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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T17","span":{"begin":204,"end":209},"obj":"Body_part"},{"id":"T18","span":{"begin":1179,"end":1193},"obj":"Body_part"},{"id":"T19","span":{"begin":1235,"end":1239},"obj":"Body_part"},{"id":"T20","span":{"begin":6337,"end":6341},"obj":"Body_part"},{"id":"T21","span":{"begin":6343,"end":6348},"obj":"Body_part"},{"id":"T22","span":{"begin":6350,"end":6355},"obj":"Body_part"},{"id":"T23","span":{"begin":6371,"end":6374},"obj":"Body_part"},{"id":"T24","span":{"begin":6418,"end":6424},"obj":"Body_part"}],"attributes":[{"id":"A17","pred":"uberon_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/UBERON_0000062"},{"id":"A18","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0002405"},{"id":"A19","pred":"uberon_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A20","pred":"uberon_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/UBERON_0001913"},{"id":"A21","pred":"uberon_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/UBERON_0001088"},{"id":"A22","pred":"uberon_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/UBERON_0001988"},{"id":"A23","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0000970"},{"id":"A24","pred":"uberon_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/UBERON_0000062"}],"text":"Coronaviruses in Humans—SARS, MERS, and COVID-19\nCoronavirus infection in humans is commonly associated with mild to severe respiratory diseases, with high fever, severe inflammation, cough, and internal organ dysfunction that can even lead to death (92). Most of the identified coronaviruses cause the common cold in humans. However, this changed when SARS-CoV was identified, paving the way for severe forms of the disease in humans (22). Our previous experience with the outbreaks of other coronaviruses, like SARS and MERS, suggests that the mode of transmission in COVID-19 as mainly human-to-human transmission via direct contact, droplets, and fomites (25). Recent studies have demonstrated that the virus could remain viable for hours in aerosols and up to days on surfaces; thus, aerosol and fomite contamination could play potent roles in the transmission of SARS-CoV-2 (257).\nThe immune response against coronavirus is vital to control and get rid of the infection. However, maladjusted immune responses may contribute to the immunopathology of the disease, resulting in impairment of pulmonary gas exchange. Understanding the interaction between CoVs and host innate immune systems could enlighten our understanding of the lung inflammation associated with this infection (24).\nSARS is a viral respiratory disease caused by a formerly unrecognized animal CoV that originated from the wet markets in southern China after adapting to the human host, thereby enabling transmission between humans (90). The SARS outbreak reported in 2002 to 2003 had 8,098 confirmed cases with 774 total deaths (9.6%) (93). The outbreak severely affected the Asia Pacific region, especially mainland China (94). Even though the case fatality rate (CFR) of SARS-CoV-2 (COVID-19) is lower than that of SARS-CoV, there exists a severe concern linked to this outbreak due to its epidemiological similarity to influenza viruses (95, 279). This can fail the public health system, resulting in a pandemic (96).\nMERS is another respiratory disease that was first reported in Saudi Arabia during the year 2012. The disease was found to have a CFR of around 35% (97). The analysis of available data sets suggests that the incubation period of SARS-CoV-2, SARS-CoV, and MERS-CoV is in almost the same range. The longest predicted incubation time of SARS-CoV-2 is 14 days. Hence, suspected individuals are isolated for 14 days to avoid the risk of further spread (98). Even though a high similarity has been reported between the genome sequence of the new coronavirus (SARS-CoV-2) and SARS-like CoVs, the comparative analysis recognized a furin-like cleavage site in the SARS-CoV-2 S protein that is missing from other SARS-like CoVs (99). The furin-like cleavage site is expected to play a role in the life cycle of the virus and disease pathogenicity and might even act as a therapeutic target for furin inhibitors. The highly contagious nature of SARS-CoV-2 compared to that of its predecessors might be the result of a stabilizing mutation that occurred in the endosome-associated-protein-like domain of nsp2 protein.\nSimilarly, the destabilizing mutation near the phosphatase domain of nsp3 proteins in SARS-CoV-2 could indicate a potential mechanism that differentiates it from other CoVs (100). Even though the CFR reported for COVID-19 is meager compared to those of the previous SARS and MERS outbreaks, it has caused more deaths than SARS and MERS combined (101). Possibly related to the viral pathogenesis is the recent finding of an 832-nucleotide (nt) deletion in ORF8, which appears to reduce the replicative fitness of the virus and leads to attenuated phenotypes of SARS-CoV-2 (256).