Timeline of Human Coronaviruses

Taxonomy: “coronaviruses”

In 1966, at the International Congress of Microbiology in Moscow,  an International Committee on Nomenclature of Viruses (ICNV) was established in order to introduce some degree of order and consistency into the naming of viruses. Seven years later the ICNV became the International Committee on Virus Taxonomy (the ICTV), which assumed the broader aim of developing a system of virus classification and nomenclature that would become a universally accepted taxonomy of viruses.

Figure 1. Old classification scheme for members of Coronaviridae vs. New classification scheme for members of Coronaviridae.

The Coronaviridae comprise a family of morphologically similar viruses that cause a wide variety of diseases in man and other animals. Following the recognition of coronaviruses as a distinct taxonomic group in 1968 (Nature 220, 650), with virus particles having a peripheral hafo in negatively stained preparations, the number of viruses classified in the group and our knowledge of their characteristics has greatly increased. There are still large gaps in our understanding of the diagnosis, pathogenesis, structure and serology of this economically and, potentially, medically important group and attempts were made to fill these gaps.

Coronaviruses are members of the subfamily Coronavirinae in the family Coronaviridae and the order Nidovirales (International Committee on Taxonomy of Viruses). This subfamily consists of four genera — Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus — on the basis of their phylogenetic relationships and genomic structures.

SARS-CoV and MERS-CoV belong to the Coronavirus genus in the Coronaviridae family and have large, positive-sense RNA genomes of 27.9 kb and 30.1 kb, respectively. Similarly to all viruses in the order Nidovirales, SARS-CoV and MERS-CoV have a unique coding strategy. Coronaviruses are important agents of gastrointestinal disease in humans, poultry, and bovines.

  • Origion of the oder “Nidovirales”

According to the ratification of taxonomic proposals from the ICTV Study Groups (https://talk.ictvonline.org/ictv/proposals/Ratification_1996.pdf), the order “Nidovirales” was approved at the 10th International Congress of Virology (ICV), held in Jerusalem from 11th-16th August 1996. was also the occasion of the 10th Plenary Meeting of the ICTV and the 25th Meeting of the Executive Committee of the ICTV.

Nidovirales is an order that contains four families (Arteriviridae, Coronaviridae, Mesoniviridae, and Roniviridae) according to the genomic classification. The name Nidovirales originates from the fact that the viruses belonging to this order have the capacity to produce during infection a 30-multiplexed complex of subgenomic messenger RNA (mRNA), hence the word “nidus” in Latin, which means to nest.

The main common traits between Nidovirales are as follows:

  1. Their unfragmented genome of RNA type with positive orientation of the genome.
  2. Nidovirales encodes structural proteins that are separated from nonstructural functional proteins.
  3. The attachment to their host cell is done through receptors on the cell surface.
  4. After which the fusion of the viral and cellular membrane is presumed to be mediated by one of the viral surface glycoproteins.
  • Origion of the family “Coronviridae”

Phylogenetically, the family Coronaviridae belongs to the order Nidovirales in group IV, with a single genomic RNA fragment, oriented in a positive direction.

On 13 May 1975, David Arthur John Tyrrell first proposed informally a taxonomy name “Coronviridae” for grouping the recognized coronaviruses, worked with J. D. Almeida, C. H. Cunningham, W. R. Dowdle, M. S. Hofstad, K. McIntosh, M. Tajima, L. Ya. Zakstelskaya, B. C. Easterday, A. Kapikian and R. W. Bingham in the First Report of the Study Group on Coronavirus, Vertebrate Virus Subcommittee, International Committee on the Taxonomy of Viruses (ICTV)(The International Classification of Viruses was a group established in 1966 to standardize the naming of viruses; the group was renamed International Committee on Taxonomy of Viruses in 1975.). Later, this proposal was approved at the third meeting of ICTV held  in Madrid, 12 and 16 September 1975 (https://talk.ictvonline.org/ictv/proposals/Ratification_1975.pdf). In the meantime, this report has been approved by Dr. H.G. Pereira, Chairman, Vertebrate Virus Subcommittee; by Dr. P.Wildy, Chairman, Coordination Subcommittee: and by Dr. F. Fenner, President, ICTV. On 3 February, 1978, the Second Report of the Study Group on Coronavirus, Vertebrate Virus Subcommittee, International Committee on the Taxonomy of Viruses (ICTV) was released.

