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1.
PLoS One ; 16(6): e0253110, 2021.
Article in English | MEDLINE | ID: covidwho-1496435

ABSTRACT

BACKGROUND: The World Health Organization recommends inpatient hospital treatment of young infants up to two months old with any sign of possible serious infection. However, each sign may have a different risk of death. The current study aims to calculate the case fatality ratio for infants with individual or combined signs of possible serious infection, stratified by inpatient or outpatient treatment. METHODS: We analysed data from the African Neonatal Sepsis Trial conducted in five sites in the Democratic Republic of the Congo, Kenya and Nigeria. Trained study nurses classified sick infants as pneumonia (fast breathing in 7-59 days old), severe pneumonia (fast breathing in 0-6 days old), clinical severe infection [severe chest indrawing, high (> = 38°C) or low body temperature (<35.5°C), stopped feeding well, or movement only when stimulated] or critical illness (convulsions, not able to feed at all, or no movement at all), and referred them to a hospital for inpatient treatment. Infants whose caregivers refused referral received outpatient treatment. The case fatality ratio by day 15 was calculated for individual and combined clinical signs and stratified by place of treatment. An infant with signs of clinical severe infection or severe pneumonia was recategorised as having low- (case fatality ratio ≤2%) or moderate- (case fatality ratio >2%) mortality risk. RESULTS: Of 7129 young infants with a possible serious infection, fast breathing (in 7-59 days old) was the most prevalent sign (26%), followed by high body temperature (20%) and severe chest indrawing (19%). Infants with pneumonia had the lowest case fatality ratio (0.2%), followed by severe pneumonia (2.0%), clinical severe infection (2.3%) and critical illness (16.9%). Infants with clinical severe infection had a wide range of case fatality ratios for individual signs (from 0.8% to 11.0%). Infants with pneumonia had similar case fatality ratio for outpatient and inpatient treatment (0.2% vs. 0.3%, p = 0.74). Infants with clinical severe infection or severe pneumonia had a lower case fatality ratio among those who received outpatient treatment compared to inpatient treatment (1.9% vs. 6.5%, p<0.0001). We recategorised infants into low-mortality risk signs (case fatality ratio ≤2%) of clinical severe infection (high body temperature, or severe chest indrawing) or severe pneumonia and moderate-mortality risk signs (case fatality ratio >2%) (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection). We found that both categories had four times lower case fatality ratio when treated as outpatient than inpatient treatment, i.e., 1.0% vs. 4.0% (p<0.0001) and 5.3% vs. 22.4% (p<0.0001), respectively. In contrast, infants with signs of critical illness had nearly two times higher case fatality ratio when treated as outpatient versus inpatient treatment (21.7% vs. 12.1%, p = 0.097). CONCLUSIONS: The mortality risk differs with clinical signs. Young infants with a possible serious infection can be grouped into those with low-mortality risk signs (high body temperature, or severe chest indrawing or severe pneumonia); moderate-mortality risk signs (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection), or high-mortality risk signs (signs of critical illness). New treatment strategies that consider differential mortality risks for the place of treatment and duration of inpatient treatment could be developed and evaluated based on these findings. CLINICAL TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.


Subject(s)
Fever/complications , Health Facilities/statistics & numerical data , Hospitalization/statistics & numerical data , Infant Mortality/trends , Infections/mortality , Pneumonia/mortality , Anti-Infective Agents/therapeutic use , Body Temperature , Democratic Republic of the Congo/epidemiology , Female , Humans , Infant , Infant, Newborn , Infections/drug therapy , Infections/epidemiology , Kenya/epidemiology , Male , Nigeria/epidemiology , Pneumonia/drug therapy , Pneumonia/epidemiology
2.
J Am Chem Soc ; 143(43): 17891-17909, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1483091

ABSTRACT

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.


