Chapter 4 - COVID-19

In late December 2019, a new, highly pathogenic human coronavirus emerged in Wuhan, China. Due to its similarity with SARS-CoV, it was named SARS-CoV-2, and the disease that it causes was designated COVID-19. SARS-CoV-2 rapidly spread throughout the world and was designed as a pandemic by the World Health Organization on March 11, 2020. As of mid-January 2022, infection with SARS-CoV-2 resulted in 328,532,929 cases and 5,542,359 deaths worldwide. COVID-19 causes respiratory diseases, including pneumonia, but also affects many other organ systems, including the nervous, cardiovascular, immune, endocrine, digestive, urinary, integumentary, and reproductive systems. This chapter also describes the effects of COVID-19 on coagulation and the special senses (smell, taste, and vision) as well as Multisystem Inflammatory Syndrome in Children, and Long COVID Syndrome. Potential animal reservoir hosts, such as bats, and potential intermediate hosts of SARS-CoV are also covered. A section compares the various diagnostic tests, including the detection of SARS-CoV-2 proteins (antigen tests), viral RNA (genetic tests), and infectious viruses (viral neutralization tests). Another section describes treatment options, including traditional and nontraditional drugs, micronutrients such as zinc, copper, selenium, and iron, as well as vitamin D supplementation. The variety of preventative measures that were implemented is also described, including personal protective equipment, social distancing, decontamination of infected surfaces, quarantine, and closure of businesses and schools. Different vaccine options are also compared. These include vaccines based on RNA, viral vectors, and inactivated viruses.

Chapter 2 - Severe acute respiratory syndrome (SARS)

In 2002, a severe-to-fatal respiratory disease began in China and was named severe acute respiratory syndrome (SARS). The causative agent was soon found to be a coronavirus and was named SARS-coronavirus (SARS-CoV). Infection was traced to contact with live palm civet cats or raccoon dogs in live animal food markets (“wet markets”) and later, person-to-person. Visiting these markets or restaurants housing these animals before preparing them for customer consumption were among the risk factors for infection in addition to frequent use of taxis and comorbidities. After its initial appearance, SARS spread rapidly through parts of Asia and then to countries around the world before almost completely disappearing in 2003. It caused 8096 cases and 774 deaths. SARS-CoV is a betacoronavirus linage B. The single-stranded RNA genome of coronaviruses is the largest among RNA viruses. The size of the genome, the inaccuracy of replication in most coronaviruses, and homogenous and heterogenous genetic recombination contribute to the high frequency of mutation. The viral spike (S) protein binds to angiotensin-converting enzyme 2 on the host cell before entry. Mutations in the S protein make a substantial contribution to viral transmission to additional host species and cell types in addition to viral virulence as the virus adapted to its new hosts. Interestingly, SARS-CoV isolates from the initial stages of the 2002–2003 epidemic were more virulent than those isolated later and are associated with a 29-nucleotide deletion in the S protein gene. Several insectivorous Chinese bats appear to serve as reservoir hosts for the ancestorial coronavirus. New forms of protection against infection were implemented in China and some other countries and include wearing face masks, thermal screening, and avoiding travel in taxis and public transportation. Their effectiveness in decreasing transmission and the rapid end of the epidemic is unknown.

Chapter 3 - Middle Eastern respiratory syndrome

Middle East respiratory virus syndrome (MERS) is a viral disease that primarily affects the respiratory system, but also has a major impact on the kidneys and nervous system and, to a lesser extent, on the intestines, liver, and heart. Over 2500 cases and 850 deaths have been confirmed as of 2019. The fatality rate is approximately 35%, more than that caused by severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 (that causes COVID-19). The first known case of MERS in humans was reported in 2012 in Saudi Arabia but the virus was present in stored serum samples from dromedary (one-humped) camels from Africa and the Middle East for decades before that time. Since then, it spread to at least 27 countries around the world, most of which are related to travel to the Arabian Peninsula. The coronavirus that causes MERS, MERS-CoV, is related to several other human coronaviruses that typically cause cold-like illness as well as to SARS-CoV and SARS-CoV-2. MERS-CoV is from the subgenus Merbecovirus, while SARS-CoV and SARS-CoV-2 are in Sarbecovirus. MERS-CoV also uses dipeptidyl peptidase 4 as its host cell receptor, while SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2. While MERS-CoV is transmittable between people in close contact with an infected person, many infections are zoonotic and are due to inhaling infectious respiratory droplets from dromedaries or consuming their raw milk or urine. Many cases are nosocomial (acquired in healthcare facilities). Fortunately, MERS-CoV only can pass through several rounds of human-to-human transmission, unlike SARS-CoV-2. Much of the pathology is due to an excessive inflammatory type of immune response caused by cytokines and chemokines, abnormal blood coagulation, and virus-induced apoptosis (programmed cell death). Bats appear to be the reservoir hosts and should be monitored for possible zoonotic transmission outside of the Middle East, in line with the One Health approach.

