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1.
Nutrients ; 12(6)2020 Jun 10.
Article in English | MEDLINE | ID: covidwho-1725886

ABSTRACT

Infection caused by the SARS-CoV-2 coronavirus worldwide has led the World Health Organization to declare a COVID-19 pandemic. Because there is no cure or treatment for this virus, it is emergingly urgent to find effective and validated methods to prevent and treat COVID-19 infection. In this context, alternatives related to nutritional therapy might help to control the infection. This narrative review proposes the importance and role of probiotics and diet as adjunct alternatives among the therapies available for the treatment of this new coronavirus. This review discusses the relationship between intestinal purine metabolism and the use of Lactobacillus gasseri and low-purine diets, particularly in individuals with hyperuricemia, as adjuvant nutritional therapies to improve the immune system and weaken viral replication, assisting in the treatment of COVID-19. These might be promising alternatives, in addition to many others that involve adequate intake of vitamins, minerals and bioactive compounds from food.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/therapy , Diet/methods , Immunomodulation/physiology , Pneumonia, Viral/therapy , Probiotics/therapeutic use , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/microbiology , Humans , Lactobacillus gasseri/immunology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/microbiology , Purines/immunology , Purines/metabolism , SARS-CoV-2 , Virus Replication/immunology
2.
Curr Med Chem ; 28(41): 8559-8594, 2021.
Article in English | MEDLINE | ID: covidwho-1690554

ABSTRACT

There is a new public health crisis threatening the world with the emergence and spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was later named novel coronavirus disease or COVID-19. It was then declared a pandemic by the World Health Organization on March 11, 2020. The virus originated in bats and was transmitted to humans through unknown intermediary animals in Wuhan, Hubei province, China, in December 2019. As of February 5, 2021, 103 million laboratory-confirmed cases and nearly 2.3 million deaths were reported globally. The number of death tolls continues to rise, and a large number of countries have been forced to maintain social distance in public place and enforce lockdown. As per literature, coronavirus is transmitted human to human or human to animal via airborne droplets. Coronavirus enters the human cell through the membrane ACE-2 exopeptidase receptor. WHO, ECDC, and ICMR advised avoiding public places and close contact with infected persons and pet animals. To date, there is no evidence of any effective treatment for COVID-19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine, and respiratory therapy. Although several therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In the present literature review, the causative agent of the pandemic, epidemiology, pathogenesis, and diagnostic techniques are discussed. Further, currently used treatment, preventive strategies along with vaccine trials and computational tools are all described in detail.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Communicable Disease Control , Humans , Hydroxychloroquine , Pandemics
3.
Rev Med Virol ; 31(5): 1-13, 2021 09.
Article in English | MEDLINE | ID: covidwho-1574052

ABSTRACT

Anti-tumour necrosis factor (TNF) biologicals, Dexamethasone and rIL-7 are of considerable interest in treating COVID-19 patients who are in danger of, or have become, seriously ill. Yet reducing sepsis mortality by lowering circulating levels of TNF lost favour when positive endpoints in earlier simplistic models could not be reproduced in well-conducted human trials. Newer information with anti-TNF biologicals has encouraged reintroducing this concept for treating COVID-19. Viral models have had encouraging outcomes, as have the effects of anti-TNF biologicals on community-acquired COVID-19 during their long-term use to treat chronic inflammatory states. The positive outcome of a large scale trial of dexamethasone, and its higher potency late in the disease, harmonises well with its capacity to enhance levels of IL-7Rα, the receptor for IL-7, a cytokine that enhances lymphocyte development and is increased during the cytokine storm. Lymphoid germinal centres required for antibody-based immunity can be harmed by TNF, and restored by reducing TNF. Thus the IL-7- enhancing activity of dexamethasone may explain its higher potency when lymphocytes are depleted later in the infection, while employing anti-TNF, for several reasons, is much more logical earlier in the infection. This implies dexamethasone could prove to be synergistic with rIL-7, currently being trialed as a COVID-19 therapeutic. The principles behind these COVID-19 therapies are consistent with the observed chronic hypoxia through reduced mitochondrial function, and also the increased severity of this disease in ApoE4-positive individuals. Many of the debilitating persistent aspects of this disease are predictably susceptible to treatment with perispinal etanercept, since they have cerebral origins.


