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1.
Eur Geriatr Med ; 12(5): 1045-1055, 2021 10.
Article in English | MEDLINE | ID: covidwho-1474202

ABSTRACT

AIMS: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards. METHODS: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year. RESULTS: A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved the influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001). CONCLUSIONS: The nosocomial pneumonia multi-component intervention did not significantly reduce the incidence of hospital-acquired pneumonia during hospitalisation but reduce subsequent hospitalisations for respiratory infections. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, NCT04347395.


Subject(s)
COVID-19 , Cross Infection , Healthcare-Associated Pneumonia , Aged , Aged, 80 and over , Cross Infection/epidemiology , Female , Healthcare-Associated Pneumonia/epidemiology , Humans , Male , SARS-CoV-2 , Treatment Outcome
2.
BMC Complement Med Ther ; 21(1): 141, 2021 May 12.
Article in English | MEDLINE | ID: covidwho-1388756

ABSTRACT

BACKGROUND: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections. METHODS: Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes. RESULTS: Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections. CONCLUSIONS: Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense.


Subject(s)
COVID-19/drug therapy , Echinacea , Immunologic Factors/pharmacology , Monocytes/drug effects , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Gene Expression , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Interferons/drug effects , Phytotherapy , Plant Extracts/therapeutic use
3.
Virusdisease ; 32(3): 589-594, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1252263

ABSTRACT

Novel coronavirus disease by SARS-CoV-2 virus (also known as COVID-19) has emerged as major health concern worldwide. While, there is no specific drugs for treating this infection till date, SARS-CoV-2 had spread to most countries around the globe. Nitric oxide (NO) gas serves as an important signaling molecule having vasodilatory effects as well as anti-microbial properties. Previous studies from the 2004 SARS-CoV infection demonstrated that NO may also help to reduce respiratory tract infection by inactivating viruses and inhibiting their replication cycle and is an effective supportive measure for treating infection in patients with pulmonary complications. NO gas inhalation is being suggested as potential therapy for managing severe acute respiratory distress syndrome in COVID-19 patients. In view of COVID-19 pandemic, several clinical trials are underway to examine the effects of NO inhalation on infected patients. Previously published reports on beneficial effects of endogenous NO and NO inhalation therapy were thoroughly searched to assess the potential of NO therapy for treating COVID-19 patients. Present report summarized the therapeutic importance of NO to reverse pulmonary hypertension, restore normal endothelial activity and produce anti-thrombotic effects. In addition to this, NO also reduces viral infection by inhibiting its replication and entry into the host cell. In absence of vaccine and effective treatment strategies, we suggest that NO inhalation therapy and NO releasing foods/compounds could be considered as an alternative measure to combat COVID-19 infection.

4.
Int Rev Immunol ; 41(2): 283-296, 2022.
Article in English | MEDLINE | ID: covidwho-1218926

ABSTRACT

Bacillus Calmette-Guérin (BCG) is a live attenuated M. bovis vaccine that was developed about 100 years ago by Albert Calmette and Camille Guérin. Many countries have been using the vaccine for decades against tuberculosis (TB). The World Health Organization (WHO) recommends a single dose of BCG for infants in TB endemic as well as leprosy high risk countries, and globally almost 130 million infants are vaccinated yearly. The role of BCG is well known in reducing neonatal and childhood death rates. Epidemiological and retrospective cross-sectional studies demonstrated that the BCG vaccination protects the children against respiratory tract infections and lowers the risk of malaria in children. In addition, BCG enhances IFN-γ and IL-10 levels, thus providing immunity against respiratory tract infection even in elderly people. The BCG is also known to provide nonspecific innate immunity against viruses and parasites, through an innate immune mechanism termed 'trained immunity' and is defined as the immunological recall of the innate immune system by epigenetic reprogramming. Based on these studies it is suggested that the BCG has the potential to act as a protective agent against COVID-19. Further proven safety records of BCG in humans, its adjuvant activity and low-cost manufacturing make it an attractive option to stop the pandemic and reduce the COVID-19 related mortality. In this review we discuss the heterologous effects of BCG, induction of trained immunity and its implication in development of a potential vaccine against COVID-19 pandemic.


