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2.
Open forum infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1787289

ABSTRACT

Background For both the current and future pandemics, there is a need for high-throughput drug screening methods to identify existing drugs with potential preventative and/or therapeutic activity. Epidemiologic studies could complement lab-focused efforts to identify possible therapeutic agents. Methods We performed a pharmacopeia-wide association study (PWAS) to identify commonly prescribed medications and medication classes that are associated with the detection of SARS-CoV-2 in older individuals (>65 years) in long-term care homes (LTCH) and the community, between January 15 th, 2020 and December 31 st, 2020, across the province of Ontario, Canada. Results 26,121 cases and 2,369,020 controls from LTCH and the community were included in this analysis. Many of the drugs and drug classes evaluated did not yield significant associations with SARS-CoV-2 detection. However, some drugs and drug classes appeared significantly associated with reduced SARS-CoV-2 detection, including cardioprotective drug classes such as statins (weighted OR 0.91, standard p-value <0.01, adjusted p-value <0.01) and beta-blockers (weighted OR 0.87, standard p-value <0.01, adjusted p-value 0.01), along with individual agents ranging from levetiracetam (weighted OR 0.70, standard p-value <0.01, adjusted p-value <0.01) to fluoxetine (weighted OR 0.86, standard p-value 0.013, adjusted p-value 0.198) to digoxin (weighted OR 0.89, standard p-value <0.01, adjusted p-value 0.02). Conclusions Using this epidemiologic approach which can be applied to current and future pandemics we have identified a variety of target drugs and drug classes that could offer therapeutic benefit in COVID-19 and may warrant further validation. Some of these agents (e.g. fluoxetine) have already been identified for their therapeutic potential.

3.
Cell Rep ; 38(10): 110502, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1757194

ABSTRACT

Since the vast majority of species solely rely on innate immunity for host defense, it stands to reason that a critical evolutionary trait like immunological memory evolved in this primitive branch of our immune system. There is ample evidence that vaccines such as bacillus Calmette-Guérin (BCG) induce protective innate immune memory responses (trained immunity) against heterologous pathogens. Here we show that while BCG vaccination significantly reduces morbidity and mortality against influenza A virus (IAV), it fails to provide protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In contrast to IAV, SARS-CoV-2 infection leads to unique pulmonary vasculature damage facilitating viral dissemination to other organs, including the bone marrow (BM), a central site for BCG-mediated trained immunity. Finally, monocytes from BCG-vaccinated individuals mount an efficient cytokine response to IAV infection, while this response is minimal following SARS-CoV-2. Collectively, our data suggest that the protective capacity of BCG vaccination is contingent on viral pathogenesis and tissue tropism.


Subject(s)
COVID-19 , Influenza A virus , BCG Vaccine , COVID-19/prevention & control , Humans , Immunity, Innate , SARS-CoV-2 , Vaccination
4.
JAMMI: Journal of the Association of Medical Microbiology & Infectious Disease Canada ; 7(1):1-7, 2022.
Article in English | CINAHL | ID: covidwho-1753324

ABSTRACT

We provide an update to the Association of Medical Microbiology and Infectious Disease Canada seasonal influenza foundation guideline on the use of antiviral drugs for influenza for the upcoming 2021–2022 influenza season in Canada. Peramivir and baloxavir marboxil were licensed in Canada in 2017 and 2020, respectively, but neither is currently marketed. Thus, this guidance continues to focus on further optimizing the use of oseltamivir and zanamivir. Important issues for this year include the implications of co-circulation of severe acute respiratory syndrome coronavirus 2 and influenza viruses;the role of diagnostic testing in relation to impact on patient management;and dosing and administration recommendations for neuraminidase inhibitors for various at-risk age groups. Une mise à jour des lignes directrices de base d'AMMI Canada sur l'utilisation de médicaments antiviraux contre l'influenza au cours de la saison grippale 2021-2022 au Canada est présentée. Le péramivir et le baloxavir marboxil ont été homologués au Canada en 2017 et en 2020, respectivement, mais ni l'un ni l'autre n'est encore commercialisé. Les lignes directrices continuent donc d'être axées sur l'optimisation de l'oseltamivir et du zanamivir. Les enjeux importants cette année incluent les effets de la cocirculation du coronavirus 2 du syndrome respiratoire aigu sévère et des virus de l'influenza, le rôle des tests diagnostiques sur la prise en charge des patients, de même que les recommandations en matière de posologie et d'administration des inhibiteurs de la neuraminidase dans divers groupes d'âge à risque.

