Whether the virus is infectious during the incubation period is uncertain. On 1 February 2020, the World Health Organization (WHO) indicated that "transmission from asymptomatic cases is likely not a major driver of transmission". 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.
The first known infections from the SARS-CoV-2 strain were discovered in Wuhan, China. The original source of viral transmission to humans and when the strain became pathogenic remains unclear. Because many of the first individuals found to be infected by the virus were workers at the Huanan Seafood Market, it has been suggested that the strain might have originated from the market. However, other research indicates that visitors may have introduced the virus to the market, which then facilitated rapid expansion of the infections.
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. 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. 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." Pangolins are protected under Chinese law, but their poaching and trading for use in traditional Chinese medicine remains common.
Microbiologists and geneticists in Texas have independently found evidence of reassortment in coronaviruses suggesting involvement of pangolins in the origin of SARS-CoV-2. 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. 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.
Phylogenetics and taxonomy
Genomic organisation of isolate Wuhan-Hu-1, the earliest sequenced sample of SARS-CoV-2
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). Its RNA sequence is approximately 30,000 bases in length. 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.
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; the number of genomes increased to 42 by 30 January 2020. 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. As of 13 March 2020,[update] 410 SARS-CoV-2 genomes sampled on five continents were publicly available.
Each SARS-CoV-2 virion is approximately 50–200 nanometres in diameter. 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. The spike protein, which has been imaged at the atomic level using cryogenic electron microscopy, is the protein responsible for allowing the virus to attach to the membrane of a host cell.
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. 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. Studies have shown that SARS-CoV-2 has a higher affinity to human ACE2 than the original SARS virus strain. SARS-CoV-2 may also use basigin to gain cell entry.
Based upon 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. The earliest case of infection currently known is thought to have been found on 17 November 2019. 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. Human-to-human transmission of the virus has been confirmed in all of these regions. On 30 January 2020, SARS-CoV-2 was designated a Public Health Emergency of International Concern by the WHO, and on 11 March 2020 the WHO declared it a pandemic.
As of 30 March 2020 (22:15 UTC), there were 784,314 confirmed cases of infection, of which approximately 81,400 were in mainland China. While the proportion of infections that result in confirmed infection or progress to diagnosable disease 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. The total number of deaths attributed to the virus was 37,638 as of 30 March 2020 (22:15 UTC); 165,288 people had recovered from infection by that time. Less than a tenth of all deaths have occurred in Hubei province, where Wuhan is located. Before 24 February 2020, the proportion was over 95%.
The basic reproduction number () of the virus has been estimated to be between 1.4 and 3.9. 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.
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"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.