Subject(s)
COVID-19 , Tuberculosis Vaccines , Aged , BCG Vaccine , COVID-19 Vaccines , Child , Cross-Sectional Studies , Humans , Infant, Newborn , Pandemics/prevention & control , Retrospective Studies , SARS-CoV-2
5.
Clin Nurs Res ; 30(7): 1107-1112, 2021 09.
Article in English | MEDLINE | ID: covidwho-1218284

ABSTRACT

A face mask is a vital component of personal protective equipment to prevent potentially contagious respiratory infections. There was a lack of evidence showing the proportion and determinants of face mask use in Ethiopia. Therefore, this study aimed to identify face mask utilization determinants to prevent spread of the Covid-19 pandemic among quarantined adults in Tigrai region, northern Ethiopia. A total of 331 participants selected using a systematic random sampling method were included in the study. An interviewer-administered questionnaire was employed. After describing the variables using frequencies, means, and standard deviations, multivariable logistic regression determined factors associated with face mask utilization to prevent COVID-19 spread. The study participants were primarily males (70%) and mean age was 30.5 (SD = 11) years. Nearly half of the participants reported they did not wear a face mask when leaving home. Face mask utilization was significantly associated with knowledge score, employment status, gender, age, and educational status of the study participants.


Subject(s)
COVID-19 , Masks , Adult , Ethiopia , Female , Humans , Male , Pandemics/prevention & control , SARS-CoV-2 , Young Adult
6.
Front Med (Lausanne) ; 8: 642313, 2021.
Article in English | MEDLINE | ID: covidwho-1211822

ABSTRACT

Macrolides (e.g., erythromycin, fidaxomicin, clarithromycin, and azithromycin) are a class of bacteriostatic antibiotics commonly employed in medicine against various gram-positive and atypical bacterial species mostly related to respiratory tract infections, besides they possess anti-inflammatory and immunomodulatory effects. Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). It was first detected in Wuhan, Hubei, China, in December 2019 and resulted in a continuing pandemic. Macrolides have been extensively researched as broad adjunctive therapy for COVID-19 due to its immunostimulant abilities. Among such class of drugs, azithromycin is described as azalide and is well-known for its ability to decrease the production of pro-inflammatory cytokines, including matrix metalloproteinases, tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8. In fact, a report recently published highlighted the effectiveness of combining azithromycin and hydroxychloroquine for COVID-19 treatment. Indeed, it has been underlined that azithromycin quickly prevents SARS-CoV-2 infection by raising the levels of both interferons and interferon-stimulated proteins at the same time which reduces the virus replication and release. In this sense, the current review aims to evaluate the applications of macrolides for the treatment of COVID-19.

7.
Virusdisease ; 32(2): 190-197, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1202859

ABSTRACT

Aerosol particles can spread respiratory infections, especially those caused by viruses; however, the perceived threat is small for many technical reasons, as identified in this article. Under controlled conditions, aerosol particles can travel up to a distance of 28 feet (or 8 m); however, such aerosol particles are less likely to have sufficient quantities of viable viruses to spread infection. Additionally, nearly all the experimental models examined the behavior of the aerosols only in confined spaces, not in open areas; these findings, therefore, cannot be considered generally applicable. In the absence of scientific information and education, only misconceptions, unfounded fears, and unsubstantiated myths will prevail. Given that an effective vaccine and drugs are still not available, prevention remains the only option of protection against SARS-CoV-2, the new coronavirus. Wearing a mask is not only necessary but also critical to reduce the probability of viral spread by contact (fomite), not aerosol, transmission.

8.
Brain Behav Immun Health ; 14: 100255, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1163390

ABSTRACT

Nitric oxide (NO) is a ubiquitous signaling molecule that is critical for supporting a plethora of processes in biological organisms. Among these, its role in the innate immune system as a first line of defense against pathogens has received less attention. In asthma, levels of exhaled NO have been utilized as a window into airway inflammation caused by allergic processes. However, respiratory infections count among the most important triggers of disease exacerbations. Among the multitude of factors that affect NO levels are psychological processes. In particular, longer lasting states of psychological stress and depression have been shown to attenuate NO production. The novel SARS-CoV-2 virus, which has caused a pandemic, and with that, sustained levels of psychological stress globally, also adversely affects NO signaling. We review evidence on the role of NO in respiratory infection, including COVID-19, and stress, and argue that boosting NO bioavailability may be beneficial in protection from infections, thus benefitting individuals who suffer from stress in asthma or SARS-CoV-2 infection.

