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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (49)

ProteinN (10)

NSP5 (10)

ComplexRdRp (8)

ProteinE (7)


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    Understanding how Victoria, Australia gained control of its second COVID-19 MESHD wave

    Authors: James M Trauer; Michael J Lydeamore; Gregory W Dalton; David V Pilcher; Michael T Meehan; Emma S McBryde; Allen C Cheng; Brett Sutton; Romain Ragonnet

    doi:10.1101/2021.04.03.21254866 Date: 2021-04-07 Source: medRxiv

    Victoria has been Australia's hardest hit state by the COVID-19 pandemic MESHD, but was successful in reversing its second wave of infections through aggressive policy interventions. The clear reversal in the epidemic trajectory combined with information on the timing and geographical scope of policy interventions offers the opportunity to estimate the relative contribution of each change. We developed a compartmental model of the COVID-19 MESHD epidemic in Victoria that incorporated age and geographical structure, and calibrated it to data on case notifications, deaths and health service needs according to the administrative divisions of Victoria's healthcare, termed clusters. We achieved a good fit to epidemiological indicators, at both the state level and for individual clusters, through a combination of time-varying processes that included changes to case detection rates, population mobility, school closures, seasonal forcing, physical distancing and use of face coverings. Estimates of the risk of hospitalisation and death MESHD among persons with disease that were needed to achieve this close fit were markedly higher than international estimates, likely reflecting the concentration of the epidemic in groups at particular risk of adverse outcomes, such as residential facilities. Otherwise, most fitted parameters were consistent with the existing literature on COVID-19 MESHD epidemiology and outcomes. We estimated a significant effect for each of the calibrated time-varying processes on reducing the risk of transmission per contact, with broad estimates of the reduction in transmission risk attributable to seasonal forcing (27.8%, 95% credible interval [95%CI] 9.26-44.7% for mid-summer compared to mid-winter), but narrower estimates for the individual-level effect of physical distancing of 12.5% (95%CI 5.69-27.9%) and of face coverings of 39.1% (95%CI 31.3-45.8%). That the multi-factorial public health interventions and mobility restrictions led to the dramatic reversal in the epidemic trajectory is supported by our model results, with the mandatory face coverings likely to have been particularly important.

    Clinical correlation of lung ultrasound profiles in patients with COVID-19 MESHD infection

    Authors: Chitrakshi Nagpal; Sanchit Kumar; Naveet Wig; Arvind Kumar; Praful Pandey; Manraj Singh Bhullar; Richa Aggarwal; kapil dev soni; Anjan Trikha

    doi:10.1101/2021.04.05.21254935 Date: 2021-04-07 Source: medRxiv

    Background: Lung ultrasound is a popular point of care test that correlates well with computed tomography for lung pathologies. While previous studies have shown its ability to detect COVID-19 MESHD related lung pathology, we aimed to evaluate the utility of lung ultrasound in the triage and prognostication of COVID-19 MESHD patients by determining its ability to predict clinical severity and outcomes. Methods: This was a prospective, cross-sectional, observational, single centre study done at JPNATC and AIIMS, New Delhi, India. Consenting eligible patients aged 18 years or more were included if hospitalised with microbiologically confirmed COVID-19 MESHD and classified as mild, moderate (respiratory rate >24/min OR SpO2<94% on room air) and severe COVID-19 MESHD (respiratory rate >30/min OR SpO2<90% on room air) at the time of enrolment. The lungs were systematically assessed with ultrasound after division into 14 zones (4 anteriorly, 4 axillary and 6 posteriorly). Clinical and laboratory parameters including arterial blood gas analysis at the time of evaluation were recorded. Patients were followed till death MESHD or discharge. The primary objective was to determine the correlation between clinical severity and lung ultrasound profiles (no. of A, B and C profiles, and the total number of areas involved). Secondary objectives included assessment of the correlation between lung ultrasound profiles and clinical outcomes and development of a statistical model incorporating ultrasound and clinical parameters to allow prediction of COVID-19 MESHD related severity and outcomes. Findings: Between October 1, 2020, and January 31,2021, patients were screened for inclusion and total n=60 patients were evaluated and included in the final analysis. The most common abnormality seen were B lines, seen in at least one zone in n=53 (88.33%) of cases. A median of 9 (IQR: 5-12) zones of the 14 assessed had a B-profile. The total number of abnormal areas (zones with a B or C profile) correlated significantly with the PaO2/FiO2 ratio ({rho}= -0.7232, p<0.0001) and SpO2/FiO2 ratio ({rho}= -0.6866, p<0.0001), and differed significantly between mild and moderate vs severe cases (p=0.0026 mild vs moderate, p<0.0001 mild vs severe, p=0.0175 moderate vs severe). The total number of B lines were predictors of mortality (p=0.0188, OR 1.03, 95% CI 1.003-1.060). Statistical models that incorporated total number of B-lines, CRP and anticoagulation use could predict mortality (p=0.0124, pseudo R2=0.1740) with an AUC= 0.7682 (95% CI=0.6176-0.9188), and the total number of involved areas and LDH levels could distinguish severe disease from mild/moderate disease (p<0.0001, Pseudo R2=0.3822), AUC = 0.8743 (95% CI=0.7752-0.9733). A simplified cut off of [≥]6 involved areas (of the 14 assessed) was 100% sensitive and 52% specific for differentiating severe disease from mild and moderate ones. Interpretation: In patients with COVID-19 MESHD, increasing involvement of the lungs as assessed by ultrasonography correlates significantly with clinical severity and outcomes. These findings may be utilized in future prospective studies to validate the use of lung ultrasound to triage and prognosticate patients with COVID-19 MESHD infection.