  • Origion of the subfamily “Coronavirinae”

In June 2009, The taxonomic proposal of subfamily “Coronavirinae” was officially approved by the ICTV in Leiden, according to the Ninth Report of the International Committee on Taxonomy of Viruses (https://talk.ictvonline.org/ictv/proposals/2008.085-122V.v4.Coronaviridae.pdf).

The proposed revision of the family Coronaviridae and the organization of the to-be-established subfamily Coronavirinae is based upon rooted phylogeny and pair-wise comparisons using Coronaviridae-wide conserved domains in replicase polyprotein pp1ab as well as the structural proteins S, E, M and N (González et al., 2003; Gorbalenya et al., 2006, 2008). The name Coronavirinae is obviously derived from the established name of this group of viruses (coronaviruses).

  • Origion of the genus “coronaviruses”

During the mid-1960s, several isolations have been made of viruses which have an unusual morphology and which cause respiratory disease in man. The structure of these viruses is identical with that of the viruses of avian infectious bronchitis and mouse hepatitis. The virions are pleomorphic bodies, 80-160 mμ in diameter, and are covered with club-shaped projections 15 mμ deep which produce a characteristic fringe around the particles. All the viruses are ether- and acid-labile and, as their replication is not inhibited by BUDR, probably have an RNA genome.

In 1967, David Arthur John Tyrrell, worked with J. D. Almeida,  identified the morphology of three previously uncharacterized human respiratory viruses that grow in organ culture. Then, on November 16, 1968, the neologism “coronaviruses” was coined by a group of virologists – J. D. Almeida, D. M. Berry, C. H. Cunningham, D. Hamre, M. S. Hofstad, L. Mallucci, K. Mcintosh and D. A. J. Tyrrell – who relayed their findings to the high-profile journal Nature in a brief annotation. As the journal reported, “these viruses are members of a previously unrecognized group which [the virologists] suggest should be called the coronaviruses, to recall the characteristic appearance by which these viruses are identified in the electron microscope.” They had compared the “characteristic ‘fringe’ of projections” on the outside of the virus with the solar corona (not, as some have suggested, the points on a crown).

1968-Nature_Virology_Coronaviruses (2)
Figure 2. Coronaviruses (artist’s impression) have a crown-like halo. This refers to the characteristic appearance of virions (the infective form of the virus) by electron microscopy, which have a fringe of large, bulbous surface projections creating an image reminiscent of a royal crown or of the solar corona. This morphology is created by the viral spike (S) peplomers, which are proteins that populate the surface of the virus and determine host tropism. Proteins that contribute to the overall structure of all coronaviruses are the spike (S), envelope (E), membrane (M) and nucleocapsid (N).

The International Committee on Nomenclature of Viruses (ICNV) was established at the Ninth International Congress for Microbiology in Moscow, in September 1966. The second meeting of the Committee was held in Mexico City at the time of the Tenth International Congress for Microbiology in Mexico City in August 1970. Following the decisions of this meeting, the First report of the International Committee on Nomenclature of Viruses, entitled “Classification and Nomenclature of Viruses,” has been produced as a monograph, edited by the President of ICNV, Professor P. Wildy and published in June 1971 by S. Karger, Basel, as No. 5 of its series “Monographs in Virology.” This report, covering the period 1966 to 1970, established five Subcommittees: Bacteriophage (now Prokaryote Virus), Invertebrate Virus, Plant Virus, Vertebrate Virus and Cryptograms. The Subcommittees were responsible for approving taxonomic proposals relevant to their groups of viruses and presenting these proposals for approval by the Executive Committee (EC), the ICNV, with the provision that “a sizable number of virologists working in the relevant field were to be consulted”. This report included the designations family, genus (group) and type species, thus establishing and setting the foundations for viral taxonomy. In this report, the “coronaviruses” was officially approved by the International Committee on Nomenclature of Viruses (ICNV)(Wildy, 1971, p. 71).