9.
Int J Environ Res Public Health ; 18(6)2021 03 22.
Article in English | MEDLINE | ID: covidwho-1154382

ABSTRACT

COVID-19 poses grave challenges for mass gatherings. One of the world's largest annual gatherings, Arbaeen, occurs in Iraq. We studied respiratory symptoms and risk and protective factors using representative sampling of Arbaeen pilgrims in 2019 to inform prevention of COVID-19 transmission. Structured sampling was used to recruit walking pilgrims. A questionnaire asked about respiratory symptoms, risk, and preventive factors, including hygiene-related resources of toilet facilities. The commonest symptom reported by the 1842 participants (63.3% male, 36.7% female) was cough (25.6%). Eating in mawkibs (rest areas) with indoor kitchens and drinking only packaged water were associated with lower risk of cough (AOR = 0.72, CI = 0.56-0.94; AOR = 0.60; CI = 0.45-0.78, p < 0.05). Facemask use was associated with increased risk of cough (AOR = 2.71, CI = 2.08-3.53, p < 0.05). Handwashing was not protective against cough, or against (one or more of) cough, fever, or breathlessness in multivariate analysis. Toilet facilities often lacked running water (32.1%) and soap (26.1%), and had shared hand towels (17%). To reduce risk of respiratory infections including COVID-19 during Arbaeen or other mass gatherings, needs include running water, soap, and hygienic hand drying options or hand sanitiser. Education on proper handwashing and facemask approaches and monitoring around food preparation and eating spaces are needed.


Subject(s)
COVID-19 , Pandemics , Female , Hand Disinfection , Humans , Iraq , Male , Masks , SARS-CoV-2
10.
Front Immunol ; 12: 632478, 2021.
Article in English | MEDLINE | ID: covidwho-1150690

ABSTRACT

Despite of the rapid development of the vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it will take several months to have enough doses and the proper infrastructure to vaccinate a good proportion of the world population. In this interim, the accessibility to the Bacille Calmette-Guerin (BCG) may mitigate the pandemic impact in some countries and the BCG vaccine offers significant advantages and flexibility in the way clinical vaccines are administered. BCG vaccination is a highly cost-effective intervention against tuberculosis (TB) and many low-and lower-middle-income countries would likely have the infrastructure, and health care personnel sufficiently familiar with the conventional TB vaccine to mount full-scale efforts to administer novel BCG-based vaccine for COVID-19. This suggests the potential for BCG to overcome future barriers to vaccine roll-out in the countries where health systems are fragile and where the effects of this new coronavirus could be catastrophic. Many studies have reported cross-protective effects of the BCG vaccine toward non-tuberculosis related diseases. Mechanistically, this cross-protective effect of the BCG vaccine can be explained, in part, by trained immunity, a recently discovered program of innate immune memory, which is characterized by non-permanent epigenetic reprogramming of macrophages that leads to increased inflammatory cytokine production and consequently potent immune responses. In this review, we summarize recent work highlighting the potential use of BCG for the treatment respiratory infectious diseases and ongoing SARS-CoV-2 clinical trials. In situations where no other specific prophylactic tools are available, the BCG vaccine could be used as a potential adjuvant, to decrease sickness of SARS-CoV-2 infection and/or to mitigate the effects of concurrent respiratory infections.


