IFNAR2 relevance in the clinical outcome of individuals with severe COVID-19

Interferons (IFNs) are a group of cytokines with antiviral, antiproliferative, antiangiogenic, and immunomodulatory activities. Type I IFNs amplify and propagate the antiviral response by interacting with their receptors, IFNAR1 and IFNAR2. In COVID-19, the IFNAR2 (interferon alpha and beta receptor subunit 2) gene has been associated with the severity of the disease, but the soluble receptor (sIFNAR2) levels have not been investigated. We aimed to evaluate the association of IFNAR2 variants (rs2236757, rs1051393, rs3153, rs2834158, and rs2229207) with COVID-19 mortality and to assess if there was a relation between the genetic variants and/or the clinical outcome, with the levels of sIFNAR2 in plasma samples from hospitalized individuals with severe COVID-19. We included 1,202 subjects with severe COVID-19. The genetic variants were determined by employing Taqman® assays. The levels of sIFNAR2 were determined with ELISA in plasma samples from a subgroup of 351 individuals. The rs2236757, rs3153, rs1051393, and rs2834158 variants were associated with mortality risk among patients with severe COVID-19. Higher levels of sIFNAR2 were observed in survivors of COVID-19 compared to the group of non-survivors, which was not related to the studied IFNAR2 genetic variants. IFNAR2, both gene, and soluble protein, are relevant in the clinical outcome of patients hospitalized with severe COVID-19

SYMPTOMATIC AND ASYMPTOMATIC SMOKERS WITHOUT AIRFLOW OBSTRUCTION: A NEW CLINICAL ENTITY?

Non-obstructed ever-smokers, with or without symptoms, have generated a great deal of information recently, but few reviews. Even individuals with normal spirometry can present changes in sputum with inflammatory biomarkers (cellular and molecular) and airways and parenchyma with remodeling; when symptomatic (cough, sputum, wheezing, and dyspnea) exacerbations are frequent affecting the individuals' quality of life, there is an increased use of health resources: more medication, emergency visits, and hospital admissions. Non-obstructed smokers may have exercise limitations, increased lung volumes, low diffusion capacity, air entrapment, peripheral airways obstruction, elevated airways resistance, and abnormal multiple breath nitrogen washout, as well as abnormalities in computed tomography studies, such as airway wall thickening, emphysema, or interstitial lung abnormalities. Quitting smoking comprises a first, inexpensive, and often abandoned intervention to arrest respiratory impairment. It is controversial whether or not this population should be treated with other medications. Further studies should be conducted to elucidate the consequences of follow-up and prognosis in this clinical entity

Genetic Factors Associated with COPD Depend on the Ancestral Caucasian/Amerindian Component in the Mexican Population

Genetic variability influences the susceptibility to and severity of complex diseases; there is a lower risk of COPD in Hispanics than in non-Hispanic Caucasians. In this study, we included 830 Mexican-Mestizo subjects; 299 were patients with COPD secondary to tobacco smoking, and 531 were smokers without COPD. We employed a customized genotyping array of single nucleotide polymorphisms (SNPs). The population structure was evaluated by principal component analysis and allele association through a logistic regression model and haplotype identification. In this study, 118 individuals were identified with a high Caucasian component and 712 with a high Amerindian component. Independent of the ancestral contribution, two SNPs were associated with a reduced risk (p ≤ 0.01) of developing COPD in the CYP2A6 (rs4105144) and CYP2B6 (rs10426235) genes; however, a haplotype was associated with an increased risk of COPD (p = 0.007, OR = 2.47) in the CHRNA5-CHRNA3 loci among smokers with a high Caucasian component. In Mexican-Mestizo smokers, there are SNPs in genes that encode proteins responsible for the metabolism of nicotine associated with a lower risk of COPD; individuals with a high Caucasian component harboring a haplotype in the CHRNA5-CHRNA3 loci have a higher risk of suffering from COPD

Aggressive fluid accumulation is associated with acute kidney injury and mortality in a cohort of patients with severe pneumonia caused by influenza A H1N1 virus.