Subject(s)
Anti-Infective Agents/chemistry , Drug Design , Phototherapy/methods , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Bacteria/drug effects , Biofilms/drug effects , Biofilms/radiation effects , Coloring Agents/chemistry , Coloring Agents/pharmacology , Equipment and Supplies/microbiology , Equipment and Supplies/virology , Escherichia coli/drug effects , Escherichia coli/physiology , Eye Diseases/drug therapy , Eye Diseases/pathology , Fungi/drug effects , Graphite/chemistry , Light , Nanoparticles/chemistry , Nanoparticles/toxicity , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Quantum Theory , Reactive Oxygen Species/metabolism , Viruses/drug effects
3.
Crit Care Med ; 49(11): 1974-1982, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1475880
4.
Naunyn Schmiedebergs Arch Pharmacol ; 394(12): 2471-2474, 2021 12.
Article in English | MEDLINE | ID: covidwho-1473989

ABSTRACT

The pathophysiological process of the disease, Covid-19, is mediated by innate immunity, with the presence of macrophages responsible for secreting type 1 and 6 interleukins (IL), tumor necrosis factor (TNF) leading to dilation of endothelial cells with a consequent increase in capillary permeability. The treatment of this disease has been much discussed, but the variability in the clinical picture, the difficulties for diagnosis and treatment, especially of those patients who have the most severe clinical condition of the disease. Immunization is an effective tool for controlling the spread and overload of health services, but its effectiveness involves high investments in the acquisition of inputs, development of vaccines, and logistics of storage and distribution. These factors can be obstacles for countries with lower economic, technological, and infrastructure indexes. Reflecting on these difficulties, we raised the possibility of adjuvant therapies with imminent research feasibility, as is the case with the use of carvacrol, a monoterpenic phenol whose has biological properties that serve as a barrier to processes mediated by free radicals, such as irritation and inflammation, due to its antioxidant action. Many authors highlighted the activity of carvacrol as a potent suppressor of COX-2 expression minimizing the acute inflammatory process, decreasing the release of some pro-inflammatory mediators such as IL-1ß, TNF-α, PGE2. Anyway, the benefits of carvacrol are numerous and the therapeutic possibilities too. With this description, the question arises: would carvacrol be a supporting treatment option, effective in minimizing the deleterious effects of Covid-19? There is still a lot to discover and research.


Subject(s)
Antioxidants/therapeutic use , COVID-19/drug therapy , COVID-19/metabolism , Cymenes/therapeutic use , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacology , COVID-19/immunology , Cymenes/pharmacology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/metabolism , Humans , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/immunology , Inflammation Mediators/metabolism
5.
Medicine (Baltimore) ; 100(19): e25923, 2021 May 14.
Article in English | MEDLINE | ID: covidwho-1455404

ABSTRACT

ABSTRACT: Blocking IL-6 pathways with sarilumab, a fully human anti-IL-6R antagonist may potentially curb the inflammatory storm of SARS-CoV2. In the present emergency scenario, we used "off-label" sarilumab in 5 elderly patients in life-threatening condition not candidates to further active measures. We suggest that sarilumab can modulate severe COVID-19-associated Cytokine Release Syndrome.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Interleukin-6/antagonists & inhibitors , Aged , Anti-Infective Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/physiopathology , Comorbidity , Critical Illness , Cytokine Release Syndrome/physiopathology , Humans , Hydroxychloroquine/therapeutic use , Male , Middle Aged , RNA, Viral , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS-CoV-2
6.
Curr Drug Discov Technol ; 17(1): 30-44, 2020.
Article in English | MEDLINE | ID: covidwho-1453168

ABSTRACT

The anti-infective potentials of the natural products are very well known for centuries and are a part of traditional healing. The foremost therapeutic classes include flavones, isoflavones, flavonols, flavanones, flavanols, proanthocyanidins, anthocyanidins, chalcones, and aurones. The chalcone or 1,3-diphenyl-2E-propene-1-one represents the class of natural products which are comprised of benzylideneacetophenone function; i.e. two aromatic moieties linked together by an α, ß-unsaturated carbonyl bridge comprising three-carbons. At present, chalcone is one of the privileged scaffolds that can be synthesized in the laboratory to derive different pharmacologically active compounds. This article is the continued form of the previously published work on anti-infective perspectives of chalcones (highlighted till 2015). The current work emphasizes on the discovery process of the chalcone in the period of 2016 to 2017 on malaria, trypanosomiasis, leishmaniasis, filaria, tuberculosis, netamodes, Human Immunodeficiency Virus (HIV), Tobacco Mosaic Virus (TMV), Severe Acute Respiratory Syndrome (SARS), and miscellaneous conditions. This review comprehensively focuses on the latest progress related with the anti-infective chalcones. The content includes the crucial structural features of chalcone scaffold including structure-activity relationship(s) along with their plausible mechanism of action(s) from the duration Jan 2016 to Dec 2017. This literature will be of prime interest to medicinal chemists in getting ideas and concepts for better rational development of potential anti-infective inhibitors.