Subject(s)
BCG Vaccine/administration & dosage , COVID-19/immunology , Animals , BCG Vaccine/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Humans , Immunity, Innate , Pandemics , SARS-CoV-2/physiology
11.
SN Compr Clin Med ; 3(6): 1261-1271, 2021.
Article in English | MEDLINE | ID: covidwho-1144436

ABSTRACT

Bacille Calmette-Guérin (BCG) vaccine has been globally used to protect infants against tuberculosis (TB) for about a century. This vaccine has been shown to provide some degree of non-specific protection from other respiratory tract infections. This advantage has encouraged researchers to investigate the potential protection of this vaccine from the coronavirus disease 2019 from different perspectives in the ongoing pandemic. In this study, we have comprehensively reviewed the latest articles on potential vaccine effectiveness of BCG on COVID-19 and summarized the possible impacts of the BCG against SARS-COV-2 in detail.

12.
Epidemiol Prev ; 44(5-6): 410-416, 2020.
Article in Italian | MEDLINE | ID: covidwho-1134604

ABSTRACT

During the COVID-19 pandemic, international organizations, institutions, and experts firstly recommended face masks for the population only in symptomatic subjects, but today various countries recommend or require their use even outdoor. In Italy, there was an obligation in closed places accessible to the public, including means of transport, and always if the safety distance was not continuously guaranteed. Various regions have long imposed obligations everywhere but at one's own home, and now the mandate has become national. This contribution critically analyses the randomised controlled trials (RCTs) on the effectiveness of medical masks in preventing respiratory infections in university/community contexts and outdoor gatherings, with questions and answers based on reasoning where possible based on evidence. It discusses whether the evidence supporting the WHO positions is weak compared to more stringent policies; it considers some underestimated adverse effects of the prolonged use of masks in the community and especially outdoors, not only by persons doing physical activity. This paper discusses some differences between SARS and COVID-19 in the potential impact of the masks and proposes to consider the most valid evidence available, avoiding prolonged/continuous use without valid needs for face masks, especially outdoors, waiting for others pragmatic RCTs that clarify conclusively a net balance between expected benefits and possible damages. KEYWORDS: facemasks effectiveness; medical masks safety - side effects; medical masks and SARS-CoV-2.


Subject(s)
COVID-19/prevention & control , Communicable Disease Control/methods , Masks , Pandemics , Communicable Disease Control/legislation & jurisprudence , Humans , Italy , Randomized Controlled Trials as Topic
13.
Ter Arkh ; 93(1): 108-113, 2021 Jan 10.
Article in Russian | MEDLINE | ID: covidwho-1134694

ABSTRACT

During a pandemic, nonspecific immunoprophylaxis of SARS-CoV-2 infection and other acute respiratory infections (ARI), which can worsen the course of COVID-19, is increasingly in demand in addition to specific immunization. BCG vaccine appears to be one of the candidate immunostimulants in this regard. At the same time, other microbe-derived preparations capable of inducing a state of trained immunity deserve attention. BCG and other bacterial immunostimulatory agents containing a large number of biologically active subunits have long been considered as objects of search for promising pharmacological substances. The review analyzes the linkages between BCG, mycobacterial adjuvants, bacterial lysates, trained immunity, muramylpeptides (MPs) and NOD2 receptors in light of the choice of a low molecular weight alternative to multicomponent bacterial immunostimulants for ARI prevention during the COVID-19 pandemic. The search for key molecules by which bacteria stimulate innate and adaptive immune responses proceeds in a spiral. On different loops of this spiral, MPs have repeatedly reproduced the nonspecific effects of multicomponent bacterial adjuvants, vaccines and immunostimulants. MPs and peptidoglycans containing MPs determine the adjuvant properties of the cell walls of mycobacteria and their peptide-glycolipid fraction (wax D). MPs were able to replace Mycobacterium tuberculosis in complete Freunds adjuvant. MPs determine the NOD2-dependent ability of BCG to induce trained immunity. Probably, MPs provide NOD2-mediated long-term prophylactic action of bacterial lysates. All of the above has prompted revisiting the previously obtained evidence of the efficacy of glucosaminylmuramyl dipeptide (GMDP) as a NOD2 agonist in treatment/prevention of respiratory infections. We speculate here that MPs, in particular GMDP, at rational dosing regimens will be able to reproduce many aspects of the nonspecific effects of BCG and multicomponent bacterial immunostimulants in preventing ARI during the COVID-19 pandemic and in the post-pandemic period.


