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1.
Struct Chem ; 31(6): 2391-2412, 2020.
Article in English | MEDLINE | ID: covidwho-1906457

ABSTRACT

Presently, the SARS-CoV-2 (COVID-19) pandemic has been spreading throughout the world. Some drugs such as lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir have been recommended for COVID-19 treatment by some researchers, but these drugs were not effective enough against this virus. This study based on in silico approaches was aimed to increase the anti-COVID-19 activities of these drugs by using caulerpin and its derivatives as an adjunct drug against SARS-CoV-2 receptor proteins: the SARS-CoV-2 main protease and the SARS-CoV-2 spike protein. Caulerpin exhibited antiviral activities against chikungunya virus and herpes simplex virus type 1. Caulerpin and some of its derivatives showed inhibitory activity against Alzheimer's disease. The web server ANCHOR revealed higher protein stability for the two receptors with disordered score (< 0.6). Molecular docking analysis showed that the binding energies of most of the caulerpin derivatives were higher than all the suggested drugs for the two receptors. Also, we deduced that inserting NH2, halogen, and vinyl groups can increase the binding affinity of caulerpin toward 6VYB and 6LU7, while inserting an alkyl group decreases the binding affinity of caulerpin toward 6VYB and 6LU7. So, we can modify the inhibitory effect of caulerpin against 6VYB and 6LU7 by inserting NH2, halogen, and vinyl groups. Based on the protein disordered results, the SARS-CoV-2 main protease and SARS-CoV-2 spike protein domain are highly stable proteins, so it is quite difficult to unstabilize their integrity by using individual drugs. Also, molecular dynamics (MD) simulation indicates that binding of the combination therapy of simeprevir and the candidate studied compounds to the receptors was stable and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. So, this study suggested that caulerpin and its derivatives could be used as a combination therapy along with lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir for disrupting the stability of SARS-CoV2 receptor proteins to increase the antiviral activity of these drugs.

2.
Crit Rev Microbiol ; 46(6): 689-702, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1730391

ABSTRACT

Intensive worldwide efforts are underway to determine both the pathogenesis of SARS-CoV-2 infection and the immune responses in COVID-19 patients in order to develop effective therapeutics and vaccines. One type of cell that may contribute to these immune responses is the γδ T lymphocyte, which plays a key role in immunosurveillance of the mucosal and epithelial barriers by rapidly responding to pathogens. Although found in low numbers in blood, γδ T cells consist the majority of tissue-resident T cells and participate in the front line of the host immune defense. Previous studies have demonstrated the critical protective role of γδ T cells in immune responses to other respiratory viruses, including SARS-CoV-1. However, no studies have profoundly investigated these cells in COVID-19 patients to date. γδ T cells can be safely expanded in vivo using existing inexpensive FDA-approved drugs such as bisphosphonate, in order to test its protective immune response to SARS-CoV-2. To support this line of research, we review insights gained from previous coronavirus research, along with recent findings, discussing the potential role of γδ T cells in controlling SARS-CoV-2. We conclude by proposing several strategies to enhance γδ T cell's antiviral function, which may be used in developing therapies for COVID-19.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , T-Lymphocyte Subsets/immunology , Animals , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Replication
3.
Disaster Med Public Health Prep ; : 1-5, 2021 Apr 30.
Article in English | MEDLINE | ID: covidwho-1704036

ABSTRACT

OBJECTIVE: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been discovered in Wuhan and spread rapidly across China and worldwide. Characteristics of infected patients are needed to get insight into the full spectrum of the disease. METHODS: Epidemiological and clinical information of 1738 diagnosed patients during February 7-26, 2020 in Wuhan Dongxihu Fangcang Hospital were analyzed. A total of 709 patients were followed up on symptom, mental health, isolation site, and medication after discharge. RESULTS: There were 852 males and 886 females in the cohort. The average age of the patients was 48.8 y. A total of 79.98% of the patients were from Wuhan, Hubei Province. The most common initial symptoms were fever, cough, and shortness of breath. Among all the patients, 1463 had complications, with respiratory distress as the most common complication. The average duration of hospitalization was 15.95 ± 14.69 d. The most common postdischarge symptom is cough. After discharge, most patients were full of energy and chose hotel as their self-isolation site. Coronavirus disease 2019 (COVID-19) Chinese medicine No.2 prescription is the medication used most commonly by the patients after discharge. CONCLUSIONS: The population is generally susceptible to SARS-CoV-2. After receiving aggressive treatment of combined Chinese and Western medicine, most patients had a good prognosis and mental health after discharge.

