Interregional Transfers for Pandemic Surges.

BACKGROUND: Hospital inpatient and intensive care unit (ICU) bed shortfalls may arise due to regional surges in volume. We sought to determine how interregional transfers could alleviate bed shortfalls during a pandemic. METHODS: We used estimates of past and projected inpatient and ICU cases of coronavirus disease 2019 (COVID-19) from 4 February 2020 to 1 October 2020. For regions with bed shortfalls (where the number of patients exceeded bed capacity), transfers to the nearest region with unused beds were simulated using an algorithm that minimized total interregional transfer distances across the United States. Model scenarios used a range of predicted COVID-19 volumes (lower, mean, and upper bounds) and non-COVID-19 volumes (20%, 50%, or 80% of baseline hospital volumes). Scenarios were created for each day of data, and worst-case scenarios were created treating all regions' peak volumes as simultaneous. Mean per-patient transfer distances were calculated by scenario. RESULTS: For the worst-case scenarios, national bed shortfalls ranged from 669 to 58 562 inpatient beds and 3208 to 31 190 ICU beds, depending on model volume parameters. Mean transfer distances to alleviate daily bed shortfalls ranged from 23 to 352 miles for inpatient and 28 to 423 miles for ICU patients, depending on volume. Under all worst-case scenarios except the highest-volume ICU scenario, interregional transfers could fully resolve bed shortfalls. To do so, mean transfer distances would be 24 to 405 miles for inpatients and 73 to 476 miles for ICU patients. CONCLUSIONS: Interregional transfers could mitigate regional bed shortfalls during pandemic hospital surges.

Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells.

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.

Altered amino acid profile in patients with SARS-CoV-2 infection.

Low plasma arginine bioavailability has been implicated in endothelial dysfunction and immune dysregulation. The role of arginine in COVID-19 is unknown, but could contribute to cellular damage if low. Our objective was to determine arginine bioavailability in adults and children with COVID-19 vs. healthy controls. We hypothesized that arginine bioavailability would be low in patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We conducted a prospective observational study of three patient cohorts; arginine bioavailability was determined in asymptomatic healthy controls, adults hospitalized with COVID-19, and hospitalized children/adolescents <21 y old with COVID-19, MIS-C, or asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified on admission screen. Mean patient plasma amino acids were compared to controls using the Student's t test. Arginine-to-ornithine ratio, a biomarker of arginase activity, and global arginine bioavailability ratio (GABR, arginine/[ornithine+citrulline]) were assessed in all three groups. A total of 80 patients were included (28 controls, 32 adults with COVID-19, and 20 pediatric patients with COVID-19/MIS-C). Mean plasma arginine and arginine bioavailability ratios were lower among adult and pediatric patients with COVID-19/MIS-C compared to controls. There was no difference between arginine bioavailability in children with COVID-19 vs. MIS-C. Adults and children with COVID-19 and MIS-C in our cohort had low arginine bioavailability compared to healthy adult controls. This may contribute to immune dysregulation and endothelial dysfunction in COVID-19. Low arginine-to-ornithine ratio in patients with COVID-19 or MIS-C suggests an elevation of arginase activity. Further study is merited to explore the role of arginine dysregulation in COVID-19.