    Statistical Modeling of deaths due to COVID-19 MESHD influenced by social isolation in Latin American countries

    Authors: Rafael Andre da Silva; Luiz Philipe de Souza Ferreira; Jean Michel Rocha Sampaio Leite Sr.; Fernanda Assuncao Tiraboschi; Thiago Maciel Valente; Vinicius Moraes de Paiva Roda; Jeniffer Johana Duarte Sanchez Sr.

    doi:10.1101/2021.04.05.21254941 Date: 2021-04-07 Source: medRxiv

    Social isolation is extremely important to minimize the effects of a pandemic. Latin American (LA) countries have similar socioeconomic characteristics and health system infrastructures. These countries face difficulties to deal with the COVID-19 pandemic MESHD and some of them had very high death rates. Government stringency index (GSI) of twelve LA countries was gathered from the Oxford COVID-19 MESHD Government Response Tracker (OxCGRT) project. GSI was calculated considering nine metrics such as school and work closures, stay-at-home requirements, among others types of social distancing and isolation measures. Population data from the United Nations Population Fund and number of deaths data was collected from the dashboard of the World Health Organization (WHO). We performed an analysis of the period March-December using a mixed linear model approach. Peru, Brazil, Chile, Bolivia, Colombia, Argentina and Ecuador had the highest death rates with an increasing trend over time, while Suriname, Venezuela, Uruguay, Paraguay and Guyana had the lowest ones, which remained steady. GSI in most countries followed the same pattern during the analyzed months. i.e., high indices at the beginning of the pandemic and lower ones in the last evaluated months, while the number of deaths increased over the whole period. Almost no country kept its GSI high for much time, especially from October to December. Time and GSI as well as their interaction were highly significant. As their interaction increases, death MESHD rate decreases. In conclusion, our statistical model explains and substantiates the need for maintaining social distancing and isolation measures over time during the pandemic.

    Covid-19 MESHD and excess mortality rates not comparable across countries

    Authors: Gabrielle E Kelly; Stefano Petti; Norman Noah

    doi:10.1101/2021.03.31.21254689 Date: 2021-04-06 Source: medRxiv

    Abstract: Evidence that more people in some countries and fewer in others are dying because of the pandemic, than is reflected by reported Covid-19 MESHD mortality rates, is derived from mortality data. Worldwide, mortality data is used to estimate the full extent of the effects of the Covid-19 pandemic MESHD, both direct and indirect; the possible short fall in the number of cases reported to the WHO; and to suggest explanations for differences between countries. Excess mortality data is largely varying across countries and is not directly proportional to Covid-19 MESHD mortality. Using publicly available databases, deaths attributed to Covid-19 MESHD in 2020 and all deaths for the years 2015-2020 were tabulated for 36 countries together with economic, health, demographic, and government response stringency index variables. Residual death rates in 2020 were calculated as excess deaths minus death MESHD rates due to Covid-19 MESHD where excess deaths were observed deaths in 2020 minus the average for 2015-2019. For about half the countries, residual deaths were negative and for half, positive. The absolute rates in some countries were double those in others. In a regression analysis, the stringency index (p=0.026) was positively associated with residual mortality. There was no evidence of spatial clustering of residual mortality. The results show that published data on mortality from Covid-19 MESHD cannot be directly comparable across countries, likely due to differences in Covid-19 MESHD death reporting. In addition, the unprecedented public health measures implemented to control the pandemic may have produced either increased or reduced excess deaths MESHD due to other diseases MESHD. Further data on cause-specific mortality is required to determine the extent to which residual mortality represents non- Covid-19 MESHD deaths MESHD and to explain differences between countries.