4.
Clin Infect Dis ; 73(9): e3066-e3073, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501031

ABSTRACT

BACKGROUND: Reports suggest that some persons previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lack detectable immunoglobulin G (IgG) antibodies. We aimed to determine the proportion IgG seronegative and predictors for seronegativity among persons previously infected with SARS-CoV-2. METHODS: We analyzed serologic data collected from healthcare workers and first responders in New York City and the Detroit metropolitan area with a history of a positive SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) test result and who were tested for IgG antibodies to SARS-CoV-2 spike protein at least 2 weeks after symptom onset. RESULTS: Of 2547 persons with previously confirmed SARS-CoV-2 infection, 160 (6.3%) were seronegative. Of 2112 previously symptomatic persons, the proportion seronegative slightly increased from 14 to 90 days post symptom onset (P = .06). The proportion seronegative ranged from 0% among 79 persons previously hospitalized to 11.0% among 308 persons with asymptomatic infections. In a multivariable model, persons who took immunosuppressive medications were more likely to be seronegative (31.9%; 95% confidence interval [CI], 10.7%-64.7%), while participants of non-Hispanic Black race/ethnicity (vs non-Hispanic White; 2.7%; 95% CI, 1.5%-4.8%), with severe obesity (vs under/normal weight; 3.9%; 95% CI, 1.7%-8.6%), or with more symptoms were less likely to be seronegative. CONCLUSIONS: In our population with previous RT-PCR-confirmed infection, approximately 1 in 16 persons lacked IgG antibodies. Absence of antibodies varied independently by illness severity, race/ethnicity, obesity, and immunosuppressive drug therapy. The proportion seronegative remained relatively stable among persons tested up to 90 days post symptom onset.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Cohort Studies , Humans , Spike Glycoprotein, Coronavirus
5.
Molecules ; 25(8)2020 Apr 18.
Article in English | MEDLINE | ID: covidwho-1450861

ABSTRACT

(1) Background: Viral respiratory infections cause life-threatening diseases in millions of people worldwide every year. Human coronavirus and several picornaviruses are responsible for worldwide epidemic outbreaks, thus representing a heavy burden to their hosts. In the absence of specific treatments for human viral infections, natural products offer an alternative in terms of innovative drug therapies. (2) Methods: We analyzed the antiviral properties of the leaves and stem bark of the mulberry tree (Morus spp.). We compared the antiviral activity of Morus spp. on enveloped and nonenveloped viral pathogens, such as human coronavirus (HCoV 229E) and different members of the Picornaviridae family-human poliovirus 1, human parechovirus 1 and 3, and human echovirus 11. The antiviral activity of 12 water and water-alcohol plant extracts of the leaves and stem bark of three different species of mulberry-Morus alba var. alba, Morus alba var. rosa, and Morus rubra-were evaluated. We also evaluated the antiviral activities of kuwanon G against HCoV-229E. (3) Results: Our results showed that several extracts reduced the viral titer and cytopathogenic effects (CPE). Leaves' water-alcohol extracts exhibited maximum antiviral activity on human coronavirus, while stem bark and leaves' water and water-alcohol extracts were the most effective on picornaviruses. (4) Conclusions: The analysis of the antiviral activities of Morus spp. offer promising applications in antiviral strategies.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus/drug effects , Morus/chemistry , Plant Extracts/pharmacology , Respiratory Tract Infections/drug therapy , Antiviral Agents/therapeutic use , Cell Line , Cytopathogenic Effect, Viral/drug effects , Flavonoids/pharmacology , Humans , Mass Spectrometry , Microbial Sensitivity Tests , Picornaviridae/drug effects , Plant Bark/chemistry , Plant Extracts/therapeutic use , Plant Leaves/chemistry
6.
Rev Panam Salud Publica ; 44: e40, 2020.
Article in English | MEDLINE | ID: covidwho-1436524

ABSTRACT

The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants' clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.