\nCoronavirus is the most prominent example of a virus that has crossed the species barrier twice from wild animals to humans during SARS and MERS outbreaks (79, 102). The possibility of crossing the species barrier for the third time has also been suspected in the case of SARS-CoV-2 (COVID-19). Bats are recognized as a possible natural reservoir host of both SARS-CoV and MERS-CoV infection. In contrast, the possible intermediary host is the palm civet for SARS-CoV and the dromedary camel for MERS-CoV infection (102). Bats are considered the ancestral hosts for both SARS and MERS (103). Bats are also considered the reservoir host of human coronaviruses like HCoV-229E and HCoV-NL63 (104). In the case of COVID-19, there are two possibilities for primary transmission: it can be transmitted either through intermediate hosts, similar to that of SARS and MERS, or directly from bats (103). The emergence paradigm put forward in the SARS outbreak suggests that SARS-CoV originated from bats (reservoir host) and later jumped to civets (intermediate host) and incorporated changes within the receptor-binding domain (RBD) to improve binding to civet ACE2. This civet-adapted virus, during their subsequent exposure to humans at live markets, promoted further adaptations that resulted in the epidemic strain (104). Transmission can also occur directly from the reservoir host to humans without RBD adaptations. The bat coronavirus that is currently in circulation maintains specific “poised” spike proteins that facilitate human infection without the requirement of any mutations or adaptations (105). Altogether, different species of bats carry a massive number of coronaviruses around the world (106).\nThe high plasticity in receptor usage, along with the feasibility of adaptive mutation and recombination, may result in frequent interspecies transmission of coronavirus from bats to animals and humans (106). The pathogenesis of most bat coronaviruses is unknown, as most of these viruses are not isolated and studied (4). Hedgehog coronavirus HKU31, a Betacoronavirus, has been identified from amur hedgehogs in China. Studies show that hedgehogs are the reservoir of Betacoronavirus, and there is evidence of recombination (107).\nThe current scientific evidence available on MERS infection suggests that the significant reservoir host, as well as the animal source of MERS infection in humans, is the dromedary camels (97). The infected dromedary camels may not show any visible signs of infection, making it challenging to identify animals actively excreting MERS-CoV that has the potential to infect humans. However, they may shed MERS-CoV through milk, urine, feces, and nasal and eye discharge and can also be found in the raw organs (108). In a study conducted to evaluate the susceptibility of animal species to MERS-CoV infection, llamas and pigs were found to be susceptible, indicating the possibility of MERS-CoV circulation in animal species other than dromedary camels (109).\nFollowing the outbreak of SARS in China, SARS-CoV-like viruses were isolated from Himalayan palm civets (Paguma larvata) and raccoon dogs (Nyctereutes procyonoides) found in a live-animal market in Guangdong, China. The animal isolates obtained from the live-animal market retained a 29-nucleotide sequence that was not present in most of the human isolates (78). These findings were critical in identifying the possibility of interspecies transmission in SARS-CoV. The higher diversity and prevalence of bat coronaviruses in this region compared to those in previous reports indicate a host/pathogen coevolution. SARS-like coronaviruses also have been found circulating in the Chinese horseshoe bat (Rhinolophus sinicus) populations. The in vitro and in vivo studies carried out on the isolated virus confirmed that there is a potential risk for the reemergence of SARS-CoV infection from the viruses that are currently circulating in the bat population (105)."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T135","span":{"begin":2663,"end":2670},"obj":"Chemical"},{"id":"T136","span":{"begin":2885,"end":2895},"obj":"Chemical"},{"id":"T137","span":{"begin":3064,"end":3071},"obj":"Chemical"},{"id":"T138","span":{"begin":3092,"end":3099},"obj":"Chemical"},{"id":"T139","span":{"begin":3175,"end":3183},"obj":"Chemical"},{"id":"T140","span":{"begin":3528,"end":3538},"obj":"Chemical"},{"id":"T141","span":{"begin":3540,"end":3542},"obj":"Chemical"},{"id":"T142","span":{"begin":5179,"end":5187},"obj":"Chemical"},{"id":"T143","span":{"begin":6962,"end":6972},"obj":"Chemical"}],"attributes":[{"id":"A135","pred":"chebi_id","subj":"T135","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A136","pred":"chebi_id","subj":"T136","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A137","pred":"chebi_id","subj":"T137","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A138","pred":"chebi_id","subj":"T138","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A139","pred":"chebi_id","subj":"T139","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A140","pred":"chebi_id","subj":"T140","obj":"http://purl.obolibrary.org/obo/CHEBI_36976"},{"id":"A141","pred":"chebi_id","subj":"T141","obj":"http://purl.obolibrary.org/obo/CHEBI_36976"},{"id":"A142","pred":"chebi_id","subj":"T142","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A143","pred":"chebi_id","subj":"T143","obj":"http://purl.obolibrary.org/obo/CHEBI_36976"}],"text":"Coronaviruses