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Severe acute respiratory syndrome coronavirus 2

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Severe acute respiratory syndrome coronavirus 2
Electron micrograph of SARS-CoV-2 virions with visible coronae
Electron micrograph of SARS-CoV-2 virions with visible coronae
Illustration of a SARS-CoV-2 virion
Illustration of a SARS-CoV-2 virion
Virus classification e
(unranked): Virus
Realm: Riboviria
Phylum: incertae sedis
Order: Nidovirales
Family: Coronaviridae
Genus: Betacoronavirus
Subgenus: Sarbecovirus
Species:
Strain:
Severe acute respiratory syndrome coronavirus 2
Synonyms
  • 2019-nCoV

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),[1][2] previously known by the provisional name 2019 novel coronavirus (2019-nCoV),[3][4][5] is the cause of the respiratory disease coronavirus disease 2019 (COVID-19). Taxonomically, it is a strain of the Severe acute respiratory syndrome-related coronavirus (SARSr-CoV),[1] a positive-sense single-stranded RNA virus.[6] It is contagious in humans, and the World Health Organization (WHO) has designated the ongoing pandemic of COVID-19 a Public Health Emergency of International Concern.[7][8][9]

SARS-CoV-2 is believed to have zoonotic origins. It has close genetic similarity to bat coronaviruses, suggesting it emerged from a bat-borne virus.[10][11][12] An intermediate animal reservoir such as a pangolin is also thought to be involved in its introduction to humans.[13][14] Chinese scientists first isolated SARS-CoV-2 7 January 2020 from patients in Wuhan, China who had had pneumonia of unknown cause in December 2019.[15] Genomic studies show relatively few mutations, so the virus likely emerged a few weeks before health authorities detected it.

The virus is primarily spread between people through close contact and via respiratory droplets produced from coughs or sneezes.[16][17][18] It enters human cells by binding to their angiotensin converting enzyme 2 (ACE2) receptors.

As of 28 March 2020, the overall rate of deaths per number of diagnosed cases is 4.6%; ranging from 0.2% to 15% according to age group and other health problems.[19] As of 1 April 2020, more than 857,000[20][21] cases of COVID-19 have been reported in 200 countries and territories, resulting in approximately 42,000[20][21] deaths. More than 178,000[20][21] people have since recovered.[20][21] While the proportion of infections that result in obvious symptoms remains unclear, one mathematical model estimated the number of people infected in Wuhan alone at 75,815 as of 25 January 2020, at a time when confirmed infections were far lower. January 2020 epidemiology studies estimate each infection results in 1.4 to 3.9 new ones when no members of the community are immune and no preventive measures taken.

Virology

Infection

Human-to-human transmission of SARS-CoV-2 has been confirmed during the 2019–20 coronavirus pandemic.[9] Transmission occurs primarily via respiratory droplets from coughs and sneezes within a range of about 2 metres (6.6 ft).[22][17] Indirect contact via contaminated surfaces is another possible cause of infection.[23] Preliminary research indicates that the virus may remain viable on plastic and steel for up to three days, but does not survive on cardboard for more than one day or on copper for more than four hours;[24] the virus is inactivated by soap, which destabilises its lipid bilayer.[25][26] Viral RNA has also been found in stool samples from infected people.[27]

Whether the virus is infectious during the incubation period is uncertain.[28] On 1 February 2020, the World Health Organization (WHO) indicated that "transmission from asymptomatic cases is likely not a major driver of transmission".[29] However, an epidemiological model of the beginning of the outbreak in China suggested that "pre-symptomatic shedding may be typical among documented infections" and that subclinical infections may have been the source of a majority of infections.[30]

Reservoir

Horseshoe bats are among the most likely natural reservoirs of SARS-CoV-2
Horseshoe bats are among the most likely natural reservoirs of SARS-CoV-2

The first known infections from the SARS-CoV-2 strain were discovered in Wuhan, China.[10] The original source of viral transmission to humans and when the strain became pathogenic remains unclear.[31][32][33] Because many of the first individuals found to be infected by the virus were workers at the Huanan Seafood Market,[34][35] it has been suggested that the strain might have originated from the market.[33][36] However, other research indicates that visitors may have introduced the virus to the market, which then facilitated rapid expansion of the infections.[31][37]

Research into the natural reservoir of the virus strain that caused the 2002–2004 SARS outbreak has resulted in the discovery of many SARS-like bat coronaviruses, most originating in the Rhinolophus genus of horseshoe bats, and two viral nucleic acid sequences found in samples taken from Rhinolophus sinicus show a resemblance of 80% to SARS-CoV-2.[12][38][39] A third viral nucleic acid sequence from Rhinolophus affinis, collected in Yunnan province and designated RaTG13, has a 96% resemblance to SARS-CoV-2.[10][40] The WHO considers bats the most likely natural reservoir of SARS-CoV-2,[41] but differences between the bat coronavirus and SARS-CoV-2 suggest that humans were infected via an intermediate host.[36]