En diciembre de 2019 fue informado a la Organización Mundial de la Salud (OMS) un brote de neumonía por coronavirus en Wuhan, provincia de Hubei, China. Al 12 de marzo de 2020, se habían notificado 125 048 casos y 4 614 muertes. El coronavirus es un virus ARN envuelto del género Betacoronavirus distribuido en aves, seres humanos y otros mamíferos. La OMS ha denominado a la nueva enfermedad por coronavirus COVID-19. Se han puesto en marcha más de 80 ensayos clínicos para evaluar un tratamiento para el coronavirus, que incluyen algunos ensayos de reposicionamiento de medicamentos para la COVID-19. En marzo de 2020 se llevó a cabo una búsqueda de los ensayos clínicos registrados en la base de datos clinicaltrials.gov. Los criterios de elegibilidad para los estudios recuperados fueron tener un número de identificación de la base de datos clinicaltrials.gov; describir el número de participantes y el período del estudio; describir las condiciones clínicas de los participantes; y emplear intervenciones con medicamentos ya estudiados o aprobados para cualquier otra enfermedad en pacientes infectados con el nuevo coronavirus SARS-CoV-2 (2019-nCoV). Es esencial destacar que este artículo solo recoge los ensayos que figuran en la base de datos clinicaltrials. gov. Se identificaron 24 ensayos clínicos relacionados con más de 20 medicamentos, como inmunoglobulina humana, interferones, cloroquina, hidroxicloroquina, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, metilprednisolona, bevacizumab y medicina tradicional china. Aunque el reposicionamiento de medicamentos tiene algunas limitaciones, el reposicionamiento de los ensayos clínicos puede representar una estrategia atractiva porque facilita el descubrimiento de nuevas clases de medicamentos; estos tienen costos más bajos y tardan menos en llegar al mercado; y existen cadenas de suministro farmacéutico que apoyan la formulación y la distribución.


A Organização Mundial da Saúde (OMS) foi informada, em dezembro de 2019, sobre um surto de pneumonia por coronavírus em Wuhan, província de Hubei (China). Posteriormente, em 12 de março de 2020, 125 048 casos e 4 614 mortes haviam sido registrados. O coronavírus é um vírus RNA envelopado do gênero Betacoronavírus, distribuído em aves e em humanos e outros mamíferos. A OMS designou a nova doença por coronavírus como COVID-19. Mais de 80 ensaios clínicos foram iniciados para testar tratamentos para o coronavírus, incluindo alguns de reposicionamento de medicamentos para o COVID-19. Assim, em março de 2020 realizou-se uma busca na base de dados clinicaltrials.gov. Os critérios de elegibilidade para os estudos recuperados foram: conter o número identificador da base de dados clinicaltrials.gov; descrever o número de participantes e o período do estudo; descrever as condições clínicas dos participantes; e utilizar intervenções para tratamento de doentes infectados com o novo coronavírus SARS-CoV-2 (2019-nCoV) com medicamentos já estudados ou aprovados para qualquer outra doença. É essencial salientar que este artigo apenas capturou ensaios listados na base de dados clinicaltrials.gov. Foram identificados 24 ensaios clínicos envolvendo mais de 20 medicamentos, tais como imunoglobulina humana, interferons, cloroquina, hidroxicloroquina, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, metilprednisolona, bevacizumabe e medicamentos chineses tradicionais. Embora o reposicionamento de medicamentos tenha algumas limitações, os ensaios clínicos de reposicionamento podem representar uma estratégia atraente, porque facilitam a descoberta de novas classes de medicamentos, têm custos mais baixos, levam menos tempo para chegar ao mercado e se beneficiam de cadeias de fornecimento farmacêutico já existentes para formulação e distribuição.