Subject(s)
Anti-Infective Agents/pharmacology , Chalcones/pharmacology , Drug Discovery/trends , Infections/drug therapy , Anti-Infective Agents/chemistry , Anti-Infective Agents/therapeutic use , Chalcones/chemistry , Chalcones/therapeutic use , Humans , Structure-Activity Relationship
7.
Syst Rev ; 10(1): 242, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1430478

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) is accelerated by the widespread and often indiscriminate use of antimicrobials in humans, animals, and the environment. In 2015, the World Health Organization recognised AMR as one of the top ten global health threats, due to its potential to neutralise humanity's advancements in western medicine by enabling the emergence of new strains of existing pathogens, many of which have no available treatments. Over the past decade, several countries, including those in low- and middle-income contexts, have started implementing interventions to tackle AMR. However, economic evidence regarding the cost-effectiveness of these interventions remains weak. To address this evidence gap, we will conduct a systematic literature review to provide a comprehensive summary on the value for money of different AMR interventions. METHODS: We aim to conduct a systematic literature review of all available economic evaluations on interventions addressing AMR and will provide a narrative synthesis of our findings. Systematic searches for relevant studies will be performed across all suitable databases as well as in grey literature sources such as unpublished studies, reports, and other relevant documents. All economic evaluation studies will be included as long as they report an economic outcome and have stated that the analysed intervention will reduce antimicrobial resistance or antimicrobial use in the abstract. Those studies reporting clinical endpoints alone will be excluded. Selection for final inclusion and data extraction will be performed by two independent reviewers. DISCUSSION: The review will be one of the first of its kind, and the most recent, to systematically review literature on the cost-effectiveness of AMR interventions, an important evidence gap in the economics of AMR. The findings will enable policy and decision-makers, particularly in resource-constrained settings, to better use available resources when selecting interventions to address AMR burdens, SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020190310.


Subject(s)
Anti-Bacterial Agents , Anti-Infective Agents , Animals , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Cost-Benefit Analysis , Drug Resistance, Bacterial , Humans , Policy , Systematic Reviews as Topic
8.
Adv Skin Wound Care ; 34(10): 517-524, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1429312

ABSTRACT

GENERAL PURPOSE: To present a scoping review of preclinical and clinical trial evidence supporting the efficacy and/or safety of major alternative wound care agents to summarize their effects on validated elements of wound bed preparation and wound management paradigms. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Differentiate the effectiveness of the topical wound care agents included in this review.2. Compare the preventive efficacy of intravenous agents administered to trauma and surgical patients.3. Select the effectiveness of products in this review that are left in place after surgical procedures.4. Identify an oral agent that can be helpful in mitigating the effects of COVID-19.


Subject(s)
Dermatologic Agents/therapeutic use , Skin Care/methods , Wound Healing/physiology , Wounds and Injuries/therapy , Anti-Infective Agents/therapeutic use , COVID-19/epidemiology , Disease Management , Humans
9.
Molecules ; 26(18)2021 Sep 11.
Article in English | MEDLINE | ID: covidwho-1410347

ABSTRACT

Current studies suggest that cariogenic bacteria in dental plaque influence the severity of COVID-19 complications since the oral cavity is a reservoir for respiratory pathogens potentially responsible for the development of hospital-acquired pneumonia. This article focuses on the association between dental plaque and COVID-19 concerning the influence of altered oral biofilm on the risk of increased severity of SARS-CoV-2 infection. Moreover, it concentrates on the usefulness of propolis, with its apitherapeutic antibacterial properties, for treating oral bacterial infections co-occurring with SARS-CoV-2 infection. A review of the literature on PubMed, Cochrane Library and Medline between 2000 and 2021 revealed 56 published articles indicating that a link between dental plaque and COVID-19 complications was probable. Furthermore, they indicated that propolis may minimize COVID-19 severity by reducing dental plaque accumulation. The possibility that improved oral health could reduce the risk of COVID-19 complications should be of interest to scientists.


Subject(s)
Biofilms , COVID-19 , Dental Caries , Dental Plaque , Mouth Diseases , Propolis/therapeutic use , Animals , Anti-Infective Agents/therapeutic use , Biofilms/drug effects , COVID-19/drug therapy , COVID-19/microbiology , Dental Caries/drug therapy , Dental Caries/microbiology , Dental Plaque/drug therapy , Dental Plaque/microbiology , Humans , Mouth Diseases/drug therapy , Mouth Diseases/microbiology , Oral Health
10.
Crit Care ; 25(1): 317, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1379797

ABSTRACT

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .


Subject(s)
Bacterial Infections/etiology , COVID-19/complications , Mycoses/etiology , Anti-Infective Agents/therapeutic use , Bacterial Infections/drug therapy , Critical Illness , Humans , Mycoses/drug therapy
11.
J Mater Chem B ; 9(38): 7878-7908, 2021 10 06.
Article in English | MEDLINE | ID: covidwho-1373457

ABSTRACT

Infectious diseases caused by bacteria, viruses, and fungi and their global spread pose a great threat to human health. The 2019 World Health Organization report predicted that infection-related mortality will be similar to cancer mortality by 2050. Particularly, the global cumulative numbers of the recent outbreak of coronavirus disease (COVID-19) have reached 110.7 million cases and over 2.4 million deaths as of February 23, 2021. Moreover, the crisis of these infectious diseases exposes the many problems of traditional diagnosis, treatment, and prevention, such as time-consuming and unselective detection methods, the emergence of drug-resistant bacteria, serious side effects, and poor drug delivery. There is an urgent need for rapid and sensitive diagnosis as well as high efficacy and low toxicity treatments. The emergence of nanomedicine has provided a promising strategy to greatly enhance detection methods and drug treatment efficacy. Owing to their unique optical, magnetic, and electrical properties, nanoparticles (NPs) have great potential for the fast and selective detection of bacteria, viruses, and fungi. NPs exhibit remarkable antibacterial activity by releasing reactive oxygen species and metal ions, exerting photothermal effects, and causing destruction of the cell membrane. Nano-based delivery systems can further improve drug permeability, reduce the side effects of drugs, and prolong systemic circulation time and drug half-life. Moreover, effective drugs against COVID-19 are still lacking. Recently, nanomedicine has shown great potential to accelerate the development of safe and novel anti-COVID-19 drugs. This article reviews the fundamental mechanisms and the latest developments in the treatment and diagnosis of bacteria, viruses, and fungi and discusses the challenges and perspectives in the application of nanomedicine.


Subject(s)
Anti-Infective Agents/therapeutic use , Communicable Diseases/drug therapy , Nanomedicine , Anti-Infective Agents/chemistry , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Communicable Diseases/diagnosis , Communicable Diseases/microbiology , Communicable Diseases/virology , Drug Carriers/chemistry , Humans , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification
12.
Curr Opin Infect Dis ; 34(4): 365-371, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1341151

ABSTRACT

PURPOSE OF REVIEW: The coronavirus disease (COVID-19) pandemic has resulted in necessary modifications of infection control policies and practices in acute healthcare facilities globally. This is often accompanied by infrastructure modifications, ward redesignations, as well as healthcare staff redeployments and changes to infection prevention and control (IPC) practices. We review the potential for both negative and positive impacts these major changes can have on nosocomial transmission of multidrug-resistant organisms (MDROs). RECENT FINDINGS: Healthcare facilities around the world have reported outbreaks of MDROs during the COVID-19 pandemic. In contrast some centres have reported a decrease in baseline rates due to a number of possible factors. SUMMARY: While implementing crucial preventive measures for COVID-19, is it important to consider any collateral effects of changes in IPC and antimicrobial stewardship program (ASP) practices. The disruption caused to IPC and ASP practices during the pandemic are likely to see a counter intuitive increase in transmission of MDROs.


Subject(s)
COVID-19/epidemiology , Cross Infection/epidemiology , Cross Infection/etiology , Cross Infection/transmission , Drug Resistance, Microbial , Drug Resistance, Multiple , SARS-CoV-2 , Acute Disease , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Cross Infection/drug therapy , Disease Outbreaks , Hospitals , Humans , Infection Control/methods , Pandemics , Public Health Surveillance
14.
Future Microbiol ; 16: 919-925, 2021 08.
Article in English | MEDLINE | ID: covidwho-1329168

ABSTRACT

In the absence of potent antimicrobial agents, it is estimated that bacterial infections could cause millions of deaths. The emergence of COVID-19, its complex pathophysiology and the high propensity of patients to coinfections has resulted in therapeutic regimes that use a cocktail of antibiotics for disease management. Suboptimal antimicrobial stewardship in this era and the slow pace of drug discovery could result in large-scale drug resistance, narrowing future antimicrobial therapeutics. Thus, judicious use of current antimicrobials is imperative to keep up with existing and emerging infectious pathogens. Here, we provide insights into the potential implications of suboptimal antimicrobial stewardship, resulting from the emergence of COVID-19, on the spread of antimicrobial resistance.


