LitCovid-sentences  

PMC:7408073 / 70864-82304 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T349 0-2 Sentence denotes 6.
T350 3-116 Sentence denotes Correlation of Pre-existing Circulating ACE2 Activity and Increased Potential to Develop Severe Forms of COVID-19
T351 117-260 Sentence denotes 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].
T352 261-638 Sentence denotes 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].
T353 639-877 Sentence denotes 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].
T354 878-996 Sentence denotes The report shows that male and advanced age were identified as independent predictors of enhanced sACE2 activity [96].
T355 997-1188 Sentence denotes Furthermore, subjects with hypertension, diabetes, dyslipidemia, or plaques also had significantly increased circulating ACE2 activity when compared with those without these pathologies [96].
T356 1189-1404 Sentence denotes 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].
T357 1405-1690 Sentence denotes 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].
T358 1691-1846 Sentence denotes 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].
T359 1847-2156 Sentence denotes 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.
T360 2157-2328 Sentence denotes Although more evidence is needed in humans, the above observations suggest that ARBs should be precautionarily avoided to reduce possible ACE2-mediated viral consequences.
T361 2329-2502 Sentence denotes 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].
T362 2503-2654 Sentence denotes 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].
T363 2655-2910 Sentence denotes 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.
T364 2911-3013 Sentence denotes Of note, ACEI and ARB antihypertensive medications are more commonly used in Europe/USA than in China.
T365 3014-3238 Sentence denotes 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].
T366 3239-3481 Sentence denotes 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].
T367 3482-3682 Sentence denotes 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].
T368 3683-3909 Sentence denotes 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.
T369 3910-4108 Sentence denotes 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).
T370 4109-4358 Sentence denotes 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.
T371 4359-4690 Sentence denotes 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.
T372 4691-4883 Sentence denotes To complete the picture, smokers and subjects on therapy with insulin tend to have an increased (although not significantly) circulating ACE2 activity when compared with control subjects [96].
T373 4884-5145 Sentence denotes On the other hand, increased ACE2 protein expression was reported in plasma and/or urine of physically active men after acute aerobic training or in renal cortices of spontaneous hypertensive, but not normotensive, rats after chronic aerobic training [149,150].
T374 5146-5375 Sentence denotes In addition, recent works reveal that asthma and other allergic diseases, which protect from developing COVID-19, were associated with significant reductions in levels of both zinc in plasma and ACE2 mRNA in airway cells [98,99].
T375 5376-5634 Sentence denotes On the other hand, as already mentioned, some patients with cardiovascular diseases (and inflammatory bowel disease) have an increased circulating ACE2 [22,49,151,152], which might explain the higher probability of elderly heart patients to develop COVID-19.
T376 5635-5864 Sentence denotes Interestingly, in a report on atrial fibrillation, increased plasma ACE2 activity was significantly associated not only with cardiac dysfunction, increasing age, male gender and hypertension, but also with vascular disease [152].
T377 5865-6106 Sentence denotes Altogether the data suggest a strong correlation between circulating ACE2 activity and the predisposition to develop the most severe symptoms of COVID-19, suggesting that circulating sACE2 might be a predictive biomarker of SARS development.
T378 6107-6342 Sentence denotes The surprising aspect is that circulating (differently from membrane bound) ACE2 is expected to protect from viral infection and clinical trials using recombinant ACE2 protein are being pursued (ClinicalTrials.gov number, NCT04287686).
T379 6343-6546 Sentence denotes However, even if it might not be detrimental, recombinant ACE2 is not expected to protect from COVID-19, as circulating ACE2 upregulation correlates with the most common comorbidities in severe COVID-19.
T380 6547-6843 Sentence denotes The correlation is extremely impressive and striking if we also consider the low prevalence of chronic renal disease in COVID-19 hospitalized patients (0–3%) [1,2,3,4,5,6,7,8,9] (prevalence of the disease in China ~11% [12]) which might be protected by a higher sACE2 and/or Zn2+ renal excretion.
T381 6844-7062 Sentence denotes Indeed, in chronic kidney disease patients without a history of cardiovascular disease, there was a significant decrease in circulating ACE2 activity and zinc levels when compared with healthy control subjects [96,97].
T382 7063-7372 Sentence denotes Since proteinuria was associated with lower blood levels of sACE2 protein [153] and chronic kidney disease patients had higher urinary zinc excretion than healthy controls [97], low sACE2 activity in chronic renal diseases and protection from SARS might derive from a higher sACE2 and/or Zn2+ renal excretion.