7.
Kardiol Pol ; 79(7-8): 773-780, 2021.
Article in English | MEDLINE | ID: covidwho-1399787

ABSTRACT

BACKGROUND: The coronavirus disease 19 (COVID-19) recently became one of the leading causes of death worldwide, similar to cardiovascular disease (CVD). Coexisting CVD may influence the prognosis of patients with COVID-19. AIMS: We analyzed the impact of CVD and the use of cardiovascular drugs on the in-hospital course and mortality of patients with COVID-19. METHODS: We retrospectively studied data for consecutive patients admitted to our hospital, with COVID-19 between March 6th and October 15th, 2020. RESULTS: 1729 patients (median interquartile range age 63 [50-75] years; women 48.8%) were included. Overall, in-hospital mortality was 12.9%. The most prevalent CVD was arterial hypertension (56.1%), followed by hyperlipidemia (27.4%), diabetes mellitus (DM) (25.7%), coronary artery disease (16.8%), heart failure (HF) (10.3%), atrial fibrillation (13.5%), and stroke (8%). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) were used in 25.0% of patients, ß-blockers in 40.7%, statins in 15.6%, and antiplatelet therapy in 19.9%. Age over 65 years (odds ratio [OR], 6.4; 95% CI, 4.3-9.6), male sex (OR, 1.4; 95% CI, 1.1-2.0), pre-existing DM (OR, 1.5; 95% CI, 1.1-2.1), and HF (OR, 2.3; 95% CI, 1.5-3.5) were independent predictors of in-hospital death, whereas treatment with ACEIs/ARBs (OR, 0.4; 95% CI, 0.3-0.6), ß-blockers (OR, 0.6; 95% CI, 0.4-0.9), statins (OR, 0.5; 95% CI, 0.3-0.8), or antiplatelet therapy (OR, 0.6; 95% CI: 0.4-0.9) was associated with lower risk of death. CONCLUSIONS: Among cardiovascular risk factors and diseases, HF and DM appeared to increase in-hospital COVID-19 mortality, whereas the use of cardiovascular drugs was associated with lower mortality.


Subject(s)
COVID-19 , Cardiovascular Agents , Cardiovascular Diseases , Hypertension , Aged , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , Female , Hospital Mortality , Hospitals , Humans , Male , Middle Aged , Poland/epidemiology , Registries , Retrospective Studies , SARS-CoV-2
8.
Int J Mol Sci ; 22(6)2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1389394

ABSTRACT

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn-Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.


Subject(s)
Antiviral Agents/chemistry , Metals/chemistry , Methisazone/chemistry , Molecular Docking Simulation , SARS-CoV-2/chemistry , Antiviral Agents/metabolism , COVID-19/drug therapy , Calcium/chemistry , Calcium/metabolism , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/metabolism , Coronavirus Papain-Like Proteases/chemistry , Coronavirus Papain-Like Proteases/metabolism , Coronavirus RNA-Dependent RNA Polymerase/chemistry , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Drug Design , Humans , Iron/chemistry , Iron/metabolism , Magnesium/chemistry , Magnesium/metabolism , Manganese/chemistry , Manganese/metabolism , Metals/metabolism , Methisazone/metabolism , Models, Molecular , Molecular Dynamics Simulation , Protein Binding , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Zinc/chemistry , Zinc/metabolism
9.
J Mol Struct ; 1230: 129891, 2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1386340

ABSTRACT

The main binding site for SARS-COV-2 spike protein in human body is human Angiotensin converting enzyme 2 (ACE2) protein receptor. Herein we present the effect of chloroquine (CLQ) on human ACE2 receptor. Molecular docking studies showed that chloroquine have a docking score is quite high compare to other well known drugs. Furthermore, molecular dynamics (MD) studies with CLQ docked ACE2 results in large fluctuations on RMSD up to 2.3 ns, indicating conformational and rotational changes due to the presence of drug molecule in the ACE2 moiety. Analysis of results showed that CLQ can effect the conformation of human ACE2 receptor. We believed that this work will help researchers to understand better the effect of CLQ on ACE2.

10.
Data Brief ; 30: 105552, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1351603

ABSTRACT

The COVID-19 outbreak is now one of the most critical crises to manage for most of the national healthcare systems in the world. In the absence of authorised pharmacological treatments, many antiretrovirals, including darunavir/cobicistat fixed combination, are used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Unfortunately, for most of them, the drug products available on the market are not designed to be administered by a nasogastric tube to inpatients of intensive care units. Therefore, their manipulation, even if it can strongly affect the product quality, is necessary for the preparation of suspension to meet patients' need. In this situation, it is urgent to provide data and guidance to support hospital pharmacists and clinicians in their activity. The data in this article indicate that darunavir/cobicistat suspensions compounded by pharmacists using as active ingredient a commercially available tablet can be stable at least for one week.

