This article is about the virus that causes SARS. For the virus that causes COVID-19, seeSARS-CoV-2. For the species to which both viruses belong, seeSARS-related coronavirus.
Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), previously known assevere acute respiratory syndrome coronavirus (SARS-CoV),[2] is acoronavirus that causes severe acute respiratory syndrome (SARS), therespiratory illness responsible for the2002–2004 SARS outbreak.[3] It is anenveloped,positive-sense,single-strandedRNA virus that infects theepithelial cells within the lungs.[4] The virus enters the host cell by binding toangiotensin-converting enzyme 2.[5] It infectshumans,bats, andpalm civets.[6][7] The SARS-CoV-1 outbreak was largely brought under control by simple public health measures. Testing people with symptoms (fever and respiratory problems), isolating and quarantining suspected cases, and restricting travel all had an effect. SARS-CoV-1 was most transmissible when patients were sick, so its spread could be effectively suppressed by isolating patients with symptoms.[8]
A virus similar to SARS-CoV-1 was discovered in late 2019. This virus, namedsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the causativepathogen ofCOVID-19, the propagation of which started theCOVID-19 pandemic.[12] The extent to which thespike proteins responsible for viral entry and the genome of the two viruses differ indicate that the two do not share a very recent common ancestor.[13]
Severe acute respiratory syndrome (SARS) is the disease caused by SARS-CoV-1. It causes an often severe illness and is marked initially by systemic symptoms ofmuscle pain,headache, andfever, followed in 2–14 days by the onset of respiratory symptoms,[14] mainly cough,dyspnea, andpneumonia. Another common finding in SARS patients is a decrease in the number of lymphocytes circulating in the blood.[15]
In the SARS outbreak of 2003, about 9% of patients with confirmed SARS-CoV-1 infection died.[16] The mortality rate was much higher for those over 60 years old, with mortality rates approaching 50% for this subset of patients.[16]
This outbreak led to many research programs, such asPredict[17] and the Understanding the Risk of Bat Coronavirus Emergence grant,[18] which aimed to identify zoonotic risks prior to spillover in humans.
Transmission of SARS-CoV-1 from mammals as biological carriers to humans
In March 2003, WHO established a global network of leading laboratories to collaborate in the identification of the causative agent of SARS. Early on, labs in the network narrowed the search to members of theparamyxovirus and coronavirus families. Early findings shared by the labs pointed to coronaviruses with increasing consistency. On 21 March, scientists from theUniversity of Hong Kong announced the isolation of a new virus that was strongly suspected to be the causative agent of SARS.[19]
Epidemiological evidence suggested azoonotic origin of the virus: more than 33% of the first detected cases of SARS in Guangdong corresponded to animal or food handlers.[20] Seroprevalence studies reinforced this zoonotic link (a high proportion of asymptomatic animal handlers at markets in Guangdong Province had antibodies against SARS-CoV).[20]
On April 12, 2003, scientists working at the Michael Smith Genome Sciences Centre inVancouver finished mapping thegenetic sequence of a coronavirus believed to be linked to SARS. The team was led byMarco Marra andCaroline Astell and worked in collaboration with theBritish Columbia Centre for Disease Control and theNational Microbiology Laboratory inWinnipeg,Manitoba, using samples from infected patients inToronto.[21][22] The map is shared with scientists worldwide via the GSC website.Donald Low ofMount Sinai Hospital in Toronto described the discovery as having been made with "unprecedented speed".[23] The sequence of the SARS coronavirus has since been confirmed by other independent groups.
Molecular epidemiological research demonstrated the virus isolated in 2002–2003 in south China and the virus isolated in the same area in late 2003 and early 2004 are different, indicating separate species-crossing events.[24]The phylogeny of the outbreakstrains shows that the southwestern provinces including Yunnan, Guizhou and Guangxi compare to the human SARS-CoV-1 better than those of the other provinces, but the viruses' evolution is a product of the host interaction and particularity.[25]
In late May 2003, studies from samples of wild animals sold as food in the local market inGuangdong, China, found a strain of SARS coronavirus could be isolated frommasked palm civets (Paguma sp.), but the animals did not always show clinical signs. The preliminary conclusion was the SARS virus crossed thespecies barrier from palm civet to humans, and more than 10,000 masked palm civets were killed in Guangdong Province. The virus was also later found inraccoon dogs (Nyctereuteus sp.),[26]ferret badgers (Melogale spp.), and domestic cats. In 2004, scientists from theChinese Center for Disease Control and Prevention of theUniversity of Hong Kong and theGuangzhou Center for Disease Control and Prevention established a genetic link between the SARS coronavirus appearing in civets and humans, confirming claims that the virus might have transmitted from the animal species to humans.[27] Infected palm civets at the market were traced to farms where no infected animals were found. It is unknown whether the virus was originally introduced to the market by civets, humans, or another animal.[26]
In 2005, two studies identified a number of SARS-like coronaviruses in Chinesebats.[28][29] Although the bat SARS virus did not replicate in cell culture, in 2008, American researchers[30] altered the genetic structure of bat SARS virus with the humanreceptor binding domain both in the bat virus and in the mice which demonstrated howzoonosis might occur in evolution.[31]Phylogenetic analysis of these viruses indicated a high probability that SARS coronavirus originated in bats and spread to humans either directly or through animals held in Chinese markets. The bats did not show any visible signs of disease, but are the likely natural reservoirs of SARS-like coronaviruses.