5.
Clin Transl Immunology ; 11(3): e1380, 2022.
Article in English | MEDLINE | ID: covidwho-1750347

ABSTRACT

Objectives: Antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in detecting previous exposures and analyzing vaccine-elicited immune responses. Here, we describe a scalable solution to detect and quantify SARS-CoV-2 antibodies, discriminate between natural infection- and vaccination-induced responses, and assess antibody-mediated inhibition of the spike-angiotensin converting enzyme 2 (ACE2) interaction. Methods: We developed methods and reagents to detect SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD) and nucleocapsid (N). We automated a surrogate neutralisation (sn)ELISA that measures inhibition of ACE2-spike or -RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard. Results: Our single-point IgG-based ELISAs accurately distinguished non-infected and infected individuals. For seroprevalence assessment (in a non-vaccinated cohort), classifying a sample as positive if antibodies were detected for ≥ 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti-spike and -RBD (but not -N) antibodies are observed. We present detailed protocols for serum/plasma or dried blood spots analysis performed manually and on automated platforms. The snELISA can be performed automatically at single points, increasing its scalability. Conclusions: Measuring antibodies to three viral antigens and identify neutralising antibodies capable of disrupting spike-ACE2 interactions in high-throughput enables large-scale analyses of humoral immune responses to SARS-CoV-2 infection and vaccination. The reagents are available to enable scaling up of standardised serological assays, permitting inter-laboratory data comparison and aggregation.

6.
J Infect Dis ; 225(5): 768-776, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1722480

ABSTRACT

BACKGROUND: We determined the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in air and on surfaces in rooms of patients hospitalized with coronavirus disease 2019 (COVID-19) and investigated patient characteristics associated with SARS-CoV-2 environmental contamination. METHODS: Nasopharyngeal swabs, surface, and air samples were collected from the rooms of 78 inpatients with COVID-19 at 6 acute care hospitals in Toronto from March to May 2020. Samples were tested for SARS-CoV-2 ribonucleic acid (RNA), cultured to determine potential infectivity, and whole viral genomes were sequenced. Association between patient factors and detection of SARS-CoV-2 RNA in surface samples were investigated. RESULTS: Severe acute respiratory syndrome coronavirus 2 RNA was detected from surfaces (125 of 474 samples; 42 of 78 patients) and air (3 of 146 samples; 3 of 45 patients); 17% (6 of 36) of surface samples from 3 patients yielded viable virus. Viral sequences from nasopharyngeal and surface samples clustered by patient. Multivariable analysis indicated hypoxia at admission, polymerase chain reaction-positive nasopharyngeal swab (cycle threshold of ≤30) on or after surface sampling date, higher Charlson comorbidity score, and shorter time from onset of illness to sampling date were significantly associated with detection of SARS-CoV-2 RNA in surface samples. CONCLUSIONS: The infrequent recovery of infectious SARS-CoV-2 virus from the environment suggests that the risk to healthcare workers from air and near-patient surfaces in acute care hospital wards is likely limited.


