COVID-19: Diagnosis and Management - Part I

History of Pandemics

Sunishtha¹, Govind Singh¹, Sanju Nanda¹, *

¹ Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, India

Abstract

Pandemic is the term coined for the widespread of a disease or infection on a very large scale and across borders. COVID-19, an outcome of the spread of coronavirus, reportedly started from China and spread to almost all the countries of the world. Though it is not for the first time that there was an outbreak of a disease at such a high magnitude but the duration for which it has continued to grapple the world with its virulence and contagious nature, it has become important to take a peek into the history of other pandemics of the world too. Before COVID -19, about 20 major outbreaks of infectious diseases took place and claimed millions of lives in a sweep. The awareness of government bodies, WHO, and non-government organizations grew better with every pandemic. Understanding the role of basic hygiene, self-immunity, social distancing, living in coherence with other living and non-living components of the planet are some positive outcomes of these pandemics. These pandemics also necessitated the need for discovering new drugs and vaccines.

This chapter describes the major pandemics in the history of mankind, the origin and types of coronaviruses, the association of different types of coronaviruses with the ranges and severity of infections, and the origin of COVID-19.

Keywords: AIDS, Black Death, Contagious, Corona, COVID-19, Ebola, Epidemic, Flu, H1N1, Host, Outbreaks, Pandemic, Plague, SARS, Swine flu, Vaccine, Virulence, WHO, Yellow fever.

* Corresponding author Sanju Nanda: Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, India; E-mail: [email protected]

INTRODUCTION

The terms pandemic, epidemic, outbreak are primarily categorized based on the number of cases of a condition often used to describe infections. These terms have described the comparison of the expected number of cases in a particular time and how far-off cases have spread in the geographical area. Some conditions, such as cancer, hypertension, violence, beneficial behaviors, or even positive behaviors, can also be defined in the same way (Morens et al., 2009).

The term ‘pandemic’, has its origin derived from the Greek words pan (meaning all) and demos (meaning the people). Pandemic refers to a spread of contagious illness that spreads across the countries or world, usually affecting a larger area than an ‘epidemic’. It is important to note that a disease that is affecting a large number of people or widespread cannot be said to be a pandemic till it is contagious (Fig. 1). For example, cancer kills many people, but it is not a contagious disease, so not included as a pandemic (WHO, 2011).

Fig. (1))

The essentials of a pandemic.

The word epidemic is derived from the two Greek words epi meaning upon or above, and demos the people. An epidemic is an outbreak of disease that rapidly spread to a large population in a short period of time. For example, severe acute respiratory syndrome (SARS) took the lives of approx. 800 people worldwide during the epidemic of 2003 (Morens et al, 2009). An outbreak is an increase beyond expectation in the number of cases of a disease or condition occurring among a specified population in a limited geographic location and period of time (Gregg, 2002). The multi-state outbreak of Salmonella Muenchen in 1981 is an example of the outbreak.

Evidence suggested that the human population has suffered from many pandemics throughout history, be it the earlier form of smallpox or Spanish flu or the recent incidence of Ebola or Covid. In world history, we can see a number of significant pandemics like cholera, dengue, plague, smallpox, AIDS, tuberculosis, influenza, West Nile disease, and severe acute respiratory syndrome (Rewar et al., 2015; Qiu et al., 2016). In 1999, WHO issued a printed paper on pandemic readiness overview, which was further revised in 2005 and 2009 while planning for an influenza pandemic. In this guidance, WHO defined different phases of pandemic and required appropriate actions for each phase. The revision includes the explanation of a pandemic and declaration of its leading phases (WHO, 2011). There have been many pandemics declared at different times as enlisted in Table 1.

The Athenian Plague

The plague has been responsible for three pandemics in history, including the 6th, 14th, and 19th centuries. The Athenian plague occurred during 430–26 B.C. It originated from Ethiopia, after that, it was distributed in Egypt and Greece. It is a well-known infectious disease primarily affecting rodents. Yersinia pestis bacteria is a causative agent of Athenian plaque that is related to the Enterobacteriaceae family. It is transferred in humans from rodents through skin-piercing by infected fleas. Transmission of bacteria in an uninfected person is possible by droplet contact, direct or indirect contact with infected material (Huremovic et al., 2017). Initial observed symptoms of the plague were headache, conjunctivitis, rashes on the whole body, and fever. After that patients showed severe symptoms like cough up blood, severe stomach cramps along with vomiting, and attacks of ineffectual retching. Generally, on the seventh or eighth-day infected persons die (Thucydides, 2017). Approximately 75000 to 100000 people died due to the plague of Athens (Litteman et al., 2009).