The name “coronavirus” is derived from the Latin “corona” and the Greek “κορώνη” (korṓnē, “garland, wreath”), meaning crown or halo. Any member of the genus Coronavirus of enveloped, single-stranded RNA viruses which have prominent projections from the envelope and are pathogens of humans, other mammals, and birds, typically causing gastrointestinal, respiratory, or neurological disease; (in form Coronavirus) the genus itself.  On 29 August 1990, another proposed genus “Torovirus” was officially approved at the 8th Plenary Meeting of the ICTVheld in Berlin (https://talk.ictvonline.org/ictv/proposals/Ratification_1990.pdf).

Debate goes on: Naming the 2019 Coronavirus

Coinciding with the Chinese New Year of 2019, a novel coronavirus outbreak was first emerged and contracted in Wuhan City of China, home to 11 million people. It is the seventh identified coronavirus that can cause diseases of the respiratory tract in humans. On January 12, 2020, this novel strain was temporarily named 2019-nCov by the World Health Organization. On 8 February 2020, China’s National Health Commission decided to temporarily call the disease “novel coronavirus pneumonia“, or “NCP“. But because viruses continue to spread from animals to people, this coronavirus won’t be novel for long.

Most recently, on 11 February 2020, the World Health Organization renamed the coronavirus involved in the recent outbreak with the hope of minimizing stigma. The World Health Organization has officially named the disease caused by the coronavirus “COVID-19″. The term “COVID-19” means ‘coronavirus disease’, with ‘CO’ meaning ‘corona’, ‘VI’ for ‘virus’, ‘D’ for ‘disease’, and ’19’ pertaining to the year it emerged, being 2019. This will replace various monikers and hashtags given to the emerging illness over the past few weeks.

COVID-19, as the virus will now be known, was decided on by the WHO, with the organization giving a number of reasons as to why it was chosen. “Under agreed guidelines between WHO, we had to find a name that did not refer to a geographical location, an animal, an individual or group of people, and which is also pronounceable and related to the disease,” said Dr Tedros Adhanom Ghebreyesus, Director-General of the WHO. “COVID-19 stands for coronavirus disease in 2019,” said Soumya Swaminathan, chief scientist at the World Health Organization in Geneva, Switzerland, at a press briefing. She explained that there are many coronaviruses, and this style of naming will provide a format for referring to new coronavirus diseases in future years. “The virus itself is named by international group of virologists who will look into the taxonomy,” she said. “But it is important to have a name for this disease that everybody uses.”

However, shortly after the WHO announced the disease’s official name, the virus causing it was named “SARS-CoV-2″ (“Severe Acute Respiratory Syndrome coronavirus 2”) by the International Committee on Taxonomy of Viruses (ICTV), the global authority on the designation and naming of viruses. In a paper posted to the bioRxiv preprint server, the committee’s study group on coronaviruses explains that this term highlights the new virus’ similarity to the SARS virus identified in 2003.

Does a virus’ name really matter?

Previous evidence would seem to suggest yes. “Swine flu,” which was actually a flu strain thought to originate in pigs, resulted in consumers shunning pork and causing great financial damage to U.S. pork farmers, despite there being no evidence that the disease could be spread via consuming pork.

MERS (Middle East Respiratory Syndrome), was first reported in Saudi Arabia in 2012 and is a particularly deadly coronavirus with around a third of people contracting it dying from the disease. However, the disease has so far been found in 27 different countries, including South Korea which reported a serious hit to its tourism industry when it reported cases in 2015. Two other diseases caused by coronaviruses were given names describing the clinical manifestations: SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). Shortly after the WHO announced the disease’s official name, the virus causing it was named SARS-CoV-2 by the International Committee on Taxonomy of Viruses. In a paper posted to the bioRxiv preprint server, the Committee’s study group on coronaviruses explains that this term highlights the new virus’ similarity to the SARS virus identified in 2003.

