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1.
Med Sci Monit ; 27: e935379, 2021 Dec 30.
Article in English | MEDLINE | ID: covidwho-1593238

ABSTRACT

BACKGROUND This retrospective study aimed to investigate outcomes and hospitalization rates in patients with a confirmed diagnosis of early COVID-19 treated at home with prescribed and non-prescribed treatments. MATERIAL AND METHODS The medical records of a cohort of 158 Italian patients with early COVID-19 treated at home were analyzed. Treatments consisted of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed. The association of treatment timeliness and of clinical variables with the duration of symptoms and with the risk of hospitalization was evaluated by logistic regression. RESULTS Patients were divided into 2 groups: group 1 (n=85) was treated at the earliest possible time (<72 h from onset of symptoms), and group 2 (n=73) was treated >72 h after the onset of symptoms. Clinical severity at the beginning of treatment was similar in the 2 groups. In group 1, symptom duration was shorter than in group 2 (median 6.0 days vs 13.0 days, P<0.001) and no hospitalizations occurred, compared with 19.18% hospitalizations in group 2. One patient in group 1 developed chest X-ray alterations and 2 patients experienced an increase in D-dimer levels, compared with 30 and 22 patients, respectively, in group 2. The main factor determining the duration of symptoms and the risk of hospitalization was the delay in starting therapy (P<0.001). CONCLUSIONS This real-world study of patients in the community showed that early diagnosis and early supportive patient management reduced the severity of COVID-19 and reduced the rate of hospitalization.


Subject(s)
COVID-19/diagnosis , COVID-19/drug therapy , Hospitalization/statistics & numerical data , Time-to-Treatment/statistics & numerical data , Aged , Aged, 80 and over , Aspirin/therapeutic use , Betamethasone/therapeutic use , Cohort Studies , Dietary Supplements , Early Diagnosis , Female , Flavonoids/therapeutic use , Follow-Up Studies , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Indomethacin/therapeutic use , Italy , Male , Middle Aged , Omeprazole/therapeutic use , Patient Acuity , Retrospective Studies , Risk Assessment , SARS-CoV-2 , Time , Treatment Outcome
2.
BMC Pharmacol Toxicol ; 22(1): 61, 2021 10 21.
Article in English | MEDLINE | ID: covidwho-1477468

ABSTRACT

BACKGROUND: The emergence and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in thelate 2019 has caused a devastating global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19). Although vaccines have been and are being developed, they are not accessible to everyone and not everyone can receive these vaccines. Also, it typically takes more than 10 years until a new therapeutic agent is approved for usage. Therefore, repurposing of known drugs can lend itself well as a key approach for significantly expediting the development of new therapies for COVID-19. METHODS: We have incorporated machine learning-based computational tools and in silico models into the drug discovery process to predict Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles of 90 potential drugs for COVID-19 treatment identified from two independent studies mainly with the purpose of mitigating late-phase failures because of inferior pharmacokinetics and toxicity. RESULTS: Here, we summarize the cardiotoxicity and general toxicity profiles of 90 potential drugs for COVID-19 treatment and outline the risks of repurposing and propose a stratification of patients accordingly. We shortlist a total of five compounds based on their non-toxic properties. CONCLUSION: In summary, this manuscript aims to provide a potentially useful source of essential knowledge on toxicity assessment of 90 compounds for healthcare practitioners and researchers to find off-label alternatives for the treatment for COVID-19. The majority of the molecules discussed in this manuscript have already moved into clinical trials and thus their known pharmacological and human safety profiles are expected to facilitate a fast track preclinical and clinical assessment for treating COVID-19.


Subject(s)
Antiviral Agents/toxicity , COVID-19/drug therapy , Drug Discovery , Drug Repositioning , Animals , Antiviral Agents/adverse effects , Captopril/therapeutic use , Cardiotoxins/toxicity , Catechols/therapeutic use , Computational Biology , Cytochrome P-450 Enzyme System/metabolism , Drug Discovery/methods , Humans , Indomethacin/therapeutic use , Linezolid/therapeutic use , Liver/drug effects , Mice , Models, Biological , Nitriles/therapeutic use , Rats , Reproduction/drug effects , Software , Valproic Acid/therapeutic use
3.
J Pharmacokinet Pharmacodyn ; 47(3): 189-198, 2020 06.
Article in English | MEDLINE | ID: covidwho-324441

ABSTRACT

To face SARS-CoV-2 pandemic various attempts are made to identify potential effective treatments by repurposing available drugs. Among them, indomethacin, an anti-inflammatory drug, was shown to have potent in-vitro antiviral properties on human SARS-CoV-1, canine CCoV, and more recently on human SARS-CoV-2 at low micromolar range. Our objective was to show that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 and to provide criteria for comparing benefits of alternative dosage regimens using a model-based approach. A multi-stage model-based approach was developed to characterize % of recovery and viral load in CCoV-infected dogs, to estimate the PK of indomethacin in dog and human using published data after administration of immediate (IR) and sustained-release (SR) formulations, and to estimate the expected antiviral activity as a function of different assumptions on the effective exposure in human. Different dosage regimens were evaluated for IR formulation (25 mg and 50 mg three-times-a-day, and 25 mg four-times-a-day), and SR formulation (75 mg once and twice-a-day). The best performing dosing regimens were: 50 mg three-times-a-day for the IR formulation, and 75 mg twice-a-day for the SR formulation. The treatment with the SR formulation at the dose of 75 mg twice-a-day is expected to achieve a complete response in three days for the treatment in patients infected by the SARS-CoV-2 coronavirus. These results suggest that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 whose potential therapeutic effect need to be further assessed in a prospective clinical trial.


Subject(s)
Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Drug Dosage Calculations , Indomethacin/administration & dosage , Indomethacin/therapeutic use , Models, Biological , Pneumonia, Viral/drug therapy , Animals , Antiviral Agents/pharmacokinetics , Betacoronavirus/drug effects , COVID-19 , Coronavirus Infections/virology , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/therapeutic use , Dogs , Humans , Indomethacin/pharmacokinetics , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Viral Load/drug effects
4.
Int J Clin Pract ; 74(9): e13535, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-276426

ABSTRACT

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2, also known as COVID-19) has led to unprecedented challenges for the global healthcare system. This novel coronavirus disease phenotype ranges from asymptomatic carriage to fulminant cytokine storm with respiratory failure, polyorgan dysfunction and death. Severe disease is characterised by exuberant inflammation resulting from high circulating cytokines such as interleukin-6 and tumour necrosis factor. These inflammatory mediators are responsible for the detrimental effects on the immune, hematologic, respiratory, renal, gastrointestinal and other body systems. In addition to inhibition of viral replication, blunting this inflammatory response before overt cytokine storm is important to improve outcomes. Although there are upcoming promising agents such as remdesivir and convalescent plasma, inexpensive, safe and widely available adjunct treatments to ameliorate disease burden would be welcome. Two potential anti-inflammatory agents include indomethacin, which has been shown in experimental models to decrease canine coronavirus levels in dogs and exhibit antiviral activity against several other viruses and the polyphenol, resveratrol, a potent antioxidant that has shown antiviral activity against several viruses.


Subject(s)
Antioxidants/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Cyclooxygenase Inhibitors/therapeutic use , Indomethacin/therapeutic use , Pneumonia, Viral/drug therapy , Resveratrol/therapeutic use , Animals , COVID-19 , Cytokines , Dogs , Humans , Pandemics , SARS-CoV-2 , Virus Replication/drug effects
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