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1.
Commun Biol ; 5(1): 764, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967632

ABSTRACT

Mammalian organs are individually controlled by autonomous circadian clocks. At the molecular level, this process is defined by the cyclical co-expression of both core transcription factors and their downstream targets across time. While interactions between these molecular clocks are necessary for proper homeostasis, these features remain undefined. Here, we utilize integrative analysis of a baboon diurnal transcriptome atlas to characterize the properties of gene networks under circadian control. We found that 53.4% (8120) of baboon genes are oscillating body-wide. Additionally, two basic network modes were observed at the systems level: daytime and nighttime mode. Daytime networks were enriched for genes involved in metabolism, while nighttime networks were enriched for genes associated with growth and cellular signaling. A substantial number of diseases only form significant disease modules at either daytime or nighttime. In addition, a majority of SARS-CoV-2-related genes and modules are rhythmically expressed, which have significant network proximities with circadian regulators. Our data suggest that synchronization amongst circadian gene networks is necessary for proper homeostatic functions and circadian regulators have close interactions with SARS-CoV-2 infection.


Subject(s)
COVID-19 , Gene Regulatory Networks , Animals , COVID-19/genetics , Circadian Rhythm/genetics , Mammals/genetics , Primates/genetics , SARS-CoV-2
2.
Commun Biol ; 5(1): 766, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967631

ABSTRACT

Studying the antibody response to SARS-CoV-2 informs on how the human immune system can respond to antigenic variants as well as other SARS-related viruses. Here, we structurally identified a YYDRxG motif encoded by IGHD3-22 in CDR H3 that facilitates antibody targeting to a functionally conserved epitope on the SARS-CoV-2 receptor binding domain. A computational search for a YYDRxG pattern in publicly available sequences uncovered 100 such antibodies, many of which can neutralize SARS-CoV-2 variants and SARS-CoV. Thus, the YYDRxG motif represents a common convergent solution for the human humoral immune system to target sarbecoviruses including the Omicron variant. These findings suggest an epitope-targeting strategy to identify potent and broadly neutralizing antibodies for design of pan-sarbecovirus vaccines and antibody therapeutics.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Epitopes/genetics , Humans , Membrane Glycoproteins/metabolism , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/metabolism
3.
Sci Rep ; 12(1): 13146, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1967629

ABSTRACT

The main protease (Mpro) of SARS-CoV-2 has been recognized as an attractive drug target because of its central role in viral replication. Our previous preliminary molecular docking studies showed that theaflavin 3-gallate (a natural bioactive molecule derived from theaflavin and found in high abundance in black tea) exhibited better docking scores than repurposed drugs (Atazanavir, Darunavir, Lopinavir). In this study, conventional and steered MD-simulations analyses revealed stronger interactions of theaflavin 3-gallate with the active site residues of Mpro than theaflavin and a standard molecule GC373 (a known inhibitor of Mpro and novel broad-spectrum anti-viral agent). Theaflavin 3-gallate inhibited Mpro protein of SARS-CoV-2 with an IC50 value of 18.48 ± 1.29 µM. Treatment of SARS-CoV-2 (Indian/a3i clade/2020 isolate) with 200 µM of theaflavin 3-gallate in vitro using Vero cells and quantifying viral transcripts demonstrated reduction of viral count by 75% (viral particles reduced from Log106.7 to Log106.1). Overall, our findings suggest that theaflavin 3-gallate effectively targets the Mpro thus limiting the replication of the SARS-CoV-2 virus in vitro.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Biflavonoids , COVID-19/drug therapy , Catechin , Chlorocebus aethiops , Coronavirus 3C Proteases , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Vero Cells
4.
Sci Rep ; 12(1): 13207, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1967628