Subject(s)
COVID-19 , Pandemics , BCG Vaccine , Cell Extracts , Humans , Immunity, Innate , Molecular Weight , SARS-CoV-2
14.
Viruses ; 13(2)2021 02 15.
Article in English | MEDLINE | ID: covidwho-1122257

ABSTRACT

Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main protease (Mpro) in the replication of SARS-CoV-2 which makes it an attractive target for antiviral drug development, including pharmaceutical repurposing and other medicinal chemistry approaches. Identification of natural products with considerable inhibitory potential against SARS-CoV-2 could be beneficial as a rapid and potent alternative with drug-likeness by comparison to de novo antiviral drug discovery approaches. Thereof, we carried out the structure-based screening of natural products from Echinacea-angustifolia, commonly used to prevent cold and other microbial respiratory infections, targeting SARS-CoV-2 Mpro. Four natural products namely, Echinacoside, Quercetagetin 7-glucoside, Levan N, Inulin from chicory, and 1,3-Dicaffeoylquinic acid, revealed significant docking energy (>-10 kcal/mol) in the SARS-CoV-2 Mpro catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (<-4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 Mpro with selected natural products showed conformational stability through molecular dynamics. Exploring the end-point net binding energy exhibited substantial contribution of Coulomb and van der Waals interactions to the stability of respective docked conformations. These results advocated the natural products from Echinacea angustifolia for further experimental studies with an elevated probability to discover the potent SARS-CoV-2 Mpro antagonist with higher affinity and drug-likeness.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Echinacea/chemistry , Protease Inhibitors/chemistry , Binding Sites , Drug Discovery , Flavones/chemistry , Fructans/chemistry , Glycosides/chemistry , Inulin/chemistry , Molecular Docking Simulation , Phytochemicals/chemistry , Protein Binding , Quinic Acid/analogs & derivatives , Quinic Acid/chemistry
15.
Ter Arkh ; 92(12): 195-200, 2020 Dec 15.
Article in Russian | MEDLINE | ID: covidwho-1090089

ABSTRACT

It has long been known that Bacillus CalmetteGurin (BCG) vaccine provides nonspecific protection against many non-mycobacterial infections, which has been discussed in the last decade through the prism of the concept of trained immunity. Within the framework of this concept, a persistent increase in resistance to various pathogens, which occurs after an infectious disease or exposure to certain microbial agents, is associated with epigenetic reprogramming of innate immune cells and their bone marrow progenitors. The COVID-19 pandemic has drawn attention of scientists and practitioners to BCG as an inducer of trained immunity. A number of epidemiological studies have suggested a negative association between the coverage of the population with BCG vaccination and the burden of SARS-CoV-2 infection. A series of independent clinical studies of the effectiveness of this vaccine in non-specific prevention of COVID-19 has been initiated in different countries. Recently, the key role of cytosolic NOD2 receptors in BCG-induced trained immunity has been proven. This actualizes the search for effective immunoactive preparations for prevention of respiratory infections in the pandemic among low molecular weight peptidoglycan fragments of the bacterial cell wall, muramylpeptides (MPs), which are known to be NOD2 agonists. The review highlights the proven and proposed linkages between BCG, MPs, NOD2 and trained immunity in the light of the COVID-19 pandemic. Analysis of the data presented indicates the prospects for preclinical and clinical studies of MPs as potential drugs for nonspecific prevention of SARS-CoV-2 infection and/or other respiratory infections in risk groups during the pandemic. First of all, attention should be paid to glucosaminylmuramyl dipeptide, approved for clinical use in Russia and a number of post-Soviet countries for the complex treatment and prevention of acute and recurrent respiratory infections.


