Coronavirus Disease 2019 Covid 19 A Clinical Guide 1St Edition Ali Gholamrezanezhad Full Chapter

Coronavirus Disease 2019 (Covid-19): A
Clinical Guide 1st Edition Ali

Gholamrezanezhad
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Coronavirus Disease 2019 (COVID-19): A Clinical Guide
Coronavirus Disease 2019 (COVID-19): A Clinical Guide
Edited by
Ali Gholamrezanezhad, MD
Keck School of Medicine, University of Southern California (USC)
Los Angeles, California, USA
Michael P. Dube, MD
Keck School of Medicine, University of Southern California (USC)
Los Angeles, California, USA
This edition first published 2023
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Library of Congress Cataloging-in-Publication Data applied for

ISBN: 9781119789680 (hardback)
Cover Design: Wiley

Cover Image: © koto_feja/Getty Brandon K.K. Fields, Natalie L. Demirjian, Ali Gholamrezanezhad
Set in 9.5/12.5pt STIXTwoText by Straive, Pondicherry, India

This book is dedicated to healthcare workers around the world and those who support them. We especially wish
to recognize Frances Marie Canchola, RN, a beloved HIV research nurse at the University of Southern
California. Frances fell ill in November 2020 and ultimately lost her life to complications of COVID-19 in
January 2021—a month after the first SARS-CoV-2 vaccines received Emergency Use Authorization in the
United States. There are countless people who now will no longer need to be hospitalized or die as a result of
this disease once they choose to be vaccinated.
—Michael P. Dube and Ali Gholamrezanezhad
To my mother, Fatemeh
For her endless support and devotion to making my life most fulfilling . . .
my wife
for her unconditional love and patience . . .
my brother
for his support in silence!
and to the “hand of god,”

a person whose company has been the greatest honor of my life, saved me in a critical time, and succored and
shaped me into the person I am proud of!
—Ali Gholamrezanezhad
vii
Contents
List of Contributors x
Preface xvii
1 COVID-19: Epidemiology 1
Phillip Quiroz, George W. Rutherford, and Michael P. Dube
2 COVID-19: Virology 22
Saeideh Najafi, Salar Tofighi, and Juliana Sobczyk
3 COVID-19: Laboratory/Serologic Diagnostics 34

Desmond Chin, Liesl S. Eibschutz, Juliana Sobczyk, Mobin Azami, Michael Jovan Repajic,
and Michael P. Dube
4 COVID-19: Radiologic Diagnosis 61

Brian P. Pogatchnik, Wakana Murakami, and Shabnam Mortazavi
5 COVID-19: Pathology Perspective 101

Elham Hatami, Hana Russo, and Grace Y. Lin
6 COVID-19: Immunology 112

Yasaswi V. Vengalasetti, Niyousha Naderi, Christian Vega, Akhilesh Kumar, and Andrew T. Catanzaro
7 COVID-19: Presentation and Symptomatology 125

Jacek Czubak, Karolina Stolarczyk, Marcin Frączek, Katarzyna Resler, Anna Orzeł, Wojciech Flieger,
and Tomasz Zatoński
8 COVID-19: Risk Stratification 149

Dominique Duncan, Rachael Garner, and Yujia Zhang
9 COVID-19: Outpatient Management in Adults 165

Michael P. Dubé
10 COVID-19: Inpatient Management 182

Angelena Lopez, Yuri Matusov, Isabel Pedraza, Victor Tapson, Jeremy Falk, and Peter Chen
viii Contents
11 COVID-19: ICU and Critical Care Management 233

Daniel Crouch, Alexandra Rose, Cameron McGuire, Jenny Yang, Mazen Odish, and Amy Bellinghausen
12 COVID-19 in Pediatrics 255

Erlinda R. Ulloa, Kaidi He, Erin Chung, Delma Nieves, David E. Michalik, and Behnoosh Afghani
13 Pharmacologic Therapeutics for COVID-19 290

Amanda M. Burkhardt, Angela Lu, Isaac Asante, and Stan Louie
14 Co-infections and Secondary Infections in COVID-19 Pneumonia 319

Sanaz Katal, Liesl S. Eibschutz, Amit Gupta, Sean K. Johnston, Lucia Flors,
and Ali Gholamrezanezhad
15 COVID-19: Neurology Perspective 339

Kiandokht Keyhanian, Raffaella Pizzolato Umeton, Babak Mohit, Brooke McNeilly, and Mehdi Ghasemi
16 COVID-19: Cardiology Perspective 361

Michael DiVita, Meshe Chonde, Megan Kamath, Darko Vucicevic, Ashley M. Fan, Arnold S. Baas,
and Jeffrey J. Hsu
17 COVID-19: Oncologic and Hematologic Considerations 389

Diana L. Hanna, Caroline I. Piatek, Binh T. Ngo, and Heinz-Josef Lenz
18 COVID-19: Dermatology Perspective 409

Sabha Mushtaq, Fabrizio Fantini, and Sebastiano Recalcati
19 COVID-19: Ophthalmology Perspective 417

Hashem Al-Marzouki, Benjamin P. Hammond, Wendy W. Huang, and Angela N. Buffenn
20 COVID-19: Nutrition Perspectives 428

Emma J. Ridley, Lee-anne S. Chapple, Aidan Burrell, Kate Fetterplace, Amy Freeman-Sanderson,
Andrea P. Marshall, and Ary Serpa Neto
21 COVID-19: Nursing Perspective 454

Michelle Zappas, Dalia Copti, Cynthia Sanchez, Janett A. Hildebrand, and Sharon O’Neill
22 COVID-19 Vaccination 472

Anurag Singh, Simran P. Kaur, Mohd Fardeen Husain Shahanshah, Bhawna Sharma,
Vijay K. Chaudhary, Sanjay Gupta, and Vandana Gupta
23 Post-COVID-19 Vaccine Imaging Findings 494

Shadi Asadollahi, Liesl S. Eibschutz, Sanaz Katal, Vorada Sakulsaengprapha,
Yasaswi Vengalasetti, Nikoo Saeedi, Sean K. Johnston, and Jennifer H. Johnston
24 COVID-19: Long-Term Pulmonary Consequences 515

Liesl S. Eibschutz, Tianyuan Fu, Boniface Yarabe, Narges Jokar, Sanaz Katal, Charlotte Sackett,
Michael Repajic, and Ching-Fei Chang
Contents ix
25 Psychological Effects and Neuropsychiatric Sequelae in COVID-19 Patients 539

Elpitha Sakka, Arturas Kalniunas, Elzbieta Vitkauskaite, Wala Salman,
Subhana Chaudhri, and Sofia Pappa
26 Mental Health Effects of the COVID-19 Pandemic on Healthcare Professionals 554

Liesl S. Eibschutz, Charlotte Sackett, Vorada Sakulsaengprapha, Masoomeh Faghankhani,
Glenn Baumann, and Sofia Pappa
27 COVID-19: Ethical Considerations in Clinical Practice 580

Kiarash Aramesh
28 Racial, Ethnic, and Other Disparities in the Epidemiology and Care of COVID-19 586
Liesl S. Eibschutz, Charlotte Sackett, Kalpana Dave, Sarah Cherukury, Christian Vega,
Mauricio Bueno, and Hector Flores
29 Global Impact of COVID-19 on Healthcare Systems 615

Liesl S. Eibschutz, Alexander A. Bruckhaus, Alexis Bennett, Dominique Duncan, Charlotte Sackett,
Kalpana Dave, Sarah Cherukury, Victoria Uram, and Calvin M. Smith
30 COVID-19: Mass Casualty Planning 651

Lee Myers
Index 658
x
List of Contributors
Behnoosh Afghani, MD Mobin Azami

Department of Pediatrics, University of California Student Research Committee, Kurdistan University
Irvine School of Medicine, Irvine, CA, USA of Medical Sciences, Sanandaj, Iran
Hospitalist, CHOC Children’s, Orange, CA, USA
Pediatric Infectious Diseases, University of California Arnold S. Baas, MD
Irvine School of Medicine, Irvine, CA, USA Division of Cardiology, Department of Medicine,
UCLA Health, Los Angeles, CA, USA
Hashem Al-Marzouki, MD
Department of Ophthalmology, College of Medicine, Glenn Baumann
King Saud bin Abdulaziz University for Health Keck School of Medicine, University of Southern
Sciences, King Abdulaziz Medical Center, Jeddah, California, Los Angeles, CA, USA
Saudi Arabia
Alexis Bennett
Kiarash Aramesh, MD, PhD Laboratory of Neuro Imaging, USC Stevens
The James F. Drane Bioethics Institute, Edinboro Neuroimaging and Informatics Institute, Keck School
University of Pennsylvania, Edinboro, PA, USA of Medicine, University of Southern California, Los
Angeles, CA, USA
Shadi Asadollahi, MD
Department of Radiology, Keck School of Amy Bellinghausen, MD
Medicine, University of Southern California, Los Division of Pulmonary, Critical Care, and Sleep
Angeles, CA, USA Medicine, Department of Medicine, University of
Russell H. Morgan Department of Radiology and California San Diego, La Jolla, CA, USA
Radiological Science, Johns Hopkins University
School of Medicine, Baltimore, MD, USA Alexander A. Bruckhaus
Laboratory of Neuro Imaging, USC Stevens
Isaac Asante, MS, PhD Neuroimaging and Informatics Institute, Keck School
Clinical Pharmacy Department, School of of Medicine, University of Southern California, Los
Pharmacy, University of Southern California, Los Angeles, CA, USA
Angeles, CA, USA
Roski Eye Institute, Keck School of Medicine, Mauricio Bueno, MD
University of Southern California, Los Department of Family Medicine, Adventist Health
Angeles, CA, USA White Memorial, Los Angeles, CA, USA
List of Contributors xi
Angela N. Buffenn, MD, MPH Sarah Cherukury

The Vision Center, Children’s Hospital Los USC Master of Public Health Program,
Angeles, Roski Eye Institute, Keck School of University of Southern California,
Medicine, University of Southern California, Los Angeles, CA, USA
Los Angeles, CA, USA
Desmond Chin, MD
Amanda M. Burkhardt, PhD Department of Radiology, Keck School of
Clinical Pharmacy Department, School of Medicine, University of Southern California,
Pharmacy, University of Southern California, Los Angeles, CA, USA
Meshe Chonde, MD
Aidan Burrell Division of Cardiology, Department of Medicine,
Australian and New Zealand Intensive Care Research UCLA Health, Los Angeles, CA, USA
Centre, School of Public Health and Preventative
Medicine, Monash University, Melbourne, VIC, Erin Chung
Australia Department of Pediatrics, University of
Intensive Care Unit, The Alfred Hospital, Washington, Seattle Children’s Hospital,
Melbourne, VIC, Australia Seattle, WA, USA
Andrew T. Catanzaro, MD Dalia Copti, MSN, FNP-C, AGACNP-BC

Adventist Healthcare, Gaithersburg, MD, USA Department of Nursing, Suzanne Dworak-Peck
School of Social Work, University of Southern
Ching-Fei Chang, MD California, Los Angeles, CA, USA
Division of Pulmonary and Critical Care, Department
of Medicine, Keck School of Medicine, University of Daniel Crouch, MD
Southern California, Los Angeles, CA, USA Division of Pulmonary, Critical Care, and Sleep
Medicine, Department of Medicine, University of
Lee-anne S. Chapple, PhD California San Diego, La Jolla, CA, USA
Adelaide Medicine School, University of Adelaide,
Adelaide, SA, Australia Jacek Czubak, MD
Intensive Care Unit, Royal Adelaide Hospital, Department and Clinic of Otolaryngology, Head
Adelaide, SA, Australia and Neck Surgery, Wroclaw Medical University,
Centre for Research Excellence in Nutritional Wrocław, Poland
Physiology, Adelaide, SA, Australia
Kalpana Dave
Vijay K. Chaudhary, PhD USC Master of Public Health Program,
Centre for Innovation in Infectious Disease Research, University of Southern California, Los
Education and Training, University of Delhi South Angeles, CA, USA
Campus, New Delhi, India
Michael DiVita, MD
Subhana Chaudhri, MD Division of Cardiology, Department of Medicine,
Greater Manchester Mental Health NHS Foundation UCLA Health, Los Angeles, CA, USA
Trust, Manchester, United Kingdom
Michael P. Dube, MD
Peter Chen, MD Department of Medicine, Division of
Department of Medicine, Division of Pulmonary Infectious Diseases, Keck School of Medicine,
and Critical Care Medicine, Cedars-Sinai Medical University of Southern California, Los
Center, Los Angeles, CA, USA Angeles, CA, USA
xii List of Contributors
Dominique Duncan, PhD Marcin Frączek, MD, PhD