Bats are likely to be the natural reservoir, that is, the host that harbored the pathogen but that does not show ill effects and serves as a source of infection. No direct progenitor of SARS-CoV was found in bat populations, but WIV16 was found in a cave inXiyang Yi Ethnic Township, Yunnan, China between 2013 and 2016, and has a 96% genetically similar virus strain.[32] The hypothesis that SARS-CoV-1 emerged through recombinations of bat SARSr-CoVs in the Yunnan cave of WIV16 or in other yet-to-be-identified bat caves is considered highly likely.[33]
A phylogenetic tree based on whole-genome sequences of SARS-CoV-1 and related coronaviruses is:
SARS-CoV-1 follows the replication strategy typical of thecoronavirus subfamily. The primary human receptor of the virus isangiotensin-converting enzyme 2 (ACE2) and hemaglutinin (HE),[43] first identified in 2003,[44][45] and the viral spike protein lacks a furin cleavage site.[46]
Human SARS-CoV-1 appears to have had a complex history ofrecombination between ancestralcoronaviruses that were hosted in several different animal groups.[47][48] In order for recombination to happen at least two SARS-CoV-1genomes must be present in the same host cell. Recombination may occur during genome replication when theRNA polymerase switches from one template to another (copy choice recombination).[48]
SARS-CoV-1 is one of seven known coronaviruses to infect humans. The other six are:[49]
^Fehr, Anthony R.; Perlman, Stanley (2015). "Coronaviruses: An Overview of Their Replication and Pathogenesis".Coronaviruses. Methods in Molecular Biology. Vol. 1282. Clifton, New Jersey, USA: Humana Press. pp. 1–23.doi:10.1007/978-1-4939-2438-7_1.ISBN978-1-4939-2437-0.ISSN1064-3745.PMC4369385.PMID25720466.SARS-CoV primarily infects epithelial cells within the lung. The virus is capable of entering macrophages and dendritic cells but only leads to an abortive infection [87,88].
^World Health Organization Regional Office for the Western Pacific (2006).SARS : how a global epidemic was stopped. [Geneva, Switzerland]: World Health Organization, Western Pacific Region.ISBN92-9061-213-4.OCLC69610735.
^National Academies of Sciences, Engineering, and Medicine; Division on Earth and Life Studies; Board On Life; Sciences; Board on Chemical Sciences and Technology; Committee on Strategies for Identifying and Addressing Potential Biodefense Vulnerabilities Posed by Synthetic Biology (2018).Biodefense in the Age of Synthetic Biology. pp. 44–45.doi:10.17226/24890.ISBN978-0-309-46518-2.PMID30629396.S2CID90767286.
^abXing‐Yi Ge; Ben Hu; Zheng‐Li Shi (2015). "BAT CORONAVIRUSES". In Lin-Fa Wang; Christopher Cowled (eds.).Bats and Viruses: A New Frontier of Emerging Infectious Diseases (First ed.). John Wiley & Sons. pp. 127–155.doi:10.1002/9781118818824.ch5.
^Stanhope, MJ; Brown, JR; Amrine-Madsen, H (Mar 2004). "Evidence from the evolutionary analysis of nucleotide sequences for a recombinant history of SARS-CoV".Infect Genet Evol.4 (1):15–9.PMID15019585.
^abZhang, XW; Yap, YL; Danchin, A (Jan 2005). "Testing the hypothesis of a recombinant origin of the SARS-associated coronavirus".Arch Virol.150 (1):1–20.PMID15480857.
^Leung, Daniel (2019-01-20)."Coronaviruses (including SARS)".Infectious Disease Advisor. Decision Support in Medicine, LLC. Archived fromthe original on 2021-04-16. Retrieved2020-08-01.