Subject(s)
Bacillus , COVID-19 , BCG Vaccine , Humans , Immunity, Innate , Pandemics , Russia , SARS-CoV-2
16.
Viruses ; 13(2)2021 02 15.
Article in English | MEDLINE | ID: covidwho-1085037

ABSTRACT

Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main protease (Mpro) in the replication of SARS-CoV-2 which makes it an attractive target for antiviral drug development, including pharmaceutical repurposing and other medicinal chemistry approaches. Identification of natural products with considerable inhibitory potential against SARS-CoV-2 could be beneficial as a rapid and potent alternative with drug-likeness by comparison to de novo antiviral drug discovery approaches. Thereof, we carried out the structure-based screening of natural products from Echinacea-angustifolia, commonly used to prevent cold and other microbial respiratory infections, targeting SARS-CoV-2 Mpro. Four natural products namely, Echinacoside, Quercetagetin 7-glucoside, Levan N, Inulin from chicory, and 1,3-Dicaffeoylquinic acid, revealed significant docking energy (>-10 kcal/mol) in the SARS-CoV-2 Mpro catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (<-4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 Mpro with selected natural products showed conformational stability through molecular dynamics. Exploring the end-point net binding energy exhibited substantial contribution of Coulomb and van der Waals interactions to the stability of respective docked conformations. These results advocated the natural products from Echinacea angustifolia for further experimental studies with an elevated probability to discover the potent SARS-CoV-2 Mpro antagonist with higher affinity and drug-likeness.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Echinacea/chemistry , Protease Inhibitors/chemistry , Binding Sites , Drug Discovery , Flavones/chemistry , Fructans/chemistry , Glycosides/chemistry , Inulin/chemistry , Molecular Docking Simulation , Phytochemicals/chemistry , Protein Binding , Quinic Acid/analogs & derivatives , Quinic Acid/chemistry
17.
Cytokine Growth Factor Rev ; 59: 101-110, 2021 06.
Article in English | MEDLINE | ID: covidwho-1014439

ABSTRACT

GM-CSF acts as a pro-inflammatory cytokine and a key growth factor produced by several immune cells such as macrophages and activated T cells. In this review, we discuss recent studies that point to the crucial role of GM-CSF in the immune response against infections. Upon induction, GM-CSF activates four main signalling networks including the JAK/STAT, PI3K, MAPK, and NFκB pathways. Many of these transduction pathways such as JAK/STAT signal via proteins commonly activated with other antiviral signalling cascades, such as those induced by IFNs. GM-CSF also helps defend against respiratory infections by regulating alveolar macrophage differentiation and enhancing innate immunity in the lungs. Here, we also summarize the numerous clinical trials that have taken advantage of GM-CSF's mechanistic attributes in immunotherapy. Moreover, we discuss how GM-CSF is used as an adjuvant in vaccines and how its activity is interfered with to reduce inflammation such as in the case of COVID-19. This review brings forth the current knowledge on the antiviral actions of GM-CSF, the associated signalling cascades, and its application in immunotherapy.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Antiviral Agents , COVID-19 Vaccines/immunology , COVID-19/immunology , Granulocyte-Macrophage Colony-Stimulating Factor , MAP Kinase Signaling System , SARS-CoV-2/immunology , Animals , Antiviral Agents/immunology , Antiviral Agents/therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Humans , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/immunology , Macrophages, Alveolar/immunology , Recombinant Proteins/immunology , Recombinant Proteins/therapeutic use
18.
Geriatr Psychol Neuropsychiatr Vieil ; 19(1): 20-29, 2021 Mar 01.
Article in French | MEDLINE | ID: covidwho-992938

ABSTRACT

After 12 months of viral circulation, the SARS-CoV-2 has infected millions of people around the world, leaving hundreds of thousands dead. With the lack of effective therapy and vaccination against COVID-19, focusing on the immediate repurposing of existing drugs gives hope of curbing the pandemic. Vitamin D is a possible candidate discussed in a high amount of publications. Randomized clinical trials show that vitamin D supplementation significantly reduces the risk of respiratory infections. There are also many evidences that hypovitaminosis D is an independent (and easily modifiable) risk factor for severe forms of COVID-19 and death. Vitamin D supplementation is a simple, safe and inexpensive measure, which is effective in correcting hypovitaminosis D found in 40-50% of the French population and in more than 80% of adults with COVID-19. In this position paper, we propose simple regimens (adapted to the pharmaceutical forms currently available in France) for vitamin D supplementation in adults with or without COVID-19.