Laboratory of Neuro Imaging, USC Stevens Department and Clinic of Otolaryngology, Head
Neuroimaging and Informatics Institute, Keck and Neck Surgery, Wroclaw Medical University,
School of Medicine of USC, University of Southern Wrocław, Poland
California, Los Angeles, CA, USA
Amy Freeman-Sanderson, PhD
Liesl S. Eibschutz, MS Graduate School of Health, University of
Department of Radiology, Keck School of Technology Sydney, Sydney, NSW, Australia
Medicine, University of Southern California, Los Speech Pathology Department & Intensive Care Unit,
Angeles, CA, USA Royal Prince Alfred Hospital, Sydney, NSW,
Australia
Masoomeh Faghankhani, MD Critical Care Division, The George Institute for
Tehran University of Medical Sciences, Global Health, Sydney, NSW, Australia
Tehran, Iran
Tianyuan Fu, MD
Jeremy Falk, MD Department of Radiology, University Hospitals
Department of Medicine, Division of Pulmonary and Cleveland Medical Center, Cleveland, OH, USA
Critical Care Medicine, Cedars-Sinai Medical Center,
Los Angeles, CA, USA Rachael Garner
Laboratory of Neuro Imaging, USC Stevens
Ashley M. Fan, PharmD Neuroimaging and Informatics Institute, Keck
Department of Pharmaceutical Services, UCLA School of Medicine of USC, University of Southern
Health, Los Angeles, CA, USA California, Los Angeles, CA, USA
Fabrizio Fantini, MD Mehdi Ghasemi, MD

Department of Dermatology, ASST Lecco, Department of Neurology, University of
Alessandro Manzoni Hospital, Lecco, Italy Massachusetts Medical School, Worcester,
MA, USA
Kate Fetterplace
Allied Health Department (Clinical Nutrition), Ali Gholamrezanezhad, MD
Royal Melbourne Hospital, Melbourne, VIC, Department of Radiology, Keck School of
Australia Medicine, University of Southern California, Los
Department of Critical Care, Melbourne Medical Angeles, CA, USA
School, The University of Melbourne, Melbourne,
VIC, Australia Amit Gupta, MD
Department of Radiology, University Hospital
Wojciech Flieger Cleveland Medical Center, Cleveland, OH, USA
School of Medicine, Medical University of Lublin,
Lublin, Poland Sanjay Gupta, PhD
Independent Scholar (former Head, Centre for
Hector Flores, MD Emerging Diseases, Department of Biotechnology),
Department of Family Medicine, Adventist Health Jaypee Institute of Information Technology,
White Memorial, Los Angeles, CA, USA Noida, India
Lucia Flors, MD, PhD Vandana Gupta, PhD

Department of Radiology, Keck School of Department of Microbiology, Ram Lal
Medicine, University of Southern California, Los Anand College, University of Delhi, New Delhi,
Angeles, CA, USA India
List of Contributors xiii
Benjamin P. Hammond, MD Arturas Kalniunas, MD

Flaum Eye Institute, University of Rochester West London NHS Trust, London, United Kingdom
Medical Center, Rochester, NY, USA
Megan Kamath, MD
Diana L. Hanna, MD
Division of Cardiology, Department of Medicine,
Division of Medical Oncology, Norris Comprehensive
Cancer Center, University of Southern California,
Hoag Cancer Center, Newport Beach, CA, USA Sanaz Katal, MD, MPH
St Vincent’s Hospital Medical Imaging Department,
Elham Hatami, MD Melbourne, Victoria, Australia
Department of Pathology, University of
California San Diego Medical Center, San Simran P. Kaur, BSc
Diego, CA, USA Department of Microbiology, Ram Lal Anand
College, University of Delhi, New Delhi, India
Kaidi He, MD
Department of Pediatrics, Children’s Hospital of
Los Angeles, Los Angeles, CA, USA Kiandokht Keyhanian, MD
Department of Neurology, University of
Janett A. Hildebrand, PhD, FNP-BC, CDE Massachusetts Medical School, Worcester, MA, USA
Department of Nursing, Suzanne Dworak-Peck
School of Social Work, University of Southern Akhilesh Kumar, MSc
California, Los Angeles, CA, USA Ochsner Clinical School, University of Queensland,
New Orleans, LA, USA
Jeffrey J. Hsu, MD, PhD
Heinz-Josef Lenz, MD
Division of Medical Oncology, Norris Comprehensive
Cancer Center, University of Southern California, Los
Veterans Affairs Greater Los Angeles Healthcare
Angeles, CA, USA
System, Los Angeles, CA, USA
Wendy W. Huang, MD Grace Y. Lin, MD, PhD

Phoenix Children’s Hospital, Ophthalmology, Department of Pathology, University of California
Phoenix, AZ, USA San Diego Medical Center, San Diego, CA, USA
Jennifer H. Johnston, MD
Angelena Lopez, MD
Department of Radiology, McGovern School of
Department of Medicine, Division of Pulmonary and
Medicine, UT Houston, Houston, TX, USA
Sean K. Johnston, MD
Department of Radiology, Keck School of
Medicine, University of Southern California, Los Stan Louie, PharmD
Angeles, CA, USA Clinical Pharmacy and Ophthalmology
Clinical Experimental Therapeutics Program,
Narges Jokar, MD Ginsburg Institute of Biomedical Technology,
Department of Molecular Imaging and Radionuclide USC School of Pharmacy,
Therapy, The Persian Gulf Nuclear Medicine USC Keck School of Medicine, University of
Research Center, Bushehr Medical University Southern California, Los Angeles, CA, USA
Hospital, Bushehr, Iran
xiv List of Contributors
Angela Lu, MS Sabha Mushtaq, MD

Department of Pharmacology and Pharmaceutical Department of Dermatology, Venereology and
Sciences, School of Pharmacy, University of Leprology, Government Medical College and
Southern California, Los Angeles, CA, USA associated hospitals, University of Jammu,
Jammu, India
Andrea P. Marshall, PhD
Gold Coast Health, Southport, QLD, Australia Lee Myers, MD
School of Nursing and Midwifery, Griffith Keck School of Medicine, University of Southern
University, Southport, QLD, Australia California, Los Angeles, CA, USA
Yuri Matusov, MD
Niyousha Naderi, MD
Department of Medicine, Division of Pulmonary
Keck School of Medicine, University of Southern
and Critical Care Medicine, Cedars-Sinai Medical
Center, Los Angeles, CA, USA
Cameron McGuire, MD Saeideh Najafi

Division of Pulmonary, Critical Care, and Sleep Department of Radiology, Keck School of
Medicine, Department of Medicine, University of Medicine, University of Southern California,
California San Diego, La Jolla, CA, USA Los Angeles, CA, USA
Brooke McNeilly, DO Ary Serpa Neto, MD, MSc, PhD

Department of Neurology, University of Australian and New Zealand Intensive Care
Massachusetts Medical School, Worcester, MA, USA Research Centre, School of Public Health and
Preventative Medicine, Monash University,
David E. Michalik, DO Melbourne, VIC, Australia
Department of Pediatrics, University of California
Irvine School of Medicine, Irvine, CA, USA Binh T. Ngo, MD
Division of Pediatric Infectious Diseases, Department of Dermatology, Keck School of
Miller Children’s and Women’s Hospital, Long Medicine, University of Southern California,
Beach, CA, USA Los Angeles, CA, USA
Babak Mohit, DrPH

Delma Nieves, MD
Sleep Disorders Center, Division of Pulmonary and
Department of Pediatrics, University of California
Critical Care Medicine, Department of Medicine,
Irvine School of Medicine, Irvine, CA, USA
University of Maryland School of Medicine,
Division of Pediatric Infectious Diseases, CHOC
Baltimore, MD, USA
Children’s, Orange, CA, USA
Shabnam Mortazavi, MD, MPH

Assistant Professor of Radiology, David Geffen School Mazen Odish, MD
of Medicine at UCLA, Los Angeles, CA, USA Division of Pulmonary, Critical Care, and Sleep
Medicine, Department of Medicine, University
Wakana Murakami, MD of California San Diego, La Jolla, CA, USA
Visiting Researcher of Radiological Sciences,
David Geffen School of Medicine at UCLA, Los Sharon O’Neill, DNP, FNP-BC, PPCNP-BC,
Angeles, CA, USA PMHNP-BC
Department of Radiology, Showa University Graduate New York University Rory Meyers College of
School of Medicine, Tokyo, Japan Nursing, New York, NY, USA
List of Contributors xv
Anna Orzeł Emma J. Ridley, PhD

School of Medicine, Medical University of Lublin, Australian and New Zealand Intensive Care Research
Lublin, Poland Centre, School of Public Health and Preventative
Medicine, Monash University, Melbourne, VIC,
Sofia Pappa, MD, PhD Australia
West London NHS Trust, London, United Kingdom Nutrition Department, The Alfred Hospital,
Faculty of Medicine, Department of Brain Melbourne, VIC, Australia
Sciences, Imperial College London, London,
United Kingdom Alexandra Rose, MD
Division of Pulmonary, Critical Care, and Sleep
Isabel Pedraza, MD Medicine, Department of Medicine, University of
Department of Medicine, Division of Pulmonary and California San Diego, La Jolla, CA, USA
Hana Russo, MD, PhD
Department of Pathology, University of
Caroline I. Piatek, MD
California San Diego Medical Center, San
Jane Anne Nohl Division of Hematology, Keck School
Diego, CA, USA
of Medicine, University of Southern California,
George W. Rutherford, MD
Raffaella Pizzolato Umeton, MD Department of Epidemiology and Biostatistics, School
Department of Neurology, University of of Medicine, and Institute for Global Health Sciences,
Massachusetts Medical School, Worcester, University of California San Francisco,
MA, USA San Francisco, CA, USA
Department of Neurology, Massachusetts
General Hospital, Harvard Medical School, Charlotte Sackett
Boston, MA, USA USC Master of Public Health Program, University of
Southern California, Los Angeles, CA, USA
Brian P. Pogatchnik, MD
Clinical Instructor in Radiology, Stanford University Nikoo Saeedi, MS
School of Medicine, Stanford, CA, USA Medical School of Islamic Azad University of
Mashhad, Mashhad, Iran
Phillip Quiroz, MPH
Keck School of Medicine at the University of Elpitha Sakka, MRes
Southern California, Los Angeles, California, USA School of Pharmacy and Biomolecular Sciences,
University of Brighton, Brighton, United Kingdom
Sebastiano Recalcati
Department of Dermatology, ASST Lecco, Alessandro
Vorada Sakulsaengprapha, MS
Manzoni Hospital, Lecco, Italy
Johns Hopkins University School of Medicine,
Baltimore, MD, USA
Michael Jovan Repajic
Department of Radiology, Keck School of
Medicine, University of Southern California, Los Wala Salman, MD
Angeles, CA, USA West London NHS Trust, London, United Kingdom
Katarzyna Resler Cynthia Sanchez, DNP, FNP-C

Department and Clinic of Otolaryngology, Head Department of Nursing, Suzanne Dworak-Peck
and Neck Surgery, Wroclaw Medical University, School of Social Work, University of Southern
Wrocław, Poland California, Los Angeles, CA, USA
xvi List of Contributors
Mohd Fardeen Husain Shahanshah, BSc Victoria Uram, MPH

Department of Microbiology, Ram Lal Anand Department of Clinical Research, University
College, University of Delhi, New Delhi, India Hospitals, Cleveland, OH, USA
Bhawna Sharma, BSc Christian Vega

Department of Microbiology, Ram Lal Anand Keck School of Medicine, University of Southern
College, University of Delhi, New Delhi, India California, Los Angeles, CA, USA
Yasaswi V. Vengalasetti, MS
Anurag Singh, BSc Department of Epidemiology and Population
Department of Microbiology, Ram Lal Anand Health, Stanford University School of Medicine,
College, University of Delhi, New Delhi, India Stanford, CA, USA
Calvin M. Smith, MD Elzbieta Vitkauskaite

Department of Internal Medicine, Nashville West London NHS Trust, London, United Kingdom
General Hospital at Meharry, Nashville, TN, USA
Darko Vucicevic, MD
Juliana Sobczyk, MD
Department of Pathology, Memorial Satilla
Hospital, HCA Healthcare, Waycross, GA, USA
Jenny Yang
Laboratory Director, St. Augustine Foot & Ankle, Inc.,
Division of Pulmonary, Critical Care, and Sleep
St. Augustine, FL, USA
Medicine, Department of Medicine, University
of California San Diego, La Jolla, CA, USA
Karolina Stolarczyk
Department and Clinic of Otolaryngology, Head Boniface Yarabe
and Neck Surgery, Wroclaw Medical University, Department of Radiology, Keck School of
Wrocław, Poland Medicine, University of Southern California,
Victor Tapson, MD
Department of Medicine, Division of Pulmonary and Michelle Zappas, DNP, FNP-BC
Critical Care Medicine, Cedars-Sinai Medical Center, Department of Nursing, Suzanne Dworak-Peck
Los Angeles, CA, USA School of Social Work, University of Southern
Salar Tofighi, MD Tomasz Zatoński, MD
Department of Radiology, Keck School of Department and Clinic of Otolaryngology, Head
Medicine, University of Southern California, Los and Neck Surgery, Wroclaw Medical University,
Angeles, CA, USA Wrocław, Poland
Erlinda R. Ulloa, MD Yujia Zhang

