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LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T424","span":{"begin":598,"end":604},"obj":"Body_part"},{"id":"T425","span":{"begin":1695,"end":1709},"obj":"Body_part"},{"id":"T426","span":{"begin":1744,"end":1750},"obj":"Body_part"},{"id":"T427","span":{"begin":2315,"end":2322},"obj":"Body_part"},{"id":"T428","span":{"begin":2343,"end":2359},"obj":"Body_part"},{"id":"T429","span":{"begin":2360,"end":2379},"obj":"Body_part"},{"id":"T430","span":{"begin":2374,"end":2379},"obj":"Body_part"},{"id":"T431","span":{"begin":4195,"end":4199},"obj":"Body_part"}],"attributes":[{"id":"A424","pred":"fma_id","subj":"T424","obj":"http://purl.org/sig/ont/fma/fma62970"},{"id":"A425","pred":"fma_id","subj":"T425","obj":"http://purl.org/sig/ont/fma/fma7101"},{"id":"A426","pred":"fma_id","subj":"T426","obj":"http://purl.org/sig/ont/fma/fma62970"},{"id":"A427","pred":"fma_id","subj":"T427","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A428","pred":"fma_id","subj":"T428","obj":"http://purl.org/sig/ont/fma/fma66326"},{"id":"A429","pred":"fma_id","subj":"T429","obj":"http://purl.org/sig/ont/fma/fma14072"},{"id":"A430","pred":"fma_id","subj":"T430","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A431","pred":"fma_id","subj":"T431","obj":"http://purl.org/sig/ont/fma/fma24728"}],"text":"Severe symptoms of COVID-19 have been described to correlate with pre-existing hypertension, diabetes, age and male gender [1,2,3,4,5,6,7,8,9]. It is not still clear whether it depends on constitutive hypertensive conditions and/or on anti-hypertensive treatments or on other age-related conditions, considering that the prevalence of hypertension in Chinese adults is ~ 23% and that only about 41% take prescribed antihypertensive medications, being calcium channel blockers the most commonly used (~ 50%) in China [11]. To this regard, there is an interesting report describing sACE2 activity in plasma samples of Spanish healthy subjects and patients, in which a total of 2572 subjects from a multicenter study (NEFRONA project, 2009–2011) was studied [96]. The report shows that male and advanced age were identified as independent predictors of enhanced sACE2 activity [96]. Furthermore, subjects with hypertension, diabetes, dyslipidemia, or plaques also had significantly increased circulating ACE2 activity when compared with those without these pathologies [96]. Notably, hypertensive (the most frequent comorbidity with COVID-19) and diabetic patients are often treated with ACE inhibitors (ACEIs) and/or with ARBs, suggesting a possible positive correlation [135,136,137,138]. Interestingly, circulating ACE2 activity is significantly increased in subjects on therapy with ARBs or taking oral antidiabetic agents as compared with non-treated patients, while treatment with ACEIs and cholecalciferol had no significant influence on circulating ACE2 activity [96]. In line with this observations, losartan (an ARB), but not lisinopril (an ACEI), was able to upregulate ACE2 activity in left ventricle of Lewis rats [75]. Nevertheless, plasma concentration of Ang (1–7) was significantly increased with both treatments when compared to vehicle-treated rats and it was significantly higher in ACEI-treated than ARB-treated rats [75], suggesting that ACE inhibition is able to induce an activation of the ACE2/Ang (1–7)/MasR pathway. Although more evidence is needed in humans, the above observations suggest that ARBs should be precautionarily avoided to reduce possible ACE2-mediated viral consequences. Indeed, under hypoxic conditions, either an ACEI or an ARB have been shown to upregulate membrane ACE2 protein expression on human pulmonary artery smooth muscle cells [58]. ACEI and ARB have been shown to work by reducing the concentration of Ang II and by inhibiting its AT1-mediated ACE2 downregulation, respectively [58]. ACEIs and ARBs might therefore play a role in the upregulation of membrane ACE2 expression under hypoxic conditions such as COVID-19, knowing that the increase of membrane bound ACE2 (before its shedding) will also increase the probability of viral entry. Of note, ACEI and ARB antihypertensive medications are more commonly used in Europe/USA than in China. Nevertheless, recent reports show that the use of ACEI/ARB medications in patients with COVID-19 is safe and ACEI/ARB exposure was not associated with a higher risk of having severe forms