Subject(s)
Antimicrobial Stewardship/methods , Bacterial Infections , COVID-19/epidemiology , Coinfection , Mycoses , Anti-Infective Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Coinfection/drug therapy , Coinfection/epidemiology , Hand Disinfection , Humans , Mycoses/drug therapy , Mycoses/epidemiology
15.
Infect Control Hosp Epidemiol ; 42(7): 864-868, 2021 07.
Article in English | MEDLINE | ID: covidwho-1316684

ABSTRACT

Rapid diagnostic testing (RDT) can provide prompt, accurate identification of infectious organisms and be a key component of antimicrobial stewardship (AMS) programs. However, their use is less widespread in Asia Pacific than western countries. Cost can be prohibitive, particularly in less resource-replete settings. A selective approach is required, possibly focusing on the initiation of antimicrobials, for differentiating bacterial versus viral infections and identifying locally relevant tropical diseases. Across Asia Pacific, more data are needed on RDT use within AMS, focusing on the impact on antimicrobial usage, patient morbidity and mortality, and cost effectiveness. Moreover, in the absence of formal guidelines, regional consensus statements to guide clinical practice are warranted. These will provide a regionally relevant definition for RDT; greater consensus on its role in managing infections; advice on implementation and overcoming barriers; and guidance on optimizing human resource capacity. By addressing these issues, the outcomes of AMS programs should improve.


Subject(s)
Anti-Infective Agents , Antimicrobial Stewardship , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Asia , Diagnostic Techniques and Procedures , Humans
16.
Infect Control Hosp Epidemiol ; 42(7): 810-816, 2021 07.
Article in English | MEDLINE | ID: covidwho-1310759

ABSTRACT

OBJECTIVE: Evaluate changes in antimicrobial use during COVID-19 and after implementation of a multispecialty COVID-19 clinical guidance team compared to pre-COVID-19 antimicrobial use. DESIGN: Retrospective observational study. SETTING: Tertiary-care academic medical center. PARTICIPANTS: Internal medicine and medical intensive care unit (MICU) provider teams and hospitalized COVID-19 patients. METHODS: Difference-in-differences analyses of antibiotic days of therapy per 1,000 patient days present (DOT) for internal medicine and MICU teams treating COVID-19 patients versus teams that did not were performed for 3 periods: before COVID-19, initial COVID-19 period, and after implementation of a multispecialty COVID-19 clinical guidance team which included daily, patient-specific antimicrobial stewardship recommendations. Patient characteristics associated with antibiotic DOT were evaluated using multivariable Poisson regression. RESULTS: In the initial COVID-19 period, compared to the pre-COVID-19 period, internal medicine and MICU teams increased weekly antimicrobial use by 145.3 DOT (95% CI, 35.1-255.5) and 204.0 DOT (95% CI, -16.9 to 424.8), respectively, compared to non-COVID-19 teams. In the intervention period, internal medicine and MICU COVID-19 teams both had significant weekly decreases of 362.3 DOT (95% CI, -443.3 to -281.2) and 226.3 DOT (95% CI, -381.2 to -71.3). Of 131 patients hospitalized with COVID-19, 86 (65.6%) received antibiotics; no specific patient factors were significantly associated with an expected change in antibiotic days. CONCLUSIONS: Antimicrobial use initially increased for COVID-19 patient care teams compared to pre-COVID-19 levels but significantly decreased after implementation of a multispecialty clinical guidance team, which may be an effective strategy to reduce unnecessary antimicrobial use.


Subject(s)
Anti-Infective Agents , COVID-19 , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Humans , Pandemics , SARS-CoV-2
17.
Ocul Immunol Inflamm ; 29(4): 751-752, 2021 May 19.
Article in English | MEDLINE | ID: covidwho-1307412

ABSTRACT

Coronavirus-19 (Covid-19), which has affected the whole world in a very short time, can infect the eye by using the Angiotensin-Converting Enzyme 2 receptor. Viral prevalence in the conjunctiva was reported to be between 3% and 16% in patients with Covid-19. Although Covid-19 has been reported to cause symptoms of conjunctivitis and rash in the eye, no complete evidence has yet been presented that the virus is transmitted from the eye. The low rate of PCR positivity in conjunctival swabs may be due to the effect of lactoferrin (LF), which is among the tear defense systems. LF, the natural protein found in tears, plays a major role in the eye's immune system. The antiviral effect of LF on the SARS-CoV pseudotype, which is in the same family as SARS-CoV-2, has been demonstrated in-vitro.