Department of Pediatrics, University of California Laboratory of Neuro Imaging, USC Stevens
Irvine School of Medicine, Irvine, CA, USA Neuroimaging and Informatics Institute, Keck
Division of Pediatric Infectious Diseases, CHOC School of Medicine of USC, University of
Children’s, Orange, CA, USA Southern California, Los Angeles, CA, USA
xvii
Preface
The astounding speed and global impact of the Outpatient management and prevention of hospitaliza-
coronavirus disease 2019 (COVID-19) pandemic was tion and disease progression have made slow but steady
unforeseen when the first cases of this illness were progress, with the availability in some settings of anti-
reported in December 2019 from Wuhan, China. By SARS-CoV-2 monoclonal antibodies. Subsequently,
the end of January 2020, nearly 8000 cases had been studies of promising oral antiviral agents have reported
reported globally from 19 countries, and the World beneficial effects of preventing hospitalization with a
Health Organization declared a Public Health more generally applicable form of treatment.
Emergency of International Concern. It soon became Sadly, the pandemic has further exposed health dis-
apparent this was not going to be a focal or controlla- parities around the globe. Minority and lower-income
ble outbreak. In the more than two years that have fol- people have disproportionally borne the brunt of
lowed, the world has truly been turned upside down COVID-19 illness and mortality, the result of environ-
with countless severe disruptions to life and econo- mental and structural disadvantages and greater nonin-
mies worldwide. fectious medical comorbidity. Viral mutation has led to
The challenges to the healthcare systems in high-, emerging SARS-CoV-2 variants that have properties of
middle-, and low-income countries alike have been increased infectivity and reduced responses to vaccines
enormous. The strain on individuals and institutions and monoclonal antibodies. The Delta variant exploded
has been dealt with by interventions of varying suc- worldwide in the summer of 2021, challenging but not
cess. The mental and physical health of workers have fully overcoming current therapies. The world will con-
been a prime focus in the global response to the tinue to monitor for variants of concern, more recently
pandemic. with the Omicron variants, and science will adapt with
The scientific community has responded rapidly, if new vaccines and therapeutics as necessary.
imperfectly at times, to the death and disability imposed In spite of terrible loss of life, disabling post-COVID
by severe acute respiratory syndrome coronavirus 2 syndromes, and damage to global economies, there is
(SARS-CoV-2). Important and dramatic advances in the reason for optimism. The first-generation messenger
care of critically ill inpatients have been made, primar- RNA and viral vector vaccines appear to be maintain-
ily using potent anti-inflammatory interventions such ing protection against severe disease, and vaccines
as glucocorticoids and tocilizumab. Multiple effective promising better protection from variants are emerg-
vaccines have been developed with record speed using ing. As the world sorts out how to make vaccines more
multiple different vaccine platforms and have been dis- generally available in lower-income countries, there is
seminated globally. Much work still needs to be done in an expectation that infection with SARS-CoV-2 will
combatting vaccine hesitancy worldwide and providing eventually become a more manageable virus along the
vaccines in the developing world. lines of other respiratory viruses such as influenza.
1
COVID-19: Epidemiology
Phillip Quiroz1, George W. Rutherford2, and Michael P. Dube3
1
Keck School of Medicine at the University of Southern California, Los Angeles, California, USA
2
Department of Epidemiology and Biostatistics, School of Medicine, and Institute for Global Health Sciences, University of California San Francisco,
San Francisco, CA, USA
3
Department of Medicine, Division of Infectious Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Abbreviations of epidemiologists in the region, who conducted origin-

related field studies in the community and nearby health
ACE2 angiotensin-converting enzyme 2 facilities. Nose and throat specimens were collected for
CDC US Centers for Disease Control and viral genomic sequencing and analysis. On 12 January
Prevention 2020, the Chinese government publicly shared the
CFR case fatality rate genetic sequence of the causative agent, a novel corona-
MERS Middle East respiratory syndrome virus that the International Committee on Taxonomy
MERS-CoV Middle East respiratory syndrome of Viruses later would christen severe acute respiratory
coronavirus distress syndrome coronavirus 2 (SARS-CoV-2).
mRNA messenger RNA SARS-CoV-2 is a novel coronavirus that belongs to
SARS severe acute respiratory syndrome the viral family Coronaviridae. A relatively large clas-
SARS-CoV-2 severe acute respiratory syndrome sification, these viruses are enveloped, positive-sense,
coronavirus 2 single-stranded RNA viruses. Typically, these cause
WHO World Health Organization mild to moderate upper respiratory tract illnesses, but
they can cause enteric, hepatic, and neurologic dis-
On 1 December 2019, the first report of a pneumonia of eases as well [3]. Four of the seven known coronavi-
unknown etiology was recognized in Wuhan, China, ruses cause only mild to moderate disease. However,
presenting with fever, malaise, dry cough, and dysp- three new coronaviruses have emerged from animal
nea [1]. Based on clinical criteria, diagnostic tests, and reservoirs over the past two decades that cause wide-
imaging, this respiratory disease was determined most spread serious illness and death. The first of these is
likely to be that of viral origin. Although its presentation SARS coronavirus (SARS-CoV), which emerged in
resembled that of other well-known viral pneumonias in November 2002 and causes SARS. The second is
the region (i.e. influenza, severe acute respiratory syn- known as the MERS coronavirus (MERS-CoV), which
drome [SARS], Middle East respiratory syndrome causes MERS. MERS was first identified in September
[MERS]), it was clear this was a novel disease. The World 2012 and continues to cause sporadic and localized
Health Organization (WHO) announced an epidemic outbreaks largely in Saudi Arabia and South Korea [4].
cluster of outbreaks of this disease in Wuhan, Hubei The third and most recent novel coronavirus to emerge
Province by 31 December 2019 [2]. This aggressive in this century is SARS-CoV-2; it is the seventh member
increase in cases understandably caught the attention of the coronavirus family known to infect humans.
Coronavirus Disease 2019 (COVID-19): A Clinical Guide, First Edition. Edited by Ali Gholamrezanezhad and Michael P. Dube.
© 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd.
2 Coronavirus Disease 2019 (COVID-19)
The first death from the novel SARS coronavirus was detected in the horseshoe bat Rhinolophus affinis from
announced by Chinese health officials on 11 January Yunnan Province, more than 1500 km from Wuhan [6].
2020 [2]. The WHO named this illness coronavirus dis- In addition, similar strains of SARS-CoV-2 were found
ease 2019 (COVID-19) according to its nomenclature earlier in other regions of China. Bats are likely reser-
on 11 February 2020 and would eventually declare the voir hosts for SARS-CoV-2; however, whether bat-CoV
outbreak a pandemic on 11 March 2020 [5]. At the time RaTG13 directly jumped to humans or transmitted
of this writing in August 2021, the SARS-CoV-2 pan- to intermediate hosts to facilitate animal-to-human
demic has left entire countries crippled and in desper- transmission remains inconclusive, and epidemiologic
ate recovery. Worldwide spread has left more than investigations are still being conducted.
4 million people dead, ranking it among the top 10 most
deadly pandemic illnesses in human history.
Animal Host
Origin In China, SARS-like viruses (SARS and MERS) have

largely made bats their natural hosts. However, bat
In the early stages of the pandemic, most cases were SARS, like other coronaviruses, will not normally
associated with individuals who had previously visited directly infect humans unless mutation or recombina-
the Huanan wholesale seafood market in the city of tion occurs in intermediate animal hosts. There are
Wuhan. It is important to note that in this market, hundreds of different coronaviruses, most of which cir-
along with seafood, large collections of various wild culate among such animals as pigs, camels, and bats.
animals were also available for purchase and consump- Generally, bat habitats are far from human activity, so
tion during this time. SARS-CoV-2 was isolated from this recombination event rarely results in disease.
environmental samples of the market by Chinese However, further human encroachment into animal
Center for Disease Control and Prevention. Suspicions habitats has increased interaction between humans and
arose that this may have originated from the same ani- animal hosts. Although this is still being studied, the
mal host, masked palm civets (Paguma larvata), as first hypothesized mechanism by which this virus
SARS-CoV. Early viral sequencing showed that SARS- obtained virulence in humans is thought to be what is
CoV-2 shares only 79.6% sequence identity with SARS- termed a zoonotic “spillover event,” in which a virus
CoV based on full-length genomic comparisons. reaches a certain mutagenic threshold and gains the
However, at the whole-genome level, it is highly identi- ability to transmit from one species to another, which,
cal (96.2%) to bat-CoV RaTG13, which was previously in the case of humans, can lead to disease (Figure 1.1) [7].
Natural Host/Reservoir Intermediate Host Acquired Virulence in Humans
Cross-Species Zoonotic
Transmission Spillover Event
2012
MERS-CoV
Human-to-
Recombination SARS-CoV-2 2019 Human Spread
Events
2002
SARS-CoV
Figure 1.1 Diagram depicting historical examples, along with the proposed mechanism for SARS-CoV-2, of other
Coronaviridae theorized recombination events leading to circulation in animals and zoonotic spillover into humans.
COVID-19: Epidemiology 3
These events, although rare, are thought to have led to infectiousness, and that the duration of viral RNA
similar outbreak-type events several times in human shedding is variable and may increase with age and ill-
history. Intermediate animal hosts of SARS-CoV and ness severity [14]. Furthermore, the short-term risk for
MERS-CoV were determined to be the masked palm reinfection (e.g. within the first several months after
civets (P. larvata) and the dromedary (Camelus drom- initial infection) is low, because prior infection has
edarius), respectively, before transmission to humans been shown to reduce the risk for infection in the sub-
occurred [8, 9]. With respect to COVID-19, genomic sequent six to seven months by 80–85% [15].
evidence has pointed to the Sunda pangolin (Manis
javanica) as a suspected intermediate host of SARS-
CoV-2. Sequence identity between pangolin-origin
coronavirus and SARS-CoV-2 is 99%, indicating that
Modes of Transmission
SARS-CoV-2 may have been passed on to humans as a
Overview
result of exposure with these mammals [10]. In addi-
tion, SARS-CoV-2 and other coronaviruses from pan- The US Centers for Disease Control and Prevention
golins use receptors (angiotensin-converting enzyme (CDC) confirmed person-to-person transmission on
2 [ACE2] receptor) with similar molecular structures 30 January 2020. Many transmission routes have been
to infect cells, bolstering the argument for the virus considered, such as surface-to-surface contact, fecal-
being enzootic in these animals. However, others oral, bloodborne, and sexual contact, but evidence points
have questioned the relationship between pangolin to droplet spread via the respiratory pathway to be the
and human infection, and this hypothesis is still being most likely principal mode of transmission [16, 17].
studied [11].
Respiratory Droplets
Infectivity and Incubation Inhalation of droplets allows the transmitted virus’s

