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1.
Cells ; 11(5)2022 02 24.
Article in English | MEDLINE | ID: covidwho-1725524

ABSTRACT

Among the first clinical symptoms of the SARS-CoV-2 infection is olfactory-gustatory deficit; this continues for weeks and, in some cases, can be persistent. We prospectively evaluated 162 patients affected by COVID-19 using a visual analogue scale (VAS) for nasal and olfactory-gustatory symptoms. Patients were checked after 7, 14, 21, 28, 90, and 180 days. A total of 118 patients (72.8%) reported an olfactory VAS < 7 at baseline (group B), and 44 (27.2%) reported anosmia (VAS ≥ 7) (group A) and underwent the Brief Smell Identification Test (B-SIT) and Burghart Taste Strips (BTS) to quantify the deficit objectively and repeated the tests to confirm the sense recovery. Group A patients showed B-SIT anosmia and hyposmia in 44.2% and 55.8% of cases, respectively. A total of 88.6% of group A patients reported ageusia with VAS ≥ 7, and BTS confirmed 81.8% of ageusia and 18.2% of hypogeusia. VAS smell recovery was recorded starting from 14 days, with normalization at 28 days. The 28-day B-SIT score showed normosmia in 90.6% of group A patients. The mean time for full recovery (VAS = 0) was shorter in group B (22.9 days) than in group A (31.9 days). Chemosensory deficit is frequently the first symptom in patients with COVID-19, and, in most cases, recovery occurs after four weeks.


Subject(s)
Ageusia , COVID-19 , Olfaction Disorders , Anosmia/etiology , COVID-19/complications , Humans , Olfaction Disorders/diagnosis , SARS-CoV-2 , Smell , Taste
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324889

ABSTRACT

The article describes the rational for inhibition of the angiotensin-converting enzyme 2 (ACE2) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent the establishment of positive feedback loops triggered by COVID-19 in some predisposed subjects. Making use of a large quantity of published reports in which human/rodent ACE2 pathway inhibitors were administered in vivo, it is hypothesized a possible therapeutic pharmacological intervention through an inhibition strategy of the zinc metalloprotease ACE2 and its downstream pathway for SARS-CoV-2 patients. Of even more interest, metal (zinc) chelators and renin inhibitors (both FDA approved drugs) may also work alone or in combination in inhibiting the positive feedback loops, initially triggered by COVID-19 and subsequently sustained by hypoxia independently on viral trigger, when both arms of renin-angiotensin system (ACE2 and ACE) are upregulated, leading to critical, advanced and untreatable stages of the disease.

3.
Adv Biol Regul ; 81: 100820, 2021 08.
Article in English | MEDLINE | ID: covidwho-1351735

ABSTRACT

The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several "converging" evidence in support of this hypothesis. SARS-CoV-2 has been shown to initially upregulate ACE2 systemic activity (early phase), which can subsequently induce compensatory responses leading to upregulation of both arms of the RAS (late phase) and consequently to critical, advanced and untreatable stages of COVID-19 disease. The main and initial actors of the process are ACE2 and ADAM17 zinc-metalloproteases, which, initially triggered by SARS-CoV-2 spike proteins, work together in increasing circulating Ang 1-7 and Ang 1-9 peptides and downstream (Mas and Angiotensin type 2 receptors) pathways with anti-inflammatory, hypotensive and antithrombotic activities. During the late phase of severe COVID-19, compensatory secretion of renin and ACE enzymes are subsequently upregulated, leading to inflammation, hypertension and thrombosis, which further sustain ACE2 and ADAM17 upregulation. Based on this hypothesis, COVID-19-phase-specific inhibition of different RAS enzymes is proposed as a pharmacological strategy against COVID-19 and vaccine-induced adverse effects. The aim is to prevent the establishment of positive feedback-loops, which can sustain hyperactivity of both arms of the RAS independently of viral trigger and, in some cases, may lead to Long-COVID syndrome.


Subject(s)
ADAM17 Protein/biosynthesis , Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/metabolism , Renin-Angiotensin System , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , ADAM17 Protein/antagonists & inhibitors , Angiotensin I/metabolism , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , COVID-19/drug therapy , Gene Expression Regulation, Enzymologic , Humans , Peptide Fragments/metabolism , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Up-Regulation
4.
Br J Pharmacol ; 179(2): 218-226, 2022 01.
Article in English | MEDLINE | ID: covidwho-1334436