Subject(s)
COVID-19 , Nasopharynx/virology , SARS-CoV-2/isolation & purification , Adult , Aged , Air Microbiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , COVID-19 Nucleic Acid Testing , Canada/epidemiology , Environmental Exposure , Health Personnel , Humans , Inpatients , Middle Aged , Pandemics/prevention & control , SARS-CoV-2/genetics
7.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329279

ABSTRACT

Summary Wildlife reservoirs of SARS-CoV-2 can lead to viral adaptation and spillback from wildlife to humans (Oude Munnink et al., 2021). In North America, there is evidence of spillover of SARS-CoV-2 from humans to white-tailed deer ( Odocoileus virginianus ), but no evidence of transmission from deer to humans (Hale et al., 2021;Kotwa et al., 2022;Kuchipudi et al., 2021). Through a multidisciplinary research collaboration for SARS-CoV-2 surveillance in Canadian wildlife, we identified a new and highly divergent lineage of SARS-CoV-2. This lineage has 76 consensus mutations including 37 previously associated with non-human animal hosts, 23 of which were not previously reported in deer. There were also mutational signatures of host adaptation under neutral selection. Phylogenetic analysis revealed an epidemiologically linked human case from the same geographic region and sampling period. Together, our findings represent the first evidence of a highly divergent lineage of SARS-CoV-2 in white-tailed deer and of deer-to-human transmission.

8.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327769

ABSTRACT

To infect cells, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) via its spike glycoprotein (S), delivering its genome upon S-mediated membrane fusion. SARS-CoV-2 uses two distinct entry pathways: 1) a surface, serine protease-dependent or 2) an endosomal, cysteine protease-dependent pathway. In investigating serine protease-independent cell-cell fusion, we found that the matrix metalloproteinases (MMPs), MMP2/9, can activate SARS-CoV-2 S fusion activity, but not that of SARS-CoV-1. Importantly, metalloproteinases activation of SARS-CoV-2 S represents a third entry pathway in cells expressing high MMP levels. This route of entry required cleavage at the S1/S2 junction in viral producer cells and differential processing of variants of concern S dictated its usage. In addition, metalloproteinase inhibitors reduced replicative Alpha infection and abrogated syncytia formation. Finally, we found that the Omicron S exhibit reduced metalloproteinase-dependent fusion and viral entry. Taken together, we identified a MMP2/9-dependent mode of activation of SARS-CoV-2 S. As MMP2/9 are released during inflammation and severe COVID-19, they may play important roles in SARS-CoV-2 S-mediated cytopathic effects, tropism, and disease outcome.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324735

ABSTRACT

This manuscript describes a new method that enables direct analysis of viral particles in unprocessed samples.Using an electrochemical readout method that requires no external reagents, we detect the SARS-CoV-2 virus in the saliva of infected patients.The approach relies on a molecular sensor tethered to the surface of a gold electrode that contains an antibody, specific to the targetof interest, which here is the SARS-CoV-2 S1 spike protein that is displayed on the viral capsule. The antibody is attached to the electrode using a negatively charged linker that is composed of DNA. When a positive potential is applied to the electrode, the sensor complex is attracted to the electrode surface. The kinetics of transport is measured using chronoamperometry and readout is possible based on the absense or precense of virus and its effect on the complex movevment on electrode surface.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322027

ABSTRACT

To meet the urgent demand for better diagnostic tools to combat the ongoing COVID-19 pandemic, we developed a homogeneous immunoassay to detect IgG antibodies against SARS-CoV-2. This assay is based on a tri-part Nanoluciferase (tNLuc) approach, in which the spike protein of SARS-CoV-2 and protein G, fused respectively to two different tNLuc tags, are used as antibody probes. Target engagement of the probes allows reconstitution of a functional luciferase in the presence of the third tNLuc component. The assay is performed directly in liquid phase of patient sera and enables rapid, quantitative and low-cost detection. We show that tNLuc maintains a similar sensitivity to ELISA, while its readouts are highly consistent with various neutralizing antibody assays. This proof-of-principle study suggests potential applications in diagnostics and disease and vaccination management.