Subject(s)
COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Dexamethasone/administration & dosage , Interleukin-17/administration & dosage , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , COVID-19/genetics , COVID-19/immunology , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/immunology , Humans , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
4.
Clin Infect Dis ; 73(11): 2073-2082, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560084

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19). METHODS: We first tested SARS-CoV-2-specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19-infected individuals (convalescent), asymptomatic polymerase chain reaction (PCR)-positive subjects, vaccinated individuals, non-intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment. RESULTS: We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2-specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2-specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity. CONCLUSIONS: Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an "off-the shelf" T-cell immunotherapy for high-risk patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Immunotherapy, Adoptive , T-Lymphocytes
5.
Clin Infect Dis ; 73(11): e4082-e4089, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1559187

ABSTRACT

BACKGROUND: Leronlimab, a monoclonal antibody blocker of C-C chemokine receptor type 5 originally developed to treat human immunodeficiency virus infection, was administered as an open-label compassionate-use therapeutic for coronavirus disease 2019 (COVID-19). METHODS: Twenty-three hospitalized severe/critical COVID-19 patients received 700 mg leronlimab subcutaneously, repeated after 7 days in 17 of 23 patients still hospitalized. Eighteen of 23 received other experimental treatments, including convalescent plasma, hydroxychloroquine, steroids, and/or tocilizumab. Five of 23 received leronlimab after blinded, placebo-controlled trials of remdesivir, sarilumab, selinexor, or tocilizumab. Outcomes and results were extracted from medical records. RESULTS: Mean age was 69.5 ±â€…14.9 years; 20 had significant comorbidities. At baseline, 22 were receiving supplemental oxygen (3 high flow, 7 mechanical ventilation). Blood showed markedly elevated inflammatory markers (ferritin, D-dimer, C-reactive protein) and an elevated neutrophil-to-lymphocyte ratio. By day 30 after initial dosing, 17 were recovered, 2 were still hospitalized, and 4 had died. Of the 7 intubated at baseline, 4 were fully recovered off oxygen, 2 were still hospitalized, and 1 had died. CONCLUSIONS: Leronlimab appeared safe and well tolerated. The high recovery rate suggested benefit, and those with lower inflammatory markers had better outcomes. Some, but not all, patients appeared to have dramatic clinical responses, indicating that unknown factors may determine responsiveness to leronlimab. Routine inflammatory and cell prognostic markers did not markedly change immediately after treatment, although interleukin-6 tended to fall. In some persons, C-reactive protein clearly dropped only after the second leronlimab dose, suggesting that a higher loading dose might be more effective. Future controlled trials will be informative.


Subject(s)
COVID-19 , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , COVID-19/therapy , HIV Antibodies , Humans , Immunization, Passive , Middle Aged , SARS-CoV-2 , Treatment Outcome
6.
Lancet Diabetes Endocrinol ; 9(5): 293-303, 2021 05.
Article in English | MEDLINE | ID: covidwho-1531930

ABSTRACT

BACKGROUND: In patients with type 2 diabetes, hyperglycaemia is an independent risk factor for COVID-19-related mortality. Associations between pre-infection prescription for glucose-lowering drugs and COVID-19-related mortality in people with type 2 diabetes have been postulated but only investigated in small studies and limited to a few agents. We investigated whether there are associations between prescription of different classes of glucose-lowering drugs and risk of COVID-19-related mortality in people with type 2 diabetes. METHODS: This was a nationwide observational cohort study done with data from the National Diabetes Audit for people with type 2 diabetes and registered with a general practice in England since 2003. Cox regression was used to estimate the hazard ratio (HR) of COVID-19-related mortality in people prescribed each class of glucose-lowering drug, with covariate adjustment with a propensity score to address confounding by demographic, socioeconomic, and clinical factors. FINDINGS: Among the 2 851 465 people with type 2 diabetes included in our analyses, 13 479 (0·5%) COVID-19-related deaths occurred during the study period (Feb 16 to Aug 31, 2020), corresponding to a rate of 8·9 per 1000 person-years (95% CI 8·7-9·0). The adjusted HR associated with recorded versus no recorded prescription was 0·77 (95% CI 0·73-0·81) for metformin and 1·42 (1·35-1·49) for insulin. Adjusted HRs for prescription of other individual classes of glucose-lowering treatment were as follows: 0·75 (0·48-1·17) for meglitinides, 0·82 (0·74-0·91) for SGLT2 inhibitors, 0·94 (0·82-1·07) for thiazolidinediones, 0·94 (0·89-0·99) for sulfonylureas, 0·94 (0·83-1·07) for GLP-1 receptor agonists, 1·07 (1·01-1·13) for DPP-4 inhibitors, and 1·26 (0·76-2·09) for α-glucosidase inhibitors. INTERPRETATION: Our results provide evidence of associations between prescription of some glucose-lowering drugs and COVID-19-related mortality, although the differences in risk are small and these findings are likely to be due to confounding by indication, in view of the use of different drug classes at different stages of type 2 diabetes disease progression. In the context of the COVID-19 pandemic, there is no clear indication to change prescribing of glucose-lowering drugs in people with type 2 diabetes. FUNDING: None.