Table 1 Chronology of pandemics.

Plague of Justinian

The Justinian plague is the first recorded pandemic that began in 541 AD, killed over 100 million people. The Justinian plague, the name given after the 6th century by Justinian I, Roman emperor of the Byzantine Empire at that time (Rosen, 2007). It was a real plague pandemic that originated in the mid-sixth century AD. The first recorded outbreak of this disease began in Egypt. Further, it spread in the capital of Turkey Constantinople caused the death of 10000 people per day, and killed around 40% of the city population. It reduced drop by drop European population by 50% between 550 AD and 700 AD (Horgan, 2014).

The Black Death

The second pandemic was a global explosion of bubonic plague, widely known as the Great Plague, which originated from China in 1334, after that in 1347 it spread in Europe. After 50 years of its origin global population reduced from 450 million and caused approx 17 to 28 million deaths in Europe during the 14th century (Huremovic, 2016; DeWitte, 2014).

Spanish Flu

The Spanish influenza pandemic of 1918-1919 first appeared in the USA. Dominating impression was mainly found in Europe, Asia, and North America, also appeared in New Zealand, India, and South Africa. It killed around 50 million people worldwide and remained a threat to public health. Around one-third of the world’s population was infected and had clear symptoms of illness. This virus-derived in toto from an unknown source appeared as an avian-like influenza virus. It appeared quite ordinary, with mild symptoms. But it was not autopsies on victims that showed unusual hemorrhagic edema in the lungs, and it affected young adults more than others (Taubenberger, 2006). In 1918, this pandemic was caused by the venomous and pestilent influenza virus, a strain of the subtype H1N1 that mostly killed young adults. Examination of the virus proved it particularly deadly, as it activates overproduction, uncontrolled production of immune cells that destroy the immune system, and death of youngster. In 1918, the French bacteriologist Charles Nicole and his colleague Lebailly C concluded that the strain was found in mammals. The causative agent of Spanish flu is a virus of the Orthomyxoviridae family, which was recognized by Richard Edwin Scope (Tsoucalas et al., 2016).

AIDS

AIDS (acquired immunodeficiency syndrome) is an autoimmune disease caused by the human immunodeficiency virus (HIV). The causative virus was firstly identified in the early 1980s in the United States, after that scientists observed some cases in Africa and Europe, and at the same time all over the world. AIDS spreads through blood, vaginal secretions, semen, breast milk and mainly transmitted through unprotected mating with an HIV-positive partner. AIDS is a fatal disease, whereas a less number of infected people remain alive with AIDS around 20 years. It is the leading infectious cause of adult death around the world. AIDS was first recognized in the 1980s, public health officers try to prevent spreading disease by providing knowledge about the virus-like how the virus transferred from person to person and how could be protected ourselves from it (Farmer and Walton 2000; Lampatey and Merywen 2002).

Smallpox

Smallpox is one the most devastating diseases known to humankind, indigenous to Europe, Arabia, and Asia for centuries, responsible for the death of three infected individuals out of ten infectious patients, and the rest remain with pocky scars on the whole body. Evidence suggested that during the 20th century the global death toll from smallpox have been estimated at around 300 million. The native people of the United States and modern-day Mexico had nil natural immunity power against smallpox and the virus deducted them below by the tens of millions. Smallpox is the first virus epidemic cured by vaccination. During the 18th century, the vaccine of smallpox was discovered by a British doctor named Edward Jenner. Around 50 million people were infected by the smallpox virus in one year- which was equal to the population of South Africa. After that WHO was established in 1948. In India, until the 1950s, annually more than a million people died due to smallpox. In 1980, WHO declared that smallpox had been eliminated from the Earth (Fenner and Henderson 1988; Gupta and Mahajan 2003; Roos, 2020).

SARS

The first case of Severe Acute Respiratory Syndrome (SARS) appeared in China in November 2002. After that, it was recognized as a global threat in March 2003. In the next few months, SARS disease spread over many continents such as North America, Europe, South America, and Asia. In the 21st century, it emerges as the first severe and readily transmissible disease. It is a viral respiratory illness caused by a coronavirus commonly known as SARS-associated coronavirus, having an incubation period of 2 to 10 days. The primary mode of transmission is respiratory droplets and direct contact. SARS-CoV has been detected mainly in stool, also detected in blood, urine, and conjunctival secretions but to a lesser extent (Christian and Poutanen 2004; Hui, 2005; WHO, 2013).