spike (S) protein to bind to the host ACE2 receptor on
The precise interval that an individual with SARS- respiratory epithelial tissue, a critical step for cell entry
CoV-2 infection can transmit infection to others is and infection [18]. Entry then allows for replication
uncertain. However, it is estimated that infected indi- and, as the viral load increases, an increased risk for
viduals are likely to be the most contagious in the ear- transmission when an infected individual coughs,
lier stages of illness when viral RNA levels from upper sneezes, sings, or talks in the proximity of an unin-
respiratory specimens are the highest. Modeling stud- fected individual. Viral load is highest in the upper res-
ies have estimated that infectivity begins two days piratory tract (nasopharynx and oropharynx) early in
before symptom onset, peaks, and then lasts for disease and increases in the lower respiratory tract
approximately seven days. Infectivity rapidly declines over time. This further suggests that the upper respira-
after 8–10 days after presentation of illness [12, 13]. tory tract is the initial site of viral replication, with
Nucleic acid detection studies (reverse transcriptase- subsequent descending infection [17].
polymerase chain reaction) support this infectious
period by demonstrating SARS-CoV-2 RNA detection
Aerosolization
in people one to three days before their symptom
onset, with the highest viral loads observed around the Although transmission most likely occurs through
day of symptom onset and a gradual decline over prolonged close-range contact (i.e. within approxi-
time [12]. The duration of nasopharyngeal reverse mately 6 ft or 2 m) and involves large respiratory
transcriptase-polymerase chain reaction positivity droplets, transmission also can occur more distantly
generally appears to be one to two weeks for asympto- via smaller respiratory droplets that can remain in
matic persons, up to three weeks or more for patients suspension or be recirculated through ventilation
with mild to moderate disease, and even longer for systems. In addition, it is likely that during aerosol-
patients with severe COVID-19 disease and/or immu- generating procedures (e.g. fiberoptic bronchoscopy)
nocompromise [12]. It is important to note that pro- the virus may be transmitted at a greater distance
longed viral RNA detection does not indicate prolonged [17, 19]. Although SARS-CoV-2 also can be potentially
transmitted over such longer distances via an airborne ing, ventilation, adequate distancing, etc.) [17]. In
route, in a nonprocedural setting this would primarily addition, providers should always practice good
occur in specific scenarios where proximity and viral surface hygiene, with the precautions that evidence
load are optimized (i.e. sneezing and/or coughing in may provide different conclusions in the future. In
close contact). The precise extent to which aerosol short, collective data suggest that live virus persists
transmission has contributed to the overall pandemic transiently on surfaces, and although it is beneficial to
is uncertain and is not thought to be the major con- practice good sanitary hygiene overall, fomites are not
tributor to overall pandemic transmission [17, 20]. thought to be a major route of transmission [17].
Regardless, there are numerous examples suggesting
aerosol transmission in some settings and evidence
Fecal-Oral
supporting proximity as a key determinant of risk,
along with duration of contact, indoor settings (i.e. SARS-Cov-2 has been detected in nonrespiratory spec-
households, healthcare settings, college dormitories, imens, including stool, blood, ocular secretions, and
homeless shelters, detention facilities, superspreader semen, but their role in infection also appears to be
events), and poor ventilation [17, 19, 21]. minimal. Fecal-oral transmission was theorized early
in the outbreak because of the known high concentra-
tion of ACE2 receptors in the small bowel [25].
Direct Surface Contact and Fomites
Although viral RNA is commonly detected in stool,
Early reports of clustered infections from China raised live virus has only rarely been isolated. Currently, no
concern of possible surface contact transmission of evidence supports fecal-oral transmission in humans,
SARS-CoV-2. Although it is plausible that touching a and studies with intragastric inoculation of SARS-
contaminated surface and subsequently contacting a CoV-2 in macaques did not result in infection [17].
mucosal surface (the eyes, nose, or mouth) could lead This is supported by an official joint report released by
to infection, there is currently no conclusive evidence the WHO and China in February 2020 stating trans-
for fomite or direct contact transmission in humans. mission through the fecal-oral route did not appear to
Early concerns of events suggesting fomite transmis- be a significant contributing factor for viral spread [26].
sion were circumstantial [22, 23]. In these early
reports, individuals using shared facilities (such as
Bloodborne
elevators and restrooms) proposed either fomite or res-
piratory transmission in those settings. In a detailed Bloodborne transmission was also hypothesized early
investigation of a large nosocomial outbreak linked to on, but the proportion of persons with viral RNA
119 confirmed cases at a hospital in South Africa, detectable in blood is currently unknown and likely
fomite transmission was proposed given the separated very small. An early study found viral RNA in only 3 of
distribution of cases in multiple wards [22]. However, 307 blood specimens. However, no replication-
the hospital did not have a universal mask policy, competent virus has been isolated from blood samples
lacked adequate ventilation, and had a substantial to this date, and there have been no documented cases
burden of infection among health care workers. As a of bloodborne transmission [27]. Moreover, there have
result, respiratory transmission from infected staff been documented reports of recipients of platelets or
could not be excluded [24]. Among healthcare work- red blood cell transfusions from donors diagnosed
ers, poor hand hygiene has been shown to be associ- with SARS-CoV-2 in which the transfused individuals
ated with increased risk for infection with SARS-CoV-2. did not experience COVID-19-related symptoms, nor
Although this might suggest increased risk for con- did they test positive for SARS-CoV-2 [26, 28].
tamination via direct contact or fomite spread, it is dif-
ficult to separate this from other hygienic practices. As
Semen and Vaginal Secretions
will be discussed in subsequent sections, hand hygiene
precautions have been shown to be highly associated Sexual transmission of SARS-CoV-2 was also an initial
with practices that decrease risk overall (mask wear- concern. However, no current evidence supports
s exual transmission of SARS-CoV-2 in semen or vagi- the outbreak, the CFR was much higher: 17.3% across
nal fluids. Although viral RNA has been found in China as a whole and greater than 20% in the center of
semen, infectious virus has not been isolated [29]. In the outbreak in Wuhan [35]. Underreporting of cases,
addition, vaginal fluid studies have been negative such as from failure to test individuals with mild dis-
except for a small number of case reports showing ease and asymptomatic infection, can greatly inflate
RNA with low viral levels [30]. the CFR. Conversely, there are concerns that during
the rapid spread of disease during a pandemic, the
CFR will underestimate disease, because the death
Asymptomatic Transmission counts do not account for any eventual deaths that
may occur in the overall pool of cases. Wide variations
People who express symptoms convey the highest (estimates ranging from <0.1% to >25%) in CFR can
risk for transmission. However, one of the more insidi- also arise from country to country as a result of extrin-
ous aspects of this virus is its ability to spread among sic or societal factors [36]. CFR, furthermore, does not
individuals who are minimally symptomatic or account for differences in age or sex; it is a cumulative
asymptomatic. Multiple studies have demonstrated that population at-risk metric. Nevertheless, this method,
asymptomatic or presymptomatic persons have the abil- along with others, was used to approximate disease
ity to spread infection, and this has been well docu- mortality and was consistent with the initial CFR
mented throughout the pandemic [31–33]. Some models reports released from China in the early stages of the
estimate the proportion of spread attributable to asymp- pandemic, outside of Hubei Province [36–38].
tomatic and presymptomatic transmission at greater
than 50% [34]. However, it is important to note that the
risk for transmission from an individual who is asymp- Serial Interval
tomatic appears to be less than from a presymptomatic In any infectious disease outbreak, the estimation of
individual, who also carries lesser risk than that from transmission dynamics is crucial to contain spread in a
one who is symptomatic [33]. The impact of asympto- new area. Of the tools used in such estimations, the
matic spread on the pandemic is undoubtedly consider- serial interval is one of the significant epidemiological
able and has led to difficulties in quantitatively tracking measures that help determine the spread of infectious
exposure in populations. Nevertheless, the concern for disease. It is required to understand the turnover of
undetected spread has shaped policy and national deci- case generation and transmissibility of the disease and
sions across the globe, forcing implementation of multi- is defined as the time between which the infector and
ple unprecedented global infection prevention measures the secondarily infected show the symptoms, that is,
that will be briefly discussed in later sections. the time interval between the onset of symptoms in
the primary (infector) and secondary cases (infected).
The estimated serial interval for SARS-CoV-2 is about
Virulence and Mortality 4.5–5 days [39].
Case Fatality Rate

Reproduction Number/Reproduction Ratio
Case fatality rate (CFR) is the total number of deaths
from disease divided by the total number of confirmed Reproduction number (R0) represents the number of
cases. As of June 2021, there have been 178 180 208 people to whom an infected person passes the disease
confirmed cases and 3 859 722 deaths worldwide. This in its next generation, with length of time determined
estimates the current worldwide CFR to be approxi- by the serial interval measure of the disease. This
mately 2.17%. There are limitations to using CFR as a value has had wide variability throughout the pan-
measure of disease mortality. For example, this num- demic. During the COVID-19 outbreak, the initial esti-
ber is dynamic, because the denominator and numera- mates of R0 were between 2.0 and 3.0. However, later
tor are based on documented cases and deaths and can studies estimated the R0 to be 3.82, with a mean
rapidly change. For example, in the earliest stages of reported R0 range of 1.90–6.49 [40]. Importantly, it is
estimated that R0 is higher for certain variants of con- 26 January 2020 to 27 February 2021 (Figure 1.2) [42].
cern, such as the alpha or delta variants [40]. This The percentage excess mortality is this difference in
increased transmissibility is of great concern as world- mortality for a given time period divided by the aver-
wide spread of variants of concern accelerates and age mortality in the same designated time frame dur-
more transmissible variants become the dominant cir- ing previous years. The estimated number of excess
culating strains. deaths peaked during the weeks ending 11 April 2020,
1 August 2020, and 2 January 2021 (Figure 1.2) [41],
with approximately 75–88% of excess deaths directly
Excess Mortality
associated with COVID-19 [42, 43].
Excess mortality is a measure used by epidemiologists Globally, it is difficult to accurately estimate the
and public health experts to assess the overall impact of total number of excess deaths. Not all countries have
pandemic disease. Because not all cases and deaths can the infrastructure to report nationwide mortality accu-
realistically be reported, this gives practical insight into rately and expeditiously, and representation from
overall impact. It is defined as the difference in mortal- poorer countries is underreported. Keeping in mind
ity in a given year compared with the average number these limitations, the WHO estimates, in 2020, a
of deaths over a given number of previous years. In the worldwide excess mortality of more than 1.8 million
United States, data from the National Vital Statistics deaths attributed directly to COVID-19, with unoffi-
System of the CDC estimated that 545 600–660 200 cial total pandemic deaths totaling more than 3 mil-
excess deaths occurred in the United States from lion people [43].
Weekly number of deaths

Comparing excess deaths including/excluding COVID-19
100,000
Light blue bars
estimate the overall
90,000 excess mortality due
to COVID-19*
80,000
70,000
60,000
50,000
40,000
30,000
20,000
10,000
0
1/14/2017 7/14/2017 1/14/2017 7/14/2018 1/14/2019 7/14/2019 1/14/2020 7/14/2020 1/14/2021
Observed Count (All Causes) Observed Count (Excluding COVID-19) Average Expected Counts (All Causes)
Figure 1.2 Excess mortality counts by week for observed all-cause mortality and observed mortality excluding COVID-19
(1 January 2017 to 1 July 2021). Overlaid trend line is average expected counts based on previous year trends. Red box:
Counts may be incomplete because only 60% of death records are submitted to National Center for Health Statistics (NCHS)
within 10 days of the date of death, and completeness varied by jurisdiction (1 February 2020 to 26 June 2021). *Number of
deaths reported is the total number of deaths received and coded as of the date of analysis and does not represent all
deaths that occurred in that period. Data are possibly incomplete because of the lag in time between when the death
occurred and when the death certificate was completed, submitted to NCHS, and processed for reporting purposes. Source:
Data are from the US Centers for Disease Control and Prevention [41].
Demographics most cases, with elderly individuals comprising the

majority of deaths despite being a smaller percentage
Overview of the overall population (Figure 1.3). Most of these
deaths occurred in those 85 years and older [45–47].
SARS-CoV-2 has shown the ability to infect all ages,
races, and ethnicities across the globe. Notably,
COVID-19 disproportionately affected different groups Sex
of individuals, with age, race, sex, and medical status all Sex demographics reported by the CDC showed that
conferring varying levels of morbidity and mortality. In females made up a slight majority (52.2%; males,
the United States, the virus has infected young adults 47.8%) of COVID-19 cases in the United States
most often. Elderly individuals (>65 years of age) were (Table 1.2) [45]. Worldwide, there was no significantly
among the most vulnerable populations in terms of observed sex difference in proportion of COVID-19
mortality [44]. Underlying comorbidities, immuno- cases [48]. Interestingly, in the United States, although
compromised status, and non-white race all are risk fac- COVID-19 affected more females than males, mortal-
tors for progression of SARS-CoV-2 infection to more ity disproportionately affected males, who account for
serious disease. In the United States, the most frequent approximately 54.2% of all COVID-19 deaths, with
comorbidities listed on death certificates of those with females comprising about 45.8% (Figure 1.4) [45]. This
COVID-19 are influenza and pneumonia (45.8%), trend was also seen in other parts of the world [49]. It
hypertension (19.8%), diabetes (16.0%), Alzheimer dis- is unclear what drives this disparity, but the cause
ease (13.5% of deaths), and sepsis (9.6%) [44]. appears to be multifactorial [50–52].
Age Race and Ethnicity

Data from the CDC, as well as other public health Sadly, racial and ethnic disparities were apparent
agencies around the world, demonstrated the ability of throughout the pandemic. Inadequate early preven-
SARS-CoV-2 to infect individuals of all ages. Age groups tion measures, testing, and social support and the
for the CDC were reported in nine categories (Table 1.1). need to work outside of the home disproportionately
The overall trend showed that young adults make up affected vulnerable and marginalized populations.
This was very well displayed in data obtained from the
Table 1.1 CDC COVID-19 case and death percentages, by Los Angeles Department of Public Health in California,
age, with respective percentages of the US population (data where Hispanics were shown to be more than 2.5
through July 2021).
times more likely to be infected with COVID-19
(Figure 1.5) than their white peers. Notably, the
Percent (%) Percent (%) Percent (%) of
Age group of cases of deaths US population age-adjusted mortality rate for Hispanics from
COVID-19 was more than three times greater than
0–4 yr 2.1 <0.1 6 for non-Latino whites (Figure 1.6). For perspective,
5–17 yr 10.4 0.1 16.3
18–29 yr 22.5 0.5 16.4 Table 1.2 CDC data of COVID-19 deaths by sex
(all age groups).
30–39 yr 16.4 1.2 13.5
40–49 yr 14.8 3.0 12.3
50–64 yr 20.2 15.3 19.2 Sex of cases of deaths US population
65–74 yr 7.4 21.6 9.6
75–84 yr 3.8 27.4 4.9 Female 52.2 45.8 50.75
≥85 yr 2.2 30.9 2 Male 47.8 54.2 49.25

