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1.
Health Promot Int ; 36(5): 1324-1333, 2021 Oct 13.
Article | MEDLINE | ID: covidwho-2107483

ABSTRACT

Global shifts toward a disease-oriented, vertical approach to health has involved limiting the right for communities to participate in decision-making. Ecuador's authoritarian legacy has forced civil society and social organizations to adopt 'coping strategies', while large protests recently derived into violent struggles. The country has been severely hit by the COVID-19 pandemic amid corruption scandals involving hospital and food purchases by government during the response. This study critically examines how Ecuador's government took into consideration 'community participation' as a value and tenet of health promotion. Our systematic textual analysis focuses on 53 consecutive resolutions by the National Emergency Operations Committee (EOC) leading the decision-making processes, which, explicitly requires community participation. Results show that the 'lifecycle' of the central government's evolving policy framing centered on law enforcement and the private sector, followed by the social sector. Further, there is no evidence of stakeholders from civil society or organizations taking part in decision-making. Having legitimized the exclusion of community participation in Ecuador's response to the COVID-19 pandemic, it is possible that the government will fail to consider the wider social implications of its impact. In particular, the limits to local governments becoming informed and making decisions without mediation by the National EOC will further impede community participation in health decision-making in the future. This implies that local knowledge and experiences will also not inform health policy.


Subject(s)
COVID-19 , Community Participation , Ecuador , Health Policy , Humans , Pandemics , SARS-CoV-2
3.
Lancet ; 398(10303): 843-855, 2021 09 04.
Article in English | MEDLINE | ID: covidwho-2106189

ABSTRACT

BACKGROUND: A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community. METHODS: PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 µg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing. FINDINGS: The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI -0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19). INTERPRETATION: Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications. FUNDING: National Institute of Health Research and United Kingdom Research Innovation.


Subject(s)
Budesonide/administration & dosage , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Administration, Inhalation , Aged , Bayes Theorem , COVID-19/mortality , Female , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , SARS-CoV-2 , Treatment Outcome
4.
Lancet ; 396(10250): 535-544, 2020 08 22.
Article in English | MEDLINE | ID: covidwho-2106188

ABSTRACT

BACKGROUND: Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level. METHODS: 35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test). FINDINGS: Seroprevalence was 5·0% (95% CI 4·7-5·4) by the point-of-care test and 4·6% (4·3-5·0) by immunoassay, with a specificity-sensitivity range of 3·7% (3·3-4·0; both tests positive) to 6·2% (5·8-6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years (<3·1% by the point-of-care test). There was substantial geographical variability, with higher prevalence around Madrid (>10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1-92·1; both tests positive) to 91·8% (86·3-95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8-16·8) to 19·3% (17·7-21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1-24·9) to 35·8% (33·1-38·5). Only 19·5% (16·3-23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test. INTERPRETATION: The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave. FUNDING: Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Antibodies, Viral/blood , Betacoronavirus/immunology , COVID-19 , Child , Child, Preschool , Female , Humans , Immunoassay , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Point-of-Care Testing , Prevalence , Risk Factors , SARS-CoV-2 , Seroepidemiologic Studies , Spain/epidemiology , Young Adult
5.
Viral Immunol ; 35(9): 579-585, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2107328

ABSTRACT

Tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) is an interesting costimulatory molecule associated with T lymphocyte activation, and it mainly exerts its biological effects by binding to its receptors herpesvirus invasion mediator (HVEM) and lymphotoxin-ß receptor. Research shows that TNFSF14 plays a critical regulatory role in immune responses to viral infection, but its role is different in different diseases. TNFSF14 can be a cytokine neutralization target during novel coronavirus infection, and anti-TNFSF14 monoclonal antibody treatment can reduce the risk of respiratory failure and mortality. When the host is infected with adenovirus, TNFSF14 can be used as an inflammatory biomarker to indicate whether there was an adenovirus infection in the host and the degree of disease caused by viral infection. When hosts suffer influenza virus infection, the TNFSF14-HVEM signaling pathway can stimulate the maturation and proliferation of memory CD8+ T cells, which helps the host immune system stimulate a second immune response against respiratory virus infection. TNFSF14 can act as an immune adjuvant and enhance the immunogenicity of the human papillomavirus (HPV) DNA vaccine when the host is infected with HPV. During hepatitis virus infection, TNFSF14 acts as a proinflammatory factor, participates in inflammation and causes tissue damage. In conclusion, TNFSF14 plays different and significant roles in diverse viral infections. This article reviews the current research on TNFSF14 in antiviral immunity.


