Leveraging metabolic modeling to identify functional metabolic alterations associated with COVID-19 disease severity.

OBJECTIVE: Since the COVID-19 pandemic began in early 2020, SARS-CoV2 has claimed more than six million lives world-wide, with over 510 million cases to date. To reduce healthcare burden, we must investigate how to prevent non-acute disease from progressing to severe infection requiring hospitalization. METHODS: To achieve this goal, we investigated metabolic signatures of both non-acute (out-patient) and severe (requiring hospitalization) COVID-19 samples by profiling the associated plasma metabolomes of 84 COVID-19 positive University of Virginia hospital patients. We utilized supervised and unsupervised machine learning and metabolic modeling approaches to identify key metabolic drivers that are predictive of COVID-19 disease severity. Using metabolic pathway enrichment analysis, we explored potential metabolic mechanisms that link these markers to disease progression. RESULTS: Enriched metabolites associated with tryptophan in non-acute COVID-19 samples suggest mitigated innate immune system inflammatory response and immunopathology related lung damage prevention. Increased prevalence of histidine- and ketone-related metabolism in severe COVID-19 samples offers potential mechanistic insight to musculoskeletal degeneration-induced muscular weakness and host metabolism that has been hijacked by SARS-CoV2 infection to increase viral replication and invasion. CONCLUSIONS: Our findings highlight the metabolic transition from an innate immune response coupled with inflammatory pathway inhibition in non-acute infection to rampant inflammation and associated metabolic systemic dysfunction in severe COVID-19.

Pseudo-outbreak of coagulase-negative staphylococcus species from blood cultures highlights unique challenges in care of critically ill patients with COVID-19

Background: In response to the COVID-19 pandemic, a dedicated intensive care unit for patients infected with SARS-CoV-2 was created at our institution. We noticed a marked increase in the number of blood cultures positive for coagulase-negative Staphylococcus species (CoNS) that highlights unique challenges that arise with the creation of new units and workflows. Methods: We reviewed all blood culture results from the COVID-19 intensive care unit (CoVICU) from April 15 to May 29. We reviewed all blood cultures taken from the oncology ward, medical intensive care unit (MICU), and emergency department (ED) for the same time frame as a comparison. We calculated contamination rates, using the clinical microbiology laboratory criteria for possible contaminants based on species and number of positive blood cultures. Results: There were 324 total blood cultures collected from the CoVICU with 27/324 (8.3%) positive for organisms deemed contaminant, 10/324 (3.1%) were positive considered bloodstream infections (BSI);the ratio of BSI:contaminant was 1:2.7. For the MICU, ED, and oncology units contamination rates were 2/197 (1%), 33/747 (4.4%), and 2/334 (0.6%), respectively;and the ratio of BSI:contaminant was 5:1, 2.2:1, and 17.5:1, respectively. There was a significant relationship between contamination rates and unit, X2(3, N = 1602) = 30.85, p < 0.001. Conclusion: Upon investigation, peripheral blood draw kits were not stocked in the CoVICU. Additionally, certain components of standard work for blood culture collection (e.g. glove exchange) could not be performed per usual practice due to isolation precautions. Peripheral blood draws were routinely performed by nurses in CoVICU and MICU while phlebotomy performed these in other comparison units. We suspect that lack of availability of blood draw kits and disruption of typical workflow in isolation rooms contributed to an unusually high number of contaminated blood cultures among patients admitted to the CoVICU. Notably, the CoVICU and MICU providers were the same pool of caregivers, further supporting a process issue related to isolation precautions. Institutions should be aware of the need for extra attention to supply chain management and examination of disruption to standard work that arise in the management of COVID-19 patients.

Feasibility of manual ventilation replacing mechanical ventilation

Background: During the COVID-19 pandemic it is anticipated that there will be a shortage of mechanical ventilators available for patients in critical condition. This has sparked many discussions about rationing resources and withholding care;however, an alternative may be to implement manual ventilation in these situations instead. Manual ventilation and a safety device were assessed for efficacy of extended use, such as may be required during this pandemic. Methods: To evaluate physical output characteristics of extended manual ventilation and efficacy of a barotrauma mitigation device, 47 medical students, nurses and medics completed two 1-hour manual ventilation sessions using the SmartLung 2000 Lung Simulator and 5300 Series Mass Flow Meter with a SPUR II resuscitator bag and endotracheal tube, mimicking a healthy adult with normal lung physiology, both with and without the Sotair device. Providers were randomised to complete their initial session either with or without the Sotair device. Findings: Collected data show wide variability in tidal volume and peak pressure in unmitigated manual breaths despite prior training and independent exploration of the resuscitation equipment prior to testing. The mean (±SD) tidal volume with bag only was 563.9±128.8 mL and with the safety device 536.1±80.9 mL (p<0.0001). The mean peak inspiratory pressure with bag only was 17.2±6.3 cm H2O and with the safety device 14.9±2.4 cm H2O (p<0.0001). Interpretation: While extended manual ventilation cannot replace mechanical ventilation, it is feasible with a safety device, which may reduce barotrauma, underventilation and overventilation. These results also demonstrate that withholding care and rationing resources may not be necessary. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.