in Humans—SARS, MERS, and COVID-19\nCoronavirus infection in humans is commonly associated with mild to severe respiratory diseases, with high fever, severe inflammation, cough, and internal organ dysfunction that can even lead to death (92). Most of the identified coronaviruses cause the common cold in humans. However, this changed when SARS-CoV was identified, paving the way for severe forms of the disease in humans (22). Our previous experience with the outbreaks of other coronaviruses, like SARS and MERS, suggests that the mode of transmission in COVID-19 as mainly human-to-human transmission via direct contact, droplets, and fomites (25). Recent studies have demonstrated that the virus could remain viable for hours in aerosols and up to days on surfaces; thus, aerosol and fomite contamination could play potent roles in the transmission of SARS-CoV-2 (257).\nThe immune response against coronavirus is vital to control and get rid of the infection. However, maladjusted immune responses may contribute to the immunopathology of the disease, resulting in impairment of pulmonary gas exchange. Understanding the interaction between CoVs and host innate immune systems could enlighten our understanding of the lung inflammation associated with this infection (24).\nSARS is a viral respiratory disease caused by a formerly unrecognized animal CoV that originated from the wet markets in southern China after adapting to the human host, thereby enabling transmission between humans (90). The SARS outbreak reported in 2002 to 2003 had 8,098 confirmed cases with 774 total deaths (9.6%) (93). The outbreak severely affected the Asia Pacific region, especially mainland China (94). Even though the case fatality rate (CFR) of SARS-CoV-2 (COVID-19) is lower than that of SARS-CoV, there exists a severe concern linked to this outbreak due to its epidemiological similarity to influenza viruses (95, 279). This can fail the public health system, resulting in a pandemic (96).\nMERS is another respiratory disease that was first reported in Saudi Arabia during the year 2012. The disease was found to have a CFR of around 35% (97). The analysis of available data sets suggests that the incubation period of SARS-CoV-2, SARS-CoV, and MERS-CoV is in almost the same range. The longest predicted incubation time of SARS-CoV-2 is 14 days. Hence, suspected individuals are isolated for 14 days to avoid the risk of further spread (98). Even though a high similarity has been reported between the genome sequence of the new coronavirus (SARS-CoV-2) and SARS-like CoVs, the comparative analysis recognized a furin-like cleavage site in the SARS-CoV-2 S protein that is missing from other SARS-like CoVs (99). The furin-like cleavage site is expected to play a role in the life cycle of the virus and disease pathogenicity and might even act as a therapeutic target for furin inhibitors. The highly contagious nature of SARS-CoV-2 compared to that of its predecessors might be the result of a stabilizing mutation that occurred in the endosome-associated-protein-like domain of nsp2 protein.\nSimilarly, the destabilizing mutation near the phosphatase domain of nsp3 proteins in SARS-CoV-2 could indicate a potential mechanism that differentiates it from other CoVs (100). Even though the CFR reported for COVID-19 is meager compared to those of the previous SARS and MERS outbreaks, it has caused more deaths than SARS and MERS combined (101). Possibly related to the viral pathogenesis is the recent finding of an 832-nucleotide (nt) deletion in ORF8, which appears to reduce the replicative fitness of the virus and leads to attenuated phenotypes of SARS-CoV-2 (256).\nCoronavirus is the most prominent example of a virus that has crossed the species barrier twice from wild animals to humans during SARS and MERS outbreaks (79, 102). The possibility of crossing the species barrier for the third time has also been suspected in the case of SARS-CoV-2 (COVID-19). Bats are recognized as a possible natural reservoir host of both SARS-CoV and MERS-CoV infection. In contrast, the possible intermediary host is the palm civet for SARS-CoV and the dromedary camel for MERS-CoV infection (102). Bats are considered the ancestral hosts for both SARS and MERS (103). Bats are also considered the reservoir host of human coronaviruses like HCoV-229E and HCoV-NL63 (104). In the case of COVID-19, there are two possibilities for