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42-608: In February 2020, electron microscope images of SARS-CoV-2 were collected at RML. Rocky Mountain Laboratories began as the Montana Board of Entomology Laboratory. It was opened in 1928 by the Montana State Board of Entomology to study Rocky Mountain spotted fever and the ticks, Dermacentor andersoni , that carry it. Local opposition to the "tick lab" was strong, as residents worried ticks would escape

84-425: A public health emergency of international concern from January 30, 2020, to May 5, 2023. SARS‑CoV‑2 is a positive-sense single-stranded RNA virus that is contagious in humans. SARS‑CoV‑2 is a strain of the species Betacoronavirus pandemicum (SARSr-CoV), as is SARS-CoV-1 , the virus that caused the 2002–2004 SARS outbreak . There are animal-borne coronavirus strains more closely related to SARS-CoV-2,

126-474: 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

168-693: A membrane protein that regulates the renin–angiotensin system. 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 (WHO) 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,

210-413: A mink euthanasia campaign rendering it virtually extinct. Each SARS-CoV-2 virion is 60–140 nanometres (2.4 × 10 –5.5 × 10  in) in diameter; its mass within the global human populace has been estimated as being between 0.1 and 10 kilograms. Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S ( spike ), E ( envelope ), M ( membrane ), and N ( nucleocapsid ) proteins;

252-421: A range of animals—such as cats, ferrets, hamsters, non-human primates, minks, tree shrews, raccoon dogs, fruit bats, and rabbits—that are susceptible and permissive to SARS-CoV-2 infection. Some institutions have advised that those infected with SARS‑CoV‑2 restrict their contact with animals. On 1   February 2020, the World Health Organization (WHO) indicated that "transmission from asymptomatic cases

294-430: A single linear RNA segment. Coronaviruses infect humans, other mammals, including livestock and companion animals, and avian species. Human coronaviruses are capable of causing illnesses ranging from the common cold to more severe diseases such as Middle East respiratory syndrome (MERS, fatality rate ~34%). SARS-CoV-2 is the seventh known coronavirus to infect people, after 229E , NL63 , OC43 , HKU1 , MERS-CoV , and

336-412: A site. The furin cleavage site PRRAR↓ is highly similar to that of the feline coronavirus , an alphacoronavirus 1 strain. 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

378-459: Is a strain of coronavirus that causes COVID-19 , the respiratory illness responsible for the COVID-19 pandemic . The virus previously had the provisional name 2019 novel coronavirus ( 2019-nCoV ), and has also been called human coronavirus 2019 ( HCoV-19 or hCoV-19 ). First identified in the city of Wuhan , Hubei, China, the World Health Organization designated the outbreak

420-477: Is another possible cause of infection. Preliminary research indicates that the virus may remain viable on plastic ( polypropylene ) and stainless steel ( AISI 304 ) for up to three days, but it does not survive on cardboard for more than one day or on copper for more than four hours. The virus is inactivated by soap, which destabilizes its lipid bilayer . Viral RNA has also been found in stool samples and semen from infected individuals. The degree to which

462-425: 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. It

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504-453: 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

546-680: Is likely to have occurred in late 2019. Epidemiological studies estimate that in the period between December 2019 and September 2020 each infection resulted in an average of 2.4–3.4 new infections when no members of the community were immune and no preventive measures were taken. However, some subsequent variants have become more infectious. The virus is airborne and primarily spreads between people through close contact and via aerosols and respiratory droplets that are exhaled when talking, breathing, or otherwise exhaling, as well as those produced from coughs and sneezes. It enters human cells by binding to angiotensin-converting enzyme 2 (ACE2),

588-725: 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. Referring to COVID-19 as the "Wuhan virus" has been described as dangerous by WHO officials, and as xenophobic by many journalists and academics. Human-to-human transmission of SARS‑CoV‑2

630-496: The United States Public Health Service used the laboratory to manufacture Yellow fever vaccine . When the human serum–base vaccine caused an outbreak of Hepatitis B that infected more than 350,000 U.S. soldiers, two researchers at the laboratory, Dr. Mason Hargett and Harry Burruss , developed an aqueous-base vaccine that combined distilled water with virus grown in chicken eggs. By the end of