12.
Molecules ; 25(21)2020 Nov 07.
Article in English | MEDLINE | ID: covidwho-1305742

ABSTRACT

Malaria control relies heavily on the small number of existing antimalarial drugs. However, recurring antimalarial drug resistance necessitates the continual generation of new antimalarial drugs with novel modes of action. In order to shift the focus from only controlling this disease towards elimination and eradication, next-generation antimalarial agents need to address the gaps in the malaria drug arsenal. This includes developing drugs for chemoprotection, treating severe malaria and blocking transmission. Plasmodial kinases are promising targets for next-generation antimalarial drug development as they mediate critical cellular processes and some are active across multiple stages of the parasite's life cycle. This review gives an update on the progress made thus far with regards to plasmodial kinase small-molecule inhibitor development.


Subject(s)
Antimalarials/pharmacology , Drug Discovery/trends , Malaria/drug therapy , Plasmodium/drug effects , Protein Kinase Inhibitors/pharmacology , Animals , Calcium/metabolism , Casein Kinase I/metabolism , Culicidae , Drug Design , Drug Resistance , Glycogen Synthase Kinase 3/metabolism , Humans , Imidazoles/pharmacology , Inhibitory Concentration 50 , Life Cycle Stages/drug effects , MAP Kinase Signaling System , Phosphotransferases/chemistry , Plasmodium/enzymology , Pyridines/pharmacology
13.
Int J Mol Sci ; 22(7)2021 Mar 30.
Article in English | MEDLINE | ID: covidwho-1299437

ABSTRACT

Host-directed therapy using drugs that target cellular pathways required for virus lifecycle or its clearance might represent an effective approach for treating infectious diseases. Changes in redox homeostasis, including intracellular glutathione (GSH) depletion, are one of the key events that favor virus replication and contribute to the pathogenesis of virus-induced disease. Redox homeostasis has an important role in maintaining an appropriate Th1/Th2 balance, which is necessary to mount an effective immune response against viral infection and to avoid excessive inflammatory responses. It is known that excessive production of reactive oxygen species (ROS) induced by viral infection activates nuclear factor (NF)-kB, which orchestrates the expression of viral and host genes involved in the viral replication and inflammatory response. Moreover, redox-regulated protein disulfide isomerase (PDI) chaperones have an essential role in catalyzing formation of disulfide bonds in viral proteins. This review aims at describing the role of GSH in modulating redox sensitive pathways, in particular that mediated by NF-kB, and PDI activity. The second part of the review discusses the effectiveness of GSH-boosting molecules as broad-spectrum antivirals acting in a multifaceted way that includes the modulation of immune and inflammatory responses.


Subject(s)
Glutathione/metabolism , Virus Diseases/drug therapy , Virus Replication/drug effects , Animals , Antiviral Agents/pharmacology , Humans , NF-kappa B/metabolism , Oxidation-Reduction/drug effects , Protein Disulfide-Isomerases/metabolism , Reactive Oxygen Species/metabolism , Virus Diseases/metabolism
14.
Int J Clin Pract ; 75(9): e14442, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1295014

ABSTRACT

OBJECTIVE: The aim of the study was to detect the frequency and course of coronavirus disease 2019 (Covid-19) infection among our rheumatology outpatients and to investigate how patient follow-up differed during Covid-19 pandemic in a tertiary University Hospital in the capital of Turkey. PATIENTS AND METHOD: Patients with inflammatory rheumatic diseases (IRDs) registered in our rheumatology clinic were assessed during their routine outpatient follow-up control or contacted via phone between July and December 2020. Patients' demographics, diagnosis, medication, comorbidities, frequency of going outside during the pandemic, work status, whether patients could attend their routine follow-up, treatment changes, access to drugs during the pandemic, and the incidence of Covid-19 infection were collected. RESULTS: A total of 320 patients with IRD were analysed; 114 (35.6%) patients were treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (methotrexate/leflunomide/sulfasalazine), 93 (29.1%) patients with biologic DMARDs (bDMARDs), 113 (35.3%) patients with glucocorticoids, and 103 (32.2%) patients with hydroxychloroquine (HCQ). A total of 15.9% of patients on HCQ experienced problems in medication supply. Only 87 (27.2%) patients presented for their routine follow-up appointment, and 38 (11.9%) of the patients changed their treatment without professional health advice. While 53 (57%) patients on biological agents continued their treatment, 31 patients (33.3%) interrupted the treatment with doctor's recommendation and 9 patients (9.6%) on their initiative, and 23 of these 31 patients had to restart treatment because of disease activation. The nasopharyngeal swab collected from 30 patients with a suspected Covid-19 contact but without any symptoms was negative. In total, there were 33 patients diagnosed with Covid-19; none of whom had severe respiratory complications or death. CONCLUSIONS: Many patients with rheumatic diseases are left without disease monitoring during the pandemic. There was no increased risk of severe Covid-19 infection among patients with IRD.