Other <0.1 <0.1 Not available
Of the 27 472 068 cases recorded, age group was available for
27 281 478 (99%) cases. Of the 495 907 deaths recorded, age Data as of July 2021. Of the 495 907 deaths recorded, sex was
group was available for 495 867 (99%) deaths. available for 494 710 (99%) deaths.
United States COVID-19 Cases By Age Group
25
20
15
10
0
0-4 Years 5-17 Years 18-29 Years 30-39 Years 40-49 Years 50-64 Years 65-74 Years 75-84 Years 85+ Years
Percent of Cases (%) Percent of United States Population (%)
United States COVID-19 Deaths By Age Group

35
30
25
20
15
10
5
0
0-4 Years 5-17 Years 18-29 Years 30-39 Years 40-49 Years 50-64 Years 65-74 Years 75-84 Years 85+ Years
Percentage of Deaths (%) Percentage of United States Population (%)
Figure 1.3 Case and death count distribution by age with corresponding percentage of US population for each respective
age group. Source: Graph data are from the US Centers for Disease Control and Prevention [45].
Cases by Sex* Deaths by Sex*

(All Age Groups) (All Age Groups)
80 80
70 70
60 60
50 50
40 40
30 30
20 20
10 10
0 0
Female Male Female Male
Percent of cases (%) Percentage of deaths (%)

Percent of United States population (%) Percent of United States population (%)
Figure 1.4 US COVID-19 cases and deaths for males and females for all age groups. *Those who were listed as “other”
constituted less than 0.001% of cases, and deaths are not graphically represented here. Source: Case and mortality data from
the US Centers for Disease Control and Prevention [45]. Data are as of July 2021.
AGE-ADJUSTED CASE RATES PER 100,000 PER

Los Angeles County Age-Adjusted Case Rates by Race/Ethnicity
2500
2000
14 DAY CUMULATIVE*
1500
1000
500
0
1-Oct-2020 1-Nov-2020 1-Dec-2020 1-Jan-2021 1-Feb-2021 1-Mar-2021 1-Apr-2021
White Latino/Hispanic Black/African American Asian
Figure 1.5 Los Angeles County age-adjusted COVID-19 case rate per 100 000 individuals by race/ethnicity, April 2020 to
June 2021. *Data are estimated reported data from the Los Angeles County Department of Public Health and do not
necessarily reflect exact amounts.
Los Angeles County Age-Adjusted Death Rates by Race/Ethnicity

AGE-ADJUSTED DEATH RATES PER 100,000
70
60
PER 14 DAY CUMULATIVE*
50
40
30
20
10
0
1-Oct-2020 1-Nov-2020 1-Dec-2020 1-Jan-2021 1-Feb-2021 1-Mar-2021 1-Apr-2021
White Latino/Hispanic Black/African American Asian
Figure 1.6 Los Angeles County age-adjusted mortality rate per 100 000 individuals by race/ethnicity, April 2020 to June
2021. *Data are estimated reported data from the Los Angeles County Department of Public Health and do not necessarily
reflect exact amounts.
in 2020, COVID-19 became the leading cause of race-respective population percentages, Hispanics
death in Los Angeles for Latino/Hispanics (where and non-Hispanic Blacks have been disproportion-
they account for 49% of the total population), outpac- ately affected in terms of disease morbidity and mor-
ing mortality rates from heart disease, cancer, and tality, with both respective mortalities outpacing their
diabetes [53]. proportions of the population (Figure 1.7) [54–56].
In terms of the US population overall, crude data Furthermore, additional studies have reported that
demonstrated that non-Hispanic whites accounted American Indian or Alaska Native, non-Hispanic
for the greatest percentage of morbidity, compris- persons were also disproportionately affected and
ing approximately 50% of cases, with Hispanic and more likely to be infected, hospitalized, or die with
non-Hispanic blacks following at 29% and 11%, COVID-19 in comparison with their white counter-
respectively (Table 1.3). However, when considering parts [55–57].
Table 1.3 CDC data of COVID-19 cases by race/ethnicity.

Race/ethnicity of cases of deaths US population
Hispanic/Latino 28.7 18.6 18.45

American Indian/Alaska Native non-Hispanic 1 1.2 0.74
Asian non-Hispanic 3.2 3.8 5.76
Black non-Hispanic 11.4 13.7 12.54
Native Hawaiian/Other Pacific Islander non-Hispanic 0.3 0.2 0.182
White non-Hispanic 50.1 58.6 60.11
Multiple/other non-Hispanic 5.3 3.8 2.22
Data as of July 2021. Of the 27 472 068 recorded cases, race/ethnicity was available for 17 382 837 (63%) cases.
sufficient cellular signals to generate an immune

Disease Prevention
response. A caveat to this is that these vaccines typi-
cally do not provide as strong an immune response
Vaccinations
(protection) as live vaccines, so several doses may be
One year into the pandemic, vaccination-based pre- required over time (booster shots) to obtain ongoing
vention was developed and implemented. Numerous immunity against diseases [60]. Sinopharm (BBIBP),
vaccines are currently in development, and several CoronaVac (Sinovac), and Covaxin are all examples of
have been approved for official use. These largely fall vaccines that use this technology. These are largely
under four technology categories: adenovirus vector used internationally in countries throughout Asia and
vaccines, inactivated viral vaccines, protein subunit Latin America; currently, they have not been approved
vaccines, and messenger RNA (mRNA) vaccines. for use in the United States.
Following is a brief overview of the more notable vac- Protein-based vaccines use fragments of proteins or
cines; these and others will be covered in greater detail protein shells that mimic viral antigens to generate an
elsewhere in the text. immune response, which is enhanced by coformula-
Viral vector vaccines use a modified, nonreplicating tion with an adjuvant substance. The antigen can be
virus that is taken up and processed by human cells, any molecule, such as structural proteins, other pep-
expressing a viral protein, generating an immune tides, or polysaccharides. Like inactivated vaccines, the
response. Several different viruses have been used as vaccine is completely “dead,” that is, replication incom-
vectors, including influenza, vesicular stomatitis virus, petent, and therefore may be less risky [60]. Vaccines
measles virus, and human and nonhuman primate that have historically used this technology include the
adenoviruses. This technology has been used histori- hepatitis B vaccine. Currently, the vaccines against
cally to develop vaccines for many diseases, including COVID-19 that implement this technology include the
malaria, Ebola, leishmaniasis, HIV, tuberculosis, and Novavax NVX-CoV2373 vaccine, the Sanofi-GSK adju-
the common cold [58, 59]. Currently, the adenovirus vanted protein subunit vaccine Vidprevtyn, the Russian
vector technology has been used to produce publicly EpiVacCorona (Vector), and the Chinese RBD-Dimer
available SARS-CoV-2 vaccines, most notably, the (Anhui Zhifei Longcom and the Institute of Medical
Oxford–AstraZeneca and the Johnson & Johnson vac- Biology of the Chinese Academy of Medical Sciences).
cines [60, 61]. The two-dose Russian Sputnik adenovi- The latter two are exclusively used in Russia, China,
ral vaccine has shown similar high efficacy [62]. Turkmenistan, and Uzbekistan [60].
Inactivated or weakened virus vaccines use a form of mRNA vaccines are a cutting-edge approach that use
the virus that has been inactivated or weakened, so it genetically engineered RNA to synthesize a structural
does not replicate or cause disease but still contains protein and generate an immune response. Although
United States Case and Population Percentages

By Race/Ethnicity (All Age Groups)
Multiple/Other Non-Hispanic
White Non-Hispanic
Native Hawaiian / Other Pacific Islander Non-Hispanic
Black Non-Hispanic
Asian Non-Hispanic
American Indian / Alaska Native Non-Hispanic
Hispanic/Latino
0 10 20 30 40 50 60 70
Percent of cases (%) Percent of United States population (%)
United States Death and Population Percentages