672-469: The index case ". The authors later published a correction that showed that shedding began earlier than first estimated, four to five days before symptoms appear. 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,

714-483: The nasal cavity is seemingly the dominant initial site of 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. Studies have identified

756-495: The N protein holds the RNA genome, and the S, E, and M proteins together create the viral envelope . Coronavirus S proteins are glycoproteins and also type I membrane proteins (membranes containing a single transmembrane domain oriented on the extracellular side). They 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 ,

798-401: The SARS‑CoV‑2 genome (matches above 90 percent may sound high, but in genomic terms it is a wide evolutionary gap ). In addition, despite similarities in a few critical amino acids, pangolin virus samples exhibit poor binding to the human ACE2 receptor. SARS‑CoV‑2 belongs to the broad family of viruses known as coronaviruses . It is a positive-sense single-stranded RNA (+ssRNA) virus, with

840-598: The amino acid sequence P RR A . This sequence is upstream of an arginine and serine which forms the S1/S2 cleavage site ( P RR A R ↓ S ) of the spike protein. Although such sites are a common naturally-occurring feature of other viruses within the Subfamily Orthocoronavirinae, it appears in few other viruses from the Beta-CoV genus, and it is unique among members of its subgenus for such

882-418: The differences between what was then called 2019-nCoV and the virus from the 2003 SARS outbreak were insufficient to make them separate viral species . Therefore, they identified 2019-nCoV as a virus of Severe acute respiratory syndrome–related coronavirus . 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

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924-645: 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 21 August 2021, 3,422 SARS‑CoV‑2 genomes, belonging to 19 strains, sampled on all continents except Antarctica were publicly available. On 11 February 2020, the International Committee on Taxonomy of Viruses announced that according to existing rules that compute hierarchical relationships among coronaviruses based on five conserved sequences of nucleic acids,

966-547: The first infection, but the mechanisms that could account for this are not known. No natural reservoir for SARS-CoV-2 has been identified. Prior to the emergence of SARS-CoV-2 as a pathogen infecting humans, there had been two previous zoonosis -based coronavirus epidemics, those caused by SARS-CoV-1 and MERS-CoV . 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

1008-499: The laboratory and cause an outbreak in the community. To allay their fears, the original laboratory building featured a small moat around its perimeter. In 1932, after spotted fever was diagnosed in other states, the federal government bought the facility and renamed it Rocky Mountain Laboratory. The laboratory expanded, adding faculty to study zoonotic diseases including typhus , tularemia , and Q-fever . During World War II ,

1050-496: The most closely known relative being the BANAL-52 bat coronavirus. SARS-CoV-2 is of zoonotic origin; its close genetic similarity to bat coronaviruses suggests it emerged from such a bat-borne virus . Research is ongoing as to whether SARS‑CoV‑2 came directly from bats or indirectly through any intermediate hosts. The virus shows little genetic diversity , indicating that the spillover event introducing SARS‑CoV‑2 to humans

1092-617: 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). Several notable variants of SARS-CoV-2 emerged in late 2020. The World Health Organization has currently declared five variants of concern , which are as follows: Other notable variants include 6 other WHO-designated variants under investigation and Cluster 5 , which emerged among mink in Denmark and resulted in

1134-627: The natural reservoir of the virus that caused the 2002–2004 SARS outbreak has resulted in the discovery of many SARS-like bat coronaviruses , most originating in horseshoe bats . The closest match by far, published in Nature (journal) in February 2022, were viruses BANAL-52 (96.8% resemblance to SARS‑CoV‑2), BANAL-103 and BANAL-236, collected in three different species of bats in Feuang , Laos. An earlier source published in February 2020 identified

1176-530: The original SARS-CoV . 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 undergo frequent recombination. The mechanism of recombination in unsegmented RNA viruses such as SARS-CoV-2 is generally by copy-choice replication, in which gene material switches from one RNA template molecule to another during replication. The SARS-CoV-2 RNA sequence