Swine flu or H1N1 Pandemic

Swine flu is a respiratory disease of the pig, commonly known as Hog or Pig Flu. Infection caused by type A influenza virus subtype of H1N1that belongs to the Orthomyxoviridae family. The novel H1N1strain is the main reason for the explosion of swine flu, the origin of this new strain is unknown. It was first identified in April 2019 at the border region of the United States and Mexico. It emerged out as the first pandemic of the 21st century in a short term of two months, involving more than 170 countries and approximately 1.7 lakh infected individuals all over the world. Globally, the illness rate of swine flu was highest in children and young adults but the hospitalization rate was higher in children below one year of age (Mir et al., 2009; Sebastian et al., 2009).

Ebola

It is defined as a neglected tropical disease (NTD), killed thousands of people. It is the largest and longest recorded pandemic in human history. The Ebola virus was the first point out in 1976 in Zaira, Yambuku, and Nzara, South Sudan as an outbreak of hemorrhagic fever. Ebola outburst started through zoonotic transmission, caused more than 30 outbreaks since 1976, with less than 1600 deaths before 2014, and since 2014 thousands of people killed in West Africa. The incubation period of the Ebola virus is 5 to 7 days. In most of the cases, it started from rural background controlled by following regular community health measures like having a view on several infected people and the patient was isolated to break the chain of virus (Troncoso, 2015; Richardson et al., 2016).

COVID-19

Coronavirus disease (COVID-19) is a highly contagious respiratory illness that was quickly spread globally within the short term after finding the first case of COVID-19 (in Wuhan, China) in December 2019. WHO announced it as a life threat worldwide on 30 January and a pandemic on 11 March 2020, caused by the novel coronavirus, subsequently named SARS-CoV-2. In this respiratory disease, a person has mild symptoms like cold and cough after some time it emerged out as a critical illness with blockage of respiratory track and high fever. It has an overall low fatality rate in youngsters and a much higher rate in older persons. The causative agent of COVID-19 (SARS-CoV-2) spread very easily by respiratory droplets generated during talking, sneezing, and coughing by an infected person. It has 5 to 6 days incubation period (Balkhair, 2020).

Origin of Coronavirus

Coronavirus word originated in 1968, given to the crown projections on their surfaces observed in the electron microscope. Corona in Latin means halo or crown. Coronaviruses mainly attack the respiratory system and give rise to some manifestations like cough and difficulty in breathing. Some people, including older adults, are at risk of severe illness from these viruses. Coronavirus is a single positive-sense RNA virus; identified in 1960. Since 1970 pathogenesis and molecular mechanisms of replication of several coronaviruses have been actively studied. International Committee established the Coronaviridae family on Taxonomy of viruses in 1975. Coronaviruses have been described for more than 50 years, infect many species of animals including humans, and primarily affect the respiratory, gastroenteritis, and nervous system (Weiss and Navas-Martin, 2005).

Coronavirus species had been categorized into three groups. Group I and II infect mammals whereas group III is exclusively found in birds. SARS-CoV has been proposed as the first member of the fourth group of coronaviruses, separated from a child affected by bronchiolitis and conjunctivitis, and causes life-threatening pneumonia. HCoV-229E and HCoV-OC43 were identified to cause the common cold. There are only three types of coronaviruses have been studied that affect human, after addition of SARS-CoV; supplementary feature of HCoV-NL63 as the fourth member will supply a significant understanding of the variation among human coronaviruses. HCoV-NL63 is an arm of the group 1 coronaviruses similarly to HCoV-229E, but the dissimilarities between them are important. These are as follows:

They have around 65% sequence similarities.

In HCoV-NL63, a single gene ORF3 takes the place of the 4A and 4B genes in HCoV-229E.

In HCoV-NL63, the 5′ region of the S gene contains a large in-frame insertion of 537 nucleotides.

With a narrow host range, HCoV-229E is fastidious in cell culture. But, efficient replication of HCoV-NL63 in monkey kidney cells has been observed.

In infants and immunocompromised patients, HCoV-229E can cause severe respiratory disease whereas HCoV-NL63 causes acute respiratory disease (Hoek et al., 2004).