primary transmission: it can be transmitted either through intermediate hosts, similar to that of SARS and MERS, or directly from bats (103). The emergence paradigm put forward in the SARS outbreak suggests that SARS-CoV originated from bats (reservoir host) and later jumped to civets (intermediate host) and incorporated changes within the receptor-binding domain (RBD) to improve binding to civet ACE2. This civet-adapted virus, during their subsequent exposure to humans at live markets, promoted further adaptations that resulted in the epidemic strain (104). Transmission can also occur directly from the reservoir host to humans without RBD adaptations. The bat coronavirus that is currently in circulation maintains specific “poised” spike proteins that facilitate human infection without the requirement of any mutations or adaptations (105). Altogether, different species of bats carry a massive number of coronaviruses around the world (106).\nThe high plasticity in receptor usage, along with the feasibility of adaptive mutation and recombination, may result in frequent interspecies transmission of coronavirus from bats to animals and humans (106). The pathogenesis of most bat coronaviruses is unknown, as most of these viruses are not isolated and studied (4). Hedgehog coronavirus HKU31, a Betacoronavirus, has been identified from amur hedgehogs in China. Studies show that hedgehogs are the reservoir of Betacoronavirus, and there is evidence of recombination (107).\nThe current scientific evidence available on MERS infection suggests that the significant reservoir host, as well as the animal source of MERS infection in humans, is the dromedary camels (97). The infected dromedary camels may not show any visible signs of infection, making it challenging to identify animals actively excreting MERS-CoV that has the potential to infect humans. However, they may shed MERS-CoV through milk, urine, feces, and nasal and eye discharge and can also be found in the raw organs (108). In a study conducted to evaluate the susceptibility of animal species to MERS-CoV infection, llamas and pigs were found to be susceptible, indicating the possibility of MERS-CoV circulation in animal species other than dromedary camels (109).\nFollowing the outbreak of SARS in China, SARS-CoV-like viruses were isolated from Himalayan palm civets (Paguma larvata) and raccoon dogs (Nyctereutes procyonoides) found in a live-animal market in Guangdong, China. The animal isolates obtained from the live-animal market retained a 29-nucleotide sequence that was not present in most of the human isolates (78). These findings were critical in identifying the possibility of interspecies transmission in SARS-CoV. The higher diversity and prevalence of bat coronaviruses in this region compared to those in previous reports indicate a host/pathogen coevolution. SARS-like coronaviruses also have been found circulating in the Chinese horseshoe bat (Rhinolophus sinicus) populations. The in vitro and in vivo studies carried out on the isolated virus confirmed that there is a potential risk for the reemergence of SARS-CoV infection from the viruses that are currently circulating in the bat population (105)."}

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T31876","span":{"begin":170,"end":182},"obj":"http://purl.obolibrary.org/obo/GO_0006954"},{"id":"T89089","span":{"begin":891,"end":906},"obj":"http://purl.obolibrary.org/obo/GO_0006955"},{"id":"T14843","span":{"begin":998,"end":1014},"obj":"http://purl.obolibrary.org/obo/GO_0006955"},{"id":"T4655","span":{"begin":1110,"end":1118},"obj":"http://purl.obolibrary.org/obo/GO_0015297"},{"id":"T3696","span":{"begin":1172,"end":1185},"obj":"http://purl.obolibrary.org/obo/GO_0045087"},{"id":"T35146","span":{"begin":1240,"end":1252},"obj":"http://purl.obolibrary.org/obo/GO_0006954"},{"id":"T86468","span":{"begin":3148,"end":3159},"obj":"http://purl.obolibrary.org/obo/GO_0016791"},{"id":"T29542","span":{"begin":3483,"end":3495},"obj":"http://purl.obolibrary.org/obo/GO_0009405"},{"id":"T18275","span":{"begin":5598,"end":5610},"obj":"http://purl.obolibrary.org/obo/GO_0009405"}],"text":"Coronaviruses in Humans—SARS, MERS, and COVID-19\nCoronavirus infection in humans is commonly associated with mild to severe respiratory diseases, with high fever, severe inflammation, cough, and internal organ dysfunction that can even lead to death (92). Most of the identified coronaviruses cause the common cold in humans. However, this changed when SARS-CoV was identified, paving the way for severe forms of the disease in humans (22). Our previous experience with the outbreaks of other coronaviruses, like SARS and MERS, suggests that the mode of transmission in COVID-19 as mainly human-to-human transmission via direct contact, droplets, and fomites (25). Recent studies have demonstrated that the virus could remain viable for hours in aerosols and up to days on surfaces; thus, aerosol and fomite contamination could play potent roles in the transmission of SARS-CoV-2 (257).