Since these incidents, the WHO has decided on names which are more generic and not related to people, places or specific animals. “Having a name matters to prevent the use of other names that can be inaccurate or stigmatizing. It also gives us a standard format to use for any future coronavirus outbreaks,” said Ghebreyesus. It may be too late, but by renaming the current virus to COVID-19, the WHO likely hopes to de-stigmatize its association with the city of Wuhan and the people who live there.

The virus is thought to have originated in the city of Wuhan in China, which led to it being frequently named the “Wuhan coronavirus,” or “Chinese coronavirus,” but neither of these were official names and some believe they may have contributed to discrimination against Chinese people. Chinese communities from around the world have been reporting racist incidents and dramatic impacts on their business including Chinese restaurants all over the world.

Diachronic discourse of the term “coronaviruses”

Meta-analysis on the diachronic discourse of a specific term  promises to articulate the unfolding chronological picture of a term since its debut on a historical time scale. The origins of terminology of the humanities, social sciences, and natural science are still pending further discoveries. The earliest usage track-down of a target term could provide an insightful and compelling argument for rigorous historical story, and finally help us penetrate to the essence of reality. However, many empirical extrapolated theories based on sole information source always turns out de facto knowledge illusions. Therefore, retaining a clear sense of the pros and cons of any retrospective information source is the necessary prerequisite to such scientific efforts.

Figure 3. Melvin S. Hofstad (5 June 1915 – 8 June 1986). Dr. Melvin S. Hofstad, distinguished Professor Emeritus at Iowa State University, died June 8, 1986, at Mary Greeley Hospital in Ames, Iowa, of acute leukaemia. He was born June 5, 1915, at Starkweather, North Dakota. He was recognized internationally as a major contributor in poultry disease research for 45 years. (Credit: American Association of Avian Pathologists)
Figure 4. David Arthur John Tyrrell  (also known as David Tyrrell)(19 June 1925 – 2 May 2005). Director Medical Research Council common cold unit 1957-90, director MRC communicable disease unit 1967-84, and deputy director MRC clinical research centre, Northwick Park, 1970-84 (b 1925; q Sheffield 1948; CBE, FRCP, FRCPath), died from prostate cancer on 2 May 2005. David Tyrrell worked closely with the World Health Organization, and was director, at the common cold unit, of the WHO Reference Centre for Respiratory Virus Infections. In 1967 he went to the Medical Research Council’s new clinical research centre at Northwick Park as director of its communicable diseases research unit, combining this work with continuing to oversee research at the unit in Salisbury. Three years later he also became deputy director to Sir Christopher Booth, director of the research centre, who found him helpful and supportive. The MRC closed the clinical research centre in 1984, and Dr Tyrrell returned to the common cold unit until the MRC closed that in 1990. (Credit: THE ROYAL SOCIETY/GODFREY ARGENT STUDIOS)

The name David Arthur John Tyrrell will forever be linked with the discovery of the common cold viruses and elucidation of their disease pathogenesis. He was a physician and virologist who directed his medical and scientific training towards the benefit of his fellow man. The area he finally chose was that of respiratory virus infection and in particular the common cold. After his graduation from medical school in Sheffield, and a three-year research fellowship at the Virology Laboratory of the Rockefeller Institute under the direction of Frank Horsfall, he was invited in 1957 by Sir Harold Himsworth FRS, Secretary of the Medical Research Council (MRC), to work at the Common Cold Unit (CCU) in Wiltshire with the aim of growing the common cold virus. David Tyrrell’s unique approach of using well-oxygenated nasal epithelial cells grown at 33 °C (the temperature of the nose) enabled him to grow rhinoviruses for the first time, as described in a series of exciting papers in the 30 January 1960 issue of The Lancet. He gained a worldwide reputation, as did the unusual volunteer-based CCU. It soon became clear that there were more than 100 different types of rhinovirus, and also other viruses that could cause the common cold, for example, the coronaviruses.