In December 2019, an extended number of pneumonia cases were found in China, caused by a newly recognized β-coronavirus, which is enveloped in a non-segmented positive-sense RNA virus. Initially, on 12 January 2020, WHO officially named this virus 2019- novel coronavirus (2019-nCoV) and disease as coronavirus disease 2019 (COVID-19). Coronavirus Study Group of the International Committee suggested the name to the new coronavirus as SARS-CoV-2 on February 11, 2020.

Types of Coronaviruses

All coronaviruses have a single-stranded RNA, size of genome up to 30kb in length and have similar morphology features. They have been united in the subfamily Coronavirinae within the family Coronaviridae which belongs to the Nidovirales order. The family consists of two subfamilies, Coronavirinae and Torovirinae. The Coronavirinae subfamily further divided into four genera, Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus as summarized in Table 2. Genera further classified into various species, containing various viruses that cause infections of cattle, horses, pigs, goats, and cats. Although, to date, it is not proven that the Torovirinae subfamily infects humans. Betacoronaviruses and Alphacoronaviruses are mainly originated from mammals, while Gammacoronaviruses and Deltacoronaviruses primarily began from avian (Wertheim et al., 2013).

Table 2 Types of coronaviruses.

The genus Alphacoronavirus includes several animal coronaviruses (PEDV, TGEV, FIPV) and human coronaviruses (HCoV-229E, HCoV-NL63). The genus Betacoronavirus comprise numerous animal coronaviruses BCoV, PHEV, GICoV, and three types of human coronaviruses i.e. HCoV-HKU1, HCoV-OC43, SARS-HCoV, and the MERS (Middle Eastern respiratory syndrome) coronavirus, SARS-related coronavirus.

Based on antigenic similarity Coronaviruses are classified into four groups, viruses in all groups can affect a large number of different host species. Several recognized human coronaviruses 229E, NL63, OC43, and HKU1 are common human viruses that easily infect immunocompromised and elder patients. These are responsible for approximately 10% mortality by causing common cold and self-limiting upper respiratory disease. MERS-CoV, SARS-CoV, and SAR-CoV-2 are also human coronaviruses but these occur less frequently than common human viruses. These viruses cause severe respiratory disease and cause up to 35% of death (Cascella et al., 2020).

Alphacoronaviruses form a distinct monophyletic group in the Coronavirinae subfamily, having similar phylogenetic properties to other coronaviruses. General characteristics make it different among coronaviruses. Alphacoronavirus having an exclusive type of nsp1, specific size, and sequence from the nsp1 protein of betacoronavirus. Gammacoronavirus is similar to the other coronaviruses only in phylogenetic relation, there are no similarities in virion morphology, genome organization, and gene composition. These characteristics make it different from other coronaviruses. Viruses of the species avian coronavirus lack an nsp1 moiety. The genus Gammacoronavirus related to the third group of human coronavirus include viruses that were segregated from birds and whales. The genus Deltacoronavirus is comprised of viruses isolated from pigs and birds. Until now various types of novel coronaviruses have been separated from bats. Many researchers suggested that human respiratory coronaviruses, MERS coronavirus, SARS coronavirus originated from an ancestor of bat viruses.

Disease Associated with Coronaviruses

Coronaviruses mainly strike on the respiratory system of mammals, birds, and humans. These are associated with pneumonia, common cold, bronchitis, severe acute respiratory syndrome (SARS), and coronavirus disease 2019 (COVID-19). From the last few years’ studies, researchers concluded that these viruses can also infect rats, mice, dogs, cats, pigs, horses, and cattle. In most cases, animals transfer the viruses to humans.

Coronavirus is a significant pathogen that mainly affects the human respiratory tract and also attacks the gut of humans. The earlier outburst of coronaviruses having severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) is earlier recognized as factors that are a major threat to public health. At the end of December 2019, numerous patients having pneumonia with unknown etiology entered hospitals.

Murine Hepatitis Virus (MHV)

Murine hepatitis virus is a commonly used laboratory strain that belongs to betacoronavirus genera; primarily infect the liver and brain. There are many strains of murine coronavirus exhibiting neurotropic and cause encephalitis with subsequent CNS demyelination. Although, the virus found in lasting infection of astrocytes, in most of the animals causes death by infecting oligodendrocytes and neurons. The animals that survive with acute infection develop a chronic progressive neurologic disease identified by outspread demyelinating lesions and CNS infiltration of lymphocytes and macrophages (Kyuwa and Stohlman 1990). It is one of the best animal models for encephalitis, hepatitis, and multiple sclerosis (Perlman, 1998).

Central Nervous System

The most frequently studied MHV strains are JHM and A59. The