Age and Comorbidities Predict COVID-19 Outcome, Regardless of Innate Immune Response Severity: A Single Institutional Cohort Study.

The COVID-19 pandemic has claimed over eight hundred thousand lives in the United States alone, with older individuals and those with comorbidities being at higher risk of severe disease and death. Although severe acute respiratory syndrome coronavirus 2-induced hyperinflammation is one of the mechanisms underlying the high mortality, the association between age and innate immune responses in COVID-19 mortality remains unclear. DESIGN: Flow cytometry of fresh blood and multiplexed inflammatory chemokine measurements of sera were performed on samples collected longitudinally from our cohort. Aggregate impact of comorbid conditions was calculated with the Charlson Comorbidity Index, and association between patient factors and outcomes was calculated via Cox proportional hazard analysis and repeated measures analysis of variance. SETTING: A cohort of severely ill COVID-19 patients requiring ICU admission was followed prospectively. PATIENTS: In total, 67 patients (46 male, age 59 ± 14 yr) were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality in our cohort was 41.8%. We identified older age (hazard ratio [HR] 1.09 [95% CI 1.07-1.11]; p = 0.001), higher comorbidity index (HR 1.24 [95% CI 1.14-1.35]; p = 0.039), and hyponatremia (HR 0.90 [95% CI 0.82-0.99]; p = 0.026) to each independently increase risk for death in COVID-19. We also found that neutrophilia (R = 0.2; p = 0.017), chemokine C-C motif ligand (CCL) 2 (R = 0.3; p = 0.043), and C-X-C motif chemokine ligand 9 (CXCL9) (R = 0.3; p = 0.050) were weakly but significantly correlated with mortality. Older age was associated with lower monocyte (R = -0.2; p = 0.006) and cluster of differentiation (CD) 16+ cell counts (R = -0.2; p = 0.002) and increased CCL11 concentration (R = 0.3; p = 0.050). Similarly, younger patients (< 65 yr) demonstrated a rise in CD4 (b-coefficient = 0.02; p = 0.036) and CD8 (0.01; p = 0.001) counts, as well as CCL20 (b-coefficient = 6.8; p = 0.036) during their ICU stay. This CD8 count rise was also associated with survival (b-coefficient = 0.01; p = 0.023). CONCLUSIONS: Age, comorbidities, and hyponatremia independently predict mortality in severe COVID-19. Neutrophilia and higher CCL2 and CXCL9 levels are also associated with higher mortality, while independent of age.

Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study.

BACKGROUND: COVID-19 causes hypercoagulability, but the association between coagulopathy and hypoxemia in critically ill patients has not been thoroughly explored. This study hypothesized that severity of coagulopathy would be associated with acute respiratory distress syndrome severity, major thrombotic events, and mortality in patients requiring intensive care unit-level care. METHODS: Viscoelastic testing by rotational thromboelastometry and coagulation factor biomarker analyses were performed in this prospective observational cohort study of critically ill COVID-19 patients from April 2020 to October 2020. Statistical analyses were performed to identify significant coagulopathic biomarkers such as fibrinolysis-inhibiting plasminogen activator inhibitor 1 and their associations with clinical outcomes such as mortality, extracorporeal membrane oxygenation requirement, occurrence of major thrombotic events, and severity of hypoxemia (arterial partial pressure of oxygen/fraction of inspired oxygen categorized into mild, moderate, and severe per the Berlin criteria). RESULTS: In total, 53 of 55 (96%) of the cohort required mechanical ventilation and 9 of 55 (16%) required extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation-naïve patients demonstrated lysis indices at 30 min indicative of fibrinolytic suppression on rotational thromboelastometry. Survivors demonstrated fewer procoagulate acute phase reactants, such as microparticle-bound tissue factor levels (odds ratio, 0.14 [0.02, 0.99]; P = 0.049). Those who did not experience significant bleeding events had smaller changes in ADAMTS13 levels compared to those who did (odds ratio, 0.05 [0, 0.7]; P = 0.026). Elevations in plasminogen activator inhibitor 1 (odds ratio, 1.95 [1.21, 3.14]; P = 0.006), d-dimer (odds ratio, 3.52 [0.99, 12.48]; P = 0.05), and factor VIII (no clot, 1.15 ± 0.28 vs. clot, 1.42 ± 0.31; P = 0.003) were also demonstrated in extracorporeal membrane oxygenation-naïve patients who experienced major thrombotic events. Plasminogen activator inhibitor 1 levels were significantly elevated during periods of severe compared to mild and moderate acute respiratory distress syndrome (severe, 44.2 ± 14.9 ng/ml vs. mild, 31.8 ± 14.7 ng/ml and moderate, 33.1 ± 15.9 ng/ml; P = 0.029 and 0.039, respectively). CONCLUSIONS: Increased inflammatory and procoagulant markers such as plasminogen activator inhibitor 1, microparticle-bound tissue factor, and von Willebrand factor levels are associated with severe hypoxemia and major thrombotic events, implicating fibrinolytic suppression in the microcirculatory system and subsequent micro- and macrovascular thrombosis in severe COVID-19.

