RESUMO
BackgroundSARS-CoV-2 infection has widely spread to the hugest public health challenge to date, COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. Spanish case-fatality rate is 11.94%, far higher to those reported in Asia or by other European countries. A multicenter retrospective study was performed of demographic, clinical, laboratory and immunological features of 574 Spanish COVID-19 hospitalized patients and their outcomes. The use of use of renin-angiotensin system blockers was also analyzed as a risk factor. ResultsIn this study, 27.7% of cases presented a mild curse, 42% a moderate one and for 30.3% of cases, the course was severe. Ages ranged from 18 to 98 (average 63.2). Fifty eight percent (58.9%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19 and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of renin-angiotensin system blockers was associated with moderate or mild disease courses. ConclusionsAge and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for immune system effectors severity-related hampering. Adaptive immunity would go exhausted and a huge ineffective and almost deleterious innate response would account for COVID-19 severity. Renin-angiotensin system blockers treatment in hypertensive patients has a protective effect as regarding COVID-19 severity.
RESUMO
We have previously shown that human embryonic stem cell derived islet progenitors (hESC-IPs), encapsulated inside an immunoprotective device, mature in vivo and ameliorate diabetes in mice. The ability to cryopreserve hESC-IPs preloaded in these devices would enhance consistency and portability, but traditional 'slow freezing' methods did not work well for cells encapsulated in the device. Vitrification is an attractive alternative cryopreservation approach. To assess the tolerance of hESC-IPs to vitrification relevant conditions, we here are reporting cell survival following excursions in tonicity, exposure to fifteen 40% v/v combinations of 4 cryoprotectants, and varied methods for addition and elution. We find that 78% survival is achieved using a protocol in which cells are abruptly (in one step) exposed to a solution containing 10% v/v each dimethyl sulfoxide, propylene glycol, ethylene glycol, and glycerol on ice, and eluted step-wise with DPBS+0.5M sucrose at 37°C. Importantly, the hESC-IPs also maintain expression of the critical islet progenitor markers PDX-1, NKX6.1, NGN3 and NEURO-D1. Thus, hESC-IPs exhibit robust tolerance to exposure to vitrification solutions in relevant conditions.