By Race/Ethnicity (All Age Groups)
Multiple/Other Non-Hispanic
White Non-Hispanic
Native Hawaiian / Other Pacific Islander Non-Hispanic
Black Non-Hispanic
Asian Non-Hispanic
American Indian / Alaska Native Non-Hispanic
Hispanic/Latino
0 10 20 30 40 50 60 70
Percent of deaths (%) Percent of United States population (%)
Figure 1.7 Case and death percentages by race/ethnicity with corresponding percentage of US population for each
respective group. Source: Data are from the US Centers for Disease Control and Prevention [45]. Data are as of July 2021.
this is a relatively new method in the arsenal of vac- The importance of vaccines cannot be understated.
cine development, this technology has been studied Successful historical examples, such as the polio,
for at least a decade before this specific application, so measles-mumps-rubella, and smallpox vaccines, have
the science is well understood. mRNA segments cod- underscored the profound importance of this technol-
ing for the coronavirus spike protein are introduced ogy in achieving herd immunity. Vaccine-mediated
into the body through an intramuscular injection to herd immunity is an essential tool in public health
trigger an immune response. Using a protective lipid and directly protects vulnerable populations with
nanoparticle coating, these particles are taken up by lesser vaccine responsiveness (i.e. elderly adults, indi-
cells, processed, coded for synthesis of spike protein, viduals with chronic disease, and immunocompro-
and presented to the immune system, triggering a mised persons). The alternative “natural immunity”
humoral and a cellular immune response. The Pfizer- method would be impractical. Although prevent-
BioNTech and Moderna vaccines are examples of this ing circulation of virus through naturally acquired
technology and are the main vaccines used by the herd immunity would occur eventually, it would also
United States and many countries throughout Europe. result in unnecessary cases and deaths and has possi-
These vaccines were approved by the US Food and bly been achieved only in close situations such as
Drug Administration for Emergency Use Authorization prisons [68].
on 11 December 2020 for Pfizer and on 18 December Current COVID-19 vaccinations have been shown to
2020 for Moderna [60, 63]. The Pfizer vaccine received not only decrease viral load but also decrease risk for
full US Food and Drug Administration approval on 23 asymptomatic transmission [69–71]. However, emerg-
August 2021. ing variants have the potential to escape some of these
The goals of vaccination are grounded on two key benefits of vaccination. Reducing transmission via
concepts: bolstering individual immunity to prevent vaccination carries important implications for reopen-
severe disease and hospitalization and to limit ing and shaping public health guidelines going for-
population-wide spread. “Herd immunity” is an indi- ward, as the CDC and national governments relax
rect form of protection resulting from enough individ- recommended prevention measures for vaccinated
uals obtaining immunity, via vaccination or infection, individuals [72]. This is a monumental finding
to the point where it minimizes further disease circu- because, as mentioned in previous sections, SARS-
lation within a population. This threshold varies from CoV-2 and its variants carry significant mortality and
pathogen to pathogen. Herd immunity to SARS- disproportionately affect the marginalized and the dis-
CoV-2 has been estimated, giving circulating strain advantaged [73]. Given the availability and promising
considerations, to require immunity in approximately results of this technology, immunity via natural circu-
70–80% of the population. However, this number will lation of the virus would be not only medically irre-
increase as newer variants arise with higher R0 and sponsible but also potentially morally unacceptable.
increased transmissibility [64].
For many viruses, the more it circulates in a popula-
Personal Protective Equipment:
tion, the more opportunities it has to replicate and/or
Respirators and Masks
mutate; SARS-CoV-2 has demonstrated this abil-
ity [65]. These mutations have the potential to produce In the United States, hospitals are required to provide
more transmissible and more virulent strains of SARS- personal protective equipment for staff working with
CoV-2. For example, the 501Y mutation (present in the patients with suspected or confirmed COVID-19,
B.1.1.7 or alpha variant) and the L452R mutation (pre- which includes the use of a gown, gloves, a respirator
sent in the B.1.617.2 or delta variant) are both associ- or medical mask, and eye or face protection for pre-
ated with higher levels of transmissibility [66]. venting transmission. N95 masks confer the greatest
Fortunately, preliminary reports of current vaccine protection, especially in conditions of greater patient
effectiveness have demonstrated protection, albeit aerosolization, such as during aerosol-generating pro-
reduced, to such variants and emphasize their need cedures and certain types of environmental cleaning.
against more virulent strains [67]. However, in the event that N95 masks are not available
or are in limited supply, surgical masks are acceptable individual, which, as previously mentioned, is thought
in many hospital settings [72, 74, 75]. to be the principal risk factor for transmission of
In the community, mask wearing with social dis- SARS-CoV-2. This method was taken from previous
tancing as an alternative to widespread lockdown was data preventing SARS and MERS infections. In a meta-
officially endorsed by the CDC in March 2020. The analysis of observational studies evaluating the rela-
CDC subsequently issued a mandate requiring masks tionship between physical distance and transmission
on public transportation and areas or times of gather- of SARS-CoV-2, SARS-CoV, and MERS-CoV, proxim-
ings (including taxis and rideshares) and at transpor- ity and risk for infection were closely associated, and
tation hubs (e.g. airports, bus or ferry terminals, the infection rate was much higher with contact
railway stations, seaports) [76]. The rationale for within 3 ft (1 m) compared with contact beyond that
community mask wearing is, regardless of symptoms, distance (12.8% versus 2.6%) [77].
preventing transmission while maintaining the day- Optimal distance is uncertain, but physical distanc-
to-day functions for individuals and the country. In ing is likely independently associated with a reduced
the United States, cloth masks or disposable masks risk for SARS-CoV-2 transmission. Current guidance
(e.g. commercially available surgical masks) were rec- suggests at least 6 ft. In the United States, the CDC rec-
ommended for the general public or in public settings ommends a minimum distance of 6 ft (2 m), whereas
with individuals outside the household to reduce the WHO recommends a minimum distance of 1 m. In
transmission of SARS-CoV-2. In addition, guidance locations where there is community transmission of
criteria for approved homemade masks were given to SARS-CoV-2 (including throughout the United States),
the public, stating that masks should be made with individuals are advised to practice social or physical
several layers, fit snugly over the face, and should not distancing in both indoor and outdoor spaces by main-
contain respiratory valves [74, 76]. taining a minimum distance from other people out-
Strategies to improve mask fit include using a mask side their household.
with an adjustable nose bridge, wearing a cloth mask Widescale shelter-in-place orders and lockdowns
over a disposable mask, knotting the ear loops of a dis- were the most aggressive form of these distancing
posable mask to secure it against the face, using masks methods. During peak outbreaks, when daily case rates
with ties rather than ear loops, and using a mask brace. and deaths were the highest, governments strongly
Some individuals may opt to wear commercially avail- encouraged or required individuals to quarantine
able KN95 respirators, but many do not meet the inside their homes, only leaving for necessities such as
advertised filtration standards. Furthermore, due to food and other items. Although one of the most contro-
necessity in the healthcare setting, N95 respirators are versial forms enacted by prevention taskforces, given
not indicated or necessary for the general public and societal and mental health considerations, studies can
should generally be reserved for healthcare workers speak to the impact of distancing on viral transmission.
who work in higher-risk environments [74, 75]. One such study involving multiple countries showed a
significant decrease in viral transmission when indi-
viduals were distanced 1 m or more from each other.
Physical Distancing
Moreover, protection was increased as the distance was
In the effort against COVID-19 spread, countries across lengthened [77]. Other studies have shown that, after
the globe used various physical distancing measures cases began to emerge, longer time periods for which
to keep clustering of individuals to a minimum. This countries waited to implement quarantine measures
included, but was not limited to, limiting the number of were associated with greater CFRs [78].
individuals in closed spaces, temporarily shutting down
schools and universities, and limiting the number of
Hand and Surface Sanitation
people during indoor shopping, gymnasium use, per-
sonal services (e.g. hair cutting, manicures), and dining. Inanimate surfaces may be potential sites for the trans-
Distancing guidelines were implemented to mini- mission of COVID-19 infection. Depending on the
mize prolonged close-range contact with an infected nature of the surface and conditions of the surrounding
environment (temperature, pH, humidity, etc.), the ventilation flow rates can lead to lower viral air con-
virus can remain viable for several hours [78]. Concern centrations and a decreased risk for exposure and
mainly stems from potential contaminated surfaces transmission of virus [83]. Although conclusions of
contacting hands, which then pass the virus to upper ventilation effects on SARS-CoV-2 transmission are
respiratory tract mucous membranes (conjunctivae, largely drawn from historical and theoretical models,
nose, mouth, etc.) through touch. Although surface they nonetheless highlight the need for improved air
contact spread is only theoretical and has not been circulation to lower airborne viral concentrations and
definitively documented, studies have shown that decrease the risk for transmission.
SARS-CoV-2 has extended longevity on certain surfaces
and through skin-to-skin contact [79, 80]. The US
Use of Outdoor Spaces
Environmental Protection Agency recommends disin-
fectants that contain quaternary ammonium com- Where possible, use of outdoor spaces can further
pounds, hydrogen peroxide, alcohol (ethanol, isopropyl reduce aerosol transmission [84]. Outdoor spaces typi-
alcohol, phenol), aldehyde, hypochlorous acid, octanoic cally offer greater physical distancing and airflow than
acid, citric acid conjugate with silver ions, sodium indoor spaces. Relatively few SARS-CoV-2 transmis-
hypochlorite, sodium bicarbonate, etc., all of which sions have been linked to outdoor setting [85].
contain key virucidal activity. Specifically, alcohols eth- Although outdoor transmission can occur, and the
anol (78–95%) and isopropanol (70–100%) have been precise settings in which this can be minimized are
used as reliable and relatively safe disinfectant options still being investigated, the odds of indoor transmis-
because they show potent virucidal activity with a neg- sion have been shown to be significantly greater [86].
ligible toxic effect on human skin [81]. In autopsy stud- Limiting the duration and frequency of personal
ies, SARS-CoV-2 remained viable on the skin for about contact, using personal protective equipment, and
nine hours but was completely inactivated within avoiding any indoor contacts may increase the safety
15 seconds of exposure to 80% alcohol [81]. of outdoor gatherings [84].
Adequate Ventilation of Indoor Spaces

A healthy amount of literature emphasizes the impor-
Global Impacts
tance of air quality and ventilation in the healthcare
Distribution
setting. There is substantial evidence, drawn from
prior studies on pandemics, that emphasizes an effec- At the time that this was written, the WHO had esti-
tive combination of air filtration and circulation can mated the total confirmed counts to be more than
reduce risk for infection. However, much of the data 200 million cases worldwide, with more than 4 million
surrounding ventilation and SARS-CoV-2 infection deaths. As discussed previously, these are confirmed
are model based, drawing conclusions from theoreti- cases only, such that the number of cases (i.e. overall
cal scenarios and calculated behaviors of similar-size disease burden) has likely been underreported [43].
microbes. Using the Wells–Riley equation, a study Geographic distribution is worldwide, as cases have
implementing calculated risk associated with various been found in nearly every country. The countries that
rates of ventilation concluded a significant theoretical had the highest disease burden were the United States
reduction in COVID-19 infection risk with adequate of America, India, and Brazil. In terms of mortality, the
ventilation of an enclosed space. Furthermore, these countries with the highest mortality burden were the
beneficial effects were compounded by those who con- United States of America, Brazil, India, and Mexico [83].
currently wore a medical-grade mask [82]. A large lit-
erature review addressing air recirculation also drew
International Response
on historical examples and the behavior of similar
microorganisms to frame the need for adequate venti- This begs the questions, what countries had the most
lation and concluded that specific filters and air success against the COVID-19 pandemic, and why
were they successful? Conversely, what was common emergencies. Such a pandemic playbook has previ-
among those who were not? There is a public health ously been proposed by the CDC to help coordinate
consensus that limiting the number of contacts pandemic influenza response [92]. This includes, but
between persons can slow COVID-19 transmission in is not limited to, concepts such as swiftly tightening
a community and give time for healthcare systems to international borders to travel and trade, supervised
respond and vaccines to be developed. Factors such as traveler isolation and well-coordinated quarantines,
population density, leadership, national wealth, infra- early implementation of physical distancing require-
structure, and equitable healthcare resources influ- ments, encouraging good hand hygiene (frequent
ence a nation’s capacity to do so [87]. handwashing, use of alcohol hand sanitizers as an
Before vaccination, the most meaningful approaches alternative, cough etiquette), and having the infra-
governments took to stop community spread were stay- structure for quick and widespread testing and contact
at-home-orders. These guidelines requested or required tracing [91, 93]. In addition to these policies, nations
people to quarantine in their homes, to leave only for must also possess the capacity to provide social sup-
absolute necessities, such as food and healthcare ports in the future, to provide mental health services,
needs [88]. Although there are multiple theoretical and adequate resources, and economic assistance to those
practical models about how stay-at-home orders and in need. This is obviously a more attainable goal for
travel restrictions slowed COVID-19 transmission, it is wealthier countries, but nevertheless, it is imperative
clear that consistency in communication and early that nations and their leaders come together and offer
implementation were key [89]. Retrospective data mutual aid in times of crisis. Sharing of wealth, infor-
show that a longer amount of time before implementa- mation, resources, intellectual property, and financial
tion of physical distancing measures was associated support are all necessary to maximize the safety and
with worse CFRs [77]. Widespread testing efforts were well-being of citizens.
valuable in the identification of cluster outbreaks.
South Korea is a good example of the impact of early
and effective measures, in which large-scale testing Conclusions
efforts in combination with contact tracing and social
distancing measures led to one of the most successful This novel SARS-CoV-2 virus was unique in many
pandemic responses in the world [90, 91]. Countries ways. An insidious, yet defining, characteristic of this
such as New Zealand succeeded by enacting strict bor- disease was its ability for asymptomatic spread.
der control. Of course, having the wealth and resources Without efficient widespread testing measures, we
to accommodate such a large and rapid disease saw a virus, seemingly isolated to a limited region of
response is crucial to improving individual and popula- China, stretch to every corner of the globe in a matter
tion outcomes. Countries with an adequate physician of months. In coordination with international leaders,
workforce and technological capacity to accommodate our global health institutions developed guidelines to
pandemic-level crises were able to detect disease ear- help contain spread, including isolation, mask wear-
lier and fared better in terms of overall mortality [77]. ing, hand hygiene practices, and nationwide shut-
downs of business and mass gatherings. However, the
aftermath of the outbreak cannot be ignored; short-
Future Outbreaks
comings must be addressed. Hospitals quickly filled to
Global trade, travel, climate change, urbanization, and capacity, and we saw our healthcare infrastructure
national wealth all play a part in global infrastructure woefully ill-equipped to handle the volume of indi-
and the ability to address worldwide pandemics. viduals affected by this disease.
Lessons learned over the course of the COVID-19 pan- Indeed, the pandemic has revealed shortcomings in
demic, compiled from multiple national responses, our health systems, notably highlighting, in the United
have created a type of framework, or a “pandemic States, the systemic racial and economic inequities that
playbook,” in which governments and public health plague them. Moreover, this virus has profoundly
agencies can model policy to stave off future pandemic reshaped how we must think about global public health
and emphasizes the magnitude of work needed to be e ngineering allowed us to address the novel challenges
done. This pandemic illness has forced us to reevaluate of the pandemic. It is essential for us to build on this
our approach to disease epidemiology, outbreaks, and progress, for the sake of the most affected dense and
how further progress can be made under these new poor populations around the world. Our institutions,
norms. Conversely, we have also seen the capacity for physicians, and healthcare leaders must take the lessons
global coordination in an unprecedented time frame. from this unprecedented event to facilitate change with
Massive mobilization of manufacturing, testing decisive action and prevent any future catastrophes like
resources, healthcare workforce, and biomedical the COVID-19 pandemic from occurring again.
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22
COVID-19: Virology
Saeideh Najafi1, Salar Tofighi1, and Juliana Sobczyk2,3
1
Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
2
Department of Pathology, Memorial Satilla Hospital, HCA Healthcare, Waycross, GA, USA
3
Laboratory Director, St. Augustine Foot & Ankle, Inc., St. Augustine, FL, USA
Abbreviations viruses. However, brain cell lines derived from neuro-

blastoma, neuroglioma, and astrocytoma cells demon-
ACE2 angiotensin-converting enzyme 2 strated high susceptibility to infection of these viruses
CoV coronavirus and enabled scientists to grow them in vitro [1]. These
ER endoplasmic reticulum viruses were unlike any viruses previously known to
HE hemagglutinin esterase cause similar symptoms. These novel viruses had fringe-
MERS Middle Eastern respiratory syndrome like projections that resembled solar corona under elec-
MERS-CoV Middle Eastern respiratory syndrome tron microscopy. Thus, in 1968, these viruses with
coronavirus characteristic surface spikes of 200 Å were proposed to
nsp nonstructural protein be named coronavirus (CoV) [2]. A study around this
NTD N-terminal domain time in Italy demonstrated the high prevalence and
ORF open reading frame common occurrence of infection with CoV through
RBD receptor-binding domain detection of antibodies using an indirect immunoperoxi-
RdRp RNA-dependent RNA polymerase dase staining technique, hemagglutination inhibition
SARS severe acute respiratory syndrome test, and plaque reduction neutralization assay [3].
SARS-CoV-2 severe acute respiratory syndrome Initially, CoV had been deemed to cause only mild
coronavirus 2 symptoms. In 2002, a new CoV emerged that caused
ssRNA single-stranded RNA symptoms of severe acute respiratory syndrome (SARS)
VoC variant of concern with a high mortality rate. This new strain, named severe
VoHC variant of high consequence acute respiratory syndrome coronavirus (SARS-CoV), is
VoI variant of interest thought to originate from bats as its natural host [4].
WHO World Health Organization Unlike previously known human CoVs that underwent
coevolution with humans and therefore caused only
In the 1960s, around the time new methods to grow minor symptoms, the sudden access of SARS-CoV to a
viruses in laboratories became available, scientists culti- new host led to severe respiratory symptoms and increased
vated two previously unknown viruses, 229E and OC43, mortality. Later, researchers isolated two new strains
from patients with symptoms of acute upper respiratory (NL63 and HKU1) of CoV from patients with pneumonia,
tract infection (Figure 2.1). These viruses had not been although these strains are believed to most commonly
detected because the prevalent primary cell types used cause mild common cold symptoms [5]. In 2012, Middle
as culture media were not susceptible to these new Eastern respiratory syndrome coronavirus (MERS-CoV)
Coronavirus Disease 2019 (COVID-19): A Clinical Guide, First Edition. Edited by Ali Gholamrezanezhad and Michael P. Dube.
© 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd.
COVID-19: Virology 23
1967 2002 2005 2019