Fluid accumulation is associated with adverse outcomes such as acute kidney injury (AKI) in critically ill patients. This study aimed to describe the factors associated with AKI in individuals with influenza A H1N1 severe pneumonia, and explore the relation of fluid accumulation with AKI and mortality.We reviewed medical records of individuals with influenza A H1N1 severe pneumonia and no history of chronic kidney disease, attending a national referral center for respiratory diseases between November 2014 and May 2015. Demographic information, risk factors for AKI, physiologic and laboratory data, outcomes and information on fluid intake and output were recorded. Categorical variables were compared using the chi-square test. Quantitative variables were compared using the Mann-Whitney test. Factors associated with AKI and mortality were identified by binary logistic regression. Linear models of fluid accumulation rates for individuals and groups were estimated using segmented linear regression.Of 60 patients studied, 43 developed AKI (71.6%). Male gender was protective for AKI (p = 0.019). AKI was associated with nephrotoxic drugs (p = 0.016); PEEP>10 cm H2O on admission (p = 0.031); mortality (p = 0.037); and fluid accumulation ≥10% (fluid overload) at day 7 of hospitalization (p = 0.00026). Mortality was associated with older age (p = 0.009); nephrotoxic drugs (p = 0.034); and higher Pneumonia Severity Index score (112 vs. 76, p = 0.008) on admission. The Deceased-AKI group had a higher rate of fluid accumulation (expressed as ml/kg/body weight) than the Survivors-No AKI group during the study period of 7 days (Survivors-No AKI = 13.31 vs. Deceased-AKI = 22.76, p = 0.019). During the highest phase of fluid accumulation, the Survivors-No AKI group had a slower rate of fluid accumulation than the Survivors-AKI group (14.91 vs. 28.49, p = 0.001).A high rate of fluid accumulation was associated with AKI and mortality. We support the approach of resuscitation in acute illness, with an early transition to neutral and then negative fluid balances

Protective Role of Genetic Variants in HSP90 Genes-Complex in COPD Secondary to Biomass-Burning Smoke Exposure and Non-Severe COPD Forms in Tobacco Smoking Subjects

Background: Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory disease characterized by airflow obstruction, commonly present in smokers and subjects exposed to noxious particles product of biomass-burning smoke (BBS). Several association studies have identified single-nucleotide polymorphisms (SNP) in coding genes related to the heat shock proteins family-genes that codify the heat shock proteins (Hsp). Hsp accomplishes critical roles in regulating immune response, antigen-processing, eliminating protein aggregates and co-activating receptors. The presence of SNPs in these genes can lead to alterations in immune responses. We aimed to evaluate the association of SNPs in the HSP90 gene complex and COPD. Methods: We enrolled 1549 participants, divided into two comparison groups; 919 tobacco-smoking subjects (cases COPD-TS n = 294 and, controls SWOC n = 625) and 630 chronic exposed to BBS (cases COPD-BBS n = 186 and controls BBES n = 444). We genotyped 2 SNPs: the rs13296 in HSP90AB1 and rs2070908 in HSP90B1. Results: Through the dominant model (GC + CC), the rs2070908 is associated with decreased risk (p < 0.01, OR = 0.6) to suffer COPD among chronic exposed BBS subjects. We found an association between rs13296 GG genotype and lower risk (p = 0.01, OR = 0.22) to suffer severe COPD-TS forms in the severity analysis. Conclusions: single-nucleotide variants in the HSP90AB1 and HSP90B1 genes are associated with decreased COPD risk in subjects exposed to BBS and the most severe forms of COPD in tobacco-smoking subjects

Fluid accumulation rate during hospitalization.

<p>(A) Estimated linear model including all study participants during the study period of 7 days. (B) Estimated linear model of one individual during the study period of 7 days.</p

Characteristics of the Acute Kidney Injury Group and the non-Acute Kidney Injury Group on admission.

<p>Characteristics of the Acute Kidney Injury Group and the non-Acute Kidney Injury Group on admission.</p

Fluid accumulation rate per groups.

<p>(A) Estimated linear model in the group of Survivors-No AKI; the Survivors-AKI Group; and the Deceased-AKI group during the study period of 7 days. (B) The different slopes in the group of Survivors-No AKI; the Survivors-AKI group; and the Deceased-AKI group during the study period of 7 days.</p

Accumulated fluid balance per day during hospitalization.

<p>Accumulated fluid balance per day during hospitalization.</p

Phase I of fluid accumulation rate.

<p>(A) Estimated linear model in the group of Survivors-No AKI; the Survivors-AKI group; and the Deceased-AKI group during Phase I. (B) The different slopes in the group of Survivors-No AKI; the Survivors-AKI group; and the Deceased-AKI group during Phase I.</p