Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19.

BACKGROUND: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings. OBJECTIVES: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies. METHODS: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies. RESULTS: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC. CONCLUSIONS: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.

Differential Ventilation Using Flow Control Valves as a Potential Bridge to Full Ventilatory Support during the COVID-19 Crisis.

BACKGROUND: During the COVID-19 pandemic, ventilator sharing was suggested to increase availability of mechanical ventilation. The safety and feasibility of ventilator sharing is unknown. METHODS: A single ventilator in pressure control mode was used with flow control valves to simultaneously ventilate two patients with different lung compliances. The system was first evaluated using high-fidelity human patient simulator mannequins and then tested for 1 h in two pairs of COVID-19 patients with acute respiratory failure. Patients were matched on positive end-expiratory pressure, fractional inspired oxygen tension, and respiratory rate. Tidal volume and peak airway pressure (PMAX) were recorded from each patient using separate independent spirometers and arterial blood gas samples drawn at 0, 30, and 60 min. The authors assessed acid-base status, oxygenation, tidal volume, and PMAX for each patient. Stability was assessed by calculating the coefficient of variation. RESULTS: The valves performed as expected in simulation, providing a stable tidal volume of 400 ml each to two mannequins with compliance ratios varying from 20:20 to 20:90 ml/cm H2O. The system was then tested in two pairs of patients. Pair 1 was a 49-yr-old woman, ideal body weight 46 kg, and a 55-yr-old man, ideal body weight 64 kg, with lung compliance 27 ml/cm H2O versus 35 ml/cm H2O. The coefficient of variation for tidal volume was 0.2 to 1.7%, and for PMAX 0 to 1.1%. Pair 2 was a 32-yr-old man, ideal body weight 62 kg, and a 56-yr-old woman, ideal body weight 46 kg, with lung compliance 12 ml/cm H2O versus 21 ml/cm H2O. The coefficient of variation for tidal volume was 0.4 to 5.6%, and for PMAX 0 to 2.1%. CONCLUSIONS: Differential ventilation using a single ventilator is feasible. Flow control valves enable delivery of stable tidal volume and PMAX similar to those provided by individual ventilators.

Correlation between respiratory syncytial virus genotype and severity of illness.

Respiratory syncytial virus (RSV) causes seasonal outbreaks of respiratory tract infections, but the viral factors associated with virulence remain unknown. To determine whether RSV genotype correlated with severity of illness, isolates were characterized by phylogenetic analysis of the RSV G gene, and a composite score was used to quantify severity of illness. During the 1998-1999 and 1999-2000 winter seasons, 137 subgroup A and 84 subgroup B isolates were identified. The severity of illness caused by subgroup A isolates did not differ from that caused by subgroup B isolates (P=.086). However, the GA3 clade was associated with significantly greater severity of illness, compared with clades GA2 (P=.004) and GA4 (P=.016). In a subpopulation of patients < or =24 months old who had no known risk factors for severe RSV disease, clade GA3 was again associated with greater severity of illness, compared with clade GA2 (P=.018). Severity of RSV infection is associated with RSV genotype.