Discovery Outbreak Discovery Outbreak
of of of of
OC43 SARS-CoV HKU1 SARS-CoV-2
1966 2004 2012

1968, new family
Discovery Discovery Outbreak
of virus,
of of of
Coronaviruses was
229E NL63 MERS-CoV
described.
Figure 2.1 Timeline of discoveries of CoVs.
emerged in Saudi Arabia. Similarly, MERS-CoV also rap- initiated the spread of the virus to other continents.
idly crossed species from bats as reservoirs and camels as On 31 January 2020, the World Health Organization
intermediate hosts to humans and caused severe respira- (WHO) declared a public health emergency of inter-
tory symptoms and high mortality [4]. Nevertheless, prior national concern. The International Committee on
to 2019, the majority of CoV types known to infect Taxonomy of Viruses renamed the new virus SARS-
humans (four of six types) primarily caused mild respira- CoV-2 and termed the illness sequelae coronavirus
tory symptoms. disease 2019 (COVID-19) [8]. Rapid worldwide trans-
In early December 2019, an unknown infectious mission led to the pandemic declaration on 11 March
agent caused an outbreak of unusual viral pneumonia 2020. The number of people infected and the geo-
in Wuhan in the Hubei province of China. The first graphical radius of SARS-CoV-2 surpassed those of
cases were linked to a seafood market, but soon wide- both MERS and SARS-CoV and caused unprece-
spread person-to-person transmission was observed [6, dented global public health and economic crises.
7]. Clusters of disease were discovered in families and
their close contacts. Many patients presented with
fever, cough, and chest discomfort. Some of the
Coronaviruses
infected individuals experienced severe dyspnea and
hypoxia with bilateral lung infiltration seen on radio-
Taxonomy
logic imaging. In January 2020, the disease’s causative
agent was determined to be the seventh CoV to infect The Coronavirus family is placed under the order
humans, SARS-CoV-2, and its genome was sequenced. Nidovirales and is also known as Coronaviridae.
In the beginning, the new CoV was known as the Coronavirinea is a subfamily under the family
2019-novel coronavirus (2019-nCoV). The disease Coronaviridae. The Coronavirinae subfamily is fur-
spread reached epidemic levels in China by February ther divided into four genera: Alphacoronavirus,
2020. Although officials worldwide executed rigorous Betacoronavirus, Gammacoronavirus, and
lockdowns as one mean to control the virus spread in Deltacoronavirus (Figure 2.2). The second subfamily
and from China, international travelers had already under Coronaviridae is Torovirinea. Torovirus and
Coronaviridae
Coronavirinea Torovirinae
Alphacoronavirus Betacoronavirus Gammacoronavirus Deltacoronavirus Torovirus Bafinivirus
Figure 2.2 Classification of CoVs.
Bafinivirus are two genera under the Torovirinae found in horseshoe bats and pangolins (RmYN02 and
subfamily. Alphacoronaviruses and Betacoronaviruses RaTG13) [2, 5, 6].
replicate in mammal hosts, Gammacoronaviruses
and Deltacoronaviruses in bird hosts, Toroviruses in
Morphology
mammal hosts, and Bafiniviruses in fish hosts [2].
The four human CoVs that have been known to cause Coronaviridae are enveloped viruses with spherical
mild symptoms are two Alphacoronaviruses (229E and (Coronaviruses), bacillar (Bafinivirus), or crescentic
NL63) and two Betacoronaviruses (OC43 and HKU1). (Toroviruses) shapes (Figure 2.3). Virions are deco-
SARS-CoV-2, SARS-CoV, and MERS-CoV belong to the rated with petal-shaped projections of homotrimeric
Betacoronaviruses. Most known Coronavirinea mem- proteins on their surfaces [2, 5]. These projections,
bers have been isolated from bat reservoirs. Bats are known as protein S, spikes, or peplomers, establish
believed to be an optimal host among mammals for the host range and facilitate the initial steps of infec-
viral evolution because they live in large colonies with tion by binding to host cell receptors and genetic
close proximity. SARS-CoV and SARS-related CoVs material injection. Another structural protein, pro-
have been isolated from bats and civets. The closest tein M, is the most abundant protein in the viral par-
genetically related species to SARS-CoV-2 have been ticle. Protein M is a dimeric protein and integrated
Figure 2.3 Structure of a CoV. Source: Created with http://BioRender.com.

COVID-19: Virology 25
Figure 2.4 Schematic of SARS-CoV-2 genome. ORF, open reading frame. Source: Created with http://BioRender.com.
into virion membranes of the Coronaviridae family. It translation to produce 15 or 16 nonstructural proteins
plays an essential role in the assembly and morpho- (nsps), depending on the virus genera. These proteins
genesis of virions. The endodomain of protein M are named from nsp1 to nsp16 in order of their posi-
forms a matrix-like lattice that supports the thick tion from 5′ to 3′. nsps function in viral replication,
membrane of CoVs [5]. The envelope in CoVs virus–host interaction, and evasion from the immune
(7–7.8 nm) is two times thicker than the average thick- system. Distal to the nsp segment, segments for struc-
ness of biologic membranes (4 nm) [2]. tural proteins S, E, M, and N are positioned. In the
The nucleocapsid (protein N) houses the viral Coronavirinea subgroup, various numbers of acces-
genomic RNA. The nucleocapsid forms a helix via sory genes, such as HE, are interspersed among struc-
attachments to basic phosphoproteins, protein N, and tural proteins [2, 4, 5].
is susceptible to treatment with detergents. In addition Viral-positive ssRNA acts as both a messenger RNA
to encapsulation, protein N participates in RNA syn- for protein transcription and a template for the synthe-
thesis, translation, and interferon antagonism [2, 5]. sis of negative ssRNA. CoVs are RNA viruses and use
Some Betacoronaviruses and Toroviruses possess RNA-dependent RNA polymerase (RdRp) to replicate
hemagglutinin esterase (HE) protein on their surface, their genome. Viral RdRp read the genome in a non-
which functions in viral attachment. Coronavirinea contiguous manner, jumping from one region to
also produce protein E, a small protein on its surface, another to synthesize RNA. A distinguishing feature
which acts in virion assembly and morphogenesis. of CoVs is they synthesize segmented subgenomic
messenger RNAs from negative-strand RNA to repli-
cate viral RNA. The nucleocapsid is assembled in the
Nucleic Acid
cytoplasm of the host cell and enters the endoplasmic
The family of Coronaviridae possesses the largest reticulum (ER), whereas the structural proteins are
genetic material among viruses (26–32 kb) that is com- assembled in the ER and Golgi apparatus. Preformed
posed of an unsegmented positive single-stranded nucleocapsids bud from the ER and Golgi systems and
RNA (ssRNA) [2]. The RNA molecule is 5′-capped and exit the host cell through exocytosis [4].
3′-polyadenylated, containing multiple open reading
frames (ORFs) (Figure 2.4). After the 5′ untranslated
Antigenicity
region, two thirds of the genome encode replicase pro-
teins (two overlapping ORF1a and ORF1b segments). The strongest antibody response against CoVs is pro-
As a result of ribosomal frameshifting, these segments voked by exposure to proteins S and N. Production of
yield two polyproteins, pp1a and pp1ab. Proteinases neutralizing antibodies by the immune system is
further process these polyproteins during and after mainly induced by protein S. These antibodies have
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21. PROOF OF THE EXISTENCE OF
LINEAR DIFFERENTIAL EQUATIONS
HAVING A PRESCRIBED
MONODROMIC GROUP.
In the theory of linear differential equations with one
independent variable , I wish to indicate an important problem, one
which very likely Riemann himself may have had in mind. This
problem is as follows: To show that there always exists a linear
differential equation of the Fuchsian class, with given singular points
and monodromic group. The problem requires the production of
functions of the variable , regular throughout the complex plane
except at the given singular points; at these points the functions may
become infinite of only finite order, and when describes circuits
about these points the functions shall undergo the prescribed linear
substitutions. The existence of such differential equations has been
shown to be probable by counting the constants, but the rigorous
proof has been obtained up to this time only in the particular case
where the fundamental equations of the given substitutions have
roots all of absolute magnitude unity. L. Schlesinger has given this
proof,[49] based upon Poincaré's theory of the Fuchsian -functions.
The theory of linear differential equations would evidently have a
more finished appearance if the problem here sketched could be
disposed of by some perfectly general method.
[49] Handbuch der Theorie der linearen Differentialgleichungen,
vol. 2, part 2, No. 366.
22. UNIFORMIZATIOM OF ANALYTIC
RELATION'S BY MEANS OF
AUTOMORPHIC FUNCTIONS.
As Poincaré was the first to prove, it is always possible to
reduce any algebraic relation between two variables to uniformity by
the use of automorphic functions of one variable. That is, if any
algebraic equation in two variables be given, there can always be
found for these variables two such single valued automorphic
functions of a single variable that their substitution renders the given
algebraic equation an identity. The generalization of this fundamental
theorem to any analytic non-algebraic relations whatever between
two variables has likewise been attempted with success by Poincaré,
[50] though by a way entirely different from that which served him in
the special problem first mentioned. From Poincaré's proof of the
possibility of reducing to uniformity an arbitrary analytic relation
between two variables, however, it does not become apparent
whether the resolving functions can be determined to meet certain
additional conditions. Namely, it is not shown whether the two single
valued functions of the one new variable can be so chosen that,
while this variable traverses the regular domain of those functions,
the totality of all regular points of the given analytic field are actually
reached and represented. On the contrary it seems to be the case,
from Poincaré's investigations, that there are beside the branch
points certain others, in general infinitely many other discrete
exceptional points of the analytic field, that can be reached only by
making the new variable approach certain limiting points of the
functions. In view of the fundamental importance of Poincaré's
formulation of the question it seems to me that an elucidation and
resolution of this difficulty is extremely desirable.
In conjunction with this problem comes up the problem of
reducing to uniformity an algebraic or any other analytic relation
among three or more complex variables—a problem which is known
to be solvable in many particular cases. Toward the solution of this
the recent investigations of Picard on algebraic functions of two
variables are to be regarded as welcome and important preliminary
studies.
[50] Bull. de la Soc. Math. de France, vol. 11 (1883).
23. FURTHER DEVELOPMENT OF THE
METHODS OF THE CALCULUS OF
VARIATIONS.
So far, I have generally mentioned problems as definite and special
as possible, in the opinion that it is just such definite and special problems
that attract us the most and from which the most lasting influence is often
exerted upon science. Nevertheless, I should like to close with a general
problem, namely with the indication of a branch of mathematics
repeatedly mentioned in this lecture—which, in spite of the considerable
advancement lately given it by Weierstrass, does not receive the general
appreciation which, in my opinion, is its due—I mean the calculus of
variations.[51]
The lack of interest in this is perhaps due in part to the need of
reliable modern text books. So much the more praiseworthy is it that A.
Kneser in a very recently published work has treated the calculus of
variations from the modern points of view and with regard to the modern
demand for rigor.[52]
The calculus of variations is, in the widest sense, the theory of the
variation of functions, and as such appears as a necessary extension of
the differential and integral calculus. In this sense, Poincaré's
investigations on the problem of three bodies, for example, form a chapter
in the calculus of variations, in so far as Poincaré derives from known
orbits by the principle of variation new orbits of similar character.
I add here a short justification of the general remarks upon the
calculus of variations made at the beginning of my lecture.
The simplest problem in the calculus of variations proper is known to
consist in finding a function of a variable such that the definite integral
assumes a minimum value as compared with the values it takes when is
replaced by other functions of with the same initial and final values.
The vanishing of the first variation in the usual sense
gives for the desired function the well-known differential equation
In order to investigate more closely the necessary and sufficient

