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Crit Care ; 25(1): 299, 2021 08 19.
Article in English | MEDLINE | ID: covidwho-1367680


BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. METHODS: This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV - AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. RESULTS: Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV - AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25-0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV - AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18-0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99-4.68). CONCLUSIONS: In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.

Acute Kidney Injury/drug therapy , Citric Acid/pharmacology , Continuous Renal Replacement Therapy/instrumentation , Heparin/pharmacology , Micropore Filters/standards , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Adult , COVID-19/complications , COVID-19/epidemiology , Citric Acid/adverse effects , Citric Acid/therapeutic use , Cohort Studies , Continuous Renal Replacement Therapy/methods , Continuous Renal Replacement Therapy/statistics & numerical data , Female , Heparin/adverse effects , Heparin/therapeutic use , Humans , Kaplan-Meier Estimate , Male , Micropore Filters/statistics & numerical data , Middle Aged , Proportional Hazards Models , Retrospective Studies
Cells ; 10(3)2021 02 27.
Article in English | MEDLINE | ID: covidwho-1122409


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.

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
BMC Microbiol ; 20(1): 265, 2020 08 26.
Article in English | MEDLINE | ID: covidwho-730206


BACKGROUND: Acetic acid has been used to clean and disinfect surfaces in the household for many decades. The antimicrobial efficacy of cleaning procedures can be considered particularly important for young, old, pregnant, immunocompromised people, but may also concern other groups, particularly with regards to the COVID-19 pandemics. This study aimed to show that acetic acid exhibit an antibacterial and antifungal activity when used for cleaning purposes and is able to destroy certain viruses. Furthermore, a disinfecting effect of laundry in a simulated washing cycle has been investigated. RESULTS: At a concentration of 10% and in presence of 1.5% citric acid, acetic acid showed a reduction of > 5-log steps according to the specifications of DIN EN 1040 and DIN EN 1275 for the following microorganisms: P. aeruginosa, E. coli, S. aureus, L. monocytogenes, K. pneumoniae, E. hirae and A. brasiliensis. For MRSA a logarithmic reduction of 3.19 was obtained. Tests on surfaces according to DIN EN 13697 showed a complete reduction (> 5-log steps) for P. aeruginosa, E. coli, S. aureus, E. hirae, A. brasiliensis and C. albicans at an acetic acid concentration of already 5%. Virucidal efficacy tests according to DIN EN 14476 and DIN EN 16777 showed a reduction of ≥4-log-steps against the Modified Vaccinia virus Ankara (MVA) for acetic acid concentrations of 5% or higher. The results suggest that acetic acid does not have a disinfecting effect on microorganisms in a dosage that is commonly used for cleaning. However, this can be achieved by increasing the concentration of acetic acid used, especially when combined with citric acid. CONCLUSIONS: Our results show a disinfecting effect of acetic acid in a concentration of 10% and in presence of 1.5% citric acid against a variety of microorganisms. A virucidal effect against enveloped viruses could also be proven. Furthermore, the results showed a considerable antimicrobial effect of acetic acid when used in domestic laundry procedures.

Acetic Acid/pharmacology , Anti-Infective Agents/pharmacology , Betacoronavirus/drug effects , Citric Acid/pharmacology , Coronavirus Infections/prevention & control , Disinfectants/pharmacology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Bacteria/drug effects , COVID-19 , Disinfection/methods , Fungi/drug effects , Humans , Norovirus/drug effects , SARS-CoV-2