Subject(s)
COVID-19/mortality , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/adverse effects , Aged , COVID-19/complications , Cohort Studies , England , Female , Humans , Male , Middle Aged , Proportional Hazards Models
7.
Ageing Res Rev ; 67: 101302, 2021 05.
Article in English | MEDLINE | ID: covidwho-1454005

ABSTRACT

BACKGROUND: Dementia is a debilitating syndrome that significantly impacts individuals over the age of 65 years. There are currently no disease-modifying treatments for dementia. Impairment of nutrient sensing pathways has been implicated in the pathogenesis of dementia, and may offer a novel treatment approach for dementia. AIMS: This systematic review collates all available evidence for Food and Drug Administration (FDA)-approved therapeutics that modify nutrient sensing in the context of preventing cognitive decline or improving cognition in ageing, mild cognitive impairment (MCI), and dementia populations. METHODS: PubMed, Embase and Web of Science databases were searched using key search terms focusing on available therapeutics such as 'metformin', 'GLP1', 'insulin' and the dementias including 'Alzheimer's disease' and 'Parkinson's disease'. Articles were screened using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). The risk of bias was assessed using the Cochrane Risk of Bias tool v 2.0 for human studies and SYRCLE's risk of bias tool for animal studies. RESULTS: Out of 2619 articles, 114 were included describing 31 different 'modulation of nutrient sensing pathway' therapeutics, 13 of which specifically were utilized in human interventional trials for normal ageing or dementia. Growth hormone secretagogues improved cognitive outcomes in human mild cognitive impairment, and potentially normal ageing populations. In animals, all investigated therapeutic classes exhibited some cognitive benefits in dementia models. While the risk of bias was relatively low in human studies, this risk in animal studies was largely unclear. CONCLUSIONS: Modulation of nutrient sensing pathway therapeutics, particularly growth hormone secretagogues, have the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Dementia , Aged , Cognitive Dysfunction/drug therapy , Disease Progression , Humans , Nutrients
8.
J Cancer Res Clin Oncol ; 147(5): 1469-1479, 2021 May.
Article in English | MEDLINE | ID: covidwho-1384445