11.
Lab Chip ; 22(6): 1171-1186, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1684131

ABSTRACT

Coronavirus disease 2019 (COVID-19) was primarily identified as a novel disease causing acute respiratory syndrome. However, as the pandemic progressed various cases of secondary organ infection and damage by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported, including a breakdown of the vascular barrier. As SARS-CoV-2 gains access to blood circulation through the lungs, the virus is first encountered by the layer of endothelial cells and immune cells that participate in host defense. Here, we developed an approach to study SARS-CoV-2 infection using vasculature-on-a-chip. We first modeled the interaction of virus alone with the endothelialized vasculature-on-a-chip, followed by the studies of the interaction of the virus exposed-endothelial cells with peripheral blood mononuclear cells (PBMCs). In an endothelial model grown on a permeable microfluidic bioscaffold under flow conditions, both human coronavirus (HCoV)-NL63 and SARS-CoV-2 presence diminished endothelial barrier function by disrupting VE-cadherin junctions and elevating the level of pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, and angiopoietin-2. Inflammatory cytokine markers were markedly more elevated upon SARS-CoV-2 infection compared to HCoV-NL63 infection. Introduction of PBMCs with monocytes into the vasculature-on-a-chip upon SARS-CoV-2 infection further exacerbated cytokine-induced endothelial dysfunction, demonstrating the compounding effects of inter-cellular crosstalk between endothelial cells and monocytes in facilitating the hyperinflammatory state. Considering the harmful effects of SARS-CoV-2 on endothelial cells, even without active virus proliferation inside the cells, a potential therapeutic approach is critical. We identified angiopoietin-1 derived peptide, QHREDGS, as a potential therapeutic capable of profoundly attenuating the inflammatory state of the cells consistent with the levels in non-infected controls, thereby improving the barrier function and endothelial cell survival against SARS-CoV-2 infection in the presence of PBMC.


Subject(s)
Angiopoietin-1 , COVID-19 , Endothelium, Vascular , Inflammation , SARS-CoV-2 , COVID-19/drug therapy , COVID-19/virology , Endothelial Cells/immunology , Endothelial Cells/virology , Endothelium, Vascular/immunology , Endothelium, Vascular/virology , Humans , Immunity, Innate , Inflammation/drug therapy , Inflammation/virology , Lab-On-A-Chip Devices , Leukocytes, Mononuclear
12.
J Immunol ; 208(2): 429-443, 2022 01 15.
Article in English | MEDLINE | ID: covidwho-1674944

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces T cell, B cell, and Ab responses that are detected for several months in recovered individuals. Whether this response resembles a typical respiratory viral infection is a matter of debate. In this study, we followed T cell and Ab responses in 24 mainly nonhospitalized human subjects who had recovered from PCR-confirmed SARS-CoV-2 infection at two time points (median of 45 and 145 d after symptom onset). Ab responses were detected in 95% of subjects, with a strong correlation between plasma and salivary anti-spike (anti-S) and anti-receptor binding domain IgG, as well as a correlation between circulating T follicular helper cells and the SARS-CoV-2-specific IgG response. T cell responses to SARS-CoV-2 peptides were determined using intracellular cytokine staining, activation markers, proliferation, and cytokine secretion. All study subjects had a T cell response to at least one SARS-CoV-2 Ag based on at least one T cell assay. CD4+ responses were largely of the Th1 phenotype, but with a lower ratio of IFN-γ- to IL-2-producing cells and a lower frequency of CD8+:CD4+ T cells than in influenza A virus (IAV)-specific memory responses within the same subjects. Analysis of secreted molecules also revealed a lower ratio of IFN-γ to IL-2 and an altered cytotoxic profile for SARS-CoV-2 S- and nucleocapsid-specific responses compared with IAV-specific responses. These data suggest that the memory T cell phenotype after a single infection with SARS-CoV-2 persists over time, with an altered cytokine and cytotoxicity profile compared with long-term memory to whole IAV within the same subjects.