In 1967, David Arthur John Tyrrell became Head of the Division of Communicable Diseases at the MRC’s Clinical Research Centre, built in association with Northwick Park Hospital, Harrow, Middlesex, and was Deputy Director of the Centre from 1970. During this time, he studied gastrointestinal infections in children, febrile convulsions, encephalitis and schizophrenia while maintaining control of research at the CCU, part of which involved determining the effectiveness of antiviral drugs.

On January 31, 1972, the National Institute of Allergy and Infectious Diseases (NIAID) sponsored an international workshop to review the relevance and relationship of the presently known coronaviruses, to identify specific problem areas of mutual concern and interest, and to offer an opportunity for free exchange of knowledge. Nearly 20 investigators participated in the workshop, which was organized by the Collaborative Program of NIAID under the direction of Dr. Robert J. Byrne and was held at the National Institutes of Health, Bethesda, Maryland. Dr. B. C. Easterday, University of Wisconsin, Madison, served as chairman. A memorandum from Dr. David Arthur John Tyrrell, chairman of the Study Group on Coronaviruses for the International Commission for the Nomenclature of Viruses, was read at the workshop.

Figure 5. Diachronic discourse of “coronavirus”, “coronaviruses”, “Coronaviridae” and “Nidovirales” in English corpus from 1963 to 2008. Google Books Ngram Corpus (GBNC) facsimiles the word frequency of “coronavirus”, “coronaviruses”, “Coronaviridae” and “Nidovirales” in English corpus from 1963 to 2008, respectively. The neologism “coronaviruses” was coined by a group of virologists – J. D. Almeida, D. M. Berry, C. H. Cunningham, D. Hamre, M. S. Hofstad, L. Mallucci, K. Mcintosh and D. A. J. Tyrrell on 16 November 1968. Later, in 1971, “coronaviruses” was officially approved by the International Committee on Nomenclature of Viruses (ICNV). The terms “Coronaviridae”, “Nidovirales” and “Coronavirinae” were officially approved by the International Committee on the Taxonomy of Viruses (ICTV) in 1975, 1996, 2009, respectively. After the initial description of coronaviruses in 1968 there was a mild increase in the numbers of printed books dealing with them, followed by several peaks, after several human epidemics: SARS-Cov in 2002-2003, HCov-NL63 in 2004 and HCov-HKU1 in 2005.

The diachronic discourse of “coronavirus” and “coronaviruses” in English corpus from 1960 to 2008 unveils that  there was a mild increase in the numbers of printed books dealing with them after the initial description of coronaviruses in 1968. Then, each human epidemic – SARS-Cov in 2002-2003, HCov-NL63 in 2004 and HCov-HKU1 in 2005 – leads to a new wave of hot research.

Timeline of human coronaviruses

Coronaviruses are named for the crown-like spikes on their surface. Coronavirus and coronavirus-like infections have been described in swine, cattle, horses, camels, cats, dogs, rodents, birds, bats, rabbits, ferrets, mink, and various wildlife species, although many coronavirus infections are subclinical.

In humans, coronaviruses are included in the spectrum of viruses that cause the common cold as well as more severe respiratory disease. There are 7 human coronaviruses known to infect humans. Of those, human coronaviruses HCov-229E (alpha coronavirus), HCov-NL63 (alpha coronavirus), HCov-OC43 (beta coronavirus), and HCov-HKU1 (beta coronavirus) are routinely responsible for mild respiratory illnesses like the common cold but can cause severe infections in immunocompromised individuals. But three members of the viral family have caused deadly outbreaks. SARS-Cov (Severe acute respiratory syndrome), MERS-Cov (Middle East respiratory syndrome), and now COVID-19 cause more severe disease, including pneumonia.

