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Biomedical subjects

Carolyn S Calfee

Publications and source records attributed to Carolyn S Calfee.

4 recordsLinked to original sources

High-affinity CD16A polymorphism associated with reduced risk ofsevere COVID-19.

CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, particularly whether it limits viral spread and disease severity or contributes to the immunopathogenesis of COVID-19. We hypothesized that the high-affinity CD16AV176 polymorphism influences these outcomes. Using an in vitro reporter system, we demonstrated that CD16AV176 is a more potent and sensitive activator than the common CD16AF176 allele. To assess its clinical relevance, we analyzed 1,027 patients hospitalized with COVID-19 from the Immunophenotyping Assessment in a COVID-19 cohort (IMPACC), a comprehensive longitudinal dataset with extensive transcriptomic, proteomic, and clinical data. The high-affinity CD16AV176 allele was associated with a significantly reduced risk of ICU admission, mechanical ventilation, and severe disease trajectories. Lower anti-SARS-CoV-2 IgG titers were correlated to CD16AV176; however, there was no difference in viral load across CD16A genotypes. Proteomic analysis revealed that participants homozygous for CD16AV176 had lower levels of inflammatory mediators. These findings suggest that CD16AV176 enhances early NK cell-mediated immune responses, limiting severe respiratory complications in COVID-19. This study identifies a protective genetic factor against severe COVID-19, informing future host-directed therapeutic strategies.

Humans↗

The influence of perceived control of asthma on health outcomes.

BACKGROUND: Psychosocial factors play an important role in outcomes of asthma. Perceived control, a measure of patients' beliefs about their ability to control their disease, has not been studied in association with asthma health outcomes METHODS: We used data from a prospective cohort study of patients who were hospitalized for asthma (n = 865). After hospital discharge, we conducted structured telephone interviews to obtain demographic characteristics, asthma history, and psychological variables. Interviews included administration of the Perceived Control of Asthma Questionnaire (PCAQ). We then prospectively measured emergency department (ED) visits and hospitalizations for asthma over time, with a median follow-up time of 1.9 years RESULTS: Greater perceived control was associated with better physical health status (mean score increment per 2-point change in PCAQ score, 1.13; 95% confidence interval [CI], 0.79 to 1.47), better asthma-related quality of life (mean score increment, -2.24; 95% CI, -2.6 to -1.83), fewer days of restricted activity due to asthma (mean increment, -1.23; 95% CI, -1.62 to -0.83), and lower asthma severity scores (mean score increment, -0.40; 95% CI, -0.53 to -0.27). In a multivariate model, greater perceived control was associated with a significantly decreased prospective risk of ED visits (hazard ratio [HR], 0.92; 95% CI, 0.86 to 0.98; p = 0.008) and hospitalizations for asthma (HR, 0.84; 95% CI, 0.78 to 0.90; p < 0.0001). There was no association found between perceived control and most aspects of preventive care or self-management CONCLUSIONS: Greater perceived control is associated with improved asthma-related health status as well as with a decreased prospective risk of severe asthma attacks resulting in emergency health-care utilization. This difference does not appear to be mediated by changes in preventive care or asthma self-management practices.

Adult↗

Recent advances in mechanical ventilation.

Important advances have been made over the past decade towards understanding the optimal approach to ventilating patients with acute respiratory failure. Evidence now supports the use of noninvasive positive pressure ventilation in selected patients with hypercapnic respiratory failure and chronic obstructive pulmonary disease, cardiogenic pulmonary edema, and for facilitating the discontinuation of ventilatory support in patients with chronic pulmonary disease. The concept of a lung protective ventilatory strategy has revolutionized the management of the acute respiratory distress syndrome. The process of liberation from mechanical ventilation is becoming more standardized, with evidence supporting daily trials of spontaneous breathing in all suitable mechanically ventilated patients. This article critically reviews the most important recent advances in mechanical ventilation and suggests future directions for further research in the field.

Acute Disease↗