ABSTRACT

Sputnik-V (Gam-COVID-Vac) is a heterologous, recombinant adenoviral (rAdv) vector-based, COVID-19 vaccine now used in > 70 countries. Yet there is a shortage of data on this vaccine's performance in diverse populations. Here, we performed a prospective cohort study to assess the reactogenicity and immunologic outcomes of Sputnik-V vaccination in Kazakhstan. COVID-19-free participants (n = 82 at baseline) were followed at day 21 after Sputnik-V dose 1 (rAd5) and dose 2 (rAd26). Self-reported local and systemic adverse events were captured using questionnaires. Blood and nasopharyngeal swabs were collected to perform SARS-CoV-2 diagnostic and immunologic assays. We observed that most of the reported adverse events were mild-to-moderate injection site or systemic reactions, no severe or potentially life-threatening conditions were reported, and dose 1 appeared to be more reactogenic than dose 2. The seroconversion rate was 97% post-dose 1, remaining the same post-dose 2. The proportion of participants with detectable virus neutralization was 83% post-dose 1, increasing to 98% post-dose 2, with the largest relative increase observed in participants without prior COVID-19 exposure. Dose 1 boosted nasal S-IgG and S-IgA, while the boosting effect of dose 2 on mucosal S-IgG, but not S-IgA, was only observed in subjects without prior COVID-19. Systemically, vaccination reduced serum levels of growth regulated oncogene (GRO), which correlated with an elevation in blood platelet count. Overall, Sputnik-V dose 1 elicited both blood and mucosal SARS-CoV-2 immunity, while the immune boosting effect of dose 2 was minimal. Thus, adjustments to the current vaccine dosing regimen are necessary to optimize immunization efficacy and cost-effectiveness. While Sputnik-V reactogenicity is similar to that of other COVID-19 vaccines, the induced alterations to the GRO/platelet axis warrant investigation of the vaccine's effects on systemic immunology.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , Immunoglobulin A , Immunoglobulin G , Mucous Membrane , Prospective Studies , SARS-CoV-2
5.
Sci Rep ; 12(1): 13118, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1967627

ABSTRACT

The pandemic caused by severe acute respiratory Coronavirus-2 (SARS-CoV-2) has been ongoing for over two years, and treatment for COVID-19, other than monoclonal antibodies, is urgently required. Accordingly, we have investigated the inhibitors of SARS-CoV-2 protein targets by high-throughput virtual screening using a marine natural products database. Considering the calculated molecular properties and availability of the compounds, (+)-usnic acid was selected as a suitable hit. In the in vitro antiviral assay of (+)-usnic acid by the immunofluorescence method, IC50 was 7.99 µM, which is similar to that of remdesivir used as a positive control. The generalized Born and surface area continuum solvation (MM/GBSA) method was performed to find the potent target of (+)-usnic acid, and the Mpro protein showed the most prominent value, -52.05 kcal/mol, among other SARS-CoV-2 protein targets. Thereafter, RMSD and protein-ligand interactions were profiled using molecular dynamics (MD) simulations. Sodium usnate (NaU) improved in vitro assay results with an IC50 of 5.33 µM and a selectivity index (SI) of 9.38. Additionally, when (+)-usnic acid was assayed against SARS-CoV-2 variants, it showed enhanced efficacy toward beta variants with an IC50 of 2.92 µM and SI of 11.1. We report the in vitro anti-SARS-CoV-2 efficacy of (+)-usnic acid in this study and propose that it has the potential to be developed as a COVID-19 treatment if its in vivo efficacy has been confirmed.


Subject(s)
COVID-19 , Coronavirus Infections , Coronavirus , Benzofurans , COVID-19/drug therapy , Coronavirus 3C Proteases , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/pharmacology , SARS-CoV-2 , Salts
6.
Sci Rep ; 12(1): 12998, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967626

ABSTRACT

To investigate whether diurnal changes in noninvasive ocular surface parameters and subjective symptoms occur in healthy subjects wearing face mask who were analyzed before and after 8 h of continuous use. In this prospective cross-sectional study, healthy volunteers attending the same workplace environment underwent a noninvasive ocular surface workup by means of Keratograph 5 M (Oculus, Wetzlar, Germany) in the same day at 2 different time points: (i) in the early morning before wearing face mask (T0); (ii) after 8 h of continuous face mask use (T1). Noninvasive break-up time (NIBUT), tear meniscus height (TMH), ocular redness and meibomian gland dropout were measured. All subjects were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire before and after 8 h of face mask wearing. Data from 20 healthy subjects (10 males and 10 females, mean age 25.1 ± 3.9 years) were included. Mean value of TMH decreased significantly from 0.29 ± 0.07 at T0 to 0.23 ± 0.07 mm at T1 (P < 0.001); conversely, mean values of NIBUT, redness score and meibomian gland dropout did not change significantly after continuous face mask wearing (always P > 0.532). Concerning ocular discomfort symptoms, mean value of OSDI score worsened significantly at T1 compared to T0 (from 12.9 ± 12.6 to 19.4 ± 12.0; P = 0.017). Continuous face mask wearing for 8 h led to decreased TMH associated with the onset of ocular discomfort symptoms in young healthy subjects.