Figure 6. Number of publications with “coronavirus” in Web of Science and PubMed. On 16 November, 1968, the neologism “coronaviruses” was coined by eight virologists – J. D. Almeida, D. M. Berry, C. H. Cunningham, D. Hamre, M. S. Hofstad, L. Mallucci, K. Mcintosh and D. A. J. Tyrrell – in a brief annotation of Nature in 1968. Coronaviruses are positive-sense single-stranded RNA viruses found in a wide variety of animals, as well as in humans. Seven strains of respiratory coronaviruses known to infect human-to-human: HCov-OC43 (1965), HCov-229E (1966), SARS-Cov (2002), HCov-NL63 (2004), HCov-HKU1 (2005), MERS-Cov (2012) and COVID-19 (2019). The COVID-19 is the seventh identified coronavirus that can can cause diseases of the respiratory tract via human-to-human transmission. Coinciding with the Chinese New Year, the COVID-19 outbreak was first contracted in Wuhan City of China, home to 11 million people.

Retrospectively, strains HCov-OC43 and HCov-229E were first identified in 1965 and 1966, respectively. On November 16, 1968, the neologism “coronaviruses” was coined by a group of virologists in a brief annotation of the high-profile journal Nature. Later, SARS-Cov, HCov-NL63, HCov-HKU1, MERS-Cov were first identified in 2002, 2004, 2005, 2012, respectively. Coinciding with the Chinese New Year of 2019, a novel coronavirus outbreak was first emerged and contracted in Wuhan City of China, home to 11 million people. It is the seventh identified coronavirus that can cause diseases of the respiratory tract in humans. On January 12, 2020, this novel strain was temporarily named 2019-nCov by the World Health Organization.

The WHO Director-General, Dr Tedros Adhanom Ghebreyesus, declared the COVID-19 outbreak a public health emergency of international concern (PHEIC) on 30 January 2020. This is the 6th time WHO has declared a PHEIC since the International Health Regulations (IHR) came into force in 2005. Before the new coronavirus declared a global emergency by the WHO, there have been five global health emergencies since such declaration was formalized: swine flu (2009), polio (2014), Ebola (2014 then again in 2019), and Zika (2016). Compared with these diseases, WHO’s preliminary estimate shows the COVID-19 has a relatively low level of mortality rate and contagiousness for now.

Figure 7. A previously unknown coronavirus is behind an outbreak of respiratory illness in China. So far, The clinical severity of the COVID-19 is unknown at this time, although fatal cases have occurred (stained yellow in this scanning electron micrograph).

In November 2002, the first known case of SARS-Cov occurred in Foshan, China. The emergence of SARS-Cov marked the first introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. SARS-CoV is a new coronavirus that emerged through recombination of bat SARS-related coronaviruses (SARSr-CoVs). The recombined virus infected civets and humans and adapted to these hosts before causing the SARS-Cov epidemic.  By July 2003 and after a total of 8,096 reported cases, including 774 deaths in 27 countries, no more infections were detected, and the SARS-Cov pandemic was declared to be over. Five additional SARS-Cov cases, resulting from zoonotic transmission, occurred in December 2003–January 2004, but no human SARS-Cov cases have been detected since. The first indication of the source of SARS-CoV was the detection of the virus in masked palm civets and a raccoon dog and the detection of antibodies against the virus in Chinese ferret badgers in a live-animal market in Shenzhen, China. However, these animals were only incidental hosts, as there was no evidence for the circulation of SARS-CoV-like viruses in palm civets in the wild or in breeding facilities. Rather, bats are the reservoir of a wide variety of coronaviruses, including SARS-CoV-like and MERS-CoV-like viruses.

In June 2012, 10 years after the first emergence of SARS-CoV, a man in Saudi Arabia died of acute pneumonia and renal failure. A novel coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), was isolated from his sputum. MERS-CoV likely spilled over from bats to dromedary camels at least 30 years ago and since then has been prevalent in dromedary camels. A cluster of cases of severe respiratory disease had occurred in April 2012 in a hospital in Jordan and was retrospectively diagnosed as MERS-CoV, and a cluster of three cases of MERS-CoV in the UK was identified in September 2012. MERS-CoV continued to emerge and spread to countries outside of the Arabian Peninsula as a result of travel of infected persons; often, these imported MERS cases resulted in nosocomial transmission. In May 2015, a single person returning from the Middle East started a nosocomial outbreak of MERS-CoV in South Korea that involved 16 hospitals and 186 patients. As of 26 April 2016, there have been 1,728 confirmed cases of MERS-CoV, including 624 deaths in 27 countries.