of COVID-19 [6,139,140,141,142,143]. Moreover, some reports show that ACEI/ARB treated patients may even be protected from COVID-19 and ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs [144,145,146,147,148]. Among these reports, one indicates that the risk of severe symptoms of COVID-19 was significantly decreased in patients who took ARB drugs (but not ACEIs) compared to patients who took no drugs [144]. Differently, another report suggests that the use of ACEIs (but not ARBs) reduced risk of death and/or critical disease [146], suggesting that some of these reports did not adjust for confounders and further analyses are need. Nevertheless, clinical trials of losartan as a treatment for COVID-19, are actually underway among patients who have not previously been treated with ARBs and/or ACEIs (NCT04312009 and NCT04311177). However, most of hypertensive/diabetic patients are ACEI- or ARB-“pretreated”, nevertheless they have an increased risk to develop SARS, therefore ACEIs and ARBs, if not detrimental, are not expected to face the disease in non-hypertensive patients. A possible beneficial effect of ACEIs in COVID-19 patients could indirectly come by reducing ACE2 substrate, Ang II, and finally limiting Ang (1–7) [but not Ang (1–9)] production and its (detrimental) effects; however, this is only a hypothetical possibility since, in this case, the ACE2/ACE pathway might be even more unbalanced."}

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T139","span":{"begin":2343,"end":2359},"obj":"Body_part"},{"id":"T140","span":{"begin":2353,"end":2359},"obj":"Body_part"},{"id":"T141","span":{"begin":4195,"end":4199},"obj":"Body_part"}],"attributes":[{"id":"A139","pred":"uberon_id","subj":"T139","obj":"http://purl.obolibrary.org/obo/UBERON_0002012"},{"id":"A140","pred":"uberon_id","subj":"T140","obj":"http://purl.obolibrary.org/obo/UBERON_0001637"},{"id":"A141","pred":"uberon_id","subj":"T141","obj":"http://purl.obolibrary.org/obo/UBERON_0001456"}],"text":"Severe symptoms of COVID-19 have been described to correlate with pre-existing hypertension, diabetes, age and male gender [1,2,3,4,5,6,7,8,9]. It is not still clear whether it depends on constitutive hypertensive conditions and/or on anti-hypertensive treatments or on other age-related conditions, considering that the prevalence of hypertension in Chinese adults is ~ 23% and that only about 41% take prescribed antihypertensive medications, being calcium channel blockers the most commonly used (~ 50%) in China [11]. To this regard, there is an interesting report describing sACE2 activity in plasma samples of Spanish healthy subjects and patients, in which a total of 2572 subjects from a multicenter study (NEFRONA project, 2009–2011) was studied [96]. The report shows that male and advanced age were identified as independent predictors of enhanced sACE2 activity [96]. Furthermore, subjects with hypertension, diabetes, dyslipidemia, or plaques also had significantly increased circulating ACE2 activity when compared with those without these pathologies [96]. Notably, hypertensive (the most frequent comorbidity with COVID-19) and diabetic patients are often treated with ACE inhibitors (ACEIs) and/or with ARBs, suggesting a possible positive correlation [135,136,137,138]. Interestingly, circulating ACE2 activity is significantly increased in subjects on therapy with ARBs or taking oral antidiabetic agents as compared with non-treated patients, while treatment with ACEIs and cholecalciferol had no significant influence on circulating ACE2 activity [96]. In line with this observations, losartan (an ARB), but not lisinopril (an ACEI), was able to upregulate ACE2 activity in left ventricle of Lewis rats [75]. Nevertheless, plasma concentration of Ang (1–7) was significantly increased with both treatments when compared to vehicle-treated rats and it was significantly higher in ACEI-treated than ARB-treated rats [75], suggesting that ACE inhibition is able to induce an activation of the ACE2/Ang (1–7)/MasR pathway. Although more evidence is needed in humans, the above observations suggest that ARBs should be precautionarily avoided to reduce possible ACE2-mediated viral consequences. Indeed, under hypoxic conditions, either an ACEI or an ARB have been shown to upregulate membrane ACE2 protein expression on human pulmonary artery smooth muscle cells [58]. ACEI and ARB have been shown to work by reducing the concentration