Chapter 1 - Introduction

Coronaviruses infect humans and multiple animal species. The seven coronaviruses of humans are the following: HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-KHU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. The former four coronaviruses usually cause mild upper respiratory disease, such as the common cold, but can also cause croup and other more serious diseases, especially in the elderly and people with comorbidities. The latter three coronaviruses cause lower respiratory tract diseases which can be severe to life-threatening. The genome of coronaviruses is positive-sense single-stranded RNA composed of 4–5 structural proteins and up to 16 nonstructural proteins. The spike protein binds to several different host target cell receptors, depending on the virus. This protein directs the host species and cell types that may be infected by each coronavirus. Coronaviruses are divided into four genera: Alpha-, Beta-, Gamma-, and Delta-voronavirus. All known human coronaviruses are alpha- and beta-coronaviruses, while gamma- and delta-coronaviruses are primarily found in birds. Human and other mammalian coronaviruses are believed to have originated in bats and rodents and entered the human population via zoonotic transmission from intermediate hosts. SARS-CoV and SARS-CoV-2 are believed to have used civet cats, raccoon dogs, and, perhaps, pangolins from live animal markets “wet markets” in China as their intermediate hosts while dromedary camels in Saudi Arabia are the intermediate host for MERS-CoV., This chapter briefly reviews basic information about the history of infectious agents in humans, an introduction to viruses and other microbes, and basic characteristics of the immune system, including vaccines, in addition to an introduction of the shared features of coronaviruses and treatment regimens.

Chapter 7 - Pulling it all together: where do we go from here?

Coronaviruses are Baltimore Class I viruses of the family Coronaviridae. Similarities and differences to other members of these groups are discussed. Proposed reservoir/intermediate hosts of severe acute respiratory system coronavirus (SARS-CoV), Middle Eastern respiratory system coronavirus, and SARS-CoV-2 are presented. Bats appear to be reservoir hosts for these and some animal coronaviruses. Other potential reservoir/intermediate hosts of pathogenic coronaviruses are presented, with particular emphasis on rodents and birds. Potential methods to predict or prevent future pandemics include the One Health Approach and SpillOver. Factors driving epidemics and pandemics are discussed, particularly microbial, host-related, and environmental factors as well as ‘The Human Factor,’ medical and behavioral interventions that decrease disease spread and severity. The author’s vision for Infectious Disease Centers (IDCs), similar to Ebola Centers, is presented. IDCs would respond to a broad range of infectious diseases, utilizing separated, negative-pressure areas of existing hospitals with specialized, trained healthcare personnel, microbiologists, public health officials, and lab technicians on call. The proposed IDCs would have stockpiles of personal protective equipment (PPE), equipment, and laboratory facilities on hand to respond to a range of infections. Equipment could include ventilators, autoclaves, dialysis equipment, and three-dimensional printers. The latter was used to produce PPE and ventilators during the COVID-19 pandemic. Other innovative plans would be encouraged, such as the conversions of a deck of a long-distance Italian ferry for patients needing an intermediate level of care during the COVID-19 pandemic. Problems associated with infectious disease epidemics in developing countries are examined, with suggestions for the inclusion of appropriate personnel, such as local cultural experts and interpreters, as well as innovative planners and, perhaps, 3-D printers.

Chapter 6 - Coronaviruses of agricultural and companion animals with the potential for zoonotic transmission

Several human coronaviruses cause high mortality rates and are highly contagious, while others cause cold-like illnesses. These viruses are believed to enter human populations by zoonotic transmission from animal intermediate hosts from live animal markets in China [severe acute respiratory syndrome coronaviruses (SARS-CoV) from palm civets/raccoon dogs and SARS-CoV-2 possibly from pangolins] or dromedary camels in the Arabian Peninsula (Middle East respiratory syndrome coronavirus). Some bats may act as reservoir hosts. While much focus on the possible reservoir and intermediate hosts for future zoonotic transmission focuses on bats or rodents, humans spend much more time with agricultural animals, including cattle, pigs, camelids, and horses, particularly pigs, which host six coronaviruses. One pig coronavirus is a deltacoronavirus, a genus that almost exclusively contains bird viruses. The species Betacoronavirus-1, represented by a bovine coronavirus, contains members that infect other animal hosts, as do the Alphacoronavirus-1 species. Humans spend large amounts of time in the company of their companion animals, such as cats and dogs. Some contact is intimate, including allowing these animals to sleep with their owners and lick their faces. In addition to possible zoonotic transmission, humans transmit coronaviruses, including SARS-CoV-2, to domestic and captive exotic cats, some of which are endangered. Human-to-cat transmission of SARS-CoV-2 has caused severe disease in juvenile domestic cats. People are also regularly in contact with animal fecal material. Some diseases caused by animal coronaviruses are typically mild, while others cause severe, life-threatening diseases. Both morbidity and mortality in agricultural animals have a great economic impact on developing and developed regions of the world. Due to close, prolonged contact between humans and agricultural and companion animals, it may be a matter of great importance to spend more time and resources studying the potential for coronaviruses of domestic animals to cause zoonotic transmission.

Chapter 5 - Coronaviruses of wild and semidomesticated animals with the potential for zoonotic transmission

Coronaviruses are present in most animal species. Some animals may then serve as a reservoir or intermediate hosts of viruses causing mild or severe to fatal diseases in humans and other animals. Infected humans may also transmit coronaviruses, such as severe acute respiratory syndrome virus (SARS-CoV)-2, to animals, including captive endangered animal species. This chapter focuses on coronaviruses of wild and semidomesticated animals, including viruses from bats, rodents, nonhuman primates, ferrets, minks, and rabbits. The ability of coronaviruses to rapidly mutate and to exchange their genetic material with other coronaviruses leads to the production of variants able to infect and adapt to new host species. Special attention is given to coronaviruses of bats and rodents since they appear to have hosted ancestral coronaviruses that indirectly lead to zoonotic transmission of highly pathogenic human viruses, including SARS-CoV, the closely related SARS-CoV-2, and Middle East respiratory syndrome virus. The RNA genomes of several bat coronaviruses, such as WIV1 and WIV16, are very similar to SARS-CoV. Coronaviruses in animals primarily cause severe disease in the respiratory, central nervous, and digestive systems but may damage other organ systems as well. Further studies on wildlife coronaviruses are advisable to avoid human epidemics or pandemics as well as to protect endangered animal species.