Covid-19 – Ressources scientifiques

Cochrane France

Université de Paris

Inserm

APHP

Living mapping of research

Living network meta-analysis

Analyse recherche thérapeutique et méta-analyse en temps-réel

A suivre +++

Mapping des Cas/décès pays par pays

Courbes d’incidence pays par pays

Limites : pas de données sur le nombre de tests réalisés

La Haute Autorité de santé a   rendu fin septembre un avis favorable à l’utilisation des tests antigéniques   sur prélèvement nasopharyngé chez les personnes qui présentent des symptômes   de la COVID-19 : fièvre, toux sèche, perte de l’odorat ou du goût, etc. Elle   en a précisé les performances requises : une sensibilité minimale supérieure   à 80% et une spécificité minimale supérieure à 99%. Dans le même temps, la   circulation du virus s’est accélérée et il est essentiel d’offrir à chacun   une prise en charge optimale et de casser les chaînes de contamination pour   endiguer l’épidémie. Pour y parvenir, il est nécessaire de prendre en compte   d’autres paramètres que la sensibilité et la spécificité des tests, qui sont   des prérequis. Il faut d’une part tester le plus grand nombre de personnes   possible pour trouver plus de malades et d’autre part disposer de résultats   le plus rapidement possible pour mettre en place les mesures d’isolement,   tracer les personnes contacts et ainsi casser les chaines de contamination.   C’est ce qui conduit la HAS à définir la stratégie d’utilisation des tests   antigéniques dans la détection du virus. Ceux qui satisfont les critères de   la HAS sont un peu moins sensibles que les tests RT-PCR, mais sont quasiment   aussi spécifiques, permettent d’obtenir un résultat en moins de 30 minutes,   et sont réalisables en dehors des seuls laboratoires d’analyses de biologie   médicale. Aujourd’hui en France, le test RT-PCR sur prélèvement nasopharyngé   reste le test de référence dans la détection du virus SARS-CoV-2. Mais la   situation épidémique et les bonnes performances des tests antigéniques   conduisent la HAS à positionner les différents tests pour trois situations   cliniques : les patients symptomatiques, les personnes asymptomatiques   contacts détectées isolément ou au sein de clusters et les personnes   asymptomatiques qui vont être intégrées à un dépistage à grande échelle de   populations ciblées. En revanche, la HAS considère qu’il n’y a pas lieu   aujourd’hui de réaliser de dépistage non ciblé en population générale, compte   tenu de l’absence de bénéfice de ce dépistage et de son probable rendement   très faible.

Revue de littérature par I3M Institute

– Revue de littérature de qualité des   papiers acceptés pertinents selon l’équipe I3M

Institut Pasteur, Paris

Ressources bibliographiques sur le   SARS-CoV-2 et COVID-19 – Site de l’Institut Pasteur, Paris

international, peer-reviewed,   open access, general medical journal that publishes research and commentary   on clinical care, health policy, and global health across all health   disciplines and countries for clinicians, investigators

In this double-blind, placebo-controlled   randomized clinical trial that included 132 participants and was terminated   early, there was not a significant difference in reverse-transcriptase   polymerase chain reaction–confirmed SARS-CoV-2 incidence between hydroxychloroquine   and placebo cohorts

Site du NCBI sur littérature   scientifique COVID

Accès à toutes les dernières   publications par pays/date/domaine (mécanism, treatment, epidemic forectasting)

→ Pratique et complet +++

ASM JOURNAL

This is, to our knowledge, the first   BAC-based reverse genetics system for the generation of infectious   rSARS-CoV-2 that displays features in vivo similar to those of a natural   viral isolate. This SARS-CoV-2 BAC-based reverse genetics will facilitate studies   addressing several important questions in the biology of SARS-CoV-2, as well   as the identification of antivirals and development of vaccines for the   treatment of SARS-CoV-2 infection and associated COVID-19 disease.

ASM JOURNAL

Characterizing the asymptomatic spread of   SARS-CoV-2 is important for understanding the COVID-19 pandemic. This study   was aimed at determining asymptomatic spread of SARS-CoV-2 in a suburban,   Southern U.S. population during a period of state restrictions and physical   distancing mandates.