criteria for the occurrence of the required minimum, we consider the
integral
Now we inquire how is to be chosen at function of , in order that the

value of this integral shall be independent of the path of integration, i.
e., of the choice of the function of the variable . The integral has
the form
where and do not contain and the vanishing of the first variation
in the sense which the new question requires gives the equation
i.e. we obtain for the function of the two variables , the partial
differential equation of the first order
The ordinary differential equation of the second order (1) and the partial
differential equation (1*) stand in the closest relation to each other. This
relation becomes immediately clear to us by the following simple
transformation
We derive from this, namely, the following facts: If we construct any

simple family of integral curves of the ordinary differential equation (1) of
the second order and then form an ordinary differential equation of the
first order
which also admits these integral curves as solutions, then the function
is always an integral of the partial differential equation (1*) of the
first order; and conversely, if denotes any solution of the partial
differential equation (1*) of the first order, all the non-singular integrals of
the ordinary differential equation (2) of the first order are at the same time
integrals of the differential equation (1) of the second order, or in short if
is an integral equation of the first order of the differential
equation (1) of the second order, represents an integral of the
partial differential equation (1*) and conversely; the integral carves of the
ordinary differential equation of the second order are therefore, at the
same time, the characteristics of the partial differential equation (1*) of the
first order.
In the present case we may find the same result by means of a
simple calculation; for this gives us the differential equations (1) and (1*)
in question in the form
where the lower indices indicate the partial derivatives with respect to
. The correctness of the affirmed relation is clear from this.
The close relation derived before and just proved between the
ordinary differential equation (1) of the second order and the partial
differential equation (1*) of the first order, is, as it seems to me, of
fundamental significance for the calculus of variations. For, from the fact
that the integral is independent of the path of integration it follows that
if we think of the left hand integral as taken along any path and the right
hand integral along an integral curve of the differential equation
With the help of equation (3) we arrive at Weierstrass's formula
where designates Weierstrass's expression, depending upon

,
Since, therefore, the solution depends only on finding an integral

which is single valued and continuous in a certain neighborhood of the
integral curve , which we are considering, the developments just
indicated lead immediately—without the introduction of the second
variation, but only by the application of the polar process to the differential
equation (1)—to the expression of Jacobi's condition and to the answer to
the question: How far this condition of Jacobi's in conjunction with
Weierstrass's condition is necessary and sufficient for the
occurrence of a minimum.
The developments indicated may be transferred without necessitating
further calculation to the case of two or more required functions, and also
to the case of a double or a multiple integral. So, for example, in the case
of a double integral
to be extended over a given region , the vanishing of the first variation

(to be understood in the usual sense)
gives the well-known differential equation of the second order
for the required function of and .

On the other hand we consider the integral
and inquire, how and are to be taken as functions of , and in
order that the value of this integral may be independent of the choice of
the surface passing through the given closed twisted curve, i. e., of the
choice of the function of the variables and .
The integral has the form
and the vanishing of the first variation
in the sense which the new formulation of the question demands, gives
the equation
i. e., we find for the functions and of the three variables , and the
differential equation of the first order
If we add to this differential equation the partial differential equation
resulting from the equations
the partial differential equation (I) for the function of the two variables
and and the simultaneous system of the two partial differential equations
of the first order (I*) for the two functions and of the three variables ,
, and stand toward one another in a relation exactly analogous to that
in which the differential equations (1) and (1*) stood in the case of the
simple integral.
It follows from the fact that the integral is independent of the
choice of the surface of integration that
if we think of the right hand integral as taken over an integral surface of

the partial differential equations
and with the help of this formula we arrive at once at the formula
which plays the same rôle for the variation of double integrals as the
previously given formula (4) for simple integrals. With the help of this
formula we can now answer the question how far Jacobi's condition in
conjunction with Weierstrass's condition is necessary and
sufficient for the occurrence of a minimum.
Connected with these developments is the modified form in which A.
Kneser,[53] beginning from other points of view, has presented
Weierstrass's theory. While Weierstrass employed to derive sufficient
conditions for the extreme values integral curves of equation (1) which
pass through a fixed point, Kneser on the other hand makes use of any
simple family of such curves and constructs for every such family a
solution, characteristic for that family, of that partial differential equation
which is to be considered as a generalization of the Jacobi-Hamilton
equation.
The problems mentioned are merely samples of problems, yet they

will suffice to show how rich, how manifold and how extensive the
mathematical science of to-day is, and the question is urged upon us
whether mathematics is doomed to the fate of those other sciences that
have split up into separate branches, whose representatives scarcely
understand one another and whose connection becomes ever more
loose. I do not believe this nor wish it. Mathematical science is in my
opinion an indivisible whole, an organism whose vitality is conditioned
upon the connection of its parts. For with all the variety of mathematical
knowledge, we are still clearly conscious of the similarity of the logical
devices, the relationship of the ideas in mathematics as a whole and the
numerous analogies in its different departments. We also notice that, the
farther a mathematical theory is developed, the more harmoniously and
uniformly does its construction proceed, and unsuspected relations are
disclosed between hitherto separate branches of the science. So it
happens that, with the extension of mathematics, its organic character is
not lost but only manifests itself the more clearly.
But, we ask, with the extension of mathematical knowledge will it not
finally become impossible for the single investigator to embrace all
departments of this knowledge? In answer let me point out how
thoroughly it is ingrained in mathematical science that every real advance
goes hand in hand with the invention of sharper tools and simpler
methods which at the same time assist in understanding earlier theories
and cast aside older more complicated developments. It is therefore
possible for the individual investigator, when he makes these sharper
tools and simpler methods his own, to find his way more easily in the
various branches of mathematics than is possible in any other science.
The organic unity of mathematics is inherent in the nature of this
science, for mathematics is the foundation of all exact knowledge of
natural phenomena. That it may completely fulfil this high mission, may
the new century bring it gifted masters and many zealous and enthusiastic
disciples.
[51] Text-books: Moigno-Lindelöf, Leçons du calcul des variations,
Paris, 1861, and A. Kneser, Lehrbuch der Variations-rechnung,
Braunschweig, 1900.
[52] As an indication of the contents of this work, it may here be noted
that for the simplest problems Kneser derives sufficient conditions of
the extreme even for the case that one limit of integration is variable,
and employs the envelope of a family of curves satisfying the
differential equations of the problem to prove the necessity of Jacobi's
conditions of the extreme. Moreover, it should be noticed that Kneser
applies Weierstrass's theory also to the inquiry for the extreme of such
quantities as are defined by differential equations.
[53] Cf. his above-mentioned textbook, §§ 14, 15, 19 and 20.
TRANSCRIBER'S NOTES
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Coronavirus Disease 2019 Covid 19 A Clinical Guide 1St Edition Ali Gholamrezanezhad Full Chapter

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Library of Congress Cataloging-­in-­Publication Data applied for

Cover Design: Wiley

Set in 9.5/12.5pt STIXTwoText by Straive, Pondicherry, India

and to the “hand of god,”

3 COVID-­19: Laboratory/Serologic Diagnostics 34

4 COVID-­19: Radiologic Diagnosis 61

5 COVID-­19: Pathology Perspective 101

6 COVID-­19: Immunology 112

7 COVID-­19: Presentation and Symptomatology 125

8 COVID-19: Risk Stratification 149

9 COVID-19: Outpatient Management in Adults 165

10 COVID-­19: Inpatient Management 182

11 COVID-­19: ICU and Critical Care Management 233

12 COVID-­19 in Pediatrics 255

13 Pharmacologic Therapeutics for COVID-­19 290

14 Co-­infections and Secondary Infections in COVID-­19 Pneumonia 319

15 COVID-­19: Neurology Perspective 339

16 COVID-­19: Cardiology Perspective 361

17 COVID-­19: Oncologic and Hematologic Considerations 389

18 COVID-­19: Dermatology Perspective 409

19 COVID-­19: Ophthalmology Perspective 417

20 COVID-­19: Nutrition Perspectives 428

21 COVID-­19: Nursing Perspective 454

22 COVID-­19 Vaccination 472

23 Post-­COVID-­19 Vaccine Imaging Findings 494

24 COVID-­19: Long-­Term Pulmonary Consequences 515

25 Psychological Effects and Neuropsychiatric Sequelae in COVID-­19 Patients 539

26 Mental Health Effects of the COVID-­19 Pandemic on Healthcare Professionals 554

27 COVID-­19: Ethical Considerations in Clinical Practice 580

29 Global Impact of COVID-­19 on Healthcare Systems 615

30 COVID-­19: Mass Casualty Planning 651

Behnoosh Afghani, MD Mobin Azami

Angela N. Buffenn, MD, MPH Sarah Cherukury

Andrew T. Catanzaro, MD Dalia Copti, MSN, FNP-­C, AGACNP-­BC

Dominique Duncan, PhD Marcin Frączek, MD, PhD

Fabrizio Fantini, MD Mehdi Ghasemi, MD

Lucia Flors, MD, PhD Vandana Gupta, PhD

Benjamin P. Hammond, MD Arturas Kalniunas, MD

Wendy W. Huang, MD Grace Y. Lin, MD, PhD

Angela Lu, MS Sabha Mushtaq, MD

Cameron McGuire, MD Saeideh Najafi

Brooke McNeilly, DO Ary Serpa Neto, MD, MSc, PhD

Babak Mohit, DrPH

Shabnam Mortazavi, MD, MPH

Anna Orzeł Emma J. Ridley, PhD

Katarzyna Resler Cynthia Sanchez, DNP, FNP-­C

Mohd Fardeen Husain Shahanshah, BSc Victoria Uram, MPH

Bhawna Sharma, BSc Christian Vega

Calvin M. Smith, MD Elzbieta Vitkauskaite

Erlinda R. Ulloa, MD Yujia Zhang

Abbreviations of epidemiologists in the region, who conducted origin-­

­Origin In China, SARS-­like viruses (SARS and MERS) have

Natural Host/Reservoir Intermediate Host Acquired Virulence in Humans

­Infectivity and Incubation Inhalation of droplets allows the transmitted virus’s

Case Fatality Rate

Weekly number of deaths

­Demographics most cases, with elderly individuals comprising the

Age Race and Ethnicity

≥85 yr 2.2 30.9 2 Male 47.8 54.2 49.25

Percent of Cases (%) Percent of United States Population (%)

Library of Congress Cataloging-in-Publication Data applied for

3 COVID-19: Laboratory/Serologic Diagnostics 34

4 COVID-19: Radiologic Diagnosis 61

5 COVID-19: Pathology Perspective 101

6 COVID-19: Immunology 112

7 COVID-19: Presentation and Symptomatology 125

10 COVID-19: Inpatient Management 182

11 COVID-19: ICU and Critical Care Management 233

12 COVID-19 in Pediatrics 255

13 Pharmacologic Therapeutics for COVID-19 290

14 Co-infections and Secondary Infections in COVID-19 Pneumonia 319

15 COVID-19: Neurology Perspective 339

16 COVID-19: Cardiology Perspective 361

17 COVID-19: Oncologic and Hematologic Considerations 389

18 COVID-19: Dermatology Perspective 409

19 COVID-19: Ophthalmology Perspective 417

20 COVID-19: Nutrition Perspectives 428

21 COVID-19: Nursing Perspective 454

22 COVID-19 Vaccination 472

23 Post-COVID-19 Vaccine Imaging Findings 494

24 COVID-19: Long-Term Pulmonary Consequences 515

25 Psychological Effects and Neuropsychiatric Sequelae in COVID-19 Patients 539

26 Mental Health Effects of the COVID-19 Pandemic on Healthcare Professionals 554

27 COVID-19: Ethical Considerations in Clinical Practice 580

29 Global Impact of COVID-19 on Healthcare Systems 615

30 COVID-19: Mass Casualty Planning 651

Andrew T. Catanzaro, MD Dalia Copti, MSN, FNP-C, AGACNP-BC

Katarzyna Resler Cynthia Sanchez, DNP, FNP-C

Abbreviations of epidemiologists in the region, who conducted origin-

Origin In China, SARS-like viruses (SARS and MERS) have

Infectivity and Incubation Inhalation of droplets allows the transmitted virus’s

Demographics most cases, with elderly individuals comprising the

Table 1.3 CDC data of COVID-19 cases by race/ethnicity.

Pandemic (COVID-19). Our World in Data. https:// executive summary. https://www.cdc.gov/nchs/