During the initial outbreak in Wuhan, China, various names were used for the virus; some names used by different sources included the "coronavirus" or "Wuhan coronavirus". In January 2020, the World Health Organization recommended "2019 novel coronavirus" (2019-nCov) as the provisional name for the virus. This was in accordance with WHO's 2015 guidance against using geographical locations, animal species, or groups of people in disease and virus names.
On 11 February 2020, the International Committee on Taxonomy of Viruses adopted the official name "severe acute respiratory syndrome coronavirus 2" (SARS‑CoV‑2). To avoid confusion with the disease SARS, the WHO sometimes refers to SARS‑CoV‑2 as "the COVID-19 virus" in public health communications and the name HCoV-19 was included in some research articles.
Human-to-human transmission of SARS‑CoV‑2 was confirmed on 20 January 2020, during the COVID-19 pandemic. Transmission was initially assumed to occur primarily via respiratory droplets from coughs and sneezes within a range of about 1.8 metres (6 ft). Laser light scattering experiments suggest that speaking is an additional mode of transmission and a far-reaching and under-researched one, indoors, with little air flow. Other studies have suggested that the virus may be airborne as well, with aerosols potentially being able to transmit the virus. During human-to-human transmission, an average 1000 infectious SARS‑CoV‑2 virions are thought to initiate a new infection.
The degree to which the virus is infectious during the incubation period is uncertain, but research has indicated that the pharynx reaches peak viral load approximately four days after infection or the first week of symptoms, and declines after. The duration of SARS-CoV-2 RNA shedding is generally between 3 and 46 days after symptom onset.
A study by a team of researchers from the University of North Carolina found that the nasal cavity is seemingly the dominant initial site for infection with subsequent aspiration-mediated virus seeding into the lungs in SARS‑CoV‑2 pathogenesis. They found that there was an infection gradient from high in proximal towards low in distal pulmonary epithelial cultures, with a focal infection in ciliated cells and type 2 pneumocytes in the airway and alveolar regions respectively.
There is some evidence of human-to-animal transmission of SARS‑CoV‑2, including examples in felids. Some institutions have advised those infected with SARS‑CoV‑2 to restrict contact with animals.
On 1February 2020, the World Health Organization (WHO) indicated that "transmission from asymptomatic cases is likely not a major driver of transmission". One meta-analysis found that 17% of infections are asymptomatic, and asymptomatic individuals were 42% less likely to transmit the virus.
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. That may explain how out of 217 onboard a cruise liner that docked at Montevideo, only 24 of 128 who tested positive for viral RNA showed symptoms. Similarly, a study of ninety-four patients hospitalized in January and February 2020 estimated patients shed the greatest amount of virus two to three days before symptoms appear and that "a substantial proportion of transmission probably occurred before first symptoms in the index case".
There is uncertainty about reinfection and long-term immunity. It is not known how common reinfection is, but reports have indicated that it is occurring with variable severity.
The first reported case of reinfection was a 33-year-old man from Hong Kong who first tested positive on 26 March 2020, was discharged on 15 April 2020 after two negative tests, and tested positive again on 15 August 2020 (142 days later), which was confirmed by whole-genome sequencing showing that the viral genomes between the episodes belong to different clades. The findings had the implications that herd immunity may not eliminate the virus if reinfection is not an uncommon occurrence and that vaccines may not be able to provide lifelong protection against the virus.
Another case study described a 25-year-old man from Nevada who tested positive for SARS‑CoV‑2 on 18 April 2020 and on 5 June 2020 (separated by two negative tests). Since genomic analyses showed significant genetic differences between the SARS‑CoV‑2 variant sampled on those two dates, the case study authors determined this was a reinfection. The man's second infection was symptomatically more severe than the first infection, but the mechanisms that could account for this are not known.
Transmission of SARS-CoV-1 and SARS‑CoV‑2 from mammals as biological carriers to humans
The first known infections from SARS‑CoV‑2 were discovered in Wuhan, China. The original source of viral transmission to humans remains unclear, as does whether the virus became pathogenic before or after the spillover event. Because many of the early infectees were workers at the Huanan Seafood Market, it has been suggested that the virus 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 March 2021 WHO report on a joint WHO–China study stated that human spillover via an intermediate animal host was the most likely explanation, with direct spillover from bats next most likely. Introduction through the food supply chain and the Huanan Seafood Market was considered another possible, but less likely, explanation.
The mutation rate estimated from early cases of SARS-CoV-2 was of 6.54×10−4 per site per year. Its viral evolution is slowed by the RNA proofreading capability of its replication machinery.
Samples taken from Rhinolophus sinicus, a species of horseshoe bats, show an 80% resemblance to SARS‑CoV‑2.