\nThe immune response against coronavirus is vital to control and get rid of the infection. However, maladjusted immune responses may contribute to the immunopathology of the disease, resulting in impairment of pulmonary gas exchange. Understanding the interaction between CoVs and host innate immune systems could enlighten our understanding of the lung inflammation associated with this infection (24).\nSARS is a viral respiratory disease caused by a formerly unrecognized animal CoV that originated from the wet markets in southern China after adapting to the human host, thereby enabling transmission between humans (90). The SARS outbreak reported in 2002 to 2003 had 8,098 confirmed cases with 774 total deaths (9.6%) (93). The outbreak severely affected the Asia Pacific region, especially mainland China (94). Even though the case fatality rate (CFR) of SARS-CoV-2 (COVID-19) is lower than that of SARS-CoV, there exists a severe concern linked to this outbreak due to its epidemiological similarity to influenza viruses (95, 279). This can fail the public health system, resulting in a pandemic (96).\nMERS is another respiratory disease that was first reported in Saudi Arabia during the year 2012. The disease was found to have a CFR of around 35% (97). The analysis of available data sets suggests that the incubation period of SARS-CoV-2, SARS-CoV, and MERS-CoV is in almost the same range. The longest predicted incubation time of SARS-CoV-2 is 14 days. Hence, suspected individuals are isolated for 14 days to avoid the risk of further spread (98). Even though a high similarity has been reported between the genome sequence of the new coronavirus (SARS-CoV-2) and SARS-like CoVs, the comparative analysis recognized a furin-like cleavage site in the SARS-CoV-2 S protein that is missing from other SARS-like CoVs (99). The furin-like cleavage site is expected to play a role in the life cycle of the virus and disease pathogenicity and might even act as a therapeutic target for furin inhibitors. The highly contagious nature of SARS-CoV-2 compared to that of its predecessors might be the result of a stabilizing mutation that occurred in the endosome-associated-protein-like domain of nsp2 protein.\nSimilarly, the destabilizing mutation near the phosphatase domain of nsp3 proteins in SARS-CoV-2 could indicate a potential mechanism that differentiates it from other CoVs (100). Even though the CFR reported for COVID-19 is meager compared to those of the previous SARS and MERS outbreaks, it has caused more deaths than SARS and MERS combined (101). Possibly related to the viral pathogenesis is the recent finding of an 832-nucleotide (nt) deletion in ORF8, which appears to reduce the replicative fitness of the virus and leads to attenuated phenotypes of SARS-CoV-2 (256).\nCoronavirus is the most prominent example of a virus that has crossed the species barrier twice from wild animals to humans during SARS and MERS outbreaks (79, 102). The possibility of crossing the species barrier for the third time has also been suspected in the case of SARS-CoV-2 (COVID-19). Bats are recognized as a possible natural reservoir host of both SARS-CoV and MERS-CoV infection. In contrast, the possible intermediary host is the palm civet for SARS-CoV and the dromedary camel for MERS-CoV infection (102). Bats are considered the ancestral hosts for both SARS and MERS (103). Bats are also considered the reservoir host of human coronaviruses like HCoV-229E and HCoV-NL63 (104). In the case of COVID-19, there are two possibilities for primary transmission: it can be transmitted either through intermediate hosts, similar to that of SARS and MERS, or directly from bats (103). The emergence paradigm put forward in the SARS outbreak suggests that SARS-CoV originated from bats (reservoir host) and later jumped to civets (intermediate host) and incorporated changes within the receptor-binding domain (RBD) to improve binding to civet ACE2. This civet-adapted virus, during their subsequent exposure to humans at live markets, promoted further adaptations that resulted in the epidemic strain (104). Transmission can also occur directly from the reservoir host to humans without RBD adaptations. The bat coronavirus that is currently in circulation maintains specific “poised” spike proteins that facilitate human infection without the requirement of any mutations or adaptations (105). Altogether, different species of bats carry a massive number of coronaviruses around the world (106).\nThe high plasticity in receptor usage, along with the feasibility of adaptive mutation and recombination, may result in frequent interspecies transmission of coronavirus from bats to animals and humans (106). The pathogenesis of most bat coronaviruses is unknown, as most of these viruses are not isolated and studied (4). Hedgehog coronavirus HKU31, a Betacoronavirus, has been identified from amur hedgehogs in China. Studies show that hedgehogs are the reservoir of Betacoronavirus, and there is evidence of recombination (107).