Delayed mechanical ventilation with prolonged high-flow nasal cannula exposure time as a risk factor for mortality in acute respiratory distress syndrome due to SARS-CoV-2.

In a high proportion of patients, infection by COVID-19 progresses to acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation (IMV) and admission to an intensive care unit (ICU). Other devices, such as a high-flow nasal cannula (HFNC), have been alternatives to IMV in settings with limited resources. This study evaluates whether HFNC exposure time prior to IMV is associated with mortality. This observational, analytical study was conducted on a historical cohort of adults with ARDS due to SARS-CoV-2 who were exposed to HFNC and subsequently underwent IMV. Univariate and multivariate logistic regression was used to analyze the impact of HFNC exposure time on mortality, controlling for multiple potential confounders. Of 325 patients with ARDS, 41 received treatment with HFNC for more than 48 h before IMV initiation. These patients had a higher mortality rate (43.9% vs. 27.1%, p: 0.027) than those using HFNC < 48 h. Univariate analysis evidenced an association between mortality and HFNC ≥ 48 h (OR 2.16. 95% CI 1.087-4.287. p: 0.028). Such an association persisted in the multivariable analysis (OR 2.21. 95% CI 1.013-4.808. p: 0.046) after controlling for age, sex, comorbidities, basal severity of infection, and complications. This study also identified a significant increase in mortality after 36 h in HFNC (46.3%, p: 0.003). In patients with ARDS due to COVID-19, HFNC exposure ≥ 48 h prior to IMV is a factor associated with mortality after controlling multiple confounders. Physiological mechanisms for such an association are need to be defined.

ImmunoTyper-SR: A computational approach for genotyping immunoglobulin heavy chain variable genes using short-read data.

Human immunoglobulin heavy chain (IGH) locus on chromosome 14 includes more than 40 functional copies of the variable gene (IGHV), which are critical for the structure of antibodies that identify and neutralize pathogenic invaders as a part of the adaptive immune system. Because of its highly repetitive sequence composition, the IGH locus has been particularly difficult to assemble or genotype when using standard short-read sequencing technologies. Here, we introduce ImmunoTyper-SR, an algorithmic tool for the genotyping and CNV analysis of the germline IGHV genes on Illumina whole-genome sequencing (WGS) data using a combinatorial optimization formulation that resolves ambiguous read mappings. We have validated ImmunoTyper-SR on 12 individuals, whose IGHV allele composition had been independently validated, as well as concordance between WGS replicates from nine individuals. We then applied ImmunoTyper-SR on 585 COVID patients to investigate the associations between IGHV alleles and anti-type I IFN autoantibodies, which were previously associated with COVID-19 severity.

Covid 19, lockdown and brief psychotic disorders

Introduction Acute and transient psychotic disorders are a rare condition entity as the sudden appearance of affective, confusional symptoms and paranoia triggered by some psychological trauma. The current pandemic caused by COVID-19 is an important psychological stressor that could favor the appearance of acute psychotic disorders. Several studies have been recently published proposing that the multifactorial stress associated with lockdown could function as a catalyst for acute psychotic disorders. Objectives To present a case of a brief psychotic disorder during the national lockdown in Spain and to review the literature about the relationship between the current pandemic and psychosis. Methods We will present a case report and a literature review. Results We report a case of a 27-year-old woman, with no previous psychiatric history. Three weeks after the start of Spain lockdown sudden symptoms appeared with psychomotor restlessness, confused speech, emotional lability, thought blocking and persecutory and referential delusions. Physical exam, blood analysis and cerebral CT scan with no alterations. Treatment was performed with aripiprazole 10 mg and lorazepam 1 mg daily with clinical improvement in one weeks. She was diagnosed of Acute transient psychotic disorder. Conclusions Stressful life events that can trigger psychosis in vulnerable individuals and the current pandemic and lockdown context could favor the appearance of acute psychotic disorders. The case reported here is in line with other current studies that show a preliminary intuition of this trend.

Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice.

Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.

[Clinical Consensus Recommendations Regarding Non-Invasive Respiratory Support in the Adult Patient with Acute Respiratory Failure Secondary to SARS-CoV-2 infection]. / Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infección por SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure.This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.

[Clinical consensus recommendations regarding non-invasive respiratory support in the adult patient with acute respiratory failure secondary to SARS-CoV-2 infection]. / Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infección por SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.