HCoV-229E and HCoV-NL63 usually cause mild infections in immunocompetent humans. Progenitors of these viruses have recently been found in African bats, and the camelids are likely intermediate hosts of HCoV-229E. HCoV-OC43 and HCov-HKU1, both of which are also mostly harmless in humans, likely originated in rodents. Recently, swine acute diarrhoea syndrome (SADS) emerged in piglets. This disease is caused by a novel strain of Rhinolophus bat coronavirus HKU2, named SADS coronavirus (SADS-CoV); there is no evidence of infection in humans.

Figure 8. Bats harbour a wide range of coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV)-like and Middle East respiratory syndrome coronavirus (MERS-CoV)-like viruses. SARS-CoV crossed the species barrier into masked palm civets and other animals in live-animal markets in China; genetic analysis suggests that this occurred in late 2002. Several people in close proximity to palm civets became infected with SARS-CoV. A MERS-CoV ancestral virus crossed the species barrier into dromedary camels; serological evidence suggests that this happened more than 30 years ago. Abundant circulation of MERS-CoV in dromedary camels results in frequent zoonotic transmission of this virus. SARS-CoV and MERS-CoV spread between humans mainly through nosocomial transmission, which results in the infection of health care workers and patients at a higher frequency than infection of their relatives. Solid arrows indicate confirmed data. Broken arrows indicate potential interspecies transmission. Black arrows indicate infection in the intermediate animals, yellow arrows indicate a mild infection in humans, and red arrows indicate a severe infection in humans or animals.
Figure 9. Severe acute respiratory syndrome coronavirus (SARS-CoV) is a new coronavirus that emerged through recombination of bat SARS-related coronaviruses (SARSr-CoVs). The recombined virus infected civets and humans and adapted to these hosts before causing the SARS epidemic. Middle East respiratory syndrome coronavirus (MERS-CoV) likely spilled over from bats to dromedary camels at least 30 years ago and since then has been prevalent in dromedary camels. HCoV-229E and HCoV-NL63 usually cause mild infections in immunocompetent humans. Progenitors of these viruses have recently been found in African bats, and the camelids are likely intermediate hosts of HCoV-229E. HCoV-OC43 and HKU1, both of which are also mostly harmless in humans, likely originated in rodents. Recently, swine acute diarrhoea syndrome (SADS) emerged in piglets. This disease is caused by a novel strain of Rhinolophus bat coronavirus HKU2, named SADS coronavirus (SADS-CoV); there is no evidence of infection in humans. Solid arrows indicate confirmed data. Broken arrows indicate potential interspecies transmission. Black arrows indicate infection in the intermediate animals, yellow arrows indicate a mild infection in humans, and red arrows indicate a severe infection in humans or animals.

Nosocomial transmission and Super spreaders

Figure 10. A microscope image of a cell infected with the novel coronavirus COVID-19, grown in culture at the University of Hong Kong. Multiple virus particles are being released from the cell surface. (Credit: John Nicholls, Leo Poon and Malik Peiris/The University of Hong Kong)

In fact, measures of infection control, rather than medical interventions, ended the SARS-Cov or MERS-CoV pandemic. Retrospectively, human‑to‑human transmission of SARS-CoV and MERS-CoV occurs mainly through nosocomial transmission (Transmission of an infectious agent by staff, equipment or the environment in a health care setting): 43.5–100% of MERS-CoV cases in individual outbreaks were linked to hospitals, and very similar observations were made for some of the SARS-Cov clusters. Transmission between family members occurred in only 13–21% of MERS-CoV cases and 22–39% of SARS-Cov cases. Transmission of MERS-CoV between patients was the most common route of infection (62–79% of cases), whereas for SARS‑CoV, infection of health care workers by infected patients was very frequent (33–42%). The predominance of nosocomial transmission is probably due to the fact that substantial virus shedding occurs only after the onset of symptoms, when most patients are already seeking medical care. An analysis of hospital surfaces after the treatment of patients with MERS-CoV showed the ubiquitous presence of viral RNA in the environment for several days after patients no longer tested positive. Moreover, many patients with SARS-Cov or MERS-CoV were infected through super spreaders (Infected individuals who each infect a disproportionately large number of secondary cases).