L’enquête EpiCoV a été élaborée par   l’Institut national de la santé et de la recherche médicale (Inserm) et la   DREES, en collaboration avec Santé publique France et l’Institut national de   la statistique et des études économiques (Insee) dans le contexte de la   pandémie de Covid-19. Cette enquête, réalisée auprès d’un échantillon   représentatif de la population, est la seule qui permet d’estimer la   diffusion de l’épidémie à un niveau national et départemental et les facteurs   notamment liés aux conditions de vie associés à l’exposition au virus. Elle   permet également d’étudier les répercussions du confinement et de l’épidémie   sur la population. D’après cette enquête, la séroprévalence du SARS-CoV-2,   c’est-à-dire la proportion de personnes avec des anticorps contre le virus,   estimée à partir de prélèvements réalisés au décours du confinement, en mai   2020, s’élève à 4,5 % en France métropolitaine parmi les personnes âgées de   15 ans ou plus. La séroprévalence est la plus élevée à Paris (9,0 %), dans   les départements de la petite couronne (9,5 %) et le Haut-Rhin (10,8 %).

US department of health & human   service

US department of health & human   service

A number of investigational   agents and drugs that are approved for other indications are currently being   studied in clinical trials for the treatment of COVID-19 and associated   complications.

US department of health &   human service

US department of health &   human service

We performed a cross-sectional   survey during 5 consecutive days in March 2020, within a tertiary referral   center, associated outpatient clinic, and two primary care outpatient   facilities in Paris. All SARS-CoV-2-positive patients hospitalized during the   study period and able to be interviewed (n = 198), hospital outpatients seen   during the previous month (n = 129), and all COVID-19-highly suspect patients   in two primary health centers (n = 63) were included. Hospitalized patients   were significantly more often male (64 vs 40%) and older (66 vs 43 years old   in median) and had significantly more comorbidities than outpatients.   Hyposmia and hypogeusia were reported by 33% of patients and occurred   significantly less frequently in hospitalized patients (12% and 13%,   respectively) than in the health centers’ outpatients (33% and 43%,   respectively) and in the hospital outpatients (65% and 60%, respectively).   Hyposmia and hypogeusia appeared more frequently after other COVID-19   symptoms. Patients with hyposmia and/or hypogeusia were significantly younger   and had significantly less respiratory severity criteria than patients   without these symptoms. Olfactory and gustatory dysfunction occurs frequently   in COVID-19, especially in young, non-severe patients. These symptoms might   be a useful tool for initial diagnostic work-up in patients with suspected   COVID-19.

US department of health &   human service

Learning from the lengthy fight against   HIV-1, influenza, and Ebola virus infection, broadly neutralizing antibodies   (bnAbs), directed at conserved regions of surface proteins crucial to virus   entry (Env, hemagglutinin, and GP, respectively), are an essential resource   for passive as well as active immunization. Rare in their emergence and   antigen recognition mode, bnAbs are active toward a large set of different   viral strains. Isolation, characterization and production of bnAbs lead to   their possible use in passive immunotherapy and form the basis for an   educated effort in the development of vaccines for universal coverage.   SARS-CoV-2-specific antibodies targeting the spike receptor binding domain   (RBD) may lead to antibody dependent enhancement (ADE) of infection, possibly   hampering the field of vaccine development. This perspective points to the   identification of conserved regions in the spike of SARS-CoV-2, SARS-CoV, and   MERS-CoV through investigation, dissection and recombinant production of   isolated moieties. These spike moieties should be capable of independent   folding and allow the detection as well as the elicitation of bnAbs, thus   setting the basis for an effective passive immunotherapy and the development   of a universal vaccine against human epidemic coronaviruses (HCoVs). SARS,   MERS and, most of all, COVID-19 demonstrate that humanity is the target of   HCoV, preparedness for future hits is thus no longer an option.

International   weekly journal of science

A recent genetic association study1   identified a gene cluster on chromosome 3 as a risk locus for respiratory   failure upon SARS-CoV-2 infection. A new study2 comprising 3,199 hospitalized   COVID-19 patients and controls finds that this is the major genetic risk   factor for severe SARS-CoV-2 infection and hospitalization (COVID-19 Host   Genetics Initiative). Here, we show that the risk is conferred by a genomic   segment of ~50 kb that is inherited from Neanderthals and is carried by ~50%   of people in South Asia and ~16% of people in Europe today.

