Advances in Medical Biochemistry, Genomics, Physiology, and Pathology

Raj Bawa, Esther H. Chang, Gerald F. Audette, Anil Diwan, Saadia A. Faiz, Raj Bawa, Esther H. Chang, Gerald F. Audette, Anil Diwan, Saadia A. Faiz

• Publisher: Jenny Stanford Publishing
• Year: 2021
• ISBN:
  9781000400854
• Edition: 1
• Topic: Medicine
• Subtopic: Pharmacology

The pace and sophistication of advances in medicine in the past two decades have necessitated a growing need for a comprehensive reference that highlights current issues in medicine. Each volume in the Current Issues in Medicine series is a stand?alone text that provides a broad survey of various critical topics—all accomplished in a user-friendly yet interconnected format. The series not only highlights current advances but also explores related topics such as translational medicine, regulatory science, neglected diseases, global pandemics, patent law, immunotoxicology, theranostics, big data, artificial intelligence, novel imaging tools, combination drug products, and novel therapies. While bridging the gap between basic research and clinical medicine, this series provides a thorough understanding of medicine's potential to address health problems from both the patient's and the provider's perspectives in a healthcare setting. The range of topics covered and the expertise of the contributing authors accurately reflect the rapidly evolving areas within medicine—from basic medical sciences to clinical specialties. Each volume is essential reading for physicians, medical students, nurses, fellows, residents, undergraduate and graduate students, educators, policymakers, and biomedical researchers. The multidisciplinary approach of the series makes it a valuable reference resource for the pharmaceutical industry, academia, and governments. However, unlike other series on medicine or medical textbooks, this series focuses on current trends, perspectives, and issues in medicine that are central to healthcare delivery in the 21st century. Volume 1 focuses on the current issues in basic medical sciences, subjects that are fundamental to the practice of medicine. Specifically, it covers medical biochemistry, genomics, physiology, and pathology. These subjects, traditionally taught in the first two years of medical school that precede clinical instruction, provide a core of basic knowledge critical to the success in clinical medicine during rotations, training, and medical practice.

Chapter 1The Age of COVID-19: Medical Facts and Fiction

Raj Bawa MS, PhD, MD ’22

Patent Law Department, Bawa Biotech LLC, Ashburn, Virginia, USA Guanine, Inc., Rensselaer, New York, USA

Albany College of Pharmacy and Health Sciences, Pharmaceutical Research Institute Albany, New York, USA Teva Pharmaceutical Industries Ltd., Israel

[email protected]

Copyright © 2022 Raj Bawa. All rights reserved. This work is free and may be used by anyone for any purpose. As a service to authors and researchers, as copyright holder, I permit unrestricted use, distribution, online posting, and reproduction of this article or unaltered excerpts therefrom, in any medium, provided the original source is clearly identified and properly credited.

I dedicate this chapter to my late mother, Mrs. Sudesh Bawa (1935– 2020), in whose memory I have established the Sudesh Bawa Medical Foundation. This section is based, in part, on discussions I have had with my 92-year-old father, Dr. S. R. Bawa, an anatomist and a retired university professor/chair. My parents were married in 1954 and exemplified how a lifelong relationship of love, dedication and perseverance gives meaning to life.

Keyqords: acute respiratory distress syndrome, angiotensin converting enzyme 2, antibody test, antigen presentation, antigen-based tests, Aspergillus fumigatus, asymptomatic hosts, B cells, biosafety level-4, Candida auris, cellular immunity, Centers for Disease Control and Prevention, Coccidioides immitis, common cold virus, contact-tracing, controlled trial, convalescent plasma, coronavirus, coronavirus 2, Coronavirus disease 2019, COVID-19, cross-reactive antibody, cytokine storm, cytotoxic T cells, killer T cells, damage-associated molecular patterns, dendritic cells, diagnostic test, direct-to-consumer, emergency use authorization, epizootic, exocytosis, genetically engineered, Golgi intermediate, herd immunity, heterologous prime-boost, humoral immunity, hyperinflammatory immune response, immunity passports, immunization information system, immunosurveillance, interferon, interleukin, long COVID, Long Haulers, lymphocytes, major histocompatibility complexes, Middle East Respiratory Syndrome, multiple organ dysfunction syndrome, N antigen, nasal mucosa, neutralization capacity, NF-κB, nucleic acid amplification test, nucleocapsid, Operation Warp Speed, over-the-counter, pandemic, panzootic, passive immunotherapy, patents, pathogenicity, pattern recognition receptors, point-of-care, polymerase chain reaction, post COVID syndrome, prion, reactive oxygen species, regulatory T cells, RNA viruses, RT-PCR test, SARS-CoV, SARS-CoV-2, scanning electron micrograph, sensitivity, serology tests, seroprevalence, Severe Acute Respiratory Syndrome, single-stranded RNA genome, Spanish Flu, specificity, T cell immunity, T cells, T helper cells, transmissibility, transmission electron micrograph, tumor necrosis factor, US Department of State, US Food and Drug Administration, vaccination, variants of concern, viral surveillance, virulence, World Health Organization, Wuhan Institute of Virology, zoonosis, zoonotic, zoonotic reservoirs, zoonotic spillover