Subject(s)
Antirheumatic Agents , COVID-19 , Rheumatic Diseases , Rheumatology , Ambulatory Care , Antirheumatic Agents/therapeutic use , Humans , Pandemics , Rheumatic Diseases/drug therapy , Rheumatic Diseases/epidemiology , SARS-CoV-2 , Turkey/epidemiology
15.
J Adv Nurs ; 77(9): 3829-3841, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1270854

ABSTRACT

AIM: This study aimed to explore the experiences of alcohol and other drug nurses transitioning to telehealth due to the COVID-19 pandemic. BACKGROUND: COVID-19 has caused immense disruption to healthcare services, and to reduce viral transmission, many services moved to off-site care delivery modalities such as telehealth. DESIGN: We used a qualitative descriptive design for this study. METHODS: Secondary analysis of semistructured interviews with alcohol and other drug nurses from Australia and New Zealand (n = 19) was conducted in July and August 2020. Data were analysed using thematic analysis and reported using COREQ guidelines. RESULTS: Three were identified: '"All our face-to-face contact ceased with clients": Changing service delivery', '"How do I do my job when I can't see you?": An anxious shift in service delivery' and '"A lot of Indigenous people don't like the FaceTiming and all that": Challenges to delivery of services through telehealth'. CONCLUSION: Participants in our study reported challenges in transitioning to telehealth modalities. The perceived loss of therapeutic communication, difficulties in assessing risks to healthcare consumers such as domestic violence and challenges delivering telehealth care to a marginalized consumer cohort need to be overcome before telehealth is considered successful in alcohol and other drug treatment. However, telehealth was a successful adjunct to existing practices for nurses working with consumers in regional or remote areas or where consumers preferred this method of service delivery. IMPACT: Nurses in this study described substantial issues with the delivery of alcohol and other drug treatment via telehealth, including a perception that telehealth was a barrier to addressing risks to consumers who use alcohol and other drugs, and difficulties working in a therapeutically beneficial way via telehealth. Telehealth is a means to reduce viral transmission through a reduction in face-to-face contact, and although it may be useful for some service functions, it may be detrimental to the clinical services nurses provide.


Subject(s)
COVID-19 , Nurses , Pharmaceutical Preparations , Telemedicine , Humans , Pandemics , SARS-CoV-2
16.
Med Hypotheses ; 153: 110622, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1270617