Subject(s)
COVID-19 , Papillomavirus Infections , Humans , Tumor Necrosis Factor Ligand Superfamily Member 14/genetics , Tumor Necrosis Factor Ligand Superfamily Member 14/metabolism , CD8-Positive T-Lymphocytes/metabolism , Antiviral Agents , Signal Transduction , Tumor Necrosis Factor-alpha
6.
Ann Med ; 54(1): 3189-3200, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2106905

ABSTRACT

INTRODUCTION: In order to identify therapeutic targets in Coronavirus disease 2019 (COVID-19), it is important to identify molecules involved in the biological responses that are modulated in COVID-19. Lysophosphatidic acids (LPAs) are involved in the pulmonary inflammation and fibrosis are one of the candidate molecules. The aim of this study was to evaluate the association between the serum levels of autotaxin (ATX), which are enzymes involved in the synthesis of lysophosphatidic acids. MATERIAL AND METHODS: We enrolled 134 subjects with COVID-19 and 58 normal healthy subjects for the study. We measured serum ATX levels longitudinally in COVID-19 patients and investigated the time course and the association with severity and clinical parameters. RESULTS: The serum ATX levels were reduced in all patients with COVID-19, irrespective of the disease severity, and were negatively associated with the serum CRP, D-dimer, and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels. DISCUSSION: Considering the biological properties of LPAs in the pulmonary inflammation and fibrosis, modulation of ATX might be compensatory biological responses to suppress immunological overreaction especially in the lung, which is an important underlying mechanism for the mortality of the disease. CONCLUSIONS: COVID-19 patients showed a decrease in the serum levels of ATX, irrespective of the disease severity. Key MessagesAutotaxin (ATX) is an enzyme involved in the synthesis of lysophosphatidic acid (LPA), which has been reported to be involved in pulmonary inflammation and fibrosis. Patients with COVID-19 show decrease in the serum levels of ATX. Modulation of ATX might be compensatory biological responses to suppress immunological overreaction.


Subject(s)
COVID-19 , Phosphoric Diester Hydrolases , Humans , COVID-19/blood , Fibrosis , Lung , Lysophospholipids , Phosphoric Diester Hydrolases/blood , SARS-CoV-2
7.
Ann Med ; 54(1): 2875-2884, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2106904

ABSTRACT

BACKGROUND: Since the emergence of the novel corona virus (SARS-Cov-2) in the late 2019 and not only the endoscopy practice and training but also the health care systems around the globe suffers. This systematic review focused the impact of Corona Virus Disease (COVID-19) on the endoscopy practice. METHODS: A web search of different databases combining different search terms describing the endoscopy practice and the COVID-19 pandemic was done. Articles were screened for selection of relevant articles in two steps: title and abstract step and full-text screening step, by two independent reviewers and any debate was solved by a third reviewer. RESULTS: Final studies included in qualitative synthesis were 47. The data shown in the relevant articles were evident for marked reduction in the volume of endoscopy, marked affection of colorectal cancer screening, impairments in the workflow, deficiency in personal protective equipment (PPE) and increased likelihood of catching the infection among both the staff and the patients. CONCLUSION: The main outcomes from this review are rescheduling of endoscopy procedures to be suitable with the situation of COVID-19 pandemic in each Country. Also, the endorsement of the importance of PPE use for health care workers and screening of COVID-19 infection pre-procedure.Key messagesThe data focussing Gastrointestinal Endoscopy and COVID-19 emerged from different areas around the globe. The data presented on the published studies were heterogeneous. However, there were remarkable reductions in the volume of GI endoscopy worldwideStaff reallocation added a burden to endoscopy practiceThere was a real risk for COVID-19 spread among both the staff and the patients.


Subject(s)
COVID-19 , Pandemics , Humans , Pandemics/prevention & control , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , Infection Control , Endoscopy, Gastrointestinal
8.
N Engl J Med ; 387(19): e56, 2022 11 10.
Article in English | MEDLINE | ID: covidwho-2106625
10.
N Engl J Med ; 387(19): 1813-1815, 2022 11 10.
Article in English | MEDLINE | ID: covidwho-2106615
11.
N Engl J Med ; 387(10): 955, 2022 09 08.
Article in English | MEDLINE | ID: covidwho-2106611
14.
Hamostaseologie ; 42(5): 285-286, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2106603

ABSTRACT

In the last couple of years sex specific health issues have continually been gaining attraction by physicians of different medical specialities. Sex differences have been described e.g. in the pathogenesis and mortality in patients affected by COVID-19, in metabolic regulation and cancer mechanisms.1 2 3 In the field of haemostasis, many aspects concerning risk factors, clinical presentation and management of thromboembolic disease and bleeding disorders also display sex differences.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombosis , Male , Female , Humans , Hemostasis , Women's Health
16.
Am J Speech Lang Pathol ; 31(6): 2825-2834, 2022 Nov 16.
Article in English | MEDLINE | ID: covidwho-2106540