of Ang II and by inhibiting its AT1-mediated ACE2 downregulation, respectively [58]. ACEIs and ARBs might therefore play a role in the upregulation of membrane ACE2 expression under hypoxic conditions such as COVID-19, knowing that the increase of membrane bound ACE2 (before its shedding) will also increase the probability of viral entry. Of note, ACEI and ARB antihypertensive medications are more commonly used in Europe/USA than in China. Nevertheless, recent reports show that the use of ACEI/ARB medications in patients with COVID-19 is safe and ACEI/ARB exposure was not associated with a higher risk of having severe forms of COVID-19 [6,139,140,141,142,143]. Moreover, some reports show that ACEI/ARB treated patients may even be protected from COVID-19 and ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs [144,145,146,147,148]. Among these reports, one indicates that the risk of severe symptoms of COVID-19 was significantly decreased in patients who took ARB drugs (but not ACEIs) compared to patients who took no drugs [144]. Differently, another report suggests that the use of ACEIs (but not ARBs) reduced risk of death and/or critical disease [146], suggesting that some of these reports did not adjust for confounders and further analyses are need. Nevertheless, clinical trials of losartan as a treatment for COVID-19, are actually underway among patients who have not previously been treated with ARBs and/or ACEIs (NCT04312009 and NCT04311177). However, most of hypertensive/diabetic patients are ACEI- or ARB-“pretreated”, nevertheless they have an increased risk to develop SARS, therefore ACEIs and ARBs, if not detrimental, are not expected to face the disease in non-hypertensive patients. A possible beneficial effect of ACEIs in COVID-19 patients could indirectly come by reducing ACE2 substrate, Ang II, and finally limiting Ang (1–7) [but not Ang (1–9)] production and its (detrimental) effects; however, this is only a hypothetical possibility since, in this case, the ACE2/ACE pathway might be even more unbalanced."}

LitCovid-PubTator

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T351","span":{"begin":0,"end":143},"obj":"Sentence"},{"id":"T352","span":{"begin":144,"end":521},"obj":"Sentence"},{"id":"T353","span":{"begin":522,"end":760},"obj":"Sentence"},{"id":"T354","span":{"begin":761,"end":879},"obj":"Sentence"},{"id":"T355","span":{"begin":880,"end":1071},"obj":"Sentence"},{"id":"T356","span":{"begin":1072,"end":1287},"obj":"Sentence"},{"id":"T357","span":{"begin":1288,"end":1573},"obj":"Sentence"},{"id":"T358","span":{"begin":1574,"end":1729},"obj":"Sentence"},{"id":"T359","span":{"begin":1730,"end":2039},"obj":"Sentence"},{"id":"T360","span":{"begin":2040,"end":2211},"obj":"Sentence"},{"id":"T361","span":{"begin":2212,"end":2385},"obj":"Sentence"},{"id":"T362","span":{"begin":2386,"end":2537},"obj":"Sentence"},{"id":"T363","span":{"begin":2538,"end":2793},"obj":"Sentence"},{"id":"T364","span":{"begin":2794,"end":2896},"obj":"Sentence"},{"id":"T365","span":{"begin":2897,"end":3121},"obj":"Sentence"},{"id":"T366","span":{"begin":3122,"end":3364},"obj":"Sentence"},{"id":"T367","span":{"begin":3365,"end":3565},"obj":"Sentence"},{"id":"T368","span":{"begin":3566,"end":3792},"obj":"Sentence"},{"id":"T369","span":{"begin":3793,"end":3991},"obj":"Sentence"},{"id":"T370","span":{"begin":3992,"end":4241},"obj":"Sentence"},{"id":"T371","span":{"begin":4242,"end":4573},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Severe symptoms of COVID-19 have been described to correlate with pre-existing hypertension, diabetes, age and male gender [1,2,3,4,5,6,7,8,9]. It is not still clear whether it depends on constitutive hypertensive conditions and/or on anti-hypertensive treatments or on other age-related conditions, considering that the prevalence of hypertension in Chinese adults is ~ 23% and that only about 41% take prescribed antihypertensive medications, being calcium channel blockers the most commonly used (~ 50%) in China [11]. To this regard, there is an interesting report describing sACE2 activity in plasma samples of Spanish healthy subjects and patients, in which a total of 2572 subjects from a multicenter study (NEFRONA project, 2009–2011) was studied [96]. The report shows that male and advanced age were identified as independent predictors of enhanced sACE2 activity [96]. Furthermore, subjects with hypertension, diabetes, dyslipidemia, or