Inhibition of the mitochondrial pyruvate carrier simultaneously mitigates hyperinflammation and hyperglycemia in COVID-19.

The relationship between diabetes and coronavirus disease 2019 (COVID-19) is bidirectional: Although individuals with diabetes and high blood glucose (hyperglycemia) are predisposed to severe COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also cause hyperglycemia and exacerbate underlying metabolic syndrome. Therefore, interventions capable of breaking the network of SARS-CoV-2 infection, hyperglycemia, and hyperinflammation, all factors that drive COVID-19 pathophysiology, are urgently needed. Here, we show that genetic ablation or pharmacological inhibition of mitochondrial pyruvate carrier (MPC) attenuates severe disease after influenza or SARS-CoV-2 pneumonia. MPC inhibition using a second-generation insulin sensitizer, MSDC-0602K (MSDC), dampened pulmonary inflammation and promoted lung recovery while concurrently reducing blood glucose levels and hyperlipidemia after viral pneumonia in obese mice. Mechanistically, MPC inhibition enhanced mitochondrial fitness and destabilized hypoxia-inducible factor-1α, leading to dampened virus-induced inflammatory responses in both murine and human lung macrophages. We further showed that MSDC enhanced responses to nirmatrelvir (the antiviral component of Paxlovid) to provide high levels of protection against severe host disease development after SARS-CoV-2 infection and suppressed cellular inflammation in human COVID-19 lung autopsies, demonstrating its translational potential for treating severe COVID-19. Collectively, we uncover a metabolic pathway that simultaneously modulates pulmonary inflammation, tissue recovery, and host metabolic health, presenting a synergistic therapeutic strategy to treat severe COVID-19, particularly in patients with underlying metabolic disease.

COVID-19 patients exhibit unique transcriptional signatures indicative of disease severity.

COVID-19 manifests a spectrum of respiratory symptoms, with the more severe often requiring hospitalization. To identify markers for disease progression, we analyzed longitudinal gene expression data from patients with confirmed SARS-CoV-2 infection admitted to the intensive care unit (ICU) for acute hypoxic respiratory failure (AHRF) as well as other ICU patients with or without AHRF and correlated results of gene set enrichment analysis with clinical features. The results were then compared with a second dataset of COVID-19 patients separated by disease stage and severity. Transcriptomic analysis revealed that enrichment of plasma cells (PCs) was characteristic of all COVID-19 patients whereas enrichment of interferon (IFN) and neutrophil gene signatures was specific to patients requiring hospitalization. Furthermore, gene expression results were used to divide AHRF COVID-19 patients into 2 groups with differences in immune profiles and clinical features indicative of severe disease. Thus, transcriptomic analysis reveals gene signatures unique to COVID-19 patients and provides opportunities for identification of the most at-risk individuals.

Cystic fibrosis learning network telehealth innovation lab during the COVID-19 pandemic: a success QI story for interdisciplinary care and agenda setting.

INTRODUCTION: The Cystic Fibrosis Foundation chronic care guidelines recommend monitoring clinical status of a patient with cystic fibrosis (CF) through quarterly interdisciplinary visits. At the beginning of the COVID-19 pandemic, the Cystic Fibrosis Learning Network (CFLN) designed and initiated a telehealth (TH) innovation lab (TH ILab) to support transition from the classic CF care model of quarterly in-person office visits to a care model that included TH. AIM: The specific aims of the TH ILab were to increase the percentage of virtual visits with interdisciplinary care (IDC) from 60% to 85% and increase the percentage of virtual visits in which patients and families participated in shared agenda setting (AS) from 52% to 85% by 31 December 2020. METHODS: The model for improvement methodology was used to determine the ILab aims, theory, interventions and measures. In the testing phase of the ILab, data related to process and outcome measures as well as learnings from plan-do-study-act cycles were collected, analysed and shared weekly with the TH ILab teams. Participating centres created processes for IDC and AS for TH visits and developed and shared quality improvement tools specific to their local context with other centres during the ILab weekly meetings and via a secure CFLN-maintained platform. RESULTS: Both specific aims were achieved ahead of the expected target date. By August 2020, 85% of the TH ILab visits provided IDC and 92% of patients were seen for CF care by teams from the TH ILab that participated in AS. CONCLUSION: Shared learning through a collaborative, data-driven process in the CFLN TH ILab rapidly led to standardised TH IDC and AS, which achieved reliable and sustainable processes which could be reproduced by other networks.

Mental health screening of patients with cystic fibrosis through telehealth during COVID-19: Evaluation of feasibility and process adoption.