Subject(s)
Antibody Formation , COVID-19/immunology , Immunity, Cellular , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Th1 Cells/immunology , Adult , Aged , Female , Humans , Male , Middle Aged , Time Factors
13.
Sci Adv ; 8(3): eabj9815, 2022 Jan 21.
Article in English | MEDLINE | ID: covidwho-1634773

ABSTRACT

Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle­formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma, and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 2 clinical trial ongoing.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/immunology , /immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19 Vaccines/adverse effects , Canada , Cell Line , Cricetinae , Drug Evaluation, Preclinical , Female , HEK293 Cells , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Liposomes/pharmacology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Nanoparticles , Spike Glycoprotein, Coronavirus/genetics , Th1 Cells/immunology
14.
Viruses ; 14(1)2021 12 30.
Article in English | MEDLINE | ID: covidwho-1580401

ABSTRACT

Medicinal chemistry optimization of a previously described stilbene inhibitor of HIV-1, 5350150 (2-(2-(5-nitro-2-thienyl)vinyl)quinoline), led to the identification of the thiazole-5-carboxamide derivative (GPS491), which retained potent anti-HIV-1 activity with reduced toxicity. In this report, we demonstrate that the block of HIV-1 replication by GPS491 is accompanied by a drastic inhibition of viral gene expression (IC50 ~ 0.25 µM), and alterations in the production of unspliced, singly spliced, and multiply spliced HIV-1 RNAs. GPS491 also inhibited the replication of adenovirus and multiple coronaviruses. Low µM doses of GPS491 reduced adenovirus infectious yield ~1000 fold, altered virus early gene expression/viral E1A RNA processing, blocked viral DNA amplification, and inhibited late (hexon) gene expression. Loss of replication of multiple coronaviruses (229E, OC43, SARS-CoV2) upon GPS491 addition was associated with the inhibition of viral structural protein expression and the formation of virus particles. Consistent with the observed changes in viral RNA processing, GPS491 treatment induced selective alterations in the accumulation/phosphorylation/function of splicing regulatory SR proteins. Our study establishes that a compound that impacts the activity of cellular factors involved in RNA processing can prevent the replication of several viruses with minimal effect on cell viability.


Subject(s)
Adenoviridae/drug effects , Antiviral Agents/pharmacology , Coronavirus/drug effects , HIV-1/drug effects , RNA Processing, Post-Transcriptional/drug effects , Thiazoles/pharmacology , Virus Replication/drug effects , Adenoviridae/physiology , Antiviral Agents/chemistry , Cell Line , Coronavirus/classification , Coronavirus/physiology , Gene Expression/drug effects , HIV-1/physiology , Humans , RNA Splicing Factors/metabolism , RNA, Viral/metabolism , Thiazoles/chemistry
15.
JAMMI: Journal of the Association of Medical Microbiology & Infectious Disease Canada ; 6(4):259-268, 2021.
Article in English | CINAHL | ID: covidwho-1566624