Subject(s)
COVID-19 , Dry Eye Syndromes , Adult , Cross-Sectional Studies , Dry Eye Syndromes/diagnosis , Female , Healthy Volunteers , Humans , Male , Masks/adverse effects , Meibomian Glands , Pandemics , Prospective Studies , Tears , Young Adult
7.
Sci Rep ; 12(1): 13123, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1967625

ABSTRACT

Fatigue, attentional deficits and cognitive fluctuations are the most characterizing symptoms of neurological involvement in Post COVID-19 syndrome (PCS). As the intraindividual variability (IIV) in cognitive performances has been recognized as a hallmark of brain-related disorders associated with cognitive deficits, it could be an interesting measure to elucidate the mechanisms subtending both the attentive impairment and the cognitive fluctuations in these patients. By referring to IIV analysis of Reaction Times (RTs), the present study aims to define the attentive impairment and its relation to fluctuations and fatigue, in patients suffering from Post COVID-19 neurological symptoms. 74 patients were enrolled. They underwent an extensive clinical and neuropsychological assessments, as well as computerized Sustained Attention and Stroop tasks. For studying IIV, RTs distributions of performances in computerized tasks were fitted with ex-Gaussian distribution, for obtaining the τ values. Finally, the Resting Motor Threshold (RMT) was also collected to estimate cortical excitability. 29 healthy volunteers served as controls. Patients showed poorer scores in Montreal Cognitive Assessment and higher RMT, in comparison with controls. In Sustained Attention Task, Mean, µ, σ and τ values were significantly higher in PCS patients (p value = < 0.0001; 0.001; 0.018 and < 0.0001, respectively). Repeated measures ANOVA comparing the RTs mean in Stroop task within-subject and between-subjects revealed significant condition and group effect (p < 0.0001 both) and significant interaction (p = 0.005), indicating worst performances in patients. The mean of the derived interference value was significantly higher in PCS patients than in controls (p = 0.036). Patients suffering from PCS show deficits in attention, both in the sustained and executive components. Both high RTs means and high IIV subtend these deficits and could explain the often-complained cognitive fluctuations in this population.


Subject(s)
COVID-19 , COVID-19/complications , Cognition , Fatigue , Humans , Neuropsychological Tests , Reaction Time
8.
Sci Rep ; 12(1): 13069, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967624

ABSTRACT

Reverse transcription quantitative PCR (RT-qPCR) assays are gold standard in diagnosing SARS-CoV-2 infection and play a major role in viral subtyping for rapid detection and monitoring of important mutations, containing the spread of new virus variants. We wanted to compare RT-qPCR melting curve analysis assays to Sanger Sequencing for detection of variants within the SARS-CoV-2 spike glycoprotein and examined their sensitivity and specificity. Samples positive for SARS-CoV-2 (n = 663 + 82) were subtyped using both Sanger sequencing and five RT-qPCR melting curve analysis assays specific for the mutations N501Y, P681H, E484K, K417N/T, and N439K. The results of the two methods were compared. The training cohort and the clinical validation cohort showed equally, or significantly better sensitivity of the assays compared to the Sanger sequencing. The agreement of the Sanger sequencing and the assays ranged from 92.6 to 100% for the training cohort and 99.4-100% for the clinical validation. The sensitivity, specificity, and turn-around time of the RT-qPCR melting curve analysis assays are well-suited for clinical monitoring of VOCs, making the assays an important tool in contact tracing and risk stratification. Furthermore, the assays were able to indicate the presence of new mutations in the complementary sequence to the mutation-specific probes.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/genetics , Humans , Mutation , Reverse Transcription , SARS-CoV-2/genetics , Sensitivity and Specificity
9.
Sci Rep ; 12(1): 12988, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967623