Key Pathogenic Factors in Coronavirus Disease 2019-Associated Coagulopathy and Acute Lung Injury Highlighted in a Patient With Copresentation of Acute Myelocytic Leukemia: A Case Report.

The role of concurrent illness in coronavirus disease 2019 (COVID-19) is unknown. Patients with leukemia may display altered thromboinflammatory responses. We report a 53-year-old man presenting with acute leukemia and COVID-19 who developed thrombotic complications and acute respiratory distress syndrome. Multiple analyses, including rotational thromboelastometry and flow cytometry on blood and bronchoalveolar lavage, are reported to characterize coagulation and immune profiles. The patient developed chemotherapy-induced neutropenia that may have protected his lungs from granulocyte-driven hyperinflammatory acute lung injury. However, neutropenia also alters viral clearing, potentially enabling ongoing viral propagation. This case depicts a precarious equilibrium between leukemia and COVID-19.

Longitudinal Recovery and Reduced Costs After 120 Sessions of Locomotor Training for Motor Incomplete Spinal Cord Injury.

OBJECTIVE: To determine the impact of long-term, body weight-supported locomotor training after chronic, incomplete spinal cord injury (SCI), and to estimate the health care costs related to lost recovery potential and preventable secondary complications that may have occurred because of visit limits imposed by insurers. DESIGN: Prospective observational cohort with longitudinal follow-up. SETTING: Eight outpatient rehabilitation centers that participate in the Christopher & Dana Reeve Foundation NeuroRecovery Network (NRN). PARTICIPANTS: Individuals with motor incomplete chronic SCI (American Spinal Injury Association Impairment Scale C or D; N=69; 0.1-45y after SCI) who completed at least 120 NRN physical therapy sessions. INTERVENTIONS: Manually assisted locomotor training (LT) in a body weight-supported treadmill environment, overground standing and stepping activities, and community integration tasks. MAIN OUTCOME MEASURES: International Standards for Neurological Classification of Spinal Cord Injury motor and sensory scores, orthostatic hypotension, bowel/bladder/sexual function, Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI), Berg Balance Scale, Modified Functional Reach, 10-m walk test, and 6-minute walk test. Longitudinal outcome measure collection occurred every 20 treatments and at 6- to 12-month follow-up after discharge from therapy. RESULTS: Significant improvement occurred for upper and lower motor strength, functional activities, psychological arousal, sensation of bowel movement, and SCI-FAI community ambulation. Extended training enabled minimal detectable changes at 60, 80, 100, and 120 sessions. After detectable change occurred, it was sustained through 120 sessions and continued 6 to 12 months after treatment. CONCLUSIONS: Delivering at least 120 sessions of LT improves recovery from incomplete chronic SCI. Because walking reduces rehospitalization, LT delivered beyond the average 20-session insurance limit can reduce rehospitalizations and long-term health costs.

Life care planning projections for individuals with motor incomplete spinal cord injury before and after locomotor training intervention: a case series.