Subject(s)
COVID-19/drug therapy , Vitamin D/therapeutic use , Adult , COVID-19/mortality , Dietary Supplements , France , Humans , Randomized Controlled Trials as Topic , Risk Factors , Survival Rate , Vitamin D Deficiency/complications , Vitamin D Deficiency/drug therapy
19.
Front Immunol ; 11: 574029, 2020.
Article in English | MEDLINE | ID: covidwho-976251

ABSTRACT

From Pauling's theories to the present, considerable understanding has been acquired of both the physiological role of vitamin C and of the impact of vitamin C supplementation on the health. Although it is well known that a balanced diet which satisfies the daily intake of vitamin C positively affects the immune system and reduces susceptibility to infections, available data do not support the theory that oral vitamin C supplements boost immunity. No current clinical recommendations support the possibility of significantly decreasing the risk of respiratory infections by using high-dose supplements of vitamin C in a well-nourished general population. Only in restricted subgroups (e.g., athletes or the military) and in subjects with a low plasma vitamin C concentration a supplementation may be justified. Furthermore, in categories at high risk of infection (i.e., the obese, diabetics, the elderly, etc.), a vitamin C supplementation can modulate inflammation, with potential positive effects on immune response to infections. The impact of an extra oral intake of vitamin C on the duration of a cold and the prevention or treatment of pneumonia is still questioned, while, based on critical illness studies, vitamin C infusion has recently been hypothesized as a treatment for COVID-19 hospitalized patients. In this review, we focused on the effects of vitamin C on immune function, summarizing the most relevant studies from the prevention and treatment of common respiratory diseases to the use of vitamin C in critical illness conditions, with the aim of clarifying its potential application during an acute SARS-CoV2 infection.


Subject(s)
Ascorbic Acid/immunology , Ascorbic Acid/therapeutic use , COVID-19/drug therapy , Common Cold/drug therapy , Common Cold/prevention & control , SARS-CoV-2 , Vitamins/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Ascorbic Acid/adverse effects , COVID-19/virology , Child , Child, Preschool , Critical Illness , Dietary Supplements , Female , Humans , Infant , Male , Middle Aged , Young Adult
20.
Euro Surveill ; 25(49)2020 12.
Article in English | MEDLINE | ID: covidwho-972565

ABSTRACT

BackgroundEvidence for face-mask wearing in the community to protect against respiratory disease is unclear.AimTo assess effectiveness of wearing face masks in the community to prevent respiratory disease, and recommend improvements to this evidence base.MethodsWe systematically searched Scopus, Embase and MEDLINE for studies evaluating respiratory disease incidence after face-mask wearing (or not). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention were performed, subgrouped by design, setting, face barrier type, and who wore the mask. Preferred outcome was influenza-like illness. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality assessment was undertaken and evidence base deficits described.Results33 studies (12 randomised control trials (RCTs)) were included. Mask wearing reduced primary infection by 6% (odds ratio (OR): 0.94; 95% CI: 0.75-1.19 for RCTs) to 61% (OR: 0.85; 95% CI: 0.32-2.27; OR: 0.39; 95% CI: 0.18-0.84 and OR: 0.61; 95% CI: 0.45-0.85 for cohort, case-control and cross-sectional studies respectively). RCTs suggested lowest secondary attack rates when both well and ill household members wore masks (OR: 0.81; 95% CI: 0.48-1.37). While RCTs might underestimate effects due to poor compliance and controls wearing masks, observational studies likely overestimate effects, as mask wearing might be associated with other risk-averse behaviours. GRADE was low or very low quality.ConclusionWearing face masks may reduce primary respiratory infection risk, probably by 6-15%. It is important to balance evidence from RCTs and observational studies when their conclusions widely differ and both are at risk of significant bias. COVID-19-specific studies are required.


Subject(s)
COVID-19/prevention & control , Eye Protective Devices , Influenza, Human/prevention & control , Masks , Picornaviridae Infections/prevention & control , Respiratory Tract Infections/prevention & control , Tuberculosis/prevention & control , COVID-19/transmission , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Humans , Influenza, Human/transmission , Picornaviridae Infections/transmission , Respiratory Protective Devices , Respiratory Tract Infections/transmission , SARS-CoV-2 , Tuberculosis/transmission
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