This retrospective analysis from 5 Maryland and Washington, DC area hospitals determines factors on hospital admission predictive of severe disease or death from COVID-19 and describes patient trajectories and outcomes categorized using the WHO COVID-19 disease severity scale.
Background: Normally, regulatory T cells (also known as T regulatory cells or Tregs) migrate into inflamed tissues, dampening inflammatory responses and hastening tissue repair (1). Patients with coronavirus disease 2019 (COVID-19) and acute respiratory distress syndrome (ARDS) have protracted hospitalizations characterized by excessive systemic inflammation (cytokine storm) and delayed lung repair, which is partly due to reduced or defective Tregs (2). Objective: To describe outcomes in 2 patients with COVID-19 and ARDS who were treated with Tregs. Case Reports: The first patient was a 69-year-old man with autism who was hospitalized from his nursing home with COVID-19-induced fever and dyspnea 1 week after initial symptom onset. Despite 5 days of receiving hydroxychloroquine and broad-spectrum antimicrobial agents, he progressed to ARDS and received tocilizumab on day 7 and mechanical ventilation beginning on day 8. Renal failure and shock developed, requiring continuous, venovenous hemofiltration and vasopressors. Refractory hypoxemia required prone positioning, neuromuscular paralysis, inhaled nitric oxide, and FIO 2 greater than 70%. We administered compassionate use, cryopreserved, allogeneic Tregs derived from cord blood (CB) and expanded ex vivo (Cellenkos) at 1 × 10 8 cells per dose intravenously on days 13 and 17. By day 17, he had returned to supine positioning, paralytics were withdrawn, inhaled nitric oxide was weaned to zero, FIO 2 was decreased to 50%, vasopressors were withdrawn, and inflammatory markers were reduced (Table 1). He was extubated on day 22. On day 25, he required a tracheostomy. He is currently receiving care in a weaning facility. The second patient was a 47-year-old man who was hospitalized for COVID-19-induced fever and dyspnea 1 week after initial symptom onset. On day 2 of his hospitalization, he received tocilizumab, and hours later, he had increasing lactate levels and required mechanical ventilation and high-dose Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=L20-0681.
OBJECTIVES: To evaluate the impact of duration of hyperoxia on neurologic outcome and mortality in patients undergoing venoarterial extracorporeal membrane oxygenation. DESIGN: A retrospective analysis of venoarterial extracorporeal membrane oxygenation patients admitted to the Johns Hopkins Hospital. The primary outcome was neurologic function at discharge defined by modified Rankin Scale, with a score of 0–3 defined as a good neurologic outcome, and a score of 4–6 defined as a poor neurologic outcome. Multivariable logistic regression analysis was performed to evaluate the association between hyperoxia and neurologic outcomes. SETTING: The Johns Hopkins Hospital Cardiovascular ICU and Cardiac Critical Care Unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured first and maximum Pao 2 values, area under the curve per minute over the first 24 hours, and duration of mild, moderate, and severe hyperoxia. Of 132 patients on venoarterial extracorporeal membrane oxygenation, 127 (96.5%) were exposed to mild hyperoxia in the first 24 hours. Poor neurologic outcomes were observed in 105 patients (79.6%) (102 with vs 3 without hyperoxia; p = 0.14). Patients with poor neurologic outcomes had longer exposure to mild (19.1 vs 15.2 hr; p = 0.01), moderate (14.6 vs 9.2 hr; p = 0.003), and severe hyperoxia (9.1 vs 4.0 hr; p = 0.003). In a multivariable analysis, patients with worse neurologic outcome experienced longer durations of mild (adjusted odds ratio, 1.10; 95% CI, 1.01–1.19; p = 0.02), moderate (adjusted odds ratio, 1.12; 95% CI, 1.04–1.22; p = 0.002), and severe (adjusted odds ratio, 1.19; 95% CI, 1.06–1.35; p = 0.003) hyperoxia. Additionally, duration of severe hyperoxia was independently associated with inhospital mortality (adjusted odds ratio, 1.18; 95% CI, 1.08–1.29; p < 0.001). CONCLUSIONS: In patients undergoing venoarterial extracorporeal membrane oxygenation, duration and severity of early hyperoxia were independently associated with poor neurologic outcomes at discharge and mortality.
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