\nThe current scientific evidence available on MERS infection suggests that the significant reservoir host, as well as the animal source of MERS infection in humans, is the dromedary camels (97). The infected dromedary camels may not show any visible signs of infection, making it challenging to identify animals actively excreting MERS-CoV that has the potential to infect humans. However, they may shed MERS-CoV through milk, urine, feces, and nasal and eye discharge and can also be found in the raw organs (108). In a study conducted to evaluate the susceptibility of animal species to MERS-CoV infection, llamas and pigs were found to be susceptible, indicating the possibility of MERS-CoV circulation in animal species other than dromedary camels (109).\nFollowing the outbreak of SARS in China, SARS-CoV-like viruses were isolated from Himalayan palm civets (Paguma larvata) and raccoon dogs (Nyctereutes procyonoides) found in a live-animal market in Guangdong, China. The animal isolates obtained from the live-animal market retained a 29-nucleotide sequence that was not present in most of the human isolates (78). These findings were critical in identifying the possibility of interspecies transmission in SARS-CoV. The higher diversity and prevalence of bat coronaviruses in this region compared to those in previous reports indicate a host/pathogen coevolution. SARS-like coronaviruses also have been found circulating in the Chinese horseshoe bat (Rhinolophus sinicus) populations. The in vitro and in vivo studies carried out on the isolated virus confirmed that there is a potential risk for the reemergence of SARS-CoV infection from the viruses that are currently circulating in the bat population (105)."}

LitCovid-sentences

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T17","span":{"begin":156,"end":161},"obj":"Phenotype"},{"id":"T18","span":{"begin":184,"end":189},"obj":"Phenotype"}],"attributes":[{"id":"A17","pred":"hp_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/HP_0001945"},{"id":"A18","pred":"hp_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/HP_0012735"}],"text":"Coronaviruses in Humans—SARS, MERS, and COVID-19\nCoronavirus infection in humans is commonly associated with mild to severe respiratory diseases, with high fever, severe inflammation, cough, and internal organ dysfunction that can even lead to death (92). Most of the identified coronaviruses cause the common cold in humans. However, this changed when SARS-CoV was identified, paving the way for severe forms of the disease in humans (22). Our previous experience with the outbreaks of other coronaviruses, like SARS and MERS, suggests that the mode of transmission in COVID-19 as mainly human-to-human transmission via direct contact, droplets, and fomites (25). Recent studies have demonstrated that the virus could remain viable for hours in aerosols and up to days on surfaces; thus, aerosol and fomite contamination could play potent roles in the transmission of SARS-CoV-2 (257).\nThe immune response against coronavirus is vital to control and get rid of the infection. However, maladjusted immune responses may contribute to the immunopathology of the disease, resulting in impairment of pulmonary gas exchange. Understanding the interaction between CoVs and host innate immune systems could enlighten our understanding of the lung inflammation associated with this infection (24).\nSARS is a viral respiratory disease caused by a formerly unrecognized animal CoV that originated from the wet markets in southern China after adapting to the human host, thereby enabling transmission between humans (90). The SARS outbreak reported in 2002 to 2003 had 8,098 confirmed cases with 774 total deaths (9.6%) (93). The outbreak severely affected the Asia Pacific region, especially mainland China (94). Even though the case fatality rate (CFR) of SARS-CoV-2 (COVID-19) is lower than that of SARS-CoV, there exists a severe concern linked to this outbreak due to its epidemiological similarity to influenza viruses (95, 279). This can fail the public health system, resulting in a pandemic (96).\nMERS is another respiratory disease that was first reported in Saudi Arabia during the year 2012. The disease was found to have a CFR of around 35% (97). The analysis of available data sets suggests that the incubation period of SARS-CoV-2, SARS-CoV, and MERS-CoV is in almost the same range. The longest predicted incubation time of SARS-CoV-2 is 14 days. Hence, suspected individuals are isolated for 14 days to avoid the risk of further spread (98). Even though a high similarity has been reported between the genome sequence of the new coronavirus (SARS-CoV-2) and SARS-like CoVs, the comparative analysis recognized a furin-like cleavage site in the SARS-CoV-2 S protein that is missing from other SARS-like CoVs (99). The furin-like cleavage site is expected to play a role in the life cycle of the virus and disease pathogenicity and might even act as a therapeutic target for furin inhibitors. The highly contagious nature of SARS-CoV-2 compared to that of its predecessors might be the result of a stabilizing mutation that occurred in the endosome-associated-protein-like domain of nsp2 protein.