1.1 Emerging Pathogens: A Clear and Present Danger

Messieurs, c’est les microbes qui auront le dernier mot. (Gentlemen, it is the microbes who will have the last word.)

—Louis Pasteur

Epidemics on the other side of the world are a threat to us all. No epidemic is just local.

—Peter Piot

Infectious diseases are a familiar enemy. Throughout history, viruses, bacteria, and parasites have killed more humans than wars and natural disasters. Viral diseases were recorded ever since humans began living together in communities with smallpox being the first reported around 10,000 BC. Smallpox was the deadliest human disease to ever exist, with a devastating 20–60% mortality rate, killing an estimated 300 million people in the 20^th century alone.¹ I would add to this list, deadly human fungi that kill at least 1.6 million people globally.² In the past century, we have faced five pandemic respiratory diseases caused by different subtypes of influenza virus. In 1918, the H1N1 Spanish Flu, infected one-third of the world’s population and killed an estimated 50–100 million people. The causative agent for this influenza pandemic was a mystery because the structure and function of viruses was unknown.³ Other influenza pandemics include the 1957 H2N2 (Asian Flu) that originated in China and killed around 4 million people worldwide, the 1968 H3N2 (Hong Kong Flu) that killed 1 million people worldwide, the 2005 H5N1 (Bird Flu)⁴ which caused a few deaths, and the 2009 H1N1 (Swine flu) which caused 18,000 deaths.

¹ S. Riedel. (2005). Edward Jenner and the history of smallpox and vaccination. Proc. Bayl. Univ. Med. Cent. 18:21–25. ² In our frantic attempts to save COVID-19 patients consigned to intensive care units on intravenous anti-infective and immunosuppressive drugs, they could be susceptible to pathogenic fungi like Candida auris, Coccidioides immitis, Aspergillus fumigatus, etc. In fact, there are reports that deadly fungi are gaining a foothold in COVID-19 patients as broad-spectrum antibiotics also wipe off beneficial bacteria that keep invading microbes in check. I fail to understand why medical students are not taught more medical mycology during the first year of medical school given that there are 300+ fungal species (out of a total of 5 million+) that cause human diseases. ³ Unlike bacteria or fungi, viruses cannot be seen under a light microscope. The electron microscope was invented in the 1940s and this sophisticated instrument can resolve viruses. During the 1918 pandemic, a viral etiology could only be identified indirectly via an ultrafiltrate from a diseased subject to induce disease in a susceptible plant or animal host, or by detecting the presence of antibodies against the disease in survivors. ⁴ Various H5N1 strains have evolved since 2005 and they are significantly different at the genome level. H5N1 is a fast-mutating, highly pathogenic avian influenza virus (HPIV) found in multiple bird species. It is both epizootic (an epidemic in non-humans) and panzootic (a disease affecting animals of many species).

In addition to influenza pandemics, coronaviruses have also caused regional epidemics prior to the current pandemic. Coronaviruses are divided into four genera, namely, alpha (α), beta (β), gamma (γ), and delta (δ), with pathology ranging from upper respiratory symptoms typical of the common cold to life-threatening lower respiratory disease. The common cold-causing coronaviruses, 229E and OC43, were first isolated in the mid-1960s, with two additional coronaviruses, NL63 and HKU1, identified in 2004 and 2005, respectively. It is well established that all are ubiquitous human pathogens. Two beta coronaviruses of zoonotic⁵ origin have caused large-scale cluster outbreaks of severe respiratory disease. They were the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) epidemic in 2003 in mainland China, and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) epidemic in 2012 in Saudi Arabia and in 2015 in South Korea. SARS-CoV spread to 26 countries before the outbreak was contained with over 8,000 people infected and a case fatality rate of approximately 10%. Regarding MERS-CoV, infections are still occurring and have been reported in almost 30 countries. While human-to-human transmission for MERS-CoV is rare, some studies show the case fatality rate to be greater than 30%.