T383 7373-7619 Sentence denotes Indeed, sACE2 is detectable in urine of healthy subjects and urinary sACE2 protein levels are elevated in patients with chronic renal diseases and in hypertensive patients treated with the Ang II type 1 receptor blocker (ARB) olmesartan [41,154].
T384 7620-7845 Sentence denotes It can, therefore, be supposed that a basal hyperactivity of ACE2 and consequent ACE/ACE2 pathway disequilibrium in blood might predispose to the development of more severe COVID-19 symptoms that involve both arms of the RAS.
T385 7846-8222 Sentence denotes In this regard, different organism predisposition to infections including SARS-CoV-2 or to pathologies associated with an increased risk to develop severe forms of SARS-CoV-2 infection might depend not only on genetic ACE2 polymorphisms and organ-specific ACE2 gene/protein expression [138,155,156,157,158,159,160,161,162,163] but also on anatomical and environmental factors.
T386 8223-8399 Sentence denotes For example, ACE2 gene variants have been associated with risk for hypertension, dyslipidemia, type 2 diabetes and cardiovascular dysfunction [138,155,156,157,158,159,160,161].
T387 8400-8644 Sentence denotes Most of these variants are intronic and located in splice-site junctions or in enhancer regions while the others are placed in the 3’ UTR promoter region, suggesting their involvement in the structure/function and expression of ACE2 gene [138].
T388 8645-8797 Sentence denotes On the other hand, COVID-19 has similar risk factors of obstructive sleep apnea (OSA), suggesting a possible association between OSA and COVID-19 [164].
T389 8798-8964 Sentence denotes Indeed, high prevalence of pre-existing OSA in COVID-19 patients has been reported [165,166], indicating that OSA could be a risk factor for severe forms of Covid-19.
T390 8965-9191 Sentence denotes OSA is characterised by repetitive airway collapse with apnea/hypopnea and intermittent hypoxaemia during sleep and it is associated with hypertension, cardiovascular disease, diabetes, obesity and systemic inflammation [167].
T391 9192-9448 Sentence denotes Most of these diseases are known to predispose to increased levels of circulating ACE2 and, as already mentioned, hypoxia has been shown to upregulate both arms of the RAS; therefore, OSA might predispose to the deleterious effects of SARS-CoV-2 infection.
T392 9449-9689 Sentence denotes In OSA patients, upper airway collapsibility under passive conditions (critical closing pressure) is higher in males than in females due to anatomical factors, i.e., longer upper airways, as upper airway length correlates with OSA severity.
T393 9690-9930 Sentence denotes Indeed, upper airways in females are less collapsible and more stable during sleep than in males [167], suggesting that an anatomical factor might contribute to and result in different gender susceptibility to COVID-19 and disease severity.
T394 9931-10112 Sentence denotes Moreover, diet (e.g., zinc assumption), physical exercise and external temperature and UV radiation are all “environmental” aspects that can seasonally influence the RAS activities.
T395 10113-10226 Sentence denotes Seasonal differences of the RAS activities leading, for example, to differences in blood pressure are well known.
T396 10227-10349 Sentence denotes Of interest, the majority of coronaviruses cause cold-like illnesses and have a relatively low mutational frequency [168].
T397 10350-10423 Sentence denotes Similarly SARS-CoV-2 seems to mutate much slower than seasonal flu [169].
T398 10424-10658 Sentence denotes Nevertheless, like influenza virus, they are responsible for seasonal episodes of common cold in humans worldwide [168], suggesting that coronaviruses may possess an ability to evade immune control that is different from seasonal flu.
T399 10659-10751 Sentence denotes For example, they might favour a relatively short-term activation/memory of immune response.
T400 10752-10888 Sentence denotes Indeed, as for SARS-CoV and MERS-CoV, a short duration of immunity after SARS-CoV-2 infection has been recently suggested [170,171,172].
T401 10889-11069 Sentence denotes Seasonal cold is an annually recurring time period characterized by the prevalence of outbreaks of cold and the season occurs during the cold period of the year in each hemisphere.
T402 11070-11440 Sentence denotes Altogether these observations suggest that seasonal predisposition to some virus infections (including SARS-CoV-2) might not depend only on environmental features that directly inactivate the viruses “unprotected” outside the host (e.g., higher ultraviolet rays and temperatures), but also on seasonal indirect effects produced in the organisms by environmental changes.