COVID-ology The COVID-19 outbreak and response have been characterized by institutional missteps, media misinformation, and economic and social upheavals. This book is intended to de-mystify and inform in a succinct and straightforward text. The lessons shared are applicable to other infectious diseases and future inevitable pandemics. Readers will learn about the origins of SARS-CoV-2, the disease it causes, clinical tests and how they work, therapeutics, and prophylactic measures such as vaccines. This information will prepare readers to be better able to respond to future emerging infectious diseases and pandemics. Key Features • Positively influences career choices within public health • Applies basic science to problems raised by the COVID-19 pandemic such as vaccine development and herd immunity • Prepares readers with context and tactics for understanding future infectious disease outbreaks • Successfully used in college senior health sciences seminars • Engaging and balanced treatment of the politicization of public health issues, especially COVID-19 COVID-ology A Field Guide Dr. Michael T. Myers, Jr., MD, MBA Cover Image Credit: Shutterstock.com First edition published 2023 by CRC Press 6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742 and by CRC Press 4 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN CRC Press is an imprint of Taylor & Francis Group, LLC © 2023 Taylor & Francis Group, LLC Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, access www. copyright. com or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750- 8400. For works that are not available on CCC please contact mpkbookspermissions@ tandf. co. uk Trademark notice: Product or corporate names may be trademarks or registered trademarks and are used only for identification and explanation without intent to infringe. ISBN: 9781032316055 (hbk) ISBN: 9781032316031 (pbk) ISBN: 9781003310525 (ebk) DOI: 10.1201/9781003310525 Typeset in Minion by Deanta Global Publishing Services, Chennai, India To all future public health leaders Contents Acknowledgments ................................................................................xv Author .................................................................................................xvii Acronyms .............................................................................................xix COVID-19 Timeline .........................................................................xxiii Introduction: Foray into the Field ....................................1 COVID-19 Update: May 9, 2022 .................................................1 A Bewildering Landscape .......................................................2 An Emerging Infectious Diseases Field Guide ....................2 Using This Field Guide ............................................................3 The Many Paths of Exploration .............................................4 Venturing into COVID-19—and EIDs ......................................4 Notes ...............................................................................................5 Chapter 1 The SARS-CoV-2 Virus .....................................................7 Field Expedition: NASA’s Ten-Word Definition of Life ..........7 Lesson Learned: NASA’s Ten-Word Definition of Life ............9 Concepts Covered in This Chapter ..........................................10 Nucleic Acids Are the Self-Sustaining Chemical System of Life ..........................................................................10 The Virus as Industrial Insurrectionist ..............................13 Virus Classification Systems ................................................15 The SARS-CoV-2 Genome ....................................................16 SARS-CoV-2 Is a Single-Stranded Positive Sense RNA Virus .........................................................................17 Protein Translation Starts with ORF1a Making NSP1–NSP11 ......................................................................17 Protein Translation Continues with ORF1b Making NSP12–NSP16 .....................................................19 Immune System Evasion and Accessory Proteins .......20 SARS-CoV-2 Life Cycle ........................................................20 vii viii • Contents SARS-CoV-2 Cell Entry, Cytoplasmic Replication, and Exit...............................................................................21 Interrupting the Virus Life Cycle ...................................21 Virus Mutability .....................................................................23 How Mutations Occur ......................................................23 Mutation Terminology .....................................................24 SARS-CoV-2 Variants .......................................................25 More Variants: Not If, but When ....................................26 Looking Back, Looking Ahead ............................................26 Future Outings ............................................................................27 Student Research Questions .................................................27 Notes ............................................................................................28 Chapter 2 The Origins of SARS-CoV-2 ............................................29 Field Expedition: The Bat Woman ...........................................29 Lesson Learned: The Bat Woman ............................................30 Concepts Covered in This Chapter ..........................................31 SARS-CoV-2: An Emerging Infectious Disease ................31 Zoonotic Spillover Theory ....................................................33 Bats as Animal Reservoirs for Lethal Zoonotic Pathogens ...........................................................................33 Laboratory Leak Theory........................................................35 Official Reviews of Laboratory Leak and Zoonotic Spillover Theories ...................................................................37 Looking Back, Looking Ahead ............................................38 Future Outings ............................................................................39 Student Research Questions .................................................39 Notes .............................................................................................41 Chapter 3 COVID-19 Disease Manifestations .................................43 Field Expedition: The Three Phases of Syphilis .....................43 Lessons Learned: The Three Phases of Syphilis......................45 Concepts Covered in This Chapter ..........................................45 COVID-19 Is a New Disease Entity ...................................46 Symptoms ...............................................................................46 COVID-19 Symptoms .....................................................46 Clinical Stages .......................................................................48 Contents • ix COVID-19 Clinical Stages ..............................................48 Host Factors ............................................................................49 COVID-19 Host Factors ...................................................49 Comorbid Conditions ...........................................................49 COVID-19 Comorbid Conditions ..................................50 Pathophysiology .....................................................................50 COVID-19 Pathophysiology ............................................50 ACE2 Receptors, Fluid Balance, and Inflammation ....50 Alveolar Epithelial Cells ...................................................51 Acute Respiratory Distress Syndrome ...........................51 PASC and MIS-C ..............................................................52 Looking Back, Looking Ahead ............................................52 Future Outings ............................................................................53 Student Research Questions .................................................53 Chapter 4 Testing ...............................................................................55 Field Expedition: Michael Mina’s Mission .............................56 Lesson Learned: Michael Mina’s Mission ...............................57 Concepts Covered in This Chapter ..........................................57 Types of Clinical Tests ...........................................................57 Performance Characteristics of Clinical Tests ...................58 “Gold Standard” or Reference Standard Test ................59 Positive and Negative Predictive Values ............................60 Clinical Test Results and Disease Probability ..............60 Bayes’s Theorem of Pre-Test Probability .............................61 Making the Correct Diagnosis of a Disease .......................61 Using Clinical Tests in Making Diagnoses ...................62 Making the Correct Diagnosis of COVID-19 ....................63 SARS-CoV-2 Clinical Tests..................................................64 Serologic Antibody Tests .................................................64 PCR Tests ...........................................................................65 RDTs ..................................................................................68 Using Clinical Tests in Making COVID-19 Diagnoses ....70 Looking Back, Looking Ahead ............................................71 Future Outings ............................................................................72 Student Research Questions .................................................72 Notes .............................................................................................72