BACKGROUND/PURPOSE: We present a retrospective case series of 2 individuals with motor-incomplete spinal cord injury (SCI) to examine differences in lifetime cost estimates before and after participation in an intensive locomotor training (LT) program. Sections of a life care plan (LCP) were used to determine the financial implications associated with equipment, home renovations, and transportation for patients who receive LT. An LCP is a viable method of quantifying outcomes following any therapeutic intervention. CASE DESCRIPTION: The LCP cases analyzed were a 61-year-old woman and a 4½-year-old boy with motor-incomplete SCI and impairments classified by the American Spinal Injury Association Impairment Scale (AIS) as AIS D and AIS C, respectively. INTERVENTIONS: Each patient received an intensive outpatient LT program 3 to 5 days per week. The 61-year-old woman received 198 sessions over 57 weeks and the 4½-year-old boy received 76 sessions over 16 weeks. OUTCOMES: The equipment, home renovation, and transportation costs of an LCP were calculated before and after LT. Prior to the implementation of LT, the 61-year-old woman had estimated lifetime costs between $150,247.00 and $199,654.00. Following LT, the estimated costs decreased to between $2010.00 and $2446.00 (a decrease of $148,237.00 and $197,208.00). Similarly, the 4-year-old boy had estimated lifetime costs for equipment, home renovation, and transportation between $535,050.00 and $771,665.00 prior to LT. However, the estimated costs decreased to between $97,260.00 and $200,047.00 (a decrease of $437,790.00 and $571,618.00) following LT. DISCUSSION: The lifetime financial costs associated with equipment, home renovations, and transportation following a motor-incomplete SCI were decreased following an intensive LT program for the 2 cases presented in this article. The LCP, including costs of rehabilitation and long-term medical and personal care costs, may be an effective tool to discern cost benefit of rehabilitation interventions.

NeuroRecovery Network provides standardization of locomotor training for persons with incomplete spinal cord injury.

OBJECTIVE: To illustrate the continuity of care afforded by a standardized locomotor training program across a multisite network setting within the Christopher and Dana Reeve Foundation NeuroRecovery Network (NRN). DESIGN: Single patient case study. SETTING: Two geographically different hospital-based outpatient facilities. PARTICIPANTS: This case highlights a 25-year-old man diagnosed with C4 motor incomplete spinal cord injury with American Spinal Injury Association Impairment Scale grade D. INTERVENTION: Standardized locomotor training program 5 sessions per week for 1.5 hours per session, for a total of 100 treatment sessions, with 40 sessions at 1 center and 60 at another. MAIN OUTCOME MEASURES: Ten-meter walk test and 6-minute walk test were assessed at admission and discharge across both facilities. For each of the 100 treatment sessions percent body weight support, average, and maximum treadmill speed were evaluated. RESULTS: Locomotor endurance, as measured by the 6-minute walk test, and overground gait speed showed consistent improvement from admission to discharge. Throughout training, the patient decreased the need for body weight support and was able to tolerate faster treadmill speeds. CONCLUSIONS: Data indicate that the patient continued to improve on both treatment parameters and walking function. Standardization across the NRN centers provided a mechanism for delivering consistent and reproducible locomotor training programs across 2 facilities without disrupting training or recovery progression.

Locomotor training: is translating evidence into practice financially feasible?

PURPOSE: Several lines of evidence suggest that locomotor training (LT) modalities, such as body weight-supported treadmill training (BWSTT), improves gait in individuals with incomplete spinal cord injury (SCI). Yet, manual BWSTT has been criticized for being cost prohibitive due to the number of staff required to perform this treatment. This study examined the financial viability of a LT program using manual BWSTT. METHODS: This retrospective study analyzed data from individuals with motor incomplete SCI who had participated in manual BWSTT in a hospital-based outpatient clinic between 2003 and 2005. Individuals were between 18 and 68 years of age and were medically stable. Descriptive statistics were performed to determine the mean for each of the following: date of injury, age, impairment, gender, total number of visits, total procedures billed, charges, basic reimbursement information, and costs associated with the treatment. RESULTS: The majority of individuals were male, classified as ASIA C, and had private insurance. Physical therapy evaluation, gait training, and therapeutic exercise were the most commonly billed procedures for all individuals. It was found that this locomotor training program, using the delivery model of one physical therapist, two physical therapy technicians, and one volunteer, was profitable. CONCLUSIONS: The findings from this study suggest that LT using manual BWSTT in a hospital-based outpatient clinic can be financially feasible when provided by one trained physical therapist, two technicians, and one well-trained volunteer.