Severe acute respiratory syndrome coronavirus   2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that   emerged in late 2019 and has caused a pandemic of acute respiratory disease,   named ‘coronavirus disease 2019’ (COVID-19), which threatens human health and   public safety. In this Review, we describe the basic virology of SARS-CoV-2,   including genomic characteristics and receptor use, highlighting its key   difference from previously known coronaviruses. We summarize current   knowledge of clinical, epidemiological and pathological features of COVID-19,   as well as recent progress in animal models and antiviral treatment   approaches for SARS-CoV-2 infection. We also discuss the potential wildlife   hosts and zoonotic origin of this emerging virus in detail.

The New England Journal of   Medecine

It’s time to change how we think about the   sensitivity of testing for Covid-19. The Food and Drug Administration (FDA)   and the scientific community are currently almost exclusively focused on test   sensitivity, a measure of how well an individual assay can detect viral   protein or RNA molecules. […] To defeat Covid-19, we believe that the FDA,   the CDC, the National Institutes of Health, and others must encourage   structured evaluations of tests in the context of planned testing regimens to   identify those that will provide the best Covid filters. Frequent use of   cheap, simple, rapid tests will accomplish that aim, even if their analytic   sensitivities are vastly inferior to those of benchmark tests.1 Such a   regimen can help us stop Covid in its tracks.

In this small study involving   older adults, adverse events associated with the mRNA-1273 vaccine were   mainly mild or moderate. The 100-μg dose induced higher binding- and   neutralizing-antibody titers than the 25-μg dose, which supports the use of   the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute   of Allergy and Infectious Diseases and others; mRNA-1273 Study   ClinicalTrials.gov number, NCT04283461. opens in new tab.)

Real-time tracking of pathogen evolution

Quelques images

REACTing : coordinating French research   response

Agence Nationale de Santé Publique

–    Veille documentaire assez complète tout en bas à droite de la page   (défaut : il faut retélécharger tous les pdf à chaque fois à bien ouvrir   celui du jour)

– Lien vers l’observatoire cartographique: GEODES à suivi indicateurs   (hospi, réa, décès,par région, classe d’age, …), intéressant +++

Revue scientifique américaine par   l’Association américaine pour l’avancement des sciences (AAAS)

A call for diagnostic tests to   report viral load

“Advocates point to new research indicating that CT values could help   doctors flag patients at high risk for serious disease. Recent findings also   suggest the numbers could help officials determine who is infectious and   should therefore be isolated and have their contacts tracked down. CT value   is an imperfect measure, advocates concede. But whether to add it to test   results “is one of the most pressing questions out there,” says Michael Mina,   a physician and epidemiologist at Harvard University’s T.H. Chan School of   Public Health.”

Revue scientifique américaine par   l’Association américaine pour l’avancement des sciences (AAAS)

In situ structural analysis of   SARS-CoV-2 spike reveals flexibility mediated by three hinges

“The spike protein (S) of severe acute respiratory syndrome coronavirus 2   (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine   development. In this study, we combined cryo–electron tomography, subtomogram   averaging, and molecular dynamics simulations to structurally analyze S in   situ. Compared with the recombinant S, the viral S was more heavily   glycosylated and occurred mostly in the closed prefusion conformation. We   show that the stalk domain of S contains three hinges, giving the head   unexpected orientational freedom. We propose that the hinges allow S to scan   the host cell surface, shielded from antibodies by an extensive glycan coat.   The structure of native S contributes to our understanding of SARS-CoV-2   infection and potentially to the development of safe vaccines.”

Revue scientifique américaine   par l’Association américaine pour l’avancement des sciences (AAAS)

Clinical outcome upon infection with   SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an   enrichment in rare variants predicted to be loss-of-function (LOF) at the 13   human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN)   immunity to influenza virus, in 659 patients with life-threatening COVID-19   pneumonia, relative to 534 subjects with asymptomatic or benign infection. By   testing these and other rare variants at these 13 loci, we experimentally   define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying   autosomal recessive or dominant deficiencies. We show that human fibroblasts   with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn   errors of TLR3- and IRF7-dependent type I IFN immunity can underlie   life-threatening COVID-19 pneumonia in patients with no prior severe   infection