ABSTRACT

Background: Most individuals with coronavirus disease 2019 (COVID-19) experience mild symptoms and are managed in the outpatient setting. The aim of this study was to determine whether self-reported symptoms at the time of diagnosis can identify patients at risk of clinical deterioration. Methods: This was a retrospective cohort study of 671 outpatients with laboratory-confirmed COVID-19 diagnosed in Toronto between March 1 and October 16, 2020. We examined the association between patients' baseline characteristics and self-reported symptoms at the time of diagnosis and the risk of subsequent hospitalization. Results: Of 671 participants, 26 (3.9%) required hospitalization. Individuals aged 65 years or older were more likely to require hospitalization (odds ratio [OR] 5.29, 95% CI 2.19 to 12.77), whereas those without medical comorbidities were unlikely to be hospitalized (OR 0.02, 95% CI 0.00 to 0.17). After adjusting for age and presence of comorbidities, sputum production (adjusted OR [aOR] 5.01, 95% CI 1.97 to 12.75), arthralgias (aOR 4.82, 95% CI 1.85 to 12.53), diarrhea (aOR 4.56, 95% CI 1.82 to 11.42), fever (aOR 3.64, 95% CI 1.50 to 8.82), chills (aOR 3.62, 95% CI 1.54 to 8.50), and fatigue (aOR 2.59, 95% CI 1.04 to 6.47) were associated with subsequent hospitalization. Conclusions: Early assessment of symptoms among outpatients with COVID-19 can help identify individuals at risk of clinical deterioration. Additional studies are needed to determine whether more intense follow-up and early intervention among high-risk individuals can alter the clinical trajectory of and outcomes among outpatients with COVID-19. Historique : La plupart des personnes atteintes de la maladie à coronavirus 2019 (COVID-19) éprouvent des symptômes légers et sont prises en charge en milieu ambulatoire. La présente étude visait à déterminer si les symptômes autodéclarés au moment du diagnostic permettent de dépister les patients à risque de détérioration clinique. Méthodologie : Les chercheurs ont réalisé la présente étude de cohorte rétrospective auprès de 671 patients ambulatoires atteints d'une COVID-19 diagnostiquée à Toronto et confirmée en laboratoire entre le 1er mars et le 16 octobre 2020. Ils ont examiné l'association entre les caractéristiques de référence et les symptômes autodéclarés des patients au moment du diagnostic, d'une part, et le risque d'hospitalisation, d'admission en soins intensifs ou de décès par la suite, d'autre part. Résultats : Des 671 participants, 26 (3,9 %) ont dû être hospitalisés, sept (1,0 %) ont été admis en soins intensifs et trois (0,4 %) sont décédés dans les 30 jours suivant le diagnostic. Les personnes de 65 ans ou plus étaient plus susceptibles de devoir être hospitalisées (RC 5,29, IC à 95 % 2,19 à 12,77) et celles qui n'avaient pas d'autres problèmes de santé l'étaient moins (RC 0,02, IC à 95 % 0,00 à 0,17). Après redressement pour tenir compte de l'âge et de la présence d'autres problèmes de santé, la production de mucus (RC ajusté [RCa] 5,01, IC à 95 % 2,11 à 13,66), les arthralgies (RCa 4,82, IC à 95 % 1,85 à 12,53), la diarrhée (RCa 4,56, IC à 95 % 1,82 à 11,42), la fièvre (RCa 3,64, IC à 95 % 1,50 à 8,82), les frissons (RCa 3,62, IC à 95 % 1,54 à 8,50) et la fatigue (RCa 2,59, IC à 95 % 1,04 à 6,47) étaient associés à des hospitalisations. Conclusions : L'évaluation précoce des symptômes des patients ambulatoires atteints de la COVID-19 peut contribuer à dépister les personnes vulnérables à une détérioration clinique. Lorsque ce facteur s'ajoute à l'âge et à l'histoire de problèmes de santé, la symptomatologie fournit plus d'information pronostique aux cliniciens qui prennent en charge les patients atteints de COVID-19 en milieu ambulatoire. D'autres études s'imposent pour déterminer si un suivi plus intense et une intervention précoce auprès des personnes très vulnérables peuvent modifier la trajectoire clinique et le pronostic des patients ambulatoires atteints de la COVID-19.

16.
Cell Biosci ; 11(1): 202, 2021 Dec 08.
Article in English | MEDLINE | ID: covidwho-1562007

ABSTRACT

BACKGROUND: The ongoing COVID-19 pandemic has resulted in 185 million recorded cases and over 4 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission. RESULTS: Here, we describe a novel, intranasally delivered COVID-19 vaccine based on a helper-dependent adenoviral (HD-Ad) vector. The vaccine (HD-Ad_RBD) produces a soluble secreted form of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and we show it induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18-hACE2 mice with HD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection. CONCLUSION: Our approaches provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.

