Emergency visits and mortality caused by ischemic heart disease attributable to fine particulate matter during the COVID-19 pandemic in Chile.

POSITION DU PROBLèME: Le confinement mis en place au deuxième trimestre 2020 a entrainé une amélioration de la qualité de l'air de Santiago, capitale et plus grande ville du Chili, caractérisée par de fortes concentrations en particules fines PM2,5 liées, en grande partie, au trafic routier. L'objectif était de mettre en évidence une potentielle réduction des visites aux urgences pour infarctus du myocarde aigu (IDM) et des décès dus à une cardiopathie ischémique (CPI) attribuable à l'émission de PM2,5, en comparant les périodes équivalentes de 2019 et de 2020. MéTHODES: À Santiago, la surveillance de la qualité de l'air se fait grâce à neuf moniteurs situés dans neuf communes différentes : Cerro Navia, Cerrillos, El Bosque, Pudahuel, Independencia, La Florida, Quilicura, Santiago centre-ville et Las Condes (classées de la plus haute à la plus basse en matière de pauvreté multidimensionnelle). La concentration moyenne quotidienne de PM2,5 a été décrite avec des séries temporelles, et les visites aux urgences pour IDM et les décès dus à une CPI ont été analysés de façon trimestrielle pour chaque année. Pour estimer l'impact de l'excès de PM2,5, les fractions de risque attribuables (FRA) pour les visites aux urgences pour IDM et les décès pour CPI ont été calculées. RéSULTATS: La moyenne quotidienne des PM2,5 a diminué dans huit des neuf communes de Santiago. Cependant, la réduction n'a été significative que dans trois communes. Les visites aux urgences pour IDM et les décès par CPI attribuables aux PM2,5 ont diminué légèrement mais significativement dans ces trois communes. Les FRA dans les autres communes sont restées similaires à 2019. CONCLUSIONS: Une réduction significative de la FRA des PM2,5 pour les décès par CPI et les visites aux urgences d'IDM n'a été observée que dans les communes avec une réduction significative de la concentration quotidienne moyenne de PM2,5 pendant la pandémie de COVID-19.

Trimeric SARS-CoV-2 Spike Proteins Produced from CHO Cells in Bioreactors Are High-Quality Antigens

The spike protein of the pandemic human corona virus is essential for its entry into human cells. In fact, most neutralizing antibodies against Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) are directed against the Virus-surface exposed spike protein, making it the antigen of choice for use in vaccines and diagnostic tests. In the current pandemic context, global demand for spike proteins has rapidly increased and could exceed hundreds of grams to kilograms annually. Coronavirus spikes are large heavily glycosylated homo-trimeric complexes, with inherent instability. The poor manufacturability now threatens the availability of these proteins for vaccines and diagnostic tests. Here, we outline scalable, Good Manufacturing Practice (GMP) compliant, and chemically defined processes for the production of two cell-secreted stabilized forms of the trimeric spike proteins (Wuhan and D614G variant). The processes are chemically defined and based on clonal suspension-CHO cell populations and on protein purification via a two-step scalable downstream process. The trimeric conformation was confirmed using electron microscopy and HPLC analysis. Binding to susceptible cells was shown using a virus-inhibition assay. The diagnostic sensitivity and specificity for detection of serum SARS-CoV-2-specific-immunoglobulin molecules was found to exceed that of spike fragments (Spike subunit-1, S1 and Receptor Binding Domain, RBD). The process described here will enable production of sufficient high-quality trimeric spike protein to meet the global demand for SARS-CoV-2 diagnostic tests and potentially vaccines.

Influence of pre-existing liver disease in the course of COVID-19. in an area with low incidence of SARSCOV2 infection

Background: Some comorbidities have been associated with a negative impact in the severity of COVID-19 course Patients with advanced chronic liver disease (CLD) may be at increased risk of severe course due to the cirrhosisassociated immune dysfunction However the actual data is scare The aim of our study was to determine the prevalence of CLD in COVID-19 patients and to analyse the course of the infection comparing with patients with non-liver disease Methods: This was a retrospective single centre study in which we included all positive SARS-Cov2 polymerase chainreactions (PCR) from March 23 2020 to April 30 2020 Clinical and biochemical data of patients with and without CLD and COVID-19 were collected using medical records Results: 447 patients with SARS-Cov2 PCR were included, 6 3% had CLD 69 7% of patients with CLD were male, with a median age of 65 5 years, with active alcohol and smoke use 75% had non-advanced liver fibrosis, most of them NAFLD. Patients with advanced liver fibrosis were younger, with a mean age of 58 (SD 9 69) years, underlying COPD (57 2%) Meanwhile patients with CLD without advanced liver fibrosis were older, with a mean age of 68 (SD 12 08) years, and had multiples comorbidities like hypertension in 71 4% and diabetes in 47 6% Hospital admission rate (92 9% vs 47 7% p<0 001) was higer in patients with CLD than those without CLD Concomitant comorbidities (diabetes 38 5 vs 16 5% p=0 011;obesity 30 8 vs 8 5% p=0 033;cancer 23 1 vs 5% p=0 027 and COPD 19 2 vs 9% p=0 009), and concomitant antibiotics treatment (19 3 vs 5%;p= 0 018) were higher in patients with CLD than those without CLD The rate of intesive care admission, respiratory support (invasive mechanical ventilation 7 7 vs 9 5% p=0 055;and continuous positive airway pressure CPAP or non-invasive positive pressure 19 2 vs 19 0% p=0 577) and median stay length (8 (5-15) vs 7 (5-13) p=0 696) were similar in both groups Mortality rate was similar in patients with and without CLD (30 8 vs 19 6% p=0 289) However, in the univariate analysis male (OR= 11 20;95% IC= 1 25-100 31;p=0 031);presence of obesity (OR= 7 20;95% CI= 1 13-45 96;p=0 037), antibiotics concomitant treatment (OR= 12;95% CI= 1 95 -73 97;p=0 007);and presence of COPD (OR=5 25 95% CI= 1-254 9 p=0 050) in multivariate analysis were associated with mortality in patients with CLD 87 5% patients with CLD died due to respiratory failure In the general mortality analysis;CLD was not a risk factor associated with mortality (OR= 1 06;95% CI= 0 35-3 18;p=0 924) like the cardiovascular diseases ( Coronary artery disease OR= 4 95;95% CI 1 51-16 27;p=0 008 and Congestive heart failure OR= 5 66;95% CI= 1 64-19 54;p=0 006) Conclusion: Patients with CLD had a low incidence of SARS-Cov2 infection, but higher risk of hospital admission with worse outcomes associated to other concomitant comorbidities and advanced fibrosis.