    Statins Are Associated with Improved 28-day Mortality in Patients Hospitalized with SARS-CoV-2 Infection MESHD

    Authors: Zoe N Memel; Jenny J Lee; Andrea S Foulkes; Raymond T Chung; Tanayott Thaweethai; Patricia P Bloom

    doi:10.1101/2021.03.27.21254373 Date: 2021-04-06 Source: medRxiv

    Background: Statins may be protective in viral infection and have been proposed as treatment in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection MESHD. Objective: We evaluated the effect of statins on mortality in four groups hospitalized with ( SARS-CoV-2) infection MESHD (continued statin, newly initiated statin, discontinued statin, never on statin). Design: In a single center cohort study of 1179 patients hospitalized with SARS-CoV-2 infection MESHD, the outcome of death MESHD, Intensive Care Unit (ICU) admission or hospital discharge was evaluated. Patients statin use, laboratory data, and co-morbidities were determined via chart review and electronic health records. Using marginal structural models to account for timing of statin initiation and competing risks, we compared the likelihood of severe outcomes in the four statin exposure groups. Setting: Academic medical center in the United States Participants: Patients hospitalized with SARS-CoV-2 infection MESHD Measurements: 28-day mortality, ICU admission, or discharge Results: Among 1179 patients, 360 were never on a statin, 311 were newly initiated on a statin, 466 were continued on a statin, and 42 had a statin discontinued. In this cohort, 154 (13.1%) patients died by 28-days. With marginal structural model analysis, statin use reduced the hazard of 28-day mortality (HR 0.566 [CI 0.372, 0.862], p = 0.008). Both new initiation of statins (HR 0.493 [CI 0.253, 0.963], p=0.038) and continuing statin therapy reduced the hazard of 28-day mortality (HR 0.270 [CI 0.114, 0.637], p=0.003). Sensitivity analysis found that statin use was associated with improved mortality for patients > 65 years, but not for patients 65 years or younger. Limitation: Observational design Conclusion: Statin therapy during hospitalization for SARS-CoV-2 infection MESHD, including new initiation and continuation of therapy, was associated with reduced short-term mortality.

    Timing is everything: the relationship between COVID outcomes and the date at which mask mandates are relaxed

    Authors: Affan Shoukat; Alison P. Galvani; Meagan C. Fitzpatrick

    doi:10.1101/2021.03.31.21254646 Date: 2021-04-06 Source: medRxiv

    Importance Several states including Texas and Mississippi have lifted their mask mandates, sparking concerns that this policy change could lead to a surge in cases and hospitalizations. Objective To estimate the increase in incidence, hospitalizations, and deaths in Texas and Mississippi following the removal of mask mandates, and to evaluate the relative reduction of these outcomes if policy change is delayed by 90 days. Design, Setting, and Participants This study uses an age-stratified compartmental model parameterized to incidence data in Texas and Mississippi to simulate increased transmission following policy change in March or June 2021, and to estimate the resulting number of incidence, hospitalizations, and deaths. Main Outcomes and Measures The increase in incidence, hospitalizations, and deaths if mask mandates are lifted on March 14 compared to lifting on June 12. Results If transmission is increased by 67% when mask mandates are lifted, we projected 11.39 (CrI: 11.22 - 11.55) million infections, 170,909 (CrI: 167,454 - 174,379) hospitalizations, and 5647 (5511 - 5804) deaths (Figure 1) in Texas from March 14 through the end of 2021. Delaying NPI lift until June reduces the average number of infections, hospitalizations, and deaths MESHD by 36%, 65%, and 62%, respectively. Proportionate differences were similar for the state of Mississippi. Peak hospitalization rates would be reduced by 79% and 63% in Texas and Mississippi, respectively. Conclusions and Relevance Removal of mask mandates in March 2021 is premature. Delaying this policy change until June 2021, when a larger fraction of the population has been vaccinated, will avert more than half of the expected COVID-19 MESHD hospitalizations and deaths, and avoid an otherwise likely strain on healthcare capacity.