17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294844

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, is capable of infecting a variety of wildlife species. Wildlife living in close contact with humans are at an increased risk of SARS-CoV-2 exposure and if infected have the potential to become a reservoir for the pathogen, making control and management more difficult. Objective: To conduct SARS-CoV-2 surveillance in urban wildlife from Ontario and Quebec, Canada, increasing our knowledge of the epidemiology of the virus and our chances of detecting spillover from humans into wildlife. Methods: Using a One Health approach, we leveraged activities of existing research, surveillance, and rehabilitation programs among multiple agencies to collect samples from 776 animals from 17 different wildlife species between June 2020 and May 2021. Samples from all animals were tested for the presence of SARS-CoV-2 viral RNA, and a subset of samples from 219 animals across 3 species (raccoons, Procyon lotor;striped skunks, Mephitis mephitis;and mink, Neovison vison) were also tested for the presence of neutralizing antibodies. Results: No evidence of SARS-CoV-2 viral RNA or neutralizing antibodies was detected in any of the tested samples. Conclusion: Although we were unable to identify positive SARS-CoV-2 cases in wildlife, continued research and surveillance activities are critical to better understand the rapidly changing landscape of susceptible animal species. Collaboration between academic, public and animal health sectors should include experts from relevant fields to build coordinated surveillance and response capacity.

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293603

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, is capable of infecting a variety of wildlife species. Wildlife living in close contact with humans are at an increased risk of SARS-CoV-2 exposure and if infected have the potential to become a reservoir for the pathogen, making control and management more difficult. Objective: To conduct SARS-CoV-2 surveillance in urban wildlife from Ontario and Quebec, Canada, increasing our knowledge of the epidemiology of the virus and our chances of detecting spillover from humans into wildlife. Methods: Using a One Health approach, we leveraged activities of existing research, surveillance, and rehabilitation programs among multiple agencies to collect samples from 776 animals from 17 different wildlife species between June 2020 and May 2021. Samples from all animals were tested for the presence of SARS-CoV-2 viral RNA, and a subset of samples from 219 animals across 3 species (raccoons, Procyon lotor;striped skunks, Mephitis mephitis;and mink, Neovison vison) were also tested for the presence of neutralizing antibodies. Results: No evidence of SARS-CoV-2 viral RNA or neutralizing antibodies was detected in any of the tested samples. Conclusion: Although we were unable to identify positive SARS-CoV-2 cases in wildlife, continued research and surveillance activities are critical to better understand the rapidly changing landscape of susceptible animal species. Collaboration between academic, public and animal health sectors should include experts from relevant fields to build coordinated surveillance and response capacity.

19.
J Infect Dis ; 225(5): 768-776, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1545982

ABSTRACT

BACKGROUND: We determined the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in air and on surfaces in rooms of patients hospitalized with coronavirus disease 2019 (COVID-19) and investigated patient characteristics associated with SARS-CoV-2 environmental contamination. METHODS: Nasopharyngeal swabs, surface, and air samples were collected from the rooms of 78 inpatients with COVID-19 at 6 acute care hospitals in Toronto from March to May 2020. Samples were tested for SARS-CoV-2 ribonucleic acid (RNA), cultured to determine potential infectivity, and whole viral genomes were sequenced. Association between patient factors and detection of SARS-CoV-2 RNA in surface samples were investigated. RESULTS: Severe acute respiratory syndrome coronavirus 2 RNA was detected from surfaces (125 of 474 samples; 42 of 78 patients) and air (3 of 146 samples; 3 of 45 patients); 17% (6 of 36) of surface samples from 3 patients yielded viable virus. Viral sequences from nasopharyngeal and surface samples clustered by patient. Multivariable analysis indicated hypoxia at admission, polymerase chain reaction-positive nasopharyngeal swab (cycle threshold of ≤30) on or after surface sampling date, higher Charlson comorbidity score, and shorter time from onset of illness to sampling date were significantly associated with detection of SARS-CoV-2 RNA in surface samples. CONCLUSIONS: The infrequent recovery of infectious SARS-CoV-2 virus from the environment suggests that the risk to healthcare workers from air and near-patient surfaces in acute care hospital wards is likely limited.