ABSTRACT

PURPOSE: During the COVID-19 pandemic, clinicians and researchers have increasingly used remote online assessments to pursue their activities, but mostly with tests not validated for videoconference administration. This study aims to validate the remote online administration of picture description in Canadian French neurotypical speakers and to explore the thematic unit (TU) checklist recently developed. METHOD: Spoken discourse elicited through the picture description task of the Western Aphasia Battery-Revised (WAB-R) was collected from Canadian French neurotypical speakers from Québec aged between 50 and 79 years old. Forty-seven participants completed the task in person, and 49 participants completed the task by videoconference. Videos of each discourse sample were transcribed using CHAT conventions. Microstructural variables were extracted using the CLAN (Computerized Language ANalysis) program, whereas thematic informativeness was scored for each sample using TUs. Chi-square tests were conducted to compare both groups on each TU; t tests were also performed on the total score of TUs and microstructural variables. RESULTS: Groups were matched on sex, age, and education variables. The t tests revealed no intergroup difference for the total TU score and for the microstructural variables (e.g., mean length of utterances and number of words per minute). Chi-square tests showed no significant intergroup difference for all 16 TUs. CONCLUSIONS: These findings support remote online assessment of the picnic scene of the WAB-R picture description in Canadian French neurotypical speakers. These results also validate the 16 TUs most consistently produced. The use of videoconference could promote and improve the recruitment of participants who are usually less accessible, such as people using assistive mobility technologies. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21476961.


Subject(s)
Aphasia , COVID-19 , Humans , Middle Aged , Aged , Language , Pandemics , Canada , Videoconferencing
17.
Commun Biol ; 5(1): 1188, 2022 Nov 05.
Article in English | MEDLINE | ID: covidwho-2106511

ABSTRACT

SARS-CoV-2 has evolved continuously and accumulated spike mutations with each variant having a different binding for the cellular ACE2 receptor. It is not known whether the interactions between such mutated spikes and ACE2 glycans are conserved among different variant lineages. Here, we focused on three ACE2 glycosylation sites (53, 90 and 322) that are geometrically close to spike binding sites and investigated the effect of their glycosylation pattern on spike affinity. These glycosylation deletions caused distinct site-specific changes in interactions with the spike and acted cooperatively. Of note, the particular interaction profiles were conserved between the SARS-CoV-2 parental virus and the variants of concern (VOCs) Delta and Omicron. Our study provides insights for a better understanding of the importance of ACE2 glycosylation on ACE2/SARS-CoV-2 spike interaction and guidance for further optimization of soluble ACE2 for therapeutic use.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Humans , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2/genetics , SARS-CoV-2/genetics , Glycosylation , Peptidyl-Dipeptidase A , Protein Binding
18.
Commun Biol ; 5(1): 1179, 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2106510

ABSTRACT

Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of α-HCoVs S proteins, we isolated a panel of antibodies against the HCoV-229E S protein and characterized their epitopes and neutralizing potential. We found that the N-terminal domain of HCoV-229E S protein is antigenically dominant wherein an antigenic supersite is present and appears conserved in HCoV-NL63, which holds potential to serve as a pan-α-HCoVs epitope. In the receptor binding domain, a neutralizing epitope is captured in the end distal to the receptor binding site, reminiscent of the locations of the SARS-CoV-2 RBD cryptic epitopes. We also identified a neutralizing antibody that recognizes the connector domain, thus representing the first S2-directed neutralizing antibody against α-HCoVs. The unraveled HCoVs S proteins antigenic similarities and variances among genera highlight the challenges faced by pan-HCoV vaccine design while supporting the feasibility of broadly effective vaccine development against a subset of HCoVs.


Subject(s)
COVID-19 , Coronavirus 229E, Human , Humans , Spike Glycoprotein, Coronavirus/genetics , SARS-CoV-2 , Antigens, Viral , Epitopes , Antibodies, Neutralizing
19.
Commun Biol ; 5(1): 1170, 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2106509

ABSTRACT

The trimeric spike (S) glycoprotein, which protrudes from the SARS-CoV-2 viral envelope, binds to human ACE2, initiated by at least one protomer's receptor binding domain (RBD) switching from a "down" (closed) to an "up" (open) state. Here, we used large-scale molecular dynamics simulations and two-dimensional replica exchange umbrella sampling calculations with more than a thousand windows and an aggregate total of 160 µs of simulation to investigate this transition with and without glycans. We find that the glycosylated spike has a higher barrier to opening and also energetically favors the down state over the up state. Analysis of the S-protein opening pathway reveals that glycans at N165 and N122 interfere with hydrogen bonds between the RBD and the N-terminal domain in the up state, while glycans at N165 and N343 can stabilize both the down and up states. Finally, we estimate how epitope exposure for several known antibodies changes along the opening path. We find that the BD-368-2 antibody's epitope is continuously exposed, explaining its high efficacy.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2 , Peptidyl-Dipeptidase A , Polysaccharides , Epitopes
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