plaques also had significantly increased circulating ACE2 activity when compared with those without these pathologies [96]. Notably, hypertensive (the most frequent comorbidity with COVID-19) and diabetic patients are often treated with ACE inhibitors (ACEIs) and/or with ARBs, suggesting a possible positive correlation [135,136,137,138]. Interestingly, circulating ACE2 activity is significantly increased in subjects on therapy with ARBs or taking oral antidiabetic agents as compared with non-treated patients, while treatment with ACEIs and cholecalciferol had no significant influence on circulating ACE2 activity [96]. In line with this observations, losartan (an ARB), but not lisinopril (an ACEI), was able to upregulate ACE2 activity in left ventricle of Lewis rats [75]. Nevertheless, plasma concentration of Ang (1–7) was significantly increased with both treatments when compared to vehicle-treated rats and it was significantly higher in ACEI-treated than ARB-treated rats [75], suggesting that ACE inhibition is able to induce an activation of the ACE2/Ang (1–7)/MasR pathway. Although more evidence is needed in humans, the above observations suggest that ARBs should be precautionarily avoided to reduce possible ACE2-mediated viral consequences. Indeed, under hypoxic conditions, either an ACEI or an ARB have been shown to upregulate membrane ACE2 protein expression on human pulmonary artery smooth muscle cells [58]. ACEI and ARB have been shown to work by reducing the concentration of Ang II and by inhibiting its AT1-mediated ACE2 downregulation, respectively [58]. ACEIs and ARBs might therefore play a role in the upregulation of membrane ACE2 expression under hypoxic conditions such as COVID-19, knowing that the increase of membrane bound ACE2 (before its shedding) will also increase the probability of viral entry. Of note, ACEI and ARB antihypertensive medications are more commonly used in Europe/USA than in China. Nevertheless, recent reports show that the use of ACEI/ARB medications in patients with COVID-19 is safe and ACEI/ARB exposure was not associated with a higher risk of having severe forms of COVID-19 [6,139,140,141,142,143]. Moreover, some reports show that ACEI/ARB treated patients may even be protected from COVID-19 and ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs [144,145,146,147,148]. Among these reports, one indicates that the risk of severe symptoms of COVID-19 was significantly decreased in patients who took ARB drugs (but not ACEIs) compared to patients who took no drugs [144]. Differently, another report suggests that the use of ACEIs (but not ARBs) reduced risk of death and/or critical disease [146], suggesting that some of these reports did not adjust for confounders and further analyses are need. Nevertheless, clinical trials of losartan as a treatment for COVID-19, are actually underway among patients who have not previously been treated with ARBs and/or ACEIs (NCT04312009 and NCT04311177). However, most of hypertensive/diabetic patients are ACEI- or ARB-“pretreated”, nevertheless they have an increased risk to develop SARS, therefore ACEIs and ARBs, if not detrimental, are not expected to face the disease in non-hypertensive patients. A possible beneficial effect of ACEIs in COVID-19 patients could indirectly come by reducing ACE2 substrate, Ang II, and finally limiting Ang (1–7) [but not Ang (1–9)] production and its (detrimental) effects; however, this is only a hypothetical possibility since, in this case, the ACE2/ACE pathway might be even more unbalanced."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T109","span":{"begin":79,"end":91},"obj":"Phenotype"},{"id":"T110","span":{"begin":335,"end":347},"obj":"Phenotype"},{"id":"T111","span":{"begin":907,"end":919},"obj":"Phenotype"},{"id":"T112","span":{"begin":931,"end":943},"obj":"Phenotype"}],"attributes":[{"id":"A109","pred":"hp_id","subj":"T109","obj":"http://purl.obolibrary.org/obo/HP_0000822"},{"id":"A110","pred":"hp_id","subj":"T110","obj":"http://purl.obolibrary.org/obo/HP_0000822"},{"id":"A111","pred":"hp_id","subj":"T111","obj":"http://purl.obolibrary.org/obo/HP_0000822"},{"id":"A112","pred":"hp_id","subj":"T112","obj":"http://purl.obolibrary.org/obo/HP_0003119"}],"text":"Severe symptoms of COVID-19 have been described to correlate with pre-existing hypertension, diabetes, age and male gender [1,2,3,4,5,6,7,8,9]. It is not still clear whether it depends on