ABSTRACT

INTRODUCTION: The severe acute respiratory syndrome-2 (SARS-CoV-2) pandemic disrupted medical care for persons with cancer including those with lymphoma. Many professional societies recommend postponing, decreasing, or stopping anti-cancer therapy in selected persons during the pandemic. Although seemingly sensible, these recommendations are not evidence-based and their impact on anxiety and health-related quality-of-life (HRQoL) is unknown. METHODS: We surveyed 2532 subjects including 1060 persons with lymphoma, 948 caregivers, and 524 normals using a purposed-designed questionnaire on a patient organization website. Respondents also completed the Zung Self-Rating Anxiety and patient respondents, the EORTC QLQ-C30 instruments to quantify anxiety, and HRQoL. We also evaluated caregiver support and an online education programme of the Chinese Society of Clinical Oncology (CSCO). Data of HRQoL from a 2019 pre-pandemic online survey of 1106 persons with lymphoma were a control. RESULTS: 33% (95% confidence interval [CI] 30, 36%) of lymphoma patients and 31% (28, 34%) of caregivers but only 21% (17, 24%) of normals had any level of anxiety (both pair-wise P < 0.001). Among lymphoma respondents, physical exercise and better caregiver support were associated with less anxiety, whereas female sex, receiving therapy, and reduced therapy intensity were associated with more anxiety. Paradoxically, lymphoma respondents during the pandemic had better HRQoL than pre-pandemic controls. Reduced therapy intensity was associated with worse HRQoL, whereas respondents who scored caregiver support and the online patient education programme high had better HRQoL. CONCLUSION: During the SARS-CoV-2 pandemic, lymphoma patients and their caregivers had significantly higher incidences of anxiety compared with normals. Lymphoma respondents reported better HRQoL compared with pre-pandemic controls. Reduced therapy intensity in persons with cancer may have unanticipated adverse effects on anxiety and HRQoL. Regular and intense support by caregivers and online education programmes alleviate anxiety and improve HRQoL.


Subject(s)
Anxiety/epidemiology , COVID-19/psychology , Lymphoma/therapy , Quality of Life/psychology , Withholding Treatment/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Caregivers/psychology , Depression/epidemiology , Female , Humans , Internet , Lymphoma/psychology , Male , Middle Aged , Psychosocial Support Systems , Risk , SARS-CoV-2 , Surveys and Questionnaires , Young Adult
9.
J Med Internet Res ; 23(7): e28346, 2021 07 08.
Article in English | MEDLINE | ID: covidwho-1314516

ABSTRACT

BACKGROUND: COVID-19 has affected individuals with lived experience of eating disorders (EDs), with many reporting higher psychological distress, higher prevalence of ED symptoms, and compensatory behaviors. The COVID-19 pandemic and the health and safety measures taken to contain its spread also disrupted routines and reduced access to familiar coping mechanisms, social support networks, and health care services. Social media and the ED communities on social media platforms have been an important source of support for individuals with EDs in the past. So far, it is unknown how discussions in online ED communities changed as offline support networks were disrupted and people spent more time at home in the first months of the COVID-19 pandemic. OBJECTIVE: The aim of this study is to identify changes in language content and style in an online ED community during the initial onset of the COVID-19 pandemic. METHODS: We extracted posts and their comments from the ED community on the social media website Reddit and concatenated them to comment threads. To analyze these threads, we applied top-down and bottom-up language analysis methods based on topic modeling with latent Dirichlet allocation and 13 indicators from the Linguistic Inquiry and Word Count program, respectively. Threads were split into prepandemic (before March 11, 2020) and midpandemic (after March 11, 2020) groups. Standardized mean differences were calculated to estimate change between pre- and midpandemic threads. RESULTS: A total of 17,715 threads (n=8772, 49.5% prepandemic threads; n=8943, 50.5% midpandemic threads) were extracted from the ED community and analyzed. The final topic model contained 21 topics. CIs excluding zero were found for standardized mean differences of 15 topics and 9 Linguistic Inquiry and Word Count categories covering themes such as ED symptoms, mental health, treatment for EDs, cognitive processing, social life, and emotions. CONCLUSIONS: Although we observed a reduction in discussions about ED symptoms, an increase in mental health and treatment-related topics was observed at the same time. This points to a change in the focus of the ED community from promoting potentially harmful weight loss methods to bringing attention to mental health and treatments for EDs. These results together with heightened cognitive processing, increased social references, and reduced inhibition of negative emotions detected in discussions indicate a shift in the ED community toward a pro-recovery orientation.