Bats are considered the most likely natural reservoir of SARS‑CoV‑2, but differences between the bat coronavirus and SARS‑CoV‑2 suggest that humans were infected via an intermediate host; although the source of introduction into humans remains unknown.
Although the role of pangolins as an intermediate host was initially posited (a study published in July 2020 suggested that pangolins are an intermediate host of SARS‑CoV‑2-like coronaviruses), subsequent studies have not substantiated their contribution to the spillover. Evidence against this hypothesis includes the fact that pangolin virus samples are too distant to SARS-CoV-2: isolates obtained from pangolins seized in Guangdong were only 92% identical in sequence to the SARS‑CoV‑2 genome. In addition, despite similarities in a few critical amino acids, pangolin virus samples exhibit poor binding to the human ACE2 receptor.
Phylogenetics and taxonomy
Genomic organisation of isolate Wuhan-Hu-1, the earliest sequenced sample of SARS-CoV-2
Like the SARS-related coronavirus implicated in the 2003 SARS outbreak, SARS‑CoV‑2 is a member of the subgenus Sarbecovirus (beta-CoV lineage B). Coronaviruses also undergo frequent recombination. Its RNA sequence is approximately 30,000 bases in length, relatively long for a coronavirus (which in turn carry the largest genomes among all RNA families) Its genome consists nearly entirely of protein-coding sequences, a trait shared with other coronaviruses.
A distinguishing feature of SARS‑CoV‑2 is its incorporation of a polybasic site cleaved by furin, which appears to be an important element enhancing its virulence. The furin protease recognizes the canonical peptide sequence RX[R/K]R↓X where the cleavage site is indicated by a down arrow and X is any amino acid. In SARS-CoV-2 the recognition site is formed by the incorporated 12 codon nucleotide sequence CCT CGG CGG GCA which corresponds to the amino acid sequence PRRA. This sequence is upstream of an arginine and serine which forms the S1/S2 cleavage site (PRRAR↓S) of the spike protein. Although such sites are a common naturally-occurring feature of other viruses, including some members of the Beta-CoV genus and other genera of coronaviruses, SARS-Cov-2 is unique among members of its subgenus for such a site.
Viral genetic sequence data can provide critical information about whether viruses separated by time and space are likely to be epidemiologically linked. 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. Examination of the topology of the phylogenetic tree at the start of the pandemic also found high similarities between human isolates. As of 7 May 2020,[update] 4,690 SARS‑CoV‑2 genomes sampled on six continents were publicly available.[clarification needed]
In July 2020, scientists reported that a more infectious SARS‑CoV‑2 variant with spike protein variant G614 has replaced D614 as the dominant form in the pandemic.
Coronavirus genomes and subgenomes encode six open reading frames (ORFs). In October 2020, researchers discovered a possible overlapping gene named ORF3d, in the SARS‑CoV‑2 genome. It is unknown if the protein produced by ORF3d has any function, but it provokes a strong immune response. ORF3d has been identified before, in a variant of coronavirus that infects pangolins.
A phylogenetic tree based on whole-genome sequences of SARS-CoV-2 and related coronaviruses is:
False-colour transmission electron micrograph of a B.1.1.7 variant coronavirus. The variant's increased transmissibility is believed to be due to changes in the structure of the spike proteins, shown here in green.
There are many thousands of variants of SARS-CoV-2, which can be grouped into the much larger clades. Several different clade nomenclatures have been proposed. Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR).
Beta: Lineage B.1.351 emerged in South Africa in May 2020, with evidence of increased transmissibility and changes to antigenicity, with some public health officials raising alarms about its impact on the efficacy of some vaccines. Notable mutations include K417N, E484K and N501Y.
Gamma: Lineage P.1 emerged in Brazil in November 2020, also with evidence of increased transmissibility and virulence, alongside changes to antigenicity. Similar concerns about vaccine efficacy have been raised. Notable mutations also include K417N, E484K and N501Y.
Delta: Lineage B.1.617.2 emerged in India in October 2020. There is also evidence of increased transmissibility and changes to antigenicity.
Each SARS-CoV-2 virion is 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. Coronavirus S proteins are glycoproteins that are divided into two functional parts (S1 and S2). In SARS-CoV-2, 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 and fuse with the membrane of a host cell; specifically, its S1 subunit catalyzes attachment, the S2 subunit fusion.
Virus infections start when viral particles bind to host surface cellular receptors.Protein modeling experiments on the spike protein of the virus soon suggested that SARS‑CoV‑2 has sufficient affinity to the receptor angiotensin converting enzyme 2 (ACE2) on 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. SARS‑CoV‑2 May also use basigin to assist in cell entry.
