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Pathogenesis COVID-19 Rush Journal Club: Pathogenesis NOVEL CORONAVIRUS SARS-COV-2. Transmission electron micrograph of SARS-CoV-2 virus particles, iso- lated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID Available at: https://www.flickr.com/photos/niaid/49597768397/in/al- bum-72157712914621487/. Accessed April 19, 2020. This document is a collection of efforts from students of Rush University. It provides brief reviews of research articles regarding COVID-19. We hope that this will be helpful to clini- cians, students, community leaders, and the general public. This document, however, does not act as a replacement of the original source documents. Please use the DOI on each page to read more. Student Editors Alice Burgess, MS3 Joseph Dodson, MS2 Audrey Sung, MS2 John Levinson, MS3 Ayesan Rewane, MSCR Student Editors in Chief Joseph deBettencourt, MS4 Lindsay Friedman, MS4 Leah Greenfield, MS3 Danesha Lewis, PhD candidate Morgan Sturgis, MS3 Travis Tran, MS3 Ashley Wehrheim, MS3 Kaitlyn Wehrheim, MS3 Bijan Zarrabi, MS3 Faculty Editors and Mentors Frank Cockerill, MD - Adjunct Professor of Medicine Mete Altintas, PhD - Director, Translational and Preclinical Studies Rachel Miller, PhD - Assistant Professor of Internal Medicine Michael Bradaric, PhD - Director of Pharmacology, Rush Medical College Brinda Bradaric, PhD - Assistant Professor, Dept of Health Sciences Jitesh Pratap, PhD - Assistant Professor, Dept of Cell and Molecular Medicine Steve Mangos, PhD - Director, Internal Medicine Drug Discovery and Imaging Core Graphic design Sam Auger, MD Beth Hall, MD Joseph deBettencourt, MS4 Is there a study you’d like us to review? Do you have questions or feedback? Please email: [email protected] COVID-19Reviews are provided by students at Rush University and edited by Rush Rushfaculty. Journal Level Club of evidence in each study, if applicable, was assessed us- ing the Oxford guidelines as presented below. More information can be found at http://www.cebm.net/2016/05/ocebm-levels-of-evidence/ Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Question Step 1 Step 2 Step 3 Step 4 Step 5 (Level 5) (Level 1*) (Level 2*) (Level 3*) (Level 4*) How common is the Local and current random sample Systematic review of surveys Local non-random sample** Case-series** n/a problem? surveys (or censuses) that allow matching to local circumstances** Is this diagnostic or Systematic review Individual cross sectional Non-consecutive studies, or studies without Case-control studies, or Mechanism-based monitoring test of cross sectional studies with studies with consistently consistently applied reference standards** “poor or non-independent reasoning accurate? consistently applied reference applied reference standard and reference standard** (Diagnosis) standard and blinding blinding What will happen if Systematic review Inception cohort studies Cohort study or control arm of randomized trial* Case-series or case- n/a we do not add a of inception cohort studies control studies, or poor therapy? quality prognostic cohort (Prognosis) study** Does this Systematic review Randomized trial Non-randomized controlled cohort/follow-up Case-series, case-control Mechanism-based intervention help? of randomized trials or n-of-1 trials or observational study with study** studies, or historically reasoning (Treatment Benefits) dramatic effect controlled studies** What are the Systematic review of randomized Individual randomized trial Non-randomized controlled cohort/follow-up Case-series, case-control, Mechanism-based COMMON harms? trials, systematic review or (exceptionally) observational study (post-marketing surveillance) provided or historically controlled reasoning (Treatment Harms) of nested case-control studies, n- study with dramatic effect there are sufficient numbers to rule out a studies** of-1 trial with the patient you are common harm. (For long-term harms the raising the question about, or duration of follow-up must be sufficient.)** observational study with dramatic effect What are the RARE Systematic review of randomized Randomized trial harms? trials or n-of-1 trial or (exceptionally) observational (Treatment Harms) study with dramatic effect Is this (early Systematic review of randomized Randomized trial Non -randomized controlled cohort/follow-up Case-series, case-control, Mechanism-based detection) test trials study** or historically controlled reasoning worthwhile? studies** (Screening) * Level may be graded down on the basis of study quality, imprecision, indirectness (study PICO does not match questions PICO), because of inconsistency between studies, or because the absolute effect size is very small; Level may be graded up if there is a large or very large effect size. ** As always, a systematic review is generally better than an individual study. How to cite the Levels of Evidence Table OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence". Oxford