Subject(s)
COVID-19/epidemiology , Feeding and Eating Disorders/psychology , Language , Pandemics , Social Media , Social Support , Emotions , Feeding and Eating Disorders/physiopathology , Humans , Latent Class Analysis , Linguistics , Mental Health , Psychological Distress , SARS-CoV-2 , Weight Loss
10.
Trials ; 21(1): 956, 2020 Nov 23.
Article in English | MEDLINE | ID: covidwho-1277966

ABSTRACT

INTRODUCTION: Influenza is an important public health problem, but data on the impact of influenza among homeless shelter residents are limited. The primary aim of this study is to evaluate whether on-site testing and antiviral treatment of influenza in residents of homeless shelters reduces influenza spread in these settings. METHODS AND ANALYSIS: This study is a stepped-wedge cluster-randomized trial of on-site testing and antiviral treatment for influenza in nine homeless shelter sites within the Seattle metropolitan area. Participants with acute respiratory illness (ARI), defined as two or more respiratory symptoms or new or worsening cough with onset in the prior 7 days, are eligible to enroll. Approximately 3200 individuals are estimated to participate from October to May across two influenza seasons. All sites will start enrollment in the control arm at the beginning of each season, with routine surveillance for ARI. Sites will be randomized at different timepoints to enter the intervention arm, with implementation of a test-and-treat strategy for individuals with two or fewer days of symptoms. Eligible individuals will be tested on-site with a point-of-care influenza test. If the influenza test is positive and symptom onset is within 48 h, participants will be administered antiviral treatment with baloxavir or oseltamivir depending upon age and comorbidities. Participants will complete a questionnaire on demographics and symptom duration and severity. The primary endpoint is the incidence of influenza in the intervention period compared to the control period, after adjusting for time trends. TRIAL REGISTRATION: ClinicalTrials.gov NCT04141917 . Registered 28 October 2019. Trial sponsor: University of Washington.


Subject(s)
COVID-19 , Homeless Persons , Influenza, Human , Antiviral Agents/adverse effects , Humans , Influenza, Human/diagnosis , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Molecular Diagnostic Techniques , Point-of-Care Systems , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
11.
CMAJ Open ; 9(2): E693-E702, 2021.
Article in English | MEDLINE | ID: covidwho-1278708

ABSTRACT

BACKGROUND: Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death. METHODS: This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data. RESULTS: Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety. INTERPRETATION: There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT04329611.


Subject(s)
Ambulatory Care , COVID-19 , Hospitalization/statistics & numerical data , Hydroxychloroquine , Respiration, Artificial/statistics & numerical data , Ambulatory Care/methods , Ambulatory Care/statistics & numerical data , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/mortality , Early Termination of Clinical Trials , Female , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Independent Living/statistics & numerical data , Male , Middle Aged , Mortality , Outcome Assessment, Health Care , Preventive Health Services/methods , SARS-CoV-2/isolation & purification , Severity of Illness Index
12.
BMJ Open ; 11(6): e046799, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1276961

ABSTRACT

INTRODUCTION: There is an urgent need to idenfy treatments for COVID-19 that reduce illness duration and hospital admission in those at higher risk of a longer illness course and complications. METHODS AND ANALYSIS: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE trial is an open-label, multiarm, prospective, adaptive platform, randomised clinical trial to evaluate potential treatments for COVID-19 in the community. A master protocol governs the addition of new interventions as they become available, as well as the inclusion and cessation of existing intervention arms via frequent interim analyses. The first three interventions are hydroxychloroquine, azithromycin and doxycycline. Eligible participants must be symptomatic in the community with possible or confirmed COVID-19 that started in the preceding 14 days and either (1) aged 65 years and over or (2) aged 50-64 years with comorbidities. Recruitment is through general practice, health service helplines, COVID-19 'hot hubs' and directly through the trial website. Participants are randomised to receive either usual care or a study drug plus usual care, and outcomes are collected via daily online symptom diary for 28 days from randomisation. The research team contacts participants and/or their study partner following days 7, 14 and 28 if the online diary is not completed. The trial has two coprimary endpoints: time to first self-report of feeling recovered from possible COVID-19 and hospital admission or death from possible COVID-19 infection, both within 28 days from randomisation. Prespecified interim analyses assess efficacy or futility of interventions and to modify randomisation probabilities that allocate more participants to interventions with better outcomes. ETHICS AND DISSEMINATION: Ethical approval Ref: 20/SC/0158 South Central - Berkshire Research Ethics Committee; IRAS Project ID: 281958; EudraCT Number: 2020-001209-22. Results will be presented to policymakers and at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN86534580.