Initial spike protein priming by transmembrane protease, serine 2 (TMPRSS2) is essential for entry of SARS‑CoV‑2. The host protein neuropilin 1 (NRP1) may aid the virus in host cell entry using ACE2. After a SARS‑CoV‑2 virion attaches to a target cell, the cell's TMPRSS2 cuts open the spike protein of the virus, exposing a fusion peptide in the S2 subunit, and the host receptor ACE2. After fusion, an endosome forms around the virion, separating it from the rest of the host cell. The virion escapes when the pH of the endosome drops or when cathepsin, a host cysteine protease, cleaves it. The virion then releases RNA into the cell and forces the cell to produce and disseminate copies of the virus, which infect more cells.
Based on the low variability exhibited among known SARS‑CoV‑2 genomic sequences, health authorities likely detected the virus within weeks of its emergence among the human population in late 2019. The earliest case of infection currently known is dated to 1 December 2019, although an earlier case could have occurred on 17 November 2019. The pandemic onset was estimated by tMRCA analysis to have occurred before the end of December 2019, but this statistical inference do not provide definitive proof of time of origins. The virus subsequently spread to all provinces of China and to more than 150 other countries across the world. Human-to-human transmission of the virus has been confirmed in all 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.
Retrospective tests collected within the Chinese surveillance system revealed no clear indication of substantial unrecognized circulation of SARS‑CoV‑2 in Wuhan during the latter part of 2019.
A meta-analysis from November 2020 estimated the basic reproduction number () of the virus to be between 2.39 and 3.44. This means each infection from the virus is expected to result in 2.39 to 3.44 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. Many forms of preventive efforts may be employed in specific circumstances to reduce the propagation of the virus.
There have been about 96,000 confirmed cases of infection in mainland China. While the proportion of infections that result in confirmed cases or progress to diagnosable disease remains unclear, one mathematical model estimated that 75,815 people were infected on 25 January 2020 in Wuhan alone, at a time when the number of confirmed cases worldwide was only 2,015. Before 24 February 2020, over 95% of all deaths from COVID-19 worldwide had occurred in Hubei province, where Wuhan is located. As of 23 June 2021, the percentage had decreased to 0.083%.
As of 23 June 2021, there have been 179,171,152 total confirmed cases of SARS‑CoV‑2 infection in the ongoing pandemic. The total number of deaths attributed to the virus is 3,883,429.
^Surveillance case definitions for human infection with novel coronavirus (nCoV): interim guidance v1, January 2020 (Report). World Health Organization. January 2020. hdl:10665/330376. WHO/2019-nCoV/Surveillance/v2020.1.
^"Naming the coronavirus disease (COVID-2019) and the virus that causes it". World Health Organization. Archived from the original on 28 February 2020. Retrieved 14 December 2020. ICTV announced “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” as the name of the new virus on 11 February 2020. This name was chosen because the virus is genetically related to the coronavirus responsible for the SARS outbreak of 2003. While related, the two viruses are different.
^"Naming the coronavirus disease (COVID-2019) and the virus that causes it". World Health Organization. Archived from the original on 28 February 2020. Retrieved 14 December 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 is [sic] intended as replacements for the official name of the virus as agreed by the ICTV.
^Klompas M, Baker MA, Rhee C (August 2020). "Airborne Transmission of SARS-CoV-2: Theoretical Considerations and Available Evidence". JAMA. 324 (5): 441–442. doi:10.1001/jama.2020.12458. PMID32749495. S2CID220500293. Investigators have demonstrated that speaking and coughing produce a mixture of both droplets and aerosols in a range of sizes, that these secretions can travel together for up to 27 feet, that it is feasible for SARS-CoV-2 to remain suspended in the air and viable for hours, that SARS-CoV-2 RNA can be recovered from air samples in hospitals, and that poor ventilation prolongs the amount of time that aerosols remain airborne.
^Rettner R (21 January 2021). "Talking is worse than coughing for spreading COVID-19 indoors". livescience.com. Retrieved 23 January 2021. In one modeled scenario, the researchers found that after a short cough, the number of infectious particles in the air would quickly fall after 1 to 7 minutes; in contrast, after speaking for 30 seconds, only after 30 minutes would the number of infectious particles fall to similar levels; and a high number of particles were still suspended after one hour. In other words, a dose of virus particles capable of causing an infection would linger in the air much longer after speech than a cough. (In this modeled scenario, the same number of droplets were admitted during a 0.5-second cough as during the course of 30 seconds of speech.)
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^Zhou H, Chen X, Hu T, Li J, Song H, Liu Y, et al. (June 2020). "A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein". Current Biology. 30 (11): 2196–2203.e3. doi:10.1016/j.cub.2020.05.023. PMID32416074.