ABSTRACT

The outbreak of COVID-19 from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world with tremendous morbidity and mortality in the elderly. In-hospital treatment addresses the multifaceted nature of the illness including initial viral replication, cytokine storm, and endothelial injury with thrombosis. We identified nine reports of early treatment outcomes in COVID-19 nursing home patients. Multi-drug therapy including hydroxychloroquine with one or more anti-infectives, corticosteroids, and antithrombotic anti-blood clotting agents can be extended to seniors in the nursing home setting without hospitalization. Data from nine studies found hydroxychloroquine-based multidrug regimens were associated with a statistically significant > 60% reduction in mortality. Going forward, we conclude that early empiric treatment for the elderly with COVID-19 in the nursing home setting (or similar congregated settings with elderly residents/patients e.g. LTF or ALF) has a reasonable probability of success and acceptable safety. This group remains our highest at-risk group and warrants acute treatment focus prior to symptoms worsening. Given the rapidity and severity of SARS-CoV-2 outbreaks in nursing homes, in-center treatment of acute COVID-19 patients is a reasonable strategy to reduce the risks of hospitalization and death. If elderly high-risk patients in such congregated nursing home type settings are allowed to worsen with no early treatment, they may be too sick and fragile to benefit from in-hospital therapeutics and are at risk for pulmonary failure, life-ending micro-thrombi of the lungs, kidneys etc. The issue is timing of therapeutics, and we argue that early treatment before hospitalization, is the right time and can potentially save lives, especially among our higher-risk elderly populations hit hardest by severe illness and death from COVID-19. We must reiterate, we are talking about 'early' treatment before the disease is far along in the disease sequelae where the patient then needs hospitalization and aggressive interventions. We are referring to the initial days e.g. day one, post infection when symptoms emerge or there is strong clinical suspicion. This early therapeutic option deserves serious and urgent consideration by the medical establishment and respective decision-makers. Doctors must be allowed their clinical discretion in how they optimally treat their patients. Doctors must be brave and trust their skilled judgements and do all to save the lives of their patients. We therefore hypothesize that early outpatient ambulatory treatment, once initiated as soon as symptoms begin in high-risk positive persons, would significantly reduce hospitalizations and prevent deaths. Specifically, the provision of early multi-drug sequenced therapy with repurposed drugs will reduce hospitalization and death in elderly patients being cared for in long-term-care facilities. The most important implications of our hypothesis are: 1) hospitalizations and deaths would be reduced 2) transmission would be reduced due to the mitigation of symptoms and 3) recovery following infection and treatment provides for natural exposure immunity that is broad based, durable, and robust (helping towards natural immunity within the population). The end result is reduced strain on hospitals and systems that would allow for other non-COVID illnesses to receive care.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Humans , Hydroxychloroquine , Nursing Homes , Outpatients
17.
Biochem Pharmacol ; 189: 114424, 2021 07.
Article in English | MEDLINE | ID: covidwho-1269238

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Three viral proteins, the spike protein (S) for attachment of virus to host cells, 3-chymotrypsin-like cysteine protease (Mpro) for digestion of viral polyproteins to functional proteins, and RNA-dependent-RNA-polymerase (RdRp) for RNA synthesis are the most critical proteins for virus infection and replication, rendering them the most important drug targets for both antibody and chemical drugs. Due to its low-fidelity polymerase, the virus is subject to frequent mutations. To date, the sequence data from tens of thousands of virus isolates have revealed hundreds of mutations. Although most mutations have a minimum consequence, a small number of non-synonymous mutations may alter the virulence and antigenicity of the mutants. To evaluate the effects of viral mutations on drug safety and efficacy, we reviewed the biochemical features of the three main proteins and their potentials as drug targets, and analyzed the mutation profiles and their impacts on RNA therapeutics. We believe that monitoring and predicting mutation-introduced protein conformational changes in the three key viral proteins and evaluating their binding affinities and enzymatic activities with the U.S. Food and Drug Administration (FDA) regulated drugs by using computational modeling and machine learning processes can provide valuable information for the consideration of drug efficacy and drug safety for drug developers and drug reviewers. Finally, we propose an interactive database for drug developers and reviewers to use in evaluating the safety and efficacy of U.S. FDA regulated drugs with regard to viral mutations.


Subject(s)
COVID-19/drug therapy , COVID-19/genetics , Mutation/genetics , RNA/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Animals , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , COVID-19/metabolism , Drug Approval/methods , Drug Development/methods , Drug Development/trends , Humans , RNA/metabolism , RNA/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism
18.
Front Psychiatry ; 12: 633551, 2021.
Article in English | MEDLINE | ID: covidwho-1268310

