PMC:7408073 / 75555-82304 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T372 0-192 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 193-454 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 455-684 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 685-943 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 944-1173 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 1174-1415 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 1416-1651 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 1652-1855 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 1856-2152 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 2153-2371 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 2372-2681 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 2682-2928 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 2929-3154 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 3155-3531 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 3532-3708 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 3709-3953 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 3954-4106 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 4107-4273 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 4274-4500 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 4501-4757 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 4758-4998 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 4999-5239 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 5240-5421 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 5422-5535 Sentence denotes Seasonal differences of the RAS activities leading, for example, to differences in blood pressure are well known.
T396 5536-5658 Sentence denotes Of interest, the majority of coronaviruses cause cold-like illnesses and have a relatively low mutational frequency [168].
T397 5659-5732 Sentence denotes Similarly SARS-CoV-2 seems to mutate much slower than seasonal flu [169].
T398 5733-5967 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 5968-6060 Sentence denotes For example, they might favour a relatively short-term activation/memory of immune response.
T400 6061-6197 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 6198-6378 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 6379-6749 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.