\nSimilarly, the destabilizing mutation near the phosphatase domain of nsp3 proteins in SARS-CoV-2 could indicate a potential mechanism that differentiates it from other CoVs (100). Even though the CFR reported for COVID-19 is meager compared to those of the previous SARS and MERS outbreaks, it has caused more deaths than SARS and MERS combined (101). Possibly related to the viral pathogenesis is the recent finding of an 832-nucleotide (nt) deletion in ORF8, which appears to reduce the replicative fitness of the virus and leads to attenuated phenotypes of SARS-CoV-2 (256).\nCoronavirus is the most prominent example of a virus that has crossed the species barrier twice from wild animals to humans during SARS and MERS outbreaks (79, 102). The possibility of crossing the species barrier for the third time has also been suspected in the case of SARS-CoV-2 (COVID-19). Bats are recognized as a possible natural reservoir host of both SARS-CoV and MERS-CoV infection. In contrast, the possible intermediary host is the palm civet for SARS-CoV and the dromedary camel for MERS-CoV infection (102). Bats are considered the ancestral hosts for both SARS and MERS (103). Bats are also considered the reservoir host of human coronaviruses like HCoV-229E and HCoV-NL63 (104). In the case of COVID-19, there are two possibilities for primary transmission: it can be transmitted either through intermediate hosts, similar to that of SARS and MERS, or directly from bats (103). The emergence paradigm put forward in the SARS outbreak suggests that SARS-CoV originated from bats (reservoir host) and later jumped to civets (intermediate host) and incorporated changes within the receptor-binding domain (RBD) to improve binding to civet ACE2. This civet-adapted virus, during their subsequent exposure to humans at live markets, promoted further adaptations that resulted in the epidemic strain (104). Transmission can also occur directly from the reservoir host to humans without RBD adaptations. The bat coronavirus that is currently in circulation maintains specific “poised” spike proteins that facilitate human infection without the requirement of any mutations or adaptations (105). Altogether, different species of bats carry a massive number of coronaviruses around the world (106).\nThe high plasticity in receptor usage, along with the feasibility of adaptive mutation and recombination, may result in frequent interspecies transmission of coronavirus from bats to animals and humans (106). The pathogenesis of most bat coronaviruses is unknown, as most of these viruses are not isolated and studied (4). Hedgehog coronavirus HKU31, a Betacoronavirus, has been identified from amur hedgehogs in China. Studies show that hedgehogs are the reservoir of Betacoronavirus, and there is evidence of recombination (107).\nThe current scientific evidence available on MERS infection suggests that the significant reservoir host, as well as the animal source of MERS infection in humans, is the dromedary camels (97). The infected dromedary camels may not show any visible signs of infection, making it challenging to identify animals actively excreting MERS-CoV that has the potential to infect humans. However, they may shed MERS-CoV through milk, urine, feces, and nasal and eye discharge and can also be found in the raw organs (108). In a study conducted to evaluate the susceptibility of animal species to MERS-CoV infection, llamas and pigs were found to be susceptible, indicating the possibility of MERS-CoV circulation in animal species other than dromedary camels (109).\nFollowing the outbreak of SARS in China, SARS-CoV-like viruses were isolated from Himalayan palm civets (Paguma larvata) and raccoon dogs (Nyctereutes procyonoides) found in a live-animal market in Guangdong, China. The animal isolates obtained from the live-animal market retained a 29-nucleotide sequence that was not present in most of the human isolates (78). These findings were critical in identifying the possibility of interspecies transmission in SARS-CoV. The higher diversity and prevalence of bat coronaviruses in this region compared to those in previous reports indicate a host/pathogen coevolution. SARS-like coronaviruses also have been found circulating in the Chinese horseshoe bat (Rhinolophus sinicus) populations. The in vitro and in vivo studies carried out on the isolated virus confirmed that there is a potential risk for the reemergence of SARS-CoV infection from the viruses that are currently circulating in the bat population (105)."}

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