ABSTRACT

As in many other countries worldwide, the coronavirus pandemic prompted the implementation of an "intelligent lockdown" in the spring of 2020 in the Netherlands, including the closure of nightlife venues and cancellation of festivals. Such restrictions and social distancing could particularly affect people who use alcohol or other drugs in recreational settings and give rise to new challenges and additional needs in the field of addiction prevention and care. To monitor changes in substance use and provide services with practical directions for tailored prevention, an anonymous web survey was set up, targeting a convenience sample aged 16 years or older through various social media and other online channels. Between May and October 2020, a total of 6,070 participants completed the survey, mainly adolescents and young adults (16-24 years old). These data were used to explore and describe changing patterns in substance use. Overall results showed declined current use compared to "pre-corona," but mask underlying variation in changing patterns, including discontinued (tobacco 10.4%, alcohol 11.3%, cannabis 16.3%, other drugs 30.4%), decreased (tobacco 23.0%, alcohol 29.1%, cannabis 17.4%, other drugs 20.7%), unchanged (tobacco 30.3%, alcohol 21.2%, cannabis 22.3%, other drugs 17.3%), increased (tobacco 29.6%, alcohol 32.1%, cannabis 32.9%, other drugs 25.3%), and (re)commenced use (tobacco 6.7%, alcohol 6.3%, cannabis 11.1%, other drugs 6.2%). Especially the use of drugs like ecstasy and nitrous oxide was discontinued or decreased due to the lack of social occasions for use. Increased use was associated with coping motives for all substance types. As measures combatting the coronavirus may need to be practiced for some time to come, possibly leading to prolonged changes in substance use with lingering "post-corona" consequences, timely and ongoing monitoring of changing patterns of substance use is vital for informing prevention services within this field.

19.
Clin Interv Aging ; 16: 1037-1046, 2021.
Article in English | MEDLINE | ID: covidwho-1266601

ABSTRACT

BACKGROUND: Remdesivir, an antiviral agent able to reduce inflammatory cascade accompanying severe, life-threatening pneumonia, became the first drug approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus 2 related severe acute respiratory syndrome (SARS CoV2). As from its previously known clinical indications, the use of remdesivir in the presence of severe renal impairment is contraindicated; however, the impact of remdesivir on renal function in aging patients has not been elucidated. SUBJECTS AND METHODS: This retrospective observational study involved 109 individuals consecutively admitted in internal medicine section, Azienda Ospedaliero Universitaria Pisana hospital, in November-December 2020 due to a confirmed diagnosis of SARS CoV2 and receiving remdesivir according to international inclusion criteria. Biochemical variables at admission were evaluated, together with slopes of estimated glomerular filtration rate (eGFR) built during remdesivir treatment. Participants were followed until discharge or exitus. RESULTS: Patients were stratified according to age (80 formed the study cohort and 29 served as controls); CKD stage III was present in 46% of them. No patients showed any sign of deteriorated renal function during remdesivir. Fourteen patients in the elderly cohort deceased; their eGFR at baseline was significantly lower. Recovered patients were characterized by a relevant eGFR gaining during remdesivir treatment. CONCLUSION: We show here for the first time as remdesivir does not influence eGFR in a cohort of elderly people hospitalized for SARS CoV2, and that eGFR gain during such treatment is coupled with a better prognosis.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Aging/physiology , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Aged, 80 and over , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/adverse effects , COVID-19/mortality , Cohort Studies , Female , Glomerular Filtration Rate , Humans , Male , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
20.
Ann Transl Med ; 9(7): 590, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1257378

ABSTRACT

Using high-flow nasal cannula (HFNC) as a "vehicle" to administer aerosolized medication has attracted clinicians' interest in recent years. In this paper, we summarize the current evidence to answer the common questions raised by clinicians about this new aerosol delivery route and best practices of administration. Benefits of trans-nasal aerosol delivery include increased comfort, ability to speak, eat, and drink for patients while meeting a range of oxygen requirements, particularly for those who need to inhale aerosolized medication for long periods. Aerosol administration via HFNC has been shown to be well tolerated by children and adults, with comparable or better delivery efficacy than other interfaces, ranging from 2-20%. In vitro and in vivo scintigraphy studies among pediatric and adult populations reported that the inhaled dose delivered via a vibrating mesh nebulizer is 2 to 3 fold greater than that via a jet nebulizer. For adults, placement of nebulizer at the inlet of humidifier increases inhaled dose while reducing rainout obstructing nasal prongs. When HFNC gas flow is set below patient inspiratory flow, aerosol deposition is higher than when the gas flow exceeds patient inspiratory flow; thus, if tolerated, titrating down HFNC gas flow during trans-nasal aerosol delivery, with close monitoring and the use of unit dose with high concentration are recommended. Trans-nasal pulmonary aerosol delivery has not been shown to increase bioaerosols generated by patients, but gas flow may disperse aerosols. Placement of a surgical or procedure mask over HFNC might reduce aerosol dispersion.

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