONCLUSIONS: Patients who required ventilatory assistance showed an increased risk of mortality, as did those who were admitted to the intensive care unit. Higher mortality was associated with higher values ​​of CRP, DHL, D-dimer, neutrophil/lymphocytes ratio, total leukocytes, and lower lymphocytes.

Biomarkers associated with COVID-19 disease progression.

The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil-lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.