ABSTRACT

The long-term impact of COVID-19 among those with mild infections is not well characterized. Among 81 adults who completed online assessments at 3- and 12-months following infection, quality of life scores did not significantly improve over time. Among 62 subjects who also completed telephone interviews, respiratory symptoms or exercise limitation were reported by 42% at a median follow-up of 387 days (IQR 251-402 days). Those with persistent respiratory symptoms scored lower on the EQ-5D visual analog score compared to those without. Persistent respiratory symptoms were associated with a lower likelihood of full-time employment at 1 year (aOR 0.09, 95%CI 0.01-0.91; P = 0.041). In an adjusted linear regression, persistent respiratory symptoms (P = 0.037) and female sex (P = 0.016) were both independent risks for increased visits to a primary care provider. This cohort study demonstrates that respiratory symptoms are frequent at 1 year following COVID-19 and more importantly, are associated with negative impacts on employment, quality of life, and health care utilization. Further research is needed to determine the pathophysiology and risk factors for persistent symptoms as well as optimal management strategies to improve the level of functioning and quality of life.


Subject(s)
COVID-19 , Quality of Life , Adult , Cohort Studies , Female , Humans , Outpatients , Patient Acceptance of Health Care , Prospective Studies
10.
Sci Rep ; 12(1): 13095, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1967622

ABSTRACT

This study evaluates the use of the Global Pharma Health Fund (GPHF) Minilab for medicine quality screening by 16 faith-based drug supply organizations located in 13 low- and middle-income countries. The study period included the year before the COVID-19 pandemic (2019) and the first year of the pandemic (2020). In total 1,919 medicine samples were screened using the GPHF Minilab, and samples showing serious quality deficiencies were subjected to compendial analysis in fully equipped laboratories. Thirty-four (1.8%) of the samples were found not to contain the declared active pharmaceutical ingredient (API), or less than 50% of the declared API, or undeclared APIs, and probably represented falsified products. Fifty-four (2.8%) of the samples were reported as substandard, although the true number of substandard medicines may have been higher due to the limited sensitivity of the GPHF Minilab. The number of probably falsified products increased during the COVID-19 pandemic, especially due to falsified preparations of chloroquine; chloroquine had been incorrectly advocated as treatment for COVID-19. The reports from this project resulted in four international WHO Medical Product Alerts and several national alerts. Within this project, the costs for GPHF Minilab analysis resulted as 25.85 € per sample. Medicine quality screening with the GPHF Minilab is a cost-effective way to contribute to the global surveillance for substandard and falsified medical products.


Subject(s)
COVID-19 , Counterfeit Drugs , Faith-Based Organizations , Financial Management , COVID-19/drug therapy , COVID-19/epidemiology , Chloroquine , Counterfeit Drugs/analysis , Developing Countries , Humans , Pandemics
11.
Sci Rep ; 12(1): 13246, 2022 Aug 02.
Article in English | MEDLINE | ID: covidwho-1967621

ABSTRACT

This study provides a novel approach to understand human perception changes in their experiences of and interactions with public greenspaces during the early months of COVID-19. Using social media data and machine learning techniques, the study delivers new understandings of how people began to feel differently about their experiences compared to pre-COVID times. The study illuminates a renewed appreciation of nature as well as an emerging but prominent pattern of emotional and spiritual experiences expressed through a social media platform. Given that most park and recreational studies have almost exclusively examined whether park use increased or decreased during the pandemic, this research provides meaningful implications beyond the simple extensional visit pattern and lends weight to the growing evidences on changing perceptions over and the positive psychological impacts of nature. The study highlights the preeminent roles parks and greenspaces play during the pandemic and guides a new direction in future park development to support more natural elements and nature-oriented experiences from which emotional and spiritual well-being outcomes can be drawn.


Subject(s)
COVID-19 , Social Media , COVID-19/epidemiology , Data Analysis , Humans , Machine Learning , Parks, Recreational , Perception
12.
Sci Rep ; 12(1): 12986, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967620

ABSTRACT

Emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its current worldwide spread have caused a pandemic of acute respiratory disease COVID-19. The virus can result in mild to severe, and even to fatal respiratory illness in humans, threatening human health and public safety. The spike (S) protein on the surface of viral membrane is responsible for viral entry into host cells. The discovery of methods to inactivate the entry of SARS-CoV-2 through disruption of the S protein binding to its cognate receptor on the host cell is an active research area. To explore other prevention strategies against the quick spread of the virus and its mutants, non-equilibrium molecular dynamics simulations have been employed to explore the possibility of manipulating the structure-activity of the SARS-CoV-2 spike glycoprotein by applying electric fields (EFs) in both the protein axial directions and in the direction perpendicular to the protein axis. We have found out the application of EFs perpendicular to the protein axis is most effective in denaturing the HR2 domain which plays critical role in viral-host membrane fusion. This finding suggests that varying irradiation angles may be an important consideration in developing EF based non-invasive technologies to inactivate the virus.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Molecular Dynamics Simulation , Protein Binding , Spike Glycoprotein, Coronavirus/metabolism , Virion/metabolism
13.
Sci Rep ; 12(1): 13155, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1967619