Centre for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653 * OCEBM Table of Evidence Working Group = Jeremy Howick, Iain Chalmers (James Lind Library), Paul Glasziou, Trish Greenhalgh, Carl Heneghan, Alessandro Liberati, Ivan Moschetti, Bob Phillips, Hazel Thornton, Olive Goddard and Mary Hodgkinson Table of Contents: Pathogenesis (1/6) Section Manuscript Reviewer (Date Posted) Mason RJ. Pathogenesis of COVID-19 from a cell biology per- John Bretzman spective. Eur Respir J 55:2000607, 2020 (4/24) Li X, et al. Molecular immune pathogenesis and diagnosis of Rob DeStefano COVID-19. J Pharm Anal 2020 [Epub ahead of print]. (4/26) Lin L, et al. Hypothesis for potential pathogenesis of SARS-CoV-2 Kaitlyn Wehrheim infection - A review of immune changes in patients with viral (4/26) pneumonia. Emerg Microbes Infect 9(1):727-732, 2020. Xiao F, et al. Evidence for gastrointestinal infection of SARS- Al Hornung CoV-2. Gastroenterology 2020 [Epub ahead of print]. (4/27) Kim D, et al. Rates of co-infection between SARS-CoV-2 and other Kevin Grudzinski respiratory pathogens. JAMA 2020 [Epub ahead of print]. (4/27) Zhang C, et al. Liver injury in COVID-19: Management and chal- Dallas Kramer lenges. Lancet Gastroenterol Hepatol 5(5):428-430, 2020. (4/27) Hendren NS, et al. Description and proposed management of Adithya Sivakumar the acute COVID-19 cardiovascular syndrome. Circulation 2020 (4/29) [Epub ahead of print]. Xu Z et al. Pathological findings of COVID-19 associated with Al Hornung acute respiratory distress syndrome. Lancet Respir Med 8(4):420- (4/30) 422, 2020 Pathogenesis Rockx B et al. Comparative pathogenesis of COVID-19, MERS, John Levinson and SARS in a nonhuman primate model. Science 2020 [Epub (4/30) ahead of print]. Li J, Fan JG. Characteristics and mechanism of liver injury in 2019 Sameera Khan coronavirus disease. J Clin Transl Hepatol 8(1):13–17, 2020. (4/30 Nikolich-Zugich J et al. SARS-CoV-2 and COVID-19 in older Danesha Lewis adults: what we may expect regarding pathogenesis, immune (5/1) responses, and outcomes. GeroScience 2020 [Epub ahead of print]. Magro C et al. Complement associated microvascular injury and Alex Hornung thrombosis in the pathogenesis of severe COVID-19 infection: A (5/1) report of five cases. Transl Res 2020 [Epub ahead of print]. Hoffmann M et al. SARS-CoV-2 Cell Entry Depends on ACE2 and John Bretzman TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. (5/2) Cell. 2020;181(2):271–280.e8. doi:10.1016/j.cell.2020.02.052 Nguyen, A. Human leukocyte antigensusceptibility map for Sameera Khan SARS-CoV-2. Journal of Virology Apr 2020, JVI.00510-20; DOI: (5/2) 10.1128/JVI.00510-20 Jin Y et al. Virology, epidemiology, pathogenesis, and control of Mira Marchioretto COVID-19. Viruses 12(4), 2020 (5/2) Table of Contents: Pathogenesis (2/6) Section Manuscript Reviewer (Date Posted) Stumpfe FM et al. SARS-CoV-2 infection in pregnancy - A review Kaitlyn Wehrheim of the current literature and possible impact on maternal and (5/2) neonatal outcome. Geburtshilfe Frauenheilkd 80(4):380-390, 2020. Kim ES et al. Clinical course and outcomes of patients with severe Kelly Harmon acute respiratory syndrome coronavirus 2 infection: A prelimi- (5/2) nary report of the first 28 patients from the Korean cohort study on COVID-19. J Korean Med Sci 35(13):e142, 2020 Xu L et al. Liver injury during highly pathogenic human corona- Bijan Zarrabi virus infections. Liver Int 2020 [Epub ahead of print]. (5/2) Zhu H et al. Cardiovascular complications in patients with Kaitlyn Wehrheim COVID-19: Consequences of viral toxicities and host immune (5/3) response. Curr Cardiol Rep 22(5):32, 2020. Diao B et al. Reduction and functional exhaustion of t cells in Kaitlyn Wehrheim patients with coronavirus disease 2019 (COVID-19). medRxiv (5/3) 2020.02.18.20024364, 2020. Bansal M. Cardiovascular disease and COVID-19. Diabetes Me- John Bretzman tab Syndr 14(3):247–250, 2020. doi:10.1016/j.dsx.2020.03.013 (5/3) D’Amico, F et al. Diarrhea during COVID-19 infection: pathogen- Al Hornung esis, epidemiology, prevention and management. Clin Gastro- (5/5) Pathogenesis enterol Hepatol. 2020 Apr 8. pii: S1542-3565(20)30481-X. doi: 10.1016/j.cgh.2020.04.001. [Epub ahead of print] Li, B. et al. Prevalence and impact of cardiovascular metabolic Rob DeStefano diseases on COVID-19 in China. Clin Res Cardiol 109, 531–538 (5/5) (2020). https://doi.org/10.1007/s00392-020-01626-9 Cheung, KS et al. Gastrointestinal manifestation of SARS-CoV_2 Kelly Harmon infection and virus load in fecal samples from the Hong Kong (5/6) cohort and systematic review and meta-analysis. Gastroenter- ology. 2020 Apr 3. pii: S0016-5085(20)30448-0. doi: 10.1053/j. gastro.2020.03.065. [Epub ahead of print] Yan, T et al. Angiotensin-converting enzyme 2 in severe acute Dallas Kramer respiratory syndrome coronavirus and SARS-CoV-2: A dou- (5/6) ble-edged sword? FASEB J. 2020 May;34(5):6017-6026.
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