1218-1819: 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: ( Bat ) Rc-o319 , 81% to SARS-CoV-2, Rhinolophus cornutus , Iwate , Japan Bat SL-ZXC21 , 88% to SARS-CoV-2, Rhinolophus pusillus , Zhoushan , Zhejiang Bat SL-ZC45 , 88% to SARS-CoV-2, Rhinolophus pusillus , Zhoushan, Zhejiang Pangolin SARSr-CoV-GX, 85.3% to SARS-CoV-2, Manis javanica , smuggled from Southeast Asia Pangolin SARSr-CoV-GD, 90.1% to SARS-CoV-2, Manis javanica , smuggled from Southeast Asia Bat RshSTT182, 92.6% to SARS-CoV-2, Rhinolophus shameli , Steung Treng , Cambodia Bat RshSTT200, 92.6% to SARS-CoV-2, Rhinolophus shameli , Steung Treng, Cambodia (Bat) RacCS203 , 91.5% to SARS-CoV-2, Rhinolophus acuminatus , Chachoengsao , Thailand (Bat) RmYN02 , 93.3% to SARS-CoV-2, Rhinolophus malayanus , Mengla , Yunnan (Bat) RpYN06 , 94.4% to SARS-CoV-2, Rhinolophus pusillus , Xishuangbanna , Yunnan (Bat) RaTG13 , 96.1% to SARS-CoV-2, Rhinolophus affinis , Mojiang , Yunnan (Bat) BANAL-52 , 96.8% to SARS-CoV-2, Rhinolophus malayanus , Vientiane , Laos SARS-CoV-2 SARS-CoV-1 , 79% to SARS-CoV-2 There are many thousands of variants of SARS-CoV-2, which can be grouped into

1260-579: 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

1302-509: The source of a majority of infections. That may explain how out of 217 on board 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 began shedding virus two to three days before symptoms appear and that "a substantial proportion of transmission probably occurred before first symptoms in

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1344-558: The source. For a virus recently acquired through a cross-species transmission, rapid evolution is expected. The mutation rate estimated from early cases of SARS-CoV-2 was of 6.54 × 10 per site per year. Coronaviruses in general have high genetic plasticity , but SARS-CoV-2's viral evolution is slowed by the RNA proofreading capability of its replication machinery. For comparison, the viral mutation rate in vivo of SARS-CoV-2 has been found to be lower than that of influenza. Research into

1386-498: The virus RaTG13 , collected in bats in Mojiang , Yunnan, China to be the closest to SARS‑CoV‑2, with 96.1% resemblance. None of the above are its direct ancestor. Bats are considered the most likely natural reservoir of SARS‑CoV‑2. Differences between the bat coronavirus and SARS‑CoV‑2 suggest that humans may have been infected via an intermediate host; although the source of introduction into humans remains unknown. Although

1428-550: 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-convened report stated that human spillover via an intermediate animal host

1470-484: 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 in the first week of symptoms and declines thereafter. 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

1512-587: The virus may be airborne as well, with aerosols potentially being able to transmit the virus. During human-to-human transmission, between 200 and 800 infectious SARS‑CoV‑2 virions are thought to initiate a new infection. If confirmed, aerosol transmission has biosafety implications because a major concern associated with the risk of working with emerging viruses in the laboratory is the generation of aerosols from various laboratory activities which are not immediately recognizable and may affect other scientific personnel. Indirect contact via contaminated surfaces

1554-422: 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

1596-647: The war, the laboratory distributed more than 1 million doses of the improved yellow fever vaccine. In the post-war decades, the laboratory broadened its scope to study chlamydia trachomatis and transmissible spongiform encephalopathies including scrapie , mad cow disease , and chronic wasting disease . In 1982, Dr. Willy Burgdorfer discovered Borrelia burgdorferi , the tick-borne bacterium that causes Lyme disease . 46°14′15″N 114°09′35″W  /  46.23737°N 114.15985°W  / 46.23737; -114.15985 SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 ( SARS‑CoV‑2 )

1638-414: 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 one, indoors, with little air flow. Other studies have suggested that

1680-452: 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

1722-496: Was suggested that the acquisition of the furin-cleavage site in the SARS-CoV-2 S protein was essential for zoonotic transfer to humans. The furin protease recognizes the canonical peptide sequence R X[ 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

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1764-541: 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. An analysis in November 2021, however, said that the earliest-known case had been misidentified and that the preponderance of early cases linked to the Huanan Market argued for it being

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