    Growth Functions as a tool to model SARS-CoV-2 pandemic trajectory and related-deaths worldwide

    Authors: Vagner Fonseca; Edson Mascarenhas; Paulo Ramos; Leandro Coelho; Diego Frias

    doi:10.1101/2021.04.01.21254495 Date: 2021-04-05 Source: medRxiv

    The international scientific community from different areas of knowledge has made efforts to provide information and methods that contribute to the adoption of the most appropriate measures to curb the spread of the COVID-19 MESHD disease. In particular, the data analysis community has been very active in publishing a large number of papers. A good part of them is related to the prediction of epidemic variables (number of cases and deaths MESHD) in different time horizons. To solve the problem of the prediction of COVID-19 MESHD, an important place is occupied by the sigmoidal growth functions, as they have often been used successfully in previous epidemic outbreaks. The objective of this work was to investigate, on a statistical basis, the ability of classical growth functions to model the data from the COVID-19 pandemic MESHD. But for that, it was necessary to establish a clear classification of the 5 types of problems that can be faced with data analysis techniques in this specific context and to define a methodology based on quantitative metrics to measure the performance in solving these different types of problems. The basic concept used was that of an epidemic wave consisting of an initial-increasing and a final-decreasing phase. A classification of the COVID-19 MESHD waves in 4 types was done based on mining data from all available countries. Thus, it was possible to determine the resolvability of each type of problem depending on the stage of the epidemic wave. The biggest conclusion was the impossibility of solving the long-term forecasting problems (problem 5 - to estimate the total value of an epidemic wave) with data from the first phase only. Using this theoretical-methodological framework, we evaluated, using metrics specifically designed for these types of problems, the performance of 3 classic growth functions: Logistics, Gompertz and Richards (a generalization of the previous two) in 2 types of problems: (1) Description of the trajectory of the epidemic and (2) Prediction of the total numbers of cases and deaths MESHD. We used data from 10 countries, 7 of them with more than 100 daily deaths on the peak day. The results show a generalized underperformance of the logistic function in all aspects and place the Gompertz function as the best cost-benefit alternative, as it has performance comparable to the Richards function, but it has one less parameter to be adjusted, in the process of regression of the model to the observed data.

    Clinical Evidence for Improved Outcomes with Histamine Antagonists and Aspirin in 22,560 COVID-19 MESHD Patients

    Authors: Cameron Mura; Saskia Preissner; Susanne Nahles; Max Heiland; Philip E. Bourne; Robert Preissner

    doi:10.1101/2021.03.29.21253914 Date: 2021-04-05 Source: medRxiv

    COVID-19 MESHD has spurred much interest in the therapeutic potential of repurposed drugs. A family of acid-reducing drugs, known as histamine H2 receptor HGNC antagonists (H2RA), competitively bind the H2R and block its stimulation by histamine; examples of such drugs are famotidine (e.g., Pepcid) and ranitidine (e.g., Zantac). A dense web of functionalities between histamine and H2RAs, on the one hand, and downstream cellular pathways, on the other hand, links disparate physiological pathways in gastrointestinal contexts (e.g., acid reduction) to the dysregulated inflammatory cascades (cytokine storm) underlying the pathophysiology of COVID-19 MESHD. Is famotidine beneficial in treating COVID-19 MESHD? This question remains unresolved, though not for lack of effort: over 10 studies have examined the potential therapeutic value of famotidine in COVID-19 MESHD, but have found conflicting results (pro-famotidine, anti-famotidine, and neutral). Given the contradictory reports, we have undertaken the new analysis reported herein. Notably, studies published thus far rest upon substantially smaller datasets than drawn upon in the pre-sent work. We analyzed a cohort of 22,560 COVID-19 MESHD patients taking H1/H2 receptor antagonists, focusing on 1,379 severe cases requiring respiratory support. We analyzed outcomes for treatment with the H1RAs loratadine (e.g., Claritin) and cetirizine (e.g., Zyrtec), the H2RA famotidine, aspirin, and a famotidine & aspirin combination. For cases that reached the point of respiratory support, we found a significantly reduced fatality risk for famotidine treatment. We did not detect a benefit from dual-histamine receptor blockade (concurrently targeting H1 and H2 receptors). Notably, famotidine combined with aspirin did exhibit a significant synergistic survival benefit (odds ratio of 0.55). The relative risk for death MESHD decreased by 32.5%--an immense benefit, given the more than 2.6 million COVID-19 MESHD-related deaths thus far. We found lower levels of serum markers for severe disease (e.g., C-reactive protein HGNC) in famotidine users, consistent with prior findings by others and with a role for famotidine in attenuating cytokine release. The large, international, multi-center retrospective study reported here, sampling over 250,000 COVID-19 MESHD cases, hopefully helps clarify the possible value of clinically-approved histamine antagonists such as famotidine. Given these findings, alongside the cost-effectiveness and mild side-effects of popular drugs like famotidine and aspirin, we suggest that further prospective clinical trials, perhaps utilizing the aspirin combination reported here, are advisable.