Revue scientifique américaine   par l’Association américaine pour l’avancement des sciences (AAAS)

Understanding humoral responses to SARS-CoV-2   is critical for improving diagnostics, therapeutics, and vaccines. Deep   serological profiling of 232 COVID-19 patients and 190 pre-COVID-19 era   controls using VirScan revealed over 800 epitopes in the SARS-CoV-2 proteome,   including 10 epitopes likely recognized by neutralizing antibodies.   Pre-existing antibodies in controls recognized SARS-CoV-2 ORF1, while only   COVID-19 patients primarily recognized spike and nucleoprotein. A machine   learning model trained on VirScan data predicted SARS-CoV-2 exposure history   with 99% sensitivity and 98% specificity; a rapid Luminex-based diagnostic   was developed from the most discriminatory SARS-CoV-2 peptides. Individuals   with more severe COVID-19 exhibited stronger and broader SARS-CoV-2   responses, weaker antibody responses to prior infections, and higher   incidence of CMV and HSV-1, possibly influenced by demographic covariates.   Among hospitalized patients, males make greater SARS-CoV-2 antibody responses   than females.

Revue scientifique américaine   par l’Association américaine pour l’avancement des sciences (AAAS)

Researchers have used CRISPR gene-editing   technology to come up with a test that detects the pandemic coronavirus in   just 5 minutes. The diagnostic doesn’t require expensive lab equipment to run   and could potentially be deployed at doctor’s offices, schools, and office   buildings.

Revue scientifique américaine   par l’Association américaine pour l’avancement des sciences (AAAS)

Advocates point to new research indicating   that CT values could help doctors flag patients at high risk for serious   disease. Recent findings also suggest the numbers could help officials   determine who is infectious and should therefore be isolated and have their   contacts tracked down. CT value is an imperfect measure, advocates concede.   But whether to add it to test results “is one of the most pressing questions   out there,” says Michael Mina, a physician and epidemiologist at Harvard   University’s T.H. Chan School of Public Health.

Revue scientifique américaine   par l’Association américaine pour l’avancement des sciences (AAAS)

The spike protein (S) of severe acute   respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry   and is the primary focus for vaccine development. In this study, we combined   cryo–electron tomography, subtomogram averaging, and molecular dynamics   simulations to structurally analyze S in situ. Compared with the recombinant   S, the viral S was more heavily glycosylated and occurred mostly in the   closed prefusion conformation. We show that the stalk domain of S contains   three hinges, giving the head unexpected orientational freedom. We propose   that the hinges allow S to scan the host cell surface, shielded from   antibodies by an extensive glycan coat. The structure of native S contributes   to our understanding of SARS-CoV-2 infection and potentially to the   development of safe vaccines

Revue scientifique américaine   par l’Association américaine pour l’avancement des sciences (AAAS)

This study confirms that serum and saliva IgG   antibodies to SARS-CoV-2 are maintained in the majority of COVID-19 patients   for at least 3 months PSO. IgG responses in saliva may serve as a surrogate   measure of systemic immunity to SARS-CoV-2 based on their correlation with   serum IgG responses.

Revue scientifique américaine   par l’Association américaine pour l’avancement des sciences (AAAS)

An urgent global quest for effective   therapies to prevent and treat COVID-19 disease is ongoing. We previously   described REGN-COV2, a cocktail of two potent neutralizing antibodies   (REGN10987+REGN10933) targeting non-overlapping epitopes on the SARS-CoV-2   spike protein. In this report, we evaluate the in vivo efficacy of this   antibody cocktail in both rhesus macaques, which may model mild disease, and   golden hamsters, which may model more severe disease. We demonstrate that   REGN-COV-2 can greatly reduce virus load in lower and upper airways and   decrease virus induced pathological sequalae when administered   prophylactically or therapeutically in rhesus macaques. Similarly,   administration in hamsters limits weight loss and decreases lung titers and   evidence of pneumonia in the lungs. Our results provide evidence of the   therapeutic potential of this antibody cocktail.

online collection of scientific,   technological and medical journals, books and reference works