ABSTRACT

There has been growing attention toward the predictive value of the coagulation parameters abnormalities in COVID-19. The aim of the study was to investigate the role of coagulation parameters namely Prothrombin concentration (PC), activated Partial thromboplastin Time (aPTT), D-Dimer (DD), Anti Thrombin III (ATIII) and fibrinogen (Fg) together with hematological, and biochemical parameters in predicting the severity of COVID-19 patients and estimating their relation to clinical outcomes in hospitalized and severe COVID-19 Patients. In a prospective study, a total of 267 newly diagnosed COVID-19 patients were enrolled. They were divided into two groups; hospitalized group which included 144 patients and non-hospitalized group that included 123 patients. According to severity, the patients were divided into severe group which included 71 patients and non-severe group that included 196 patients who were admitted to ward or not hospitalized. Clinical evaluation, measurement of coagulation parameters, biochemical indices, outcome and survival data were recorded. Hospitalized and severe patients were older and commonly presented with dyspnea (P ≤ 0.001). Differences in coagulation parameters were highly significant in hospitalized and severe groups in almost all parameters, same for inflammatory markers. D-dimer, AT-III and LDH showed excellent independently prediction of severity risk. With a cut-off of > 2.0 ng/L, the sensitivity and specificity of D dimer in predicting severity were 76% and 93%, respectively. Patients with coagulation abnormalities showed worse survival than those without (p = 0.002). Early assessment and dynamic monitoring of coagulation parameters may be a benchmark in the prediction of COVID-19 severity and death.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Blood Coagulation , Fibrin Fibrinogen Degradation Products , Humans , Partial Thromboplastin Time , Prospective Studies
14.
Sci Rep ; 12(1): 13039, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967618

ABSTRACT

Several universities around the world have resumed in-person teaching after successful vaccination campaigns have covered 70/80% of the population. In this study, we combine a new compartmental model with an optimal control formulation to discover, among different non-pharmaceutical interventions, the best prevention strategy to maximize on-campus activities while keeping spread under control. Composed of two interconnected Susceptible-Exposed-Infected-Quarantined-Recovered (SEIQR) structures, the model enables staff-to-staff infections, student-to-staff cross infections, student-to-student infections, and environment-to-individual infections. Then, we model input variables representing the implementation of different non-pharmaceutical interventions and formulate and solve optimal control problems for four desired scenarios: minimum number of cases, minimum intervention, minimum non-quarantine intervention, and minimum quarantine intervention. Our results reveal the particular significance of mask wearing and social distancing in universities with vaccinated population (with proportions according to UK data). The study also reveals that quarantining infected students has a higher importance than quarantining staff. In contrast, other measures such as environmental disinfection seems to be less important.


Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Quarantine , SARS-CoV-2 , United Kingdom/epidemiology , Universities
15.
Sci Rep ; 12(1): 13175, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1967617

ABSTRACT

Forced quarantine and nationwide lockdowns have been a primary response by many jurisdictions in their attempt at COVID-19 elimination or containment, yet the associated mental health burden is not fully understood. Using an eight country cross-sectional design, this study investigates the association between COVID-19 induced quarantine and/or isolation on probable generalized anxiety disorder (GAD) and major depressive episode (MDE) psychological outcomes approximately eight months after the pandemic was declared. Overall, 9027 adults participated, and 2937 (32.5%) were indicated with GAD and/or MDE. Reported quarantine and/or isolation was common, with 1199 (13.8%) confined for travel or health requirements, 566 (6.5%) for being close contact, 720 (8.3%) for having COVID-19 symptoms, and 457 (5.3%) for being COVID-19 positive. Compared to those not quarantining or isolating, the adjusted estimated relative risks of GAD and/or MDE associated with quarantine and/or isolation was significant (p < 0.001), ranging from 1.24 (95% confidence interval [CI]: 1.07, 1.43) for travel/health to 1.37 (95% CI 1.19, 1.59) for COVID-19 symptom isolation reasons. While almost universally employed, quarantine and/or isolation is associated with a heavy mental health toll. Preventive strategies are needed, such as minimizing time-limits imposed and providing clear rationale and information, together with additional treatment and rehabilitation resources.