constitutive hypertensive conditions and/or on anti-hypertensive treatments or on other age-related conditions, considering that the prevalence of hypertension in Chinese adults is ~ 23% and that only about 41% take prescribed antihypertensive medications, being calcium channel blockers the most commonly used (~ 50%) in China [11]. To this regard, there is an interesting report describing sACE2 activity in plasma samples of Spanish healthy subjects and patients, in which a total of 2572 subjects from a multicenter study (NEFRONA project, 2009–2011) was studied [96]. The report shows that male and advanced age were identified as independent predictors of enhanced sACE2 activity [96]. Furthermore, subjects with hypertension, diabetes, dyslipidemia, or plaques also had significantly increased circulating ACE2 activity when compared with those without these pathologies [96]. Notably, hypertensive (the most frequent comorbidity with COVID-19) and diabetic patients are often treated with ACE inhibitors (ACEIs) and/or with ARBs, suggesting a possible positive correlation [135,136,137,138]. Interestingly, circulating ACE2 activity is significantly increased in subjects on therapy with ARBs or taking oral antidiabetic agents as compared with non-treated patients, while treatment with ACEIs and cholecalciferol had no significant influence on circulating ACE2 activity [96]. In line with this observations, losartan (an ARB), but not lisinopril (an ACEI), was able to upregulate ACE2 activity in left ventricle of Lewis rats [75]. Nevertheless, plasma concentration of Ang (1–7) was significantly increased with both treatments when compared to vehicle-treated rats and it was significantly higher in ACEI-treated than ARB-treated rats [75], suggesting that ACE inhibition is able to induce an activation of the ACE2/Ang (1–7)/MasR pathway. Although more evidence is needed in humans, the above observations suggest that ARBs should be precautionarily avoided to reduce possible ACE2-mediated viral consequences. Indeed, under hypoxic conditions, either an ACEI or an ARB have been shown to upregulate membrane ACE2 protein expression on human pulmonary artery smooth muscle cells [58]. ACEI and ARB have been shown to work by reducing the concentration of Ang II and by inhibiting its AT1-mediated ACE2 downregulation, respectively [58]. ACEIs and ARBs might therefore play a role in the upregulation of membrane ACE2 expression under hypoxic conditions such as COVID-19, knowing that the increase of membrane bound ACE2 (before its shedding) will also increase the probability of viral entry. Of note, ACEI and ARB antihypertensive medications are more commonly used in Europe/USA than in China. Nevertheless, recent reports show that the use of ACEI/ARB medications in patients with COVID-19 is safe and ACEI/ARB exposure was not associated with a higher risk of having severe forms of COVID-19 [6,139,140,141,142,143]. Moreover, some reports show that ACEI/ARB treated patients may even be protected from COVID-19 and ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs [144,145,146,147,148]. Among these reports, one indicates that the risk of severe symptoms of COVID-19 was significantly decreased in patients who took ARB drugs (but not ACEIs) compared to patients who took no drugs [144]. Differently, another report suggests that the use of ACEIs (but not ARBs) reduced risk of death and/or critical disease [146], suggesting that some of these reports did not adjust for confounders and further analyses are need. Nevertheless, clinical trials of losartan as a treatment for COVID-19, are actually underway among patients who have not previously been treated with ARBs and/or ACEIs (NCT04312009 and NCT04311177). However, most of hypertensive/diabetic patients are ACEI- or ARB-“pretreated”, nevertheless they have an increased risk to develop SARS, therefore ACEIs and ARBs, if not detrimental, are not expected to face the disease in non-hypertensive patients. A possible beneficial effect of ACEIs in COVID-19 patients could indirectly come by reducing ACE2 substrate, Ang II, and finally limiting Ang (1–7) [but not Ang (1–9)] production and its (detrimental) effects; however, this is only a hypothetical possibility since, in this case, the ACE2/ACE pathway might be even more unbalanced."}

2_test

PMC:7408073 / 70981-75554 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7408073 / 70981-75554 JSON TXT