ABSTRACT

The present work provides arguments for the involvement of anti-vector immunity and of SARS-CoV-2 variants on the efficacy of ChAdOx1 nCoV-19 vaccine. First, it is suggested that anti-vector immunity takes place as homologous vaccination with ChAdOx1 nCoV-19 vaccine is applied and interferes with vaccine efficacy when the interval between prime and booster doses is less than 3 months. Second, longitudinal studies suggest that ChAdOx1 nCoV-19 vaccine provides suboptimal efficacy against SARS-CoV-2 Alpha variant, which appears to have an increased transmissibility among vaccinated people. At the moment, ChAdOx1 nCoV-19 vaccine is able to reduce the severity of symptoms and transmissibility. However, if the vaccinated individuals do not maintain physical preventive measures, they could turn into potential spreaders, thus suggesting that mass vaccination will not quickly solve the pandemic. Possible consequences of SARS-CoV-2 evolution and of repeated anti-SARS-CoV-2 vaccinations are discussed and adoption of an influenza-like vaccination strategy is suggested.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Vaccines , Humans
5.
Cells ; 10(7)2021 07 11.
Article in English | MEDLINE | ID: covidwho-1308299

ABSTRACT

Since the end of 2019, the medical-scientific community has been facing a terrible pandemic caused by a new airborne viral agent known as SARS-CoV2. Already in the early stages of the pandemic, following the discovery that the virus uses the ACE2 cell receptor as a molecular target to infect the cells of our body, it was hypothesized that the renin-angiotensin-aldosterone system was involved in the pathogenesis of the disease. Since then, numerous studies have been published on the subject, but the exact role of the renin-angiotensin-aldosterone system in the pathogenesis of COVID-19 is still a matter of debate. RAAS represents an important protagonist in the pathogenesis of COVID-19, providing the virus with the receptor of entry into host cells and determining its organotropism. Furthermore, following infection, the virus is able to cause an increase in plasma ACE2 activity, compromising the normal function of the RAAS. This dysfunction could contribute to the establishment of the thrombo-inflammatory state characteristic of severe forms of COVID-19. Drugs targeting RAAS represent promising therapeutic options for COVID-19 sufferers.


Subject(s)
COVID-19/metabolism , Renin-Angiotensin System , SARS-CoV-2/physiology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/drug therapy , COVID-19/pathology , Drug Discovery , Humans , Molecular Targeted Therapy , Renin-Angiotensin System/drug effects , SARS-CoV-2/drug effects
6.
Cells ; 10(3)2021 02 27.
Article in English | MEDLINE | ID: covidwho-1122409

ABSTRACT

The article describes the rationale for the administration of zinc-chelating agents in COVID-19 patients. In a previous work I have highlighted that the binding of the SARS-CoV spike proteins to the zinc-metalloprotease ACE2 has been shown to induce ACE2 shedding by activating the zinc-metalloprotease ADAM17, which ultimately leads to systemic upregulation of ACE2 activity. Moreover, based on experimental models, it was also shown the detrimental effect of the excessive systemic activity of ACE2 through its downstream pathways, which leads to "clinical" manifestations resembling COVID-19. In this regard, strong upregulation of circulating ACE2 activity was recently reported in COVID-19 patients, thus supporting the previous hypothesis that COVID-19 may derive from upregulation of ACE2 activity. Based on this, a reasonable hypothesis of using inhibitors that curb the upregulation of both ACE2 and ADAM17 zinc-metalloprotease activities and consequent positive feedback-loops (initially triggered by SARS-CoV-2 and subsequently sustained independently on viral trigger) is proposed as therapy for COVID-19. In particular, zinc-chelating agents such as citrate and ethylenediaminetetraacetic acid (EDTA) alone or in combination are expected to act in protecting from COVID-19 at different levels thanks to their both anticoagulant properties and inhibitory activity on zinc-metalloproteases. Several arguments are presented in support of this hypothesis and based on the current knowledge of both beneficial/harmful effects and cost/effectiveness, the use of chelating agents in the prevention and therapy of COVID-19 is proposed. In this regard, clinical trials (currently absent) employing citrate/EDTA in COVID-19 are urgently needed in order to shed more light on the efficacy of zinc chelators against SARS-CoV-2 infection in vivo.


Subject(s)
COVID-19/drug therapy , Chelating Agents/pharmacology , Citric Acid/pharmacology , Edetic Acid/pharmacology , Renin-Angiotensin System/drug effects , Zinc/metabolism , ADAM17 Protein/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Anticoagulants/pharmacology , COVID-19/metabolism , COVID-19/therapy , Drug Discovery , Humans , Immunization, Passive/adverse effects , SARS-CoV-2/drug effects , Up-Regulation/drug effects
7.
Cells ; 9(7):1704, 2020.
Article | WHO COVID | ID: covidwho-654981

ABSTRACT

The article describes the rationale for inhibition of the renin-angiotensin system (RAS) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent positive feedback-loop mechanisms. Based purely on experimental studies in which RAS pathway inhibitors were administered in vivo to humans/rodents, a reasonable hypothesis of using inhibitors that block both ACE and ACE2 zinc metalloproteases and their downstream pathways in COVID-19 patients will be proposed. In particular, metal (zinc) chelators and renin inhibitors may work alone or in combination to inhibit the positive feedback loops (initially triggered by SARS-CoV-2 and subsequently sustained by hypoxia independently on viral trigger) as both arms of renin-angiotensin system are upregulated, leading to critical, advanced and untreatable stages of the disease.

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