Subject(s)
COVID-19 , Depressive Disorder, Major , Adult , Anxiety/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Cross-Sectional Studies , Depression , Depressive Disorder, Major/epidemiology , Humans , Pandemics/prevention & control , Quarantine/psychology
16.
Sci Rep ; 12(1): 13197, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1967616

ABSTRACT

We propose that technical analysis tools developed to give buy/sell signals in asset trading can be applied to analyze time series datasets in the natural sciences, and we show this explicitly for a study of WHO COVID-19 data. Notably, reliable short term forecasting can provide potentially lifesaving insights into logistical planning, and in particular, into the optimal allocation of resources such as hospital staff and equipment. By reinterpreting COVID-19 daily cases in terms of candlesticks, we are able to apply some of the most popular stock market technical indicators to obtain predictive power over the course of the pandemics. By providing a quantitative assessment of MACD, RSI, and candlestick analyses, we show their statistical significance in making predictions for both stock market data and WHO COVID-19 data. In particular, we show the utility of this novel approach by considering the identification of the beginnings of subsequent waves of the pandemic. Finally, our new methods are used to assess whether current health policies are impacting the growth in new COVID-19 cases.


Subject(s)
COVID-19 , COVID-19/epidemiology , Forecasting , Humans , Pandemics , Time Factors
17.
Sci Data ; 9(1): 454, 2022 07 30.
Article in English | MEDLINE | ID: covidwho-1967615

ABSTRACT

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.


Subject(s)
COVID-19 , Hospitalization , Humans , Pandemics , Prospective Studies , SARS-CoV-2
18.
Sci Data ; 9(1): 462, 2022 08 01.
Article in English | MEDLINE | ID: covidwho-1967614

ABSTRACT

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages.


Subject(s)
COVID-19 , Centers for Disease Control and Prevention, U.S. , Forecasting , Humans , Pandemics , United States/epidemiology
19.
Nat Commun ; 13(1): 4466, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1967604

ABSTRACT

SARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk of breakthrough infection in a fully vaccinated cohort. SARS-CoV-2 anti-spike IgG levels were measured before first SARS-CoV-2 vaccination and at day 21-28, 90 and 180, as well as after booster vaccination. Breakthrough infections were captured through the Danish National Microbiology database. incidence rate ratio (IRR) for breakthrough infection at time-updated anti-spike IgG levels was determined using Poisson regression. Among 6076 participants, 127 and 364 breakthrough infections due to Delta and Omicron variants were observed. IRR was 0.29 (95% CI 0.15-0.56) for breakthrough infection with the Delta variant, comparing the highest and lowest quintiles of anti-spike IgG. For Omicron, no significant differences in IRR were observed. These results suggest that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with Omicron.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19 Vaccines , Humans , Immunoglobulin G
20.
Nat Commun ; 13(1): 4480, 2022 Aug 02.
Article in English | MEDLINE | ID: covidwho-1967603

ABSTRACT

REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, has been approved as a treatment for high-risk patients infected with SARS-CoV-2 within five days of their diagnosis. We performed a retrospective cohort study, and used data repositories of Israel's largest healthcare organization to determine the real-world effectiveness of REGEN-COV treatment against COVID-19-related hospitalization, severe disease, and death. We compared patients infected with Delta variant and treated with REGEN-COV (n = 289) to those infected but not-treated with REGEN-COV (n = 1,296). Demographic and clinical characteristics were used to match patients and for further adjustment as part of the C0x model. Estimated treatment effectiveness was defined as one minus the hazard ratio. Treatment effectiveness of REGEN-COV was 56.4% (95% CI: 23.7-75.1%) in preventing COVID-19 hospitalization, 59.2% (95% CI: 19.9-79.2%) in preventing severe COVID-19, and 93.5% (95% CI: 52.1-99.1%) in preventing COVID-19 death in the 28 days after treatment. In conclusion, REGEN-COV was effective in reducing the risk of severe sequelae in high-risk COVID-19 patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Antibodies, Viral/therapeutic use , COVID-19/drug therapy , Drug Combinations , Humans , Retrospective Studies
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