Subject(s)
COVID-19/complications , Eye Infections, Viral/prevention & control , Lactoferrin/therapeutic use , SARS-CoV-2 , Anti-Infective Agents/therapeutic use , COVID-19/virology , Eye Infections, Viral/etiology , Humans
18.
Lancet Respir Med ; 9(10): 1130-1140, 2021 10.
Article in English | MEDLINE | ID: covidwho-1305334

ABSTRACT

BACKGROUND: The antibacterial, anti-inflammatory, and antiviral properties of azithromycin suggest therapeutic potential against COVID-19. Randomised data in mild-to-moderate disease are not available. We assessed whether azithromycin is effective in reducing hospital admission in patients with mild-to-moderate COVID-19. METHODS: This prospective, open-label, randomised superiority trial was done at 19 hospitals in the UK. We enrolled adults aged at least 18 years presenting to hospitals with clinically diagnosed, highly probable or confirmed COVID-19 infection, with fewer than 14 days of symptoms, who were considered suitable for initial ambulatory management. Patients were randomly assigned (1:1) to azithromycin (500 mg once daily orally for 14 days) plus standard care or to standard care alone. The primary outcome was death or hospital admission from any cause over the 28 days from randomisation. The primary and safety outcomes were assessed according to the intention-to-treat principle. This trial is registered at ClinicalTrials.gov (NCT04381962) and recruitment is closed. FINDINGS: 298 participants were enrolled from June 3, 2020, to Jan 29, 2021. Three participants withdrew consent and requested removal of all data, and three further participants withdrew consent after randomisation, thus, the primary outcome was assessed in 292 participants (145 in the azithromycin group and 147 in the standard care group). The mean age of the participants was 45·9 years (SD 14·9). 15 (10%) participants in the azithromycin group and 17 (12%) in the standard care group were admitted to hospital or died during the study (adjusted OR 0·91 [95% CI 0·43-1·92], p=0·80). No serious adverse events were reported. INTERPRETATION: In patients with mild-to-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospital admission or death. Our findings do not support the use of azithromycin in patients with mild-to-moderate COVID-19. FUNDING: National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford and Pfizer.


Subject(s)
Anti-Infective Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Patient Admission/statistics & numerical data , Adult , COVID-19/virology , Female , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Standard of Care/statistics & numerical data , Treatment Outcome
19.
Nutr Diabetes ; 11(1): 20, 2021 06 23.
Article in English | MEDLINE | ID: covidwho-1281688

ABSTRACT

Defences to pathogens such as SarCoV2 in mammals involves interactions between immune functions and metabolic pathways to eradicate infection while preventing hyperinflammation. Amino acid metabolic pathways represent with other antimicrobial agent potential targets for therapeutic strategies. iNOS-mediated production of NO from Arg is involved in the innate inflammatory response to pathogens and NO overproduction can induce hyperinflammation. The two Arg-catabolising enzymes Arg1 and IDO1 reduce the hyperinflammation by an immunosuppressive effect via either Arg starvation (for Arg1) or via the immunoregulatory activity of the Arg-derived metabolites Kyn (for IDO1). In response to amino acid abundance mTOR activates the host protein translation and Coronaviruses use this machinery for their own protein synthesis and replication. In contrast GCN2, the sensor of amino acid starvation, activates pathways that restrict inflammation and viral replication. Gln depletion alters the immune response that become more suppressive, by favouring a regulatory T phenotype rather than a Th1 phenotype. Proliferating activated immune cells are highly dependent on Ser, activation and differentiation of T cells need enough Ser and dietary Ser restriction can inhibit their proliferation. Cys is strictly required for T-cell proliferation because they cannot convert Met to Cys. Restricting Met inhibits both viral RNA cap methylation and replication, and the proliferation of infected cells with an increased requirement for Met. Phe catabolism produces antimicrobial metabolites resulting in the inhibition of microbial growth and an immunosuppressive activity towards T lymphocytes.


Subject(s)
Amino Acids/metabolism , Immunity, Innate , Infections/therapy , Animals , Anti-Infective Agents/therapeutic use , Arginine/metabolism , Humans , Infections/metabolism , Inflammation/metabolism , Nitric Oxide Synthase Type II/metabolism , Signal Transduction , T-Lymphocytes/metabolism , TOR Serine-Threonine Kinases/metabolism , Virus Replication
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