A metagenomic study published in 2019 previously revealed that SARS-CoV, the strain of the virus that causes SARS, was the most widely distributed coronavirus among a sample of Sunda pangolins.[42] On 7 February 2020, it was announced that researchers from Guangzhou had discovered a pangolin sample with a viral nucleic acid sequence "99% identical" to SARS-CoV-2.[43] When released, the results clarified that "the receptor-binding domain of the S protein of the newly discovered Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference."[44] Pangolins are protected under Chinese law, but their poaching and trading for use in traditional Chinese medicine remains common.[45][46]

Microbiologists and geneticists in Texas have independently found evidence of reassortment in coronaviruses suggesting involvement of pangolins in the origin of SARS-CoV-2.[47] However, pangolin coronaviruses found to date only share at most 92% of their whole genomes with SARS-CoV-2, making them less similar than RaTG13 to SARS-CoV-2.[48] This is insufficient to prove pangolins to be the intermediate host; in comparison, the SARS virus responsible for the 2002–2004 outbreak shared 99.8% of its genome with a known civet coronavirus.[36]

Phylogenetics and taxonomy

Genomic information
SARS-CoV-2 genome.svg
Genomic organisation of isolate Wuhan-Hu-1, the earliest sequenced sample of SARS-CoV-2
NCBI genome ID MN908947
Genome size 29,903 bases
Year of completion 2020

SARS-CoV-2 belongs to the broad family of viruses known as coronaviruses. It is a positive-sense single-stranded RNA (+ssRNA) virus. Other coronaviruses are capable of causing illnesses ranging from the common cold to more severe diseases such as Middle East respiratory syndrome (MERS). It is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and the original SARS-CoV.[49]

Like the SARS-related coronavirus strain implicated in the 2003 SARS outbreak, SARS-CoV-2 is a member of the subgenus Sarbecovirus (beta-CoV lineage B).[15][50][51] Its RNA sequence is approximately 30,000 bases in length.[6] SARS-CoV-2 is unique among known betacoronaviruses in its incorporation of a polybasic cleavage site, a characteristic known to increase pathogenicity and transmissibility in other viruses.[33][52][53]

With a sufficient number of sequenced genomes, it is possible to reconstruct a phylogenetic tree of the mutation history of a family of viruses. By 12 January 2020, five genomes of SARS-CoV-2 had been isolated from Wuhan and reported by the Chinese Center for Disease Control and Prevention (CCDC) and other institutions;[6][54] the number of genomes increased to 42 by 30 January 2020.[55] A phylogenetic analysis of those samples showed they were "highly related with at most seven mutations relative to a common ancestor", implying that the first human infection occurred in November or December 2019.[55] As of 13 March 2020, 410 SARS-CoV-2 genomes sampled on five continents were publicly available.[56]

On 11 February 2020, the International Committee on Taxonomy of Viruses (ICTV) announced that according to existing rules that compute hierarchical relationships among coronaviruses on the basis of five conserved sequences of nucleic acids, the differences between what was then called 2019-nCoV and the virus strain from the 2003 SARS outbreak were insufficient to make them separate viral species. Therefore, they identified 2019-nCoV as a strain of Severe acute respiratory syndrome-related coronavirus.[1]

Structural biology

Structure of a SARSr-CoV virion
Structure of a SARSr-CoV virion

Each SARS-CoV-2 virion is approximately 50–200 nanometres in diameter.[57] Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins; the N protein holds the RNA genome, and the S, E, and M proteins together create the viral envelope.[58] The spike protein, which has been imaged at the atomic level using cryogenic electron microscopy,[59][60] is the protein responsible for allowing the virus to attach to the membrane of a host cell.[58]

SARS-CoV-2 spike homotrimer with one protein subunit highlighted; ACE2 binding domain highlighted
SARS-CoV-2 spike homotrimer with one protein subunit highlighted; ACE2 binding domain in magenta

Protein modeling experiments on the spike protein of the virus soon suggested that SARS-CoV-2 has sufficient affinity to the angiotensin converting enzyme 2 (ACE2) receptors of human cells to use them as a mechanism of cell entry.[61] By 22 January 2020, a group in China working with the full virus genome and a group in the United States using reverse genetics methods independently and experimentally demonstrated that ACE2 could act as the receptor for SARS-CoV-2.[10][62][63][64][65][66] Studies have shown that SARS-CoV-2 has a higher affinity to human ACE2 than the original SARS virus strain.[59] SARS-CoV-2 may also use basigin to gain cell entry.[67]

SARS-CoV-2 emerging from a human cell
SARS-CoV-2 emerging from a human cell
Digitally colourised electron micrographs of SARS-CoV-2 (yellow) emerging from human cells cultured in a laboratory

Initial spike protein priming by transmembrane protease, serine 2 (TMPRSS2) is essential for entry of SARS-CoV-2.[68] After a SARS-CoV-2 virion attaches to a target cell, the cell's protease TMPRSS2 cuts open the spike protein of the virus, exposing a fusion peptide. The virion then releases RNA into the cell, forcing the cell to produce copies of the virus that are disseminated to infect more cells.[69][better source needed] SARS-CoV-2 produces at least three virulence factors that promote shedding of new virions from host cells and inhibit immune response.[58]