This study investigates the   association between the treatment with hydroxychloroquine and mortality in   patients admitted with COVID-19. Routinely recorded, clinical data, up to the   24th of April 2020, from the 2075 patients with COVID-19, admitted in 17 hospitals   in Spain between the 1st of March and the 20th of April 2020 were used. The   following variables were extracted for this study: age, gender, temperature,   and saturation of oxygen on admission, treatment with hydroxychloroquine,   azithromycin, heparin, steroids, tocilizumab, a combination of lopinavir with   ritonavir, and oseltamivir, together with data on mortality. Multivariable   logistic regression models were used to investigate the associations. At the   time of collecting the data, 301 patients had died, 1449 had been discharged   home from the hospitals, 240 were still admitted, and 85 had been transferred   to hospitals not included in the study. Median follow-up time was 8 (IQR   5–12) days. Hydroxychloroquine had been used in 1857 patients. Hydroxychloroquine   was associated with lower mortality when the model was adjusted for age and   gender, with OR (95% CI): 0.44 (0.29–0.67). This association remained   significant when saturation of oxygen < 90% and temperature > 37 °C   were added to de model with OR 0.45 (0.30–0.68) p < 0.001, and also when   all the other drugs, and time of admission, were included as covariates. The   association between hydroxychloroquine and lower mortality observed in this   study can be acknowledged by clinicians in hospitals and in the community.   Randomized-controlled trials to assess the causal effects of   hydroxychloroquine in different therapeutic regimes are required.

Revue scientifique médicale   hebdomadaire britannique

Genomic evidence for reinfection   with SARS-CoV-2: a case study

“These findings suggest that the patient was infected by SARS-CoV-2 on two   separate occasions by a genetically distinct virus. Thus, previous exposure   to SARS-CoV-2 might not guarantee total immunity in all cases. All   individuals, whether previously diagnosed with COVID-19 or not, should take   identical precautions to avoid infection with SARS-CoV-2. The implications of   reinfections could be relevant for vaccine development and application.”

Revue scientifique médicale   hebdomadaire britannique

Our findings suggest that environmental   contamination leading to SARS-CoV-2 transmission is unlikely to occur in   real-life conditions, provided that standard cleaning procedures and   precautions are enforced. These data would support Goldman’s point that the   chance of transmission through inanimate surfaces is less frequent than   hitherto recognised

Revue scientifique médicale   hebdomadaire britannique

To summarise, false-positive   COVID-19 swab test results might be increasingly likely in the current   epidemiological climate in the UK, with substantial consequences at the   personal, health system, and societal levels (panel). Several measures might   help to minimise false-positive results and mitigate possible consequences.   Firstly, stricter standards should be imposed in laboratory testing. This   includes the development and implementation of external quality assessment   schemes and internal quality systems, such as automatic blinded replication   of a small number of tests for performance monitoring to ensure   false-positive and false-negative rates remain low, and to permit withdrawal   of a malfunctioning test at the earliest possibility. Secondly, pretest   probability assessments should be considered, and clear evidence-based   guidelines on interpretation of test results developed. Thirdly, policies   regarding the testing and prevention of virus transmission in health-care   workers might need adjustments, with an immediate second test implemented for   any health-care worker testing positive. Finally, research is urgently   required into the clinical and epidemiological significance of prolonged   virus shedding and the role of people recovering from COVID-19 in disease   transmission.

Revue scientifique médicale   hebdomadaire britannique

These findings suggest that the patient was   infected by SARS-CoV-2 on two separate occasions by a genetically distinct   virus. Thus, previous exposure to SARS-CoV-2 might not guarantee total   immunity in all cases. All individuals, whether previously diagnosed with   COVID-19 or not, should take identical precautions to avoid infection with   SARS-CoV-2. The implications of reinfections could be relevant for vaccine   development and application.

Revue scientifique médicale   hebdomadaire britannique

Patients with cancer with different tumour   types have differing susceptibility to SARS-CoV-2 infection and COVID-19   phenotypes. We generated individualised risk tables for patients with cancer,   considering age, sex, and tumour subtype. Our results could be useful to   assist physicians in informed risk–benefit discussions to explain COVID-19   risk and enable an evidenced-based approach to national social isolation   policies.

Revue scientifique médicale   hebdomadaire britannique

The more we realise how much SARS-CoV-2 has   changed the world, the more we question the suitability of our prevention,   management, and drug development strategies with respect to other major   pathogens