Original Article: PDF OnlyRescue Therapy for Severe COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS) with Tissue Plasminogen Activator (tPA) A Case SeriesBarrett, Christopher D. MD1,2; Oren-Grinberg, Achikem MD3; Chao, Edward MD, FACS4; Moraco, Andrew H. MD5; Martin, Matthew J. MD, FACS6; Reddy, Srinivas H. MD, FACS4; Ilg, Annette M. MD3,7; Jhunjhunwala, Rashi MD, MA1; Uribe, Marco MD4; Moore, Hunter B. MD, PhD8; Moore, Ernest E. MD, FACS8,9; Baedorf-Kassis, Elias N.10; Krajewski, Megan L.3; Talmor, Daniel S. MD, MPH3; Shaefi, Shahzad MD, MPH3; Yaffe, Michael B. MD, PhD, FACS1,2Author Information 1Division of Acute Care Surgery, Trauma and Surgical Critical Care, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA USA 2Koch Institute for Integrative Cancer Research, Center for Precision Cancer Medicine, Departments of Biological Engineering and Biology, Massachusetts Institute of Technology, Cambridge MA, USA 3Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA USA 4Division of Trauma and Surgical Critical Care, Department of Surgery, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY USA 5Division of Pulmonary and Critical Care, Department of Medicine, St. Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA USA 6Department of Surgery, Scripps Mercy Hospital, San Diego, CA USA 7Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA USA 8Department of Surgery, University of Colorado Denver, Aurora, CO USA 9Ernest E Moore Shock Trauma Center at Denver Health, Department of Surgery, Denver, CO USA 10Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA USA Correspondence: Michael B. Yaffe, MD, PhD, FACS, MIT, UNITED STATES E-mail: firstname.lastname@example.org, Ph: 617-452-2103, Fax: 617-452-2978 Conflicts of Interest: CDB, HBM, EEM, and MBY have patents pending related to both coagulation/fibrinolysis diagnostics and therapeutic fibrinolytics, and are passive co-founders and holds stock options in Thrombo Therapeutics, Inc. HBM and EEM have received grant support from Haemonetics and Instrumentation Laboratories. MBY has previously received a gift of Alteplase (tPA) from Genentech, and owns stock options as a co-founder of Merrimack Pharmaceuticals. All other authors have nothing to disclose. Author Contribution Statement: CDB, SS, AMI, AOG, EC, AHM, MU, MJM, SHR, and MBY prepared the manuscript with critical input and revisions from EEM, HBM, RJ, ENMK, MLK, and DST. This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections. Journal of Trauma and Acute Care Surgery: May 14, 2020 - Volume Publish Ahead of Print - Issue - doi: 10.1097/TA.0000000000002786 Free PAP Metrics Abstract The COVID-19 pandemic has led to unprecedented stresses on modern medical systems, overwhelming the resource infrastructure in numerous countries while presenting a unique series of pathophysiologic clinical findings. Thrombotic coagulopathy is common in critically ill patients suffering from COVID-19, with associated high rates of respiratory failure requiring prolonged periods of mechanical ventilation. Here we report a case series of five patients suffering from profound, medically refractory COVID-19 associated respiratory failure who were treated with fibrinolytic therapy using tissue plasminogen activator (tPA, Alteplase). All five patients appeared to have an improved respiratory status following tPA administration: one patient had an initial marked improvement that partially regressed after several hours, one patient had transient improvements that were not sustained, and three patients had sustained clinical improvements following tPA administration. © 2020 Lippincott Williams & Wilkins, Inc.