INTRODUCTION: Persons with cystic fibrosis (CF) have higher rates of depression and anxiety compared to the general population. The Cystic Fibrosis Foundation guidelines recommend annual screening for depression and anxiety for people with CF. COVID-19 and related social distancing has created challenges for administration of mental health screening by CF centers. The aim of this quality improvement project was to evaluate the feasibility of implementing mental health screening during multidisciplinary telehealth appointments for adult patients with CF during COVID-19, adoption of screening by CF mental health providers, and patient screening results before and after introduction of telehealth. METHOD: Patients were screened via telehealth using the PHQ-9 and GAD-7 between April and October 2020. RESULTS: CF mental health providers implemented a mental health screening process via telehealth and 93.9% of patients seen during that time completed the screening. The screening did not increase clinic visit length and no significant differences were found between rates of depression and anxiety and 2019 clinic rates. DISCUSSION: Implementation of mental health screening during a multidisciplinary telehealth clinic is feasible and can be adopted by providers and patients, even when health systems operations are impacted by COVID-19. It allows CF centers to maintain adherence to mental health screening and treatment guidelines. This method of screening can be applied to other patient populations and systems of care to expand access to mental health services during COVID-19 and beyond. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Real-World Outcomes in Cystic Fibrosis Telemedicine Clinical Care in a Time of a Global Pandemic.

BACKGROUND: During the COVID-19 pandemic, the University of Virginia adult cystic fibrosis (CF) center transitioned from in-person clinical encounters to a model that included interdisciplinary telemedicine. The pandemic presented an unprecedented opportunity to assess the impact of the interdisciplinary telemedicine model on clinical CF outcomes. RESEARCH QUESTION: What are the clinical outcomes of a care model that includes interdisciplinary telemedicine (IDC-TM) compared with in-person clinical care for patients with CF during the COVID-19 pandemic? STUDY DESIGN AND METHODS: Adults with CF were included. The prepandemic year was defined as March 17, 2019, through March 16, 2020, and the pandemic year (PY) was defined as March 17, 2020, through March 16, 2021. Patients were enrolled starting in the PY. Prepandemic data were gathered retrospectively. Telemedicine visits were defined as clinical encounters via secured video communication. Hybrid visits were in-person evaluations by physician, with in-clinic video communication by other team members. In-person visits were encounters with in-person providers only. All encounters included previsit screening. Outcomes were lung function, BMI, exacerbations, and antibiotic use. FEV1 percent predicted, exacerbations, and antibiotic use were adjusted for the effect of elexacaftor/tezacaftor/ivacaftor treatment. RESULTS: One hundred twenty-four patients participated. One hundred ten patients were analyzed (mean age, 35 years; range, 18-69 years). Ninety-five percent had access to telemedicine (n = 105). Telemedicine visits accounted for 64% of encounters (n = 260), hybrid visits with telemedicine support accounted for 28% of encounters (n = 114), and in-person visits accounted for 7% of encounters (n = 30). No difference in lung function or exacerbation rate during the PY was found. BMI increased from 25 to 26 kg/m2 (t100 = -4.72; P < .001). Antibiotic use decreased from 316 to 124 episodes (z = 8.81; P < .0001). INTERPRETATION: This CF care model, which includes IDC-TM, successfully monitored lung function and BMI, identified exacerbations, and followed guidelines-based care during the pandemic. A significant decrease in antibiotic use suggests that social mitigation strategies were protective. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04402801; URL: www. CLINICALTRIALS: gov.

Home spirometry utilisation in telemedicine clinic for cystic fibrosis care during COVID-19 pandemic: a quality improvement process.

IntroductionThe Cystic Fibrosis (CF) Foundation chronic care guidelines recommend monitoring spirometry during quarterly multidisciplinary visits to identify early lung function decline. During the COVID-19 pandemic, the CF adult clinic at University of Virginia (UVA) transitioned from the classic CF care model to a model that included quarterly multidisciplinary telemedicine visits. While using telemedicine, CF care needed to include spirometry monitoring. Only a fraction of adult CF patients at UVA owned and used home spirometers (HS) in March 2020. AIM: The specific aims of this quality improvement (QI) project were to increase the percentage of eligible adult CF patients who owned an HSs from 37% to 85% and to increase the percentage of adult CF patients seen at UVA with available spirometry in telemedicine from 50% to 95% by 31 December 2020. METHODS: Following the Model for Improvement QI methodology, a standardised process was developed for monitoring forced expiratory volume in 1 s with HS during multidisciplinary telemedicine visits during the COVID-19 pandemic. INTERVENTION: (1) HSs were distributed to eligible patients and (2) Home spirometry was monitored in eligible patients with each telemedicine visit and results were used for clinical care decisions. RESULTS: Both specific aims were achieved ahead of expected date. In March 2020, the beginning of the pandemic, 37% (49/131) of patients owned an HS and 50% (9/18) of patients seen via telemedicine performed spirometry at home. By September 2020, 97% (127/131) of adult patients at UVA owned an HS and by October 2020, 96% (24/25) of patients provided spirometry results during their telemedicine encounters. CONCLUSION: Employing QI tools to standardise the process of monitoring spirometry data with home devices via telemedicine is reliable and sustainable and can be replicated across centres that provide care for patients with CF.