Subject(s)
COVID-19 , Aged , Humans , Hydroxychloroquine , Prospective Studies , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
13.
J Am Geriatr Soc ; 69(9): 2455-2463, 2021 09.
Article in English | MEDLINE | ID: covidwho-1276708

ABSTRACT

Geriatricians and others must embrace the emerging field of geroscience. Until recently geroscience research was pursued in laboratory animals, but now this field requires specialized expertise in the care of vulnerable older patients with multiple chronic diseases and geriatric syndromes, the population likely to benefit the most from emerging therapies. While chronological aging measures the inevitable passage of clock time that occurs equally for everyone, biological aging varies among individuals, and importantly, it is modifiable. Advances in our understanding of biological aging, the discovery of strategies for modifying its rate, and an appreciation of aging as a shared risk factor for chronic diseases have jointly led to the Geroscience Hypothesis. This hypothesis states that interventions modifying aging biology can slow its progression-resulting in the delay or prevention of the onset of multiple diseases and disorders. Here we wish to report on the Third Geroscience Summit held at National Institutes of Health on November 4-5, 2019, which highlighted the importance of engaging other disciplines including clinicians. Involvement by scientists with expertise in clinical trials, health outcomes research, behavioral and social sciences, health policy, and economics is urgently needed to translate geroscience discoveries from the bench to clinical care and health policy. Adding to the urgency of broadening this geroscience coalition is the emergence of biological aging as one the most important modifiable factors of COVID-19, combined with the inability of our society to once again recognize and confront aging as a priority and opportunity when facing these types of public health emergencies.


Subject(s)
Chronic Disease/prevention & control , Chronobiology Discipline , Geriatrics , Health Policy , Aged , Aged, 80 and over , Aging , COVID-19 , Female , Humans , Male , SARS-CoV-2
14.
Biosens Bioelectron ; 190: 113414, 2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1252505

ABSTRACT

Antibody detection methods for viral infections have received broad attention due to the COVID-19 pandemic. In addition, there remains an ever-increasing need to quantitatively evaluate the immune response to develop vaccines and treatments for COVID-19. Here, we report an analytical method for the rapid and quantitative detection of SARS-CoV-2 antibody in human serum by fluorescence polarization immunoassay (FPIA). A recombinant SARS-CoV-2 receptor binding domain (RBD) protein labeled with HiLyte Fluor 647 (F-RBD) was prepared and used for FPIA. When the anti-RBD antibody in human serum binds to F-RBD, the degree of polarization (P) increases by suppressing the rotational diffusion of F-RBD. The measurement procedure required only mixing a reagent containing F-RBD with serum sample and measuring the P value with a portable fluorescence polarization analyzer after 15 min incubation. We evaluated analytical performance of the developed FPIA system using 30 samples: 20 COVID-19 positive sera and 10 negative sera. The receiver operating characteristic curve drawn with the obtained results showed that this FPIA system had high accuracy for discriminating COVID-19 positive or negative serum (AUC = 0.965). The total measurement time was about 20 min, and the serum volume required for measurement was 0.25 µL. Therefore, we successfully developed the FPIA system that enables rapid and easy quantification of SARS-CoV-2 antibody. It is believed that our FPIA system will facilitate rapid on-site identification of infected persons and deepen understanding of the immune response to COVID-19.


Subject(s)
Biosensing Techniques , COVID-19 , Antibodies, Viral , Fluorescence Polarization Immunoassay , Humans , Pandemics , SARS-CoV-2
15.
Ann Med Psychol (Paris) ; 2021 May 28.
Article in French | MEDLINE | ID: covidwho-1252416

ABSTRACT

The epidemic context of Covid-19 and the containment measures, put in place since 16 March 2020, has significantly increased the number of emergencies calls in call center (SAMU). In the department of Pas-de-Calais, one step of the crisis measures was setting up a psychiatric regulation line, which aims to manage calls with strong emotional valence (in connexion with containment, anxiety related to the epidemic context, or break in psychiatric cares for people suffering of mental disorders). This psychiatric hotline was provided from 20 March 2020 to 15 May 2020 by fifteen psychiatric careers (psychiatrists, psychologists and psychiatric nurses) from the network of the medical-psychological emergency unit (unit of the emergency call center which aims to manage people involved in psychotraumatic events). In total, 556 calls were answered, i.e. an average of 9,8 calls per day. The typology of calls was in a quarter of the cases anxiety related to the fear of being infected, in the second quarter, adjustment disorders related to containment, and for about half of the calls, psychiatrics symptoms whether it was preexisting and increased by the discontinuation of care, or context-induced. The benefits identified by this device were as follows: -the discharge of time-consuming calls for the medical dispatcher assistant, -the expertise of a mental health professional, knowing the mental health network, to make the decision more fluid. Last but not least, it is interesting to note that the presence of the psychiatric regulator in the regulation room allowed a transfer of calls and a reciprocal acculturation. In view of the relevance of the establishment of a psychiatric regulation line in the epidemic context of Covid-19, it seems interesting to consider the sustainability of this system, which is part of a global context of evolution of the provision of emergency care.