    Assessing the impact of multiple comorbidities on fatal outcome in young COVID-19 MESHD

    Authors: Paulino Monroy Castillero; Eitan Friedman; Arturo Revuelta Herrera; Arik Yochelis

    doi:10.1101/2021.03.29.21254599 Date: 2021-03-31 Source: medRxiv

    A Bayesian analysis with the use of a rank-biserial correlation algorithm was applied to identify the impact of multiple comorbid conditions on fatal COVID-19 MESHD outcome in young adult cases (40-50 years). The demonstration was conducted for a publicly available database provided by the Mexican authority, in the absence of other alternative free-access repositories with information per patient. The methodology here proposed showed that even in the face of small sample sizes, it is possible to highlight deleterious synergistic comorbid conditions. Young adult cases with COVID-19 MESHD and co-existing diabetes MESHD, obesity MESHD, hypertension MESHD, CRF HGNC, or COPD MESHD were found more likely to have a fatal outcome compared with having no co-morbidities ( X2-6 HGNC times). With the methodology proposed, we show that having diabetes MESHD or hypertension MESHD in addition to CRF HGNC increased risk for mortality more than what is expected from independent effect (adverse synergistic effect), whereas in patients with obesity MESHD, the additional presence of diabetes MESHD or hypertension MESHD do not increase markedly the death MESHD risk due to COVID-19 MESHD. Quantitative analysis of having two comorbidities highlights the combinations of morbid conditions that are more likely to be associated with fatal outcomes in younger adults COVID-19 MESHD cases in a clinically applicable manner. The clinical implication of this method needs to be prospectively assessed.

    Second wave mortality among patients hospitalised for COVID-19 MESHD in Sweden: a nationwide observational cohort study

    Authors: Kristoffer Stralin; Erik Wahlstrom; Sten Walther; Anna M Bennet-Bark; Mona Heurgren; Thomas Linden; Johanna Holm; Hakan Hanberger

    doi:10.1101/2021.03.29.21254557 Date: 2021-03-31 Source: medRxiv

    Background During the first pandemic wave, a substantial decline in mortality was seen among hospitalized COVID-19 MESHD patients. We aimed to study if the decreased mortality continued during the second wave, using data compiled by the Swedish National Board of Health and Welfare. Method Retrospective nationwide observational study of all patients hospitalized in Sweden between March 1 HGNCst and December 31st, 2020, with SARS-CoV-2 RNA positivity 14 days before to 5 days after admission and a discharge code for COVID-19 MESHD. Outcome was 60-day all-cause mortality. Poisson regression was used to estimate the relative risk (RR) for death MESHD by month of admission, adjusting for age, sex, socioeconomic data, comorbidity, care dependency, and country of birth. Findings A total of 32 452 patients were included. December had the highest number of admissions/month (n=8253) followed by April (n=6430). The 60-day crude mortality decreased from 24.7% (95% CI, 23.0%-26.5%) for March to 10.4% (95% CI, 8.9%-12.1%) for July-September (as reported previously), later increased to 19.9% (95% CI, 19.1-20.8) for December. RR for 60-day death for December (reference) was higher than those for June to November (RR ranging from 0.74 to 0.89; 95% CI <1 for all months). SARS-CoV-2 variants of concern were only sporadically found in Sweden before January 2021. Interpretation The decreased mortality of hospitalized COVID-19 MESHD patients after the first wave turned and increased during the second wave.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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