Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.

Sick from what? Trauma during the SARS-CoV-2 pandemic.

BACKGROUND: We present the case of two brothers with identical mechanisms of injury presenting simultaneously, one with SARS-Cov-2 respiratory failure and the other in hemorrhagic shock. SUMMARY: Healthcare globally and in the United States met novel challenges during the unprecedented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) health crisis. The effect of SARS-CoV-2 on hospital and health care delivery systems has been widely reported. Elective surgical procedures were suspended; however, trauma and acute care services remained active and faced unique challenges during this pandemic. Trauma patients by their nature of injury require rapid assessment and treatment to include invasive emergency operations. Not only do trauma centers have to adapt to limited resources and new procedures limiting exposure, they are also met with the confounding issue of trauma patients concomitantly presenting with SARS-CoV-2 respiratory illness. CONCLUSION: Trauma care providers must now contend with SARS-CoV-2 on the differential for patients presenting with trauma. This is demonstrated by our case of two brothers with identical mechanisms of injury presenting simultaneously, one in shock from respiratory failure and the other hemorrhagic.

Where did the patients go? Changes in acute appendicitis presentation and severity of illness during the coronavirus disease 2019 pandemic: A retrospective cohort study.

BACKGROUND: The coronavirus disease 2019 pandemic restricted movement of individuals and altered provision of health care, abruptly transforming health care-use behaviors. It serves as a natural experiment to explore changes in presentations for surgical diseases including acute appendicitis. The objective was to determine if the pandemic was associated with changes in incidence of acute appendicitis compared to a historical control and to determine if there were associated changes in disease severity. METHODS: The study is a retrospective, multicenter cohort study of adults (N = 956) presenting with appendicitis in nonpandemic versus pandemic time periods (December 1, 2019-March 10, 2020 versus March 11, 2020-May 16, 2020). Corresponding time periods in 2018 and 2019 composed the historical control. Primary outcome was mean biweekly counts of all appendicitis presentations, then stratified by complicated (n = 209) and uncomplicated (n = 747) disease. Trends in presentations were compared using difference-in-differences methodology. Changes in odds of presenting with complicated disease were assessed via clustered multivariable logistic regression. RESULTS: There was a 29% decrease in mean biweekly appendicitis presentations from 5.4 to 3.8 (rate ratio = 0.71 [0.51, 0.98]) after the pandemic declaration, with a significant difference in differences compared with historical control (P = .003). Stratified by severity, the decrease was significant for uncomplicated appendicitis (rate ratio = 0.65 [95% confidence interval 0.47-0.91]) when compared with historical control (P = .03) but not for complicated appendicitis (rate ratio = 0.89 [95% confidence interval 0.52-1.52]); (P = .49). The odds of presenting with complicated disease did not change (adjusted odds ratio 1.36 [95% confidence interval 0.83-2.25]). CONCLUSION: The pandemic was associated with decreased incidence of uncomplicated appendicitis without an accompanying increase in complicated disease. Changes in individual health care-use behaviors may underlie these differences, suggesting that some cases of uncomplicated appendicitis may resolve without progression to complicated disease.