Epidemiology

Micrograph of SARS-CoV-2 virus particles, isolated from a patient
Micrograph of SARS-CoV-2 virions (red) isolated from a patient during the 2019–20 coronavirus pandemic

Based on the low variability exhibited among known SARS-CoV-2 genomic sequences, the strain is thought to have been detected by health authorities within weeks of its emergence among the human population in late 2019.[31][70] The earliest case of infection currently known is thought to have been found on 17 November 2019.[71] The virus subsequently spread to all provinces of China and to more than one hundred other countries in Asia, Europe, North America, South America, Africa, and Oceania.[20] Human-to-human transmission of the virus has been confirmed in all of these regions.[9][72][73][74][75][76] On 30 January 2020, SARS-CoV-2 was designated a Public Health Emergency of International Concern by the WHO,[8][77] and on 11 March 2020 the WHO declared it a pandemic.[78][7]

As of 1 April 2020 (01:00 UTC), there were 857,487 confirmed cases of infection, of which approximately 81,400 were in mainland China.[20][21] While the proportion of infections that result in confirmed infection or progress to diagnosable disease remains unclear,[79] one mathematical model estimated the number of people infected in Wuhan alone at 75,815 as of 25 January 2020, at a time when confirmed infections were far lower.[80] The total number of deaths attributed to the virus was 42,107 as of 1 April 2020 (01:00 UTC); 178,034 people had recovered from infection by that time.[20] Less than a tenth of all deaths have occurred in Hubei province, where Wuhan is located.[20] Before 24 February 2020, the proportion was over 95%.[81][82]

The basic reproduction number () of the virus has been estimated to be between 1.4 and 3.9.[83][84] This means that each infection from the virus is expected to result in 1.4 to 3.9 new infections when no members of the community are immune and no preventive measures are taken. The reproduction number may be higher in densely populated conditions such as those found on cruise ships.[85]

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Further reading

  • Brüssow H (March 2020). "The Novel Coronavirus – A Snapshot of Current Knowledge". Microbial Biotechnology. 2020: 1–6. doi:10.1111/1751-7915.13557. PMID 32144890.
  • Habibzadeh P, Stoneman EK (February 2020). "The Novel Coronavirus: A Bird's Eye View". The International Journal of Occupational and Environmental Medicine. 11 (2): 65–71. doi:10.15171/ijoem.2020.1921. PMID 32020915.
  • World Health Organization (2 March 2020). Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected human cases: interim guidance, 2 March 2020 (Report). World Health Organization. hdl:10665/331329. WHO/COVID-19/laboratory/2020.4. License: CC BY-NC-SA 3.0.
  • World Health Organization best practices for the naming of new human infectious diseases (Report). World Health Organization. May 2015. hdl:10665/163636. WHO/HSE/FOS/15.1.
  • "Coronavirus Disease 2019 (COVID-19) Symptoms". Centers for Disease Control and Prevention. United States. 10 February 2020. Archived from the original on 30 January 2020.
  • Fox D (24 January 2020). "What you need to know about the Wuhan coronavirus". Nature. doi:10.1038/d41586-020-00209-y. ISSN 0028-0836.
  • "Naming the coronavirus disease (COVID-2019) and the virus that causes it". World Health Organization. Archived from the original on 28 February 2020. Retrieved 24 February 2020. From a risk communications perspective, using the name SARS can have unintended consequences in terms of creating unnecessary fear for some populations.... For that reason and others, WHO has begun referring to the virus as "the virus responsible for COVID-19" or "the COVID-19 virus" when communicating with the public. Neither of these designations are [sic] intended as replacements for the official name of the virus as agreed by the ICTV.
  • Taylor-Coleman J (5 February 2020). "How the new coronavirus will finally get a proper name". BBC News. Archived from the original on 5 February 2020. Retrieved 6 February 2020.
  • Huang P (22 January 2020). "How Does Wuhan Coronavirus Compare with MERS, SARS and the Common Cold?". NPR. Archived from the original on 2 February 2020. Retrieved 3 February 2020.
  • Yam K (12 March 2020). "GOP lawmakers continue to use 'Wuhan virus' or 'Chinese coronavirus'". NBC News. Archived from the original on 14 March 2020. Retrieved 19 March 2020.
  • Harmon A (4 March 2020). "We Spoke to Six Americans with Coronavirus". The New York Times. Archived from the original on 13 March 2020. Retrieved 16 March 2020.
  • Hui M (18 March 2020). "Why won't the WHO call the coronavirus by its name, SARS-CoV-2?". Quartz. Retrieved 26 March 2020.
  • Dorman S (11 March 2020). "McCarthy knocks Dems after they claim saying 'Chinese coronavirus' is racist". Fox News. Archived from the original on 12 March 2020. Retrieved 12 March 2020.
  • "Wuhan virus sees Olympic football qualifiers moved". Xinhua. 22 January 2020. Archived from the original on 22 January 2020. Retrieved 29 March 2020.

External links

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