⁵ See, htt­ps:­//e­n.w­iki­ped­ia.­org­/wi­ki/­Zoo­nos­is: “A zoonosis (plural zoonoses, or zoonotic diseases) is an infectious disease caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite, or prion) that has jumped from an animal (usually a vertebrate) to a human. Typically, the first infected human transmits the infectious agent to at least one other human, who, in turn, infects others.”

Development of vaccines, antibiotics, and dramatically improved sanitation has greatly reduced morbidity and mortality from pathogenic microbes. As a result, we have become more complacent about the potential threat posed by our tiny, yet mighty, adversaries. In fact, world health bodies and politicians’ response to global infectious disease threats has been poor as other priorities have generally taken precedence. Sadly, that same pattern initially unfolded and was on full display at the onset of the coronavirus disease 2019 (COVID-19) crisis. Except, this time around, governments, politicians, and health organizations were eventually forced to act.

The year 2020 will forever be marked by the presence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the associated COVID-19 pandemic. COVID-19 has had a catastrophic effect on the world’s demographics resulting in ~3.76 million deaths. After the first cases of this predominantly respiratory viral illness were first “officially” reported by the Chinese government in late December 2019, SARS-CoV-2 rapidly circumvented the globe in a matter of weeks, compelling the World Health Organization (WHO) to declare it as a global pandemic on March 11, 2020. As of June 8, 2021, globally, there have been 174,591,505 coronavirus cases and 3,757,419 deaths, and 157,941,391 patients have recovered from COVID-19⁶ (Fig. 1.1). Virtually overnight, this pandemic profoundly altered the world as it struggled to contain SARS-CoV-2 while mitigating its health, economic, and social impact. For a global pandemic to occur, the following requirements are needed: emergence of a new human microbe; reduced or minimal population immunity to that microbe; and a relatively simple mode of transmission from one person to another. The SARS-CoV-2 virus fulfills all three of these criteria.

⁶ Worldometer. COVID-19 outbreak live update. Available at: htt­ps:­//w­ww.­wor­ldo­met­ers­.in­fo/­cor­ona­vir­us (accessed on June 8, 2021). Another authoritative source is the Johns Hopkins Coronavirus Resource Center: htt­ps:­//c­oro­nav­iru­s.j­hu.­edu­/.

Figure 1.1 World map of total confirmed COVID-19 cases per million people. The confirmed counts shown here are lower than the total counts. The main reason for this is limited testing and challenges in the attribution of the cause of death. Source: Our World In Data (CC BY 4.0).

For the past three decades, infectious viruses have emerged to pose great threats to human health and society (Fig. 1.2). In this regard, hemorrhagic fever viruses (Lassa, Ebola), novel coronaviruses and highly pathogenic influenza are the prime culprits. Viral emergence from a zoonotic reservoir is common, and coronaviruses (CoVs) are no exception. CoVs infect a wide range of species and have been isolated from dogs, cats, horses, cattle, swine, chickens, turkeys, and humans with clinical signs of disease (and coronaviruses have frequently expanded their host range). Most human coronaviruses are thought to have originated from bats. Coronavirus strains that infect humans generally cause mild symptoms though animal coronaviruses have caused outbreaks of severe respiratory disease in humans, including SARS, MERS, and now, COVID-19. SARS-CoV spread r...

Table of contents

• Cover
• Half-Title Page
• Title Page
• Copyright Page
• Dedication
• Table of Contents
• Corresponding Authors
• Note from the Series Editor
• 101. Engraving of the Bust of Hippocrates; Papyrus Fragment Showing the Hippocratic Oath; Facade of the Temple of Asclepius
• 1. The Age of COVID-19: Medical Facts and Fiction
• Section 1 Medical Biochemistry and Genomics
• Section 2 Human Physiology and Pathology
• Index