Subject(s)
COVID-19 , Nasopharynx/virology , SARS-CoV-2/isolation & purification , Adult , Aged , Air Microbiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , COVID-19 Nucleic Acid Testing , Canada/epidemiology , Environmental Exposure , Health Personnel , Humans , Inpatients , Middle Aged , Pandemics/prevention & control , SARS-CoV-2/genetics
20.
Can J Anaesth ; 67(9): 1217-1248, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1536371

ABSTRACT

PURPOSE: We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products. SOURCE: Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology. PRINCIPAL FINDINGS: No eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density. CONCLUSIONS: High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.


RéSUMé: OBJECTIF: Nous avons réalisé deux comptes rendus sur commande de l'Organisation mondiale de la santé pour guider l'utilisation de canules nasales à haut débit (CNHD) chez les patients ayant contracté le coronavirus (COVID-19). Nous avons synthétisé les données probantes concernant leur efficacité et leur innocuité (compte rendu 1), ainsi que les risques de dispersion des gouttelettes, de génération d'aérosols, et de transmission associée d'éléments viraux (compte rendu 2). SOURCE: Des recherches de littérature ont été réalisées dans les bases de données Ovid MEDLINE, Embase, Web of Science, ainsi que dans les bases de données chinoises et medRxiv. Compte rendu 1 : nous avons synthétisé les résultats d'études randomisées contrôlées (ERC) comparant les CNHD à une oxygénothérapie conventionnelle chez des patients en état critique atteints d'insuffisance respiratoire hypoxémique aiguë. Compte rendu 2 : nous avons résumé sous forme narrative les constatations d'études évaluant la dispersion de gouttelettes, la génération d'aérosols ou la transmission infectieuse associées aux CNHD. Pour les deux comptes rendus, des réviseurs appariés ont réalisé la sélection des études, l'extraction des données et l'évaluation du risque de biais de manière indépendante. Nous avons évalué la certitude des données probantes en nous fondant sur la méthodologie GRADE. CONSTATATIONS PRINCIPALES: Aucune étude éligible n'incluait de patients atteints de COVID-19. Compte rendu 1 : 12 ERC (n = 1989 patients) ont fourni des données probantes de certitude faible selon lesquelles les CNHD réduiraient la ventilation invasive (risque relatif [RR], 0,85; intervalle de confiance [IC] 95 %, 0,74 à 0,99) et l'intensification de l'oxygénothérapie (RR, 0,71; IC 95 %, 0,51 à 0,98) chez les patients atteints d'insuffisance respiratoire. Les résultats n'ont pas démontré de différences en matière de mortalité (certitude modérée), ni de durée du séjour hospitalier ou à l'unité des soins intensifs (certitude modérée et faible, respectivement). Compte rendu 2 : quatre études évaluant la dispersion de gouttelettes et trois évaluant la génération et la dispersion d'aérosols ont fourni des données probantes de très faible certitude. Deux études de simulation et une étude croisée ont donné des résultats mitigés quant à l'effet des CNHD sur la dispersion des gouttelettes. Bien que deux études de simulation n'aient rapporté aucune augmentation associée concernant la dispersion d'aérosols, l'une a rapporté que des taux de débit plus élevés étaient associés à des régions à densité d'aérosols élevée plus grandes. CONCLUSION: Les canules nasales à haut débit pourraient réduire la nécessité de recourir à la ventilation invasive et l'escalade des traitements par rapport à l'oxygénothérapie conventionnelle chez les patients atteints de COVID-19 souffrant d'insuffisance respiratoire hypoxémique aiguë. Cet avantage doit être soupesé contre le risque inconnu de transmission atmosphérique.


Subject(s)
Coronavirus Infections/therapy , Oxygen Inhalation Therapy/methods , Pneumonia, Viral/therapy , Respiratory Insufficiency/therapy , Aerosols , COVID-19 , Cannula , Coronavirus Infections/complications , Coronavirus Infections/mortality , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Randomized Controlled Trials as Topic , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/virology
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