16.
Adv Ther ; 38(7): 3550-3588, 2021 07.
Article in English | MEDLINE | ID: covidwho-1252244

ABSTRACT

People with multiple sclerosis (MS) are at risk for infections that can result in amplification of baseline symptoms and possibly trigger clinical relapses. Vaccination can prevent infection through the activation of humoral and cellular immune responses. This is particularly pertinent in the era of emerging novel vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). MS disease-modifying therapies (DMTs), which affect the immune system, may impact immune responses to COVID-19 vaccines in people with MS. The objective of this article is to provide information on immune system responses to vaccinations and review previous studies of vaccine responses in people with MS to support the safety and importance of receiving currently available and emerging COVID-19 vaccines. Immunological studies have shown that coordinated interactions between T and B lymphocytes of the adaptive immune system are key to successful generation of immunological memory and production of neutralizing antibodies following recognition of vaccine antigens by innate immune cells. CD4+ T cells are essential to facilitate CD8+ T cell and B cell activation, while B cells drive and sustain T cell memory. Data suggest that some classes of DMT, including type 1 interferons and glatiramer acetate, may not significantly impair the response to vaccination. DMTs-such as sphingosine-1-phosphate receptor modulators, which sequester lymphocytes from circulation; alemtuzumab; and anti-CD20 therapies, which rely on depleting populations of immune cells-have been shown to attenuate responses to conventional vaccines. Currently, three COVID-19 vaccines have been granted emergency use authorization in the USA on the basis of promising interim findings of ongoing trials. Because analyses of these vaccines in people with MS are not available, decisions regarding COVID-19 vaccination and DMT choice should be informed by data and expert consensus, and personalized with considerations for disease burden, risk of infection, and other factors.


Subject(s)
COVID-19 , Multiple Sclerosis , COVID-19 Vaccines , Glatiramer Acetate , Humans , SARS-CoV-2
17.
Clin Ther ; 43(6): e157-e162, 2021 06.
Article in English | MEDLINE | ID: covidwho-1245896

ABSTRACT

The use of monoclonal antibodies in children with certain conditions and at high risk for severe COVID-19 has been approved by the US Food and Drug Administration under the Emergency Use Authorization mechanism of the Federal Food, Drug, and Cosmetic Act. No data on the tolerability or efficacy of these therapies in persons <18 years of age are available; there is risk. Whether they will work is unknown, but they could. A disproportionate number of these children who meet the criteria for treatment with mAbs are from communities of black, Native American, and other race. How should health systems, hospitals, and clinicians balance the tensions between being seen as experimenting with an untested drug as opposed to withholding a potentially life-saving treatment? This article identifies, analyzes, and makes recommendations on the methods by which health systems, hospitals, and individual clinicians can ethically balance these tensions.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Antibodies, Monoclonal , Child , Humans , SARS-CoV-2 , United States , United States Food and Drug Administration
18.
Int J Endocrinol ; 2021: 5563960, 2021.
Article in English | MEDLINE | ID: covidwho-1247434

