June 23/30, 2020 e933 Existing American Heart Association cardiopulmonary resuscitation (CPR) guidelines do not address the challenges of providing resuscitation in the setting of the coronavirus disease 2019 (COVID-19) global pandemic, wherein rescuers must continuously balance the immediate needs of the patients with their own safety. To address this gap, the American Heart Association, in collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, The Society of Critical Care Anesthesiologists, and American Society of Anesthesiologists, and with the support of the American Association of Critical Care Nurses and National Association of EMS Physicians, has compiled interim guidance to help rescuers treat individuals with cardiac arrest with suspected or confirmed COVID-19.Over the past 2 decades, there has been a steady improvement in survival after cardiac arrest occurring both inside and outside the hospital. 1 That success has relied on initiating proven resuscitation interventions such as high-quality chest compressions and defibrillation within seconds to minutes. The evolving and expanding outbreak of severe acute respiratory syndrome coronavirus 2 infections has created important challenges to such resuscitation efforts and requires potential modifications of established processes and practices. The challenge is to ensure that patients with or without COVID-19 who experience cardiac arrest get the best possible chance of survival without compromising the safety of rescuers, who will be needed to care for future patients. Complicating the emergency response to both out-of-hospital and in-hospital cardiac arrest is that COVID-19 is highly transmissible, particularly during resuscitation, and carries a high morbidity and mortality.Approximately 12% to 19% of COVID-positive patients require hospital admission, and 3% to 6% become critically ill. [2][3][4] Hypoxemic respiratory failure secondary to acute respiratory distress syndrome, myocardial injury, ventricular arrhythmias, and shock are common among critically ill patients and predispose them to cardiac arrest, [5][6][7][8] as do some of the proposed treatments such as hydroxychloroquine and azithromycin, which can prolong the QT. 9 With infections currently growing exponentially in the United States and internationally, the percentage of patients with cardiac arrests and COVID-19 is likely to increase.Healthcare workers are already the highest-risk profession for contracting the disease. 10 This risk is compounded by worldwide shortages of personal protective equipment (PPE). Resuscitations carry added risk to healthcare workers for many reasons. First, the administration of CPR involves performing numerous aerosol-generating procedures, including chest compressions, positive-pressure ventilation, and establishment of an advanced airway. During those procedures, viral particles can remain suspended in the air with a half-life of ≈1 hour and

Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel cause the autosomal recessive disease, cystic fibrosis (CF). The most common mutation is ΔF508, which deletes phenylalanine508. In vitro studies indicate that CFTR-ΔF508 is misprocessed, though in vivo consequences of the mutation are uncertain. To better understand effects of the ΔF508 mutation, we produced CFTRΔF508/ΔF508 pigs. Our biochemical, immunocytochemical and electrophysiological data on CFTR-ΔF508 in newborn pigs paralleled in vitro results. They also indicated that CFTRΔF508/ΔF508 airway epithelia retain a small residual CFTR conductance; maximal stimulation produced ~6% of wild-type function. Interestingly, cAMP agonists were less potent at stimulating current in CFTRΔF508/ΔF508 epithelia, suggesting that quantitative tests of maximal anion current may overestimate transport under physiological conditions. Despite residual CFTR function, four older CFTRΔF508/ΔF508 pigs developed lung disease strikingly similar to human CF. These results suggest that this limited CFTR activity is insufficient to prevent lung or gastrointestinal disease in CF pigs. These data also suggest that studies of recombinant CFTR-ΔF508 misprocessing predict in vivo behavior, which validates its use in biochemical and drug discovery experiments. These findings help elucidate the molecular pathogenesis of the common CF mutation and will guide strategies for developing new therapeutics.

Human lungs are constantly exposed to bacteria in the environment, yet the prevailing dogma is that healthy lungs are sterile. DNA sequencing-based studies of pulmonary bacterial diversity challenge this notion. However, DNA-based microbial analysis currently fails to distinguish between DNA from live bacteria and that from bacteria that have been killed by lung immune mechanisms, potentially causing overestimation of bacterial abundance and diversity. We investigated whether bacterial DNA recovered from lungs represents live or dead bacteria in bronchoalveolar lavage (BAL) fluid and lung samples in young healthy pigs. Live bacterial DNA was DNase I resistant and became DNase I sensitive upon human antimicrobial-mediated killing in vitro. We determined live and total bacterial DNA loads in porcine BAL fluid and lung tissue by comparing DNase I-treated versus untreated samples. In contrast to the case for BAL fluid, we were unable to culture bacteria from most lung homogenates. Surprisingly, total bacterial DNA was abundant in both BAL fluid and lung homogenates. In BAL fluid, 63% was DNase I sensitive. In 6 out of 11 lung homogenates, all bacterial DNA was DNase I sensitive, suggesting a predominance of dead bacteria; in the remaining homogenates, 94% was DNase I sensitive, and bacterial diversity determined by 16S rRNA gene sequencing was similar in DNase I-treated and untreated samples. Healthy pig lungs are mostly sterile yet contain abundant DNase I-sensitive DNA from inhaled and aspirated bacteria killed by pulmonary host defense mechanisms. This approach and conceptual framework will improve analysis of the lung microbiome in disease.

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