Impact of COVID-19 on social determinants of health for adults with cystic fibrosis.

INTRODUCTION: Outcomes in cystic fibrosis are influenced by multiple factors, including social determinants of health. Low socioeconomic status has been shown to be associated with lung function decline, increased exacerbation rates, increased health care utilization, and decreased survival in cystic fibrosis. The COVID-19 pandemic disrupted the US economy, placing people with cystic fibrosis at risk for negative impacts due to changes in social determinants of health. METHODS: To characterize the impact of COVID-19-related changes in social determinants of health in the adult cystic fibrosis population, a social determinants of health questionnaire was designed and distributed to patients as part of a quality improvement project. RESULTS: Of 132 patients contacted, 76 (57.6%) responses were received. Of these responses, 22 (28.9%) answered yes to at least one question that indicated an undesired change in social determinants of health. Patients with stable employment prior to COVID-19 were more likely to endorse undesired change in all domains of the questionnaire, and the undesired changes were most likely to be related to employment, insurance security, and access to medications. Patients receiving disability were more likely to report hardship related to utilities and food security compared with patients previously employed or unemployed. Of patients endorsing risk of socioeconomic hardship, 21 (95.5%) were contacted by a social worker and provided resources. CONCLUSION: Utilizing a social determinants of health questionnaire to screen for social instability in the context of COVID-19 is feasible and beneficial for patients with cystic fibrosis. Identifying social issues early during the pandemic and implementing processes to provide resources may help patients with cystic fibrosis mitigate social hardship and maintain access to health care and medications.

Preserving Multidisciplinary Care Model and Patient Safety During Reopening of Ambulatory Cystic Fibrosis Clinic for Nonurgent Care: A Hybrid Telehealth Model.

Introduction: The University of Virginia's (UVA's) adult cystic fibrosis (CF) program implemented a rapid and successful transition to telemedicine care mid-March of 2020 in response to the coronavirus disease 2019 (COVID-19) pandemic. In May 2020, the adult UVA CF program redesigned the care model to adjust to the reopening of ambulatory operations and introduced hybrid clinics. The goal remained to minimize person-to-person contacts for patients and care team members (CTMs) while ensuring patient access to quarterly, coproduced, synchronous, multidisciplinary CF care, similar to pre-COVID-19 era regular CF care. Methods: Using quality improvement tools, the UVA adult CF program created a standardized hybrid model of care for in-clinic visits, which included combined components of in-person and synchronous virtual interactions with members of the multidisciplinary team. Results: A total of 16 hybrid visits occurred between May 14 and June 11, 2020. All hybrid visits were multidisciplinary and fulfilled patient requests to see CTMs. All patients seen by hybrid encounter participated in coproduced agenda setting, underwent spirometry, and obtained blood work; 75% provided sputum for surveillance culture. Each hybrid visit type was attended by an average of four CTMs and amounted to 63 separate interactions. Of these interactions, 28 were completed virtually, reducing in-person contacts and personal protection equipment utilization by 44% compared with a fully in-person model of care. Conclusions: Combining in-person and telehealth components in a multidisciplinary CF care model reduces patient and staff interactions and personal protective equipment utilization. The hybrid model of in-person/remote combined care enables reliable access to biological data to support medical decision making while mitigating the risks of person-to-person contact for patients and staff.

A Feasibility Study of Urgent Implementation of Cystic Fibrosis Multidisciplinary Telemedicine Clinic in the Face of COVID-19 Pandemic: Single-Center Experience.

Introduction: The coronavirus 2019 (COVID-19) pandemic has become a major world health problem. All U.S. states have advised their cystic fibrosis (CF) populations to socially isolate. Major health care payors such as Medicare and most private insurance companies have agreed to reimburse health care providers for telemedicine and telephone visits. Methods: The CF adult team at the University of Virginia (UVA) transitioned from face-to-face clinics to multidisciplinary telemedicine clinics by using WebEx® (Cisco Systems, San Jose, CA), a Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliant platform. Interventions: Patients were contacted before scheduled visits and triaged into: (1) patients eligible for the multidisciplinary telemedicine clinic, (2) patients to be seen in clinic urgently due to acute needs, and (3) stable patients who can be rescheduled at a later time. Ineligible patients for the telemedicine clinic due to lack of access to technology were followed up via telephone. Results: A total of 63 patients were scheduled to be seen in the UVA clinic over 4 weeks, 10 clinic days. Of these patients, 20 (32%) rescheduled their appointment. In addition, 2 patients (3%) were seen in clinic for acute needs and 38 (60%) were seen by the multidisciplinary team through telemedicine. Conclusions: In the context of the COVID-19 pandemic, implementing a telemedicine clinic process that serves the needs of a multidisciplinary care team is paramount to preserving the CF care model. Through a systematic design and test process, a feasible and sustainable program was created that can be utilized by other multidisciplinary programs to adapt to their context.