ABSTRACT

Although the numbers of aged populations have risen considerably in the last few decades, the current coronavirus disease 2019 (COVID-19) has revealed an extensive vulnerability among these populations. Sarcopenia is an age-related disorder that increases hospitalization, dependencies, and mortality in older adults. It starts to develop in midlife or even earlier as a result of unbalanced diet/poor nutrition and low levels of physical activity, in addition to chronic disorders such as obesity and diabetes mellitus. Given that social isolation is adopted as the most protective measure against COVID-19, the level of physical activity and the intake of adequate diet have considerably declined, especially among older adults-denoting an increased possibility for developing sarcopenia. Research also shows a higher vulnerability of sarcopenic people to COVID-19 as well as the development of wasting disorders such as sarcopenia and cachexia in a considerable proportion of symptomatic and recovering COVID-19 patients. Muscular wasting in COVID-19 is associated with poor prognosis. Accordingly, early detection and proper management of sarcopenia and wasting conditions in older adults and COVID-19 patients may minimize morbidity and mortality during the current COVID-19 crisis. This review explored different aspects of screening for sarcopenia, stressing their relevance to the detection of altered muscular structure and performance in patients with COVID-19. Current guidelines recommend prior evaluation of muscle strength by simple measures such as grip strength to identify individuals with proven weakness who then would be screened for muscle mass loss. The latter is best measured by MRI and CT. However, due to the high cost and radiation risk entailed by these techniques, other simpler and cheaper techniques such as DXA and ultrasound are given preference. Muscle loss in COVID-19 patients was measured during the acute phase by CT scanning of the pectoralis muscle simultaneously during a routine check for lung fibrosis, which seems to be an efficient evaluation of sarcopenia among those patients with no additional cost. In recovering patients, muscle strength and physical performance have been evaluated by electromyography and traditional tests such as the six-minute walk test. Effective preventive and therapeutic interventions are necessary in order to prevent muscle loss and associated physical decline in COVID-19 patients.

19.
Rev Gaucha Enferm ; 42(spe): e20200292, 2021.
Article in English, Portuguese | MEDLINE | ID: covidwho-1243889

ABSTRACT

OBJECTIVE: To reflect on the relationship between the nomophobia and the pandemic of COVID-19 and the nursing contributions to deal with this issue and its consequences. METHOD: This reflective and theoretical study was based on the dialogue between the scientific literature on the subject and in dialogue and conceptual perspective of comprehensive care. RESULTS: Nursing strives to harmonize observed problems and can support individuals to reflect and discover a potential harmful habit regarding the use of cell phones, especially when undergoing treatments for other diagnoses. FINAL CONSIDERATIONS: Nursing, when accessing the emotional and subjective aspects of those under their care, helps to alleviate the symptoms of nomophobia and, in tune with the patient, promotes harmony in the face of the COVID-19 pandemic.


Subject(s)
COVID-19/epidemiology , Cell Phone , Pandemics , Phobic Disorders/nursing , Social Isolation/psychology , COVID-19/psychology , Humans , Phobic Disorders/psychology
20.
Front Psychiatry ; 12: 639393, 2021.
Article in English | MEDLINE | ID: covidwho-1241207

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) pandemic has impacted people with substance use disorders (SUDs) worldwide, and healthcare systems have reorganized their services in response to the pandemic. Methods: One week after the announcement of the COVID-19 as a pandemic, in a global survey, 177 addiction medicine professionals described COVID-19-related health responses in their own 77 countries in terms of SUD treatment and harm reduction services. The health responses were categorized around (1) managerial measures and systems, (2) logistics, (3) service providers, and (4) vulnerable groups. Results: Respondents from over 88% of countries reported that core medical and psychiatric care for SUDs had continued; however, only 56% of countries reported having had any business continuity plan, and 37.5% of countries reported shortages of methadone or buprenorphine supplies. Participants of 41% of countries reported partial discontinuation of harm-reduction services such as needle and syringe programs and condom distribution. Fifty-seven percent of overdose prevention interventions and 81% of outreach services were also negatively impacted. Conclusions: Participants reported that SUD treatment and harm-reduction services had been significantly impacted globally early during the COVID-19 pandemic. Based on our findings, we highlight several issues and complications resulting from the pandemic concerning people with SUDs that should be tackled more efficiently during the future waves or similar pandemics. The issues and potential strategies comprise the following: (1) helping policymakers to generate business continuity plans, (2) maintaining the use of evidence-based interventions for people with SUDs, (3) being prepared for adequate medication supplies, (4) integrating harm reduction programs with other treatment modalities, and (5) having specific considerations for vulnerable groups such as immigrants and refugees.

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