Coronaviruses are so named because of their characteristic solar corona (crown-like) appearance when observed under an electron microscope. This appearance is produced by the peplomers of the spike [S] glycoprotein radiating from the virus lipid envelope.
Coronaviruses are a group of large, enveloped, positive-sense, single-stranded RNA viruses belonging to the order Nidovirales, family Coronaviridae, subfamily Coronavirinae. Twenty-six different species are known and have been divided into four genera (alpha, beta, gamma and delta) characterized by different antigenic cross-reactivity and genetic makeup. Only the alpha- and betacoronavirus genera include strains pathogenic to humans.
The first known coronavirus, the avian infectious bronchitis virus, was isolated in 1937 and was the cause of devastating infections in chicken. The first human coronavirus was isolated from the nasal cavity and propagated on human ciliated embryonic trachea cells in vitro by Tyrrell and Bynoe in 1965. However, coronaviruses have been present in humans for at least 500-800 years, and all originated in bats.
Coronaviruses have long been recognized as important veterinary pathogens, causing respiratory and enteric diseases in mammals as well as in birds. Of the known coronavirus species, only six have been known to cause disease in humans: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory virus coronavirus (MERS-CoV).
The first four are endemic locally; they have been associated mainly with mild, selflimiting disease, whereas the latter two can cause severe illness. SARS-CoV and MERS-CoV are betacoronaviruses, and are among the pathogens included in the World Health Organization’s list of high-priority threats (A research and development blueprint for action to prevent epidemics (World Health Organization, revised February 2018)).
Given the high prevalence and wide distribution of coronaviruses, their large genetic diversity as well as the frequent recombination of their genomes, and increasing activity at the human animal interface, these viruses represent an ongoing threat to human health. This fact again became evident in late 2019 and early 2020, when a novel coronavirus was discovered to be the cause of a large and rapidly spreading outbreak of respiratory disease, including pneumonia, in Wuhan, China (WHO statement regarding cluster of pneumonia cases in Wuhan, China (World Health Organization, January 9, 2020); Emergencies: Novel coronavirus 2019 (World Health Organization). The virus, provisionally designated 2019-nCoV, was isolated and the viral genome sequenced. 2019-nCoV was characterized as a betacoronavirus, and thus became the seventh discrete coronavirus species capable of causing human disease.
Facts about 2019-nCoV
In late 2019, a new coronavirus began causing febrile respiratory illness in China. The virus, provisionally known as 2019-nCoV, was first detected in the urban center of Wuhan. Initial cases were linked to a wholesale seafood market, which was immediately closed. 2019-nCoV was sequenced and identified as a betacoronavirus belonging to the sarbecovirus subgenus, with 75-80% similarity in genetic sequence to SARS-CoV. The as-yet-unidentified animal host of 2019-nCoV is presumed to be a bat; an intermediate host may also have been involved. Although the initial cases were traced to zoonotic transmission, human-to-human transmission was soon documented, both in healthcare settings and in familial clusters.
Following an incubation ranging from 2-14 days, 2019-nCoV infection manifests as respiratory illness ranging from mild to severe, with symptoms that include fever, cough and dyspnea. Chest CT scan reveals the presence of bilateral ground-glass opacities (Huang, C. et al., 2020; Centers for Disease Control and Prevention (CDC) — 2019 novel coronavirus, Wuhan, China). In an early description of 41 clinical cases, patients had serious, sometimes fatal, pneumonia. 15 Clinical presentations were very similar to those of SARS-CoV. Patients with the most severe illnesses developed acute respiratory distress, requiring ICU admission and oxygen therapy. The mortality rate in this early patient set was approximately 15%, and primarily involved patients with serious underlying illnesses or onditions.
Without effective drugs or vaccines against the infectious agent, physical interventions such as isolation and quarantine are the most effective means of controlling a coronaviral infections with epidemic potential; however, patients are typically asymptomatic during the incubation period, which ranges from 2-14 days (mean 4 days) in the case of SARS and from 2-15 days (mean 5 days) in the case of MERS. Authorities are often reluctant to impose these measures because of their economic and social impact; however, without other means of control of the epidemic spread of SARS, there was no alternative. The success of these measures was demonstrated in Singapore, where application of infection control measures resulted in a decrease in the reproduction number (secondary infection rate) from 7 at week 1 to <1 after week 2. In Taiwan, the application of Level A quarantine (that of potentially exposed contacts of suspected SARS patients) resulted in the prevention of approximately 461 additional cases and 62 additional deaths; the use of Level B quarantine (that of travelers arriving from affected areas), in contrast, reduced the number of new cases and deaths by only about 5%. CDC recommends use of airborne infection isolation procedures in the care of all confirmed MERS infections in that country.
Hygienic measures are recommended to prevent the spread of disease in situations where individuals are in contact with patients or contaminated fomites. Washing hands with soap and water or with alcohol-based handrubs is effective for interrupting virus transmission. The SARS virus is able to survive on surfaces for up to six days, but can be inactivated by washing with bleach, 75% ethanol, household detergents, chemical disinfectants such as povidone-iodine, or heating.
The MERS virus is capable of surviving for up to 48 hours at 200C and for 24 hours at 300C. Personal protective equipment, including eye protection, is recommended for health care personnel, as well as surgical masks or N-95 disposable filtering respirators. Airborne precautions should be applied especially when performing aerosol-generating procedures such as intubation. All potentially infectious specimens should be handled and transported with caution, and must be tested in laboratories meeting WHO BSL3 standards.
As a result of the SARS outbreak, WHO revised the rules for reporting infectious diseases by its member states. The previous reporting requirements, formulated in 1951, required reporting for plague, cholera and yellow fever only, and the resulting delay in reporting cases early in the outbreak was likely to have contributed to its rapid spread. The efficient and collaborative international response to the MERS outbreak a decade later testifies to the improvements made.