Figure 11. Major routes of nosocomial transmission of SARS-CoV, MERS-CoV and Ebola epidemics. The main risk factors for colonization and subsequent nosocomial infection with each other include close physical proximity to patients who are infected or colonized with viruses (or to the rooms of these patients); a long period of hospitalization; hospitalization in long-term facilities, surgical units or intensive-care units; the presence of a urinary catheter; and the administration of multiple courses of antibiotics. Many antibiotics increase the density of organisms in the gastrointestinal tract, which, in turn, facilitates the spread of these organisms through faecal contamination of the hospital environment, including inanimate objects and the hands of health care workers and visitors. Viruses may survive for long periods on environmental surfaces, including medical equipment, toilets, bed rails and doorknobs, and are tolerant to heat, chlorine and some alcohol preparations. IV, intravenous.
Figure 12. Beyond epidemic models. Super spreader means infected individuals who each infect a disproportionately large number of secondary cases. The criteria for a “super spreader” – think of Typhoid Mary – are not exact, but the revelation that one person has transmitted the disease to more than 10 people is cause for international alarm. ‘Typhoid’ Mary Mallone was a super spreader, infecting 51 people. A single person with cavitary tuberculosis at a Minnesota bar in 1992 infected 41 people with the disease. Fourteen developed ‘active’ tuberculosis, accounting for more than a third of all cases in the state that year. A single Chinese patient gave the new coronavirus to 14 healthcare workers, raising concerns the person may be a “super spreader” capable of transmitting to many people through casual contact.

Will history repeat itself?

Evidences reveals that each epidemic outbreak occurs mainly through nosocomial transmission via an infectious agent by staff, equipment or the environment in a health care setting. Nosocomial Infections (NI) also known as hospital-acquired/associated infections (HAI) are acquired during hospitalization, which are not present or incubating at the time of admission to a hospital. The risk of acquiring such infections in a hospital is greater because of the increased pool of circulating organisms where you have a large number of ill people, and also where most of the people are themselves are more vulnerable due to their own illness. Nosocomial infections are the target of infection-control staff who constantly attempt to avoid such infections taking place. Unfortunately, the risk of nosocomial transmission is routinely underestimated in clinical practice.

Recent evidences reveals that the majority of SARS-CoV, MERS-CoV and Ebola cases were associated with nosocomial transmission in hospitals, resulting at least in part from the use of aerosol-generating procedures in patients with respiratory disease. In particular, nosocomial super-spreader events appear to have driven large outbreaks within and between health care settings. Unfortunately, the similar pattern is still repreating in COVID-19 outbreak, the third epidemic caused by coronavirus in the 21st century. Single-center case series of the 138 consecutive hospitalized patients with confirmed novel coronavirus (COVID-19)–infected pneumonia (NCIP) at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020 were collected and analyzed. In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of COVID-19 was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.

Scientific advancements since those pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of human coronaviruses and the development of therapeutics. Why the seemingly rapid progress in this field was followed by a deadlock that has not yet been overcome merits serious attention. However, certain SARS-CoV-like viruses found in bats have recently been shown to be able to infect human cells without prior adaptation, which indicates that SARS-Cov or MERS-CoV could re‑emerge.

In the field of combating emerging coronaviruses, it was recommended that more effort should go into investigating the biology and pathogenesis of coronaviruses, the correlation between antibody levels in serum and secretions and resistance to infection, cellular and humoral aspects of immunity to diseases caused by coronaviruses in virology, molecular biology, genomics, and immunology. Beyond the medical and therapeutic countermeasures, lessons from those HCoV outbreaks also highlight the need for prophylactic measures, as well as social mobilization and socialgovernance for the next viral attack in sociocultural perspective. 

The farther back we can look, the farther forward we can see. This is a positivist tenet, not merely for combating emerging coronaviruses but for the vitality of science and the promotion of social progress.

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