Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (2227)

ProteinN (575)

NSP5 (418)

ComplexRdRp (253)

ProteinE (148)


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SARS-CoV-2 Proteins
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    Fixed dosing of tocilizumab in ICU admitted COVID-19 MESHD patients is a superior choice compared to bodyweight based dosing; an observational population pharmacokinetic and pharmacodynamic study

    Authors: Dirk Jan A.R. Moes; David J. van Westerloo; Sandra M. Arend; Jesse J. Swen; Annick de Vries; Henk-Jan Guchelaar; Simone A. Joosten; Mark G.J. de Boer; Teun van Gelder; Judith van Paassen

    doi:10.1101/2021.05.10.21256933 Date: 2021-05-12 Source: medRxiv

    Introduction Tocilizumab improves outcome, including survival, in intensive care unit (ICU) admitted COVID-19 MESHD patients. The currently applied dosage of 8 mg/kg is based on use of this drug for other indications, however is has not formally been investigated for COVID-19 MESHD. In this study pharmacokinetics and dynamics of tocilizumab were investigated in ICU admitted COVID-19 MESHD patients. Methods This was an open-label, single-center observational pharmacokinetic and -dynamic evaluation study. Enrolled patients, with polymerase chain reaction confirmed Covid-19 MESHD were admitted to the ICU for mechanical ventilation or high flow nasal canula oxygen support. All patients were 18 years of age or older and received tocilizumab within 24 hours after admission to the ICU and received 6 mg dexamethasone daily as concomitant therapy. Results 29 patients were enrolled between 15 December 2020 and 15 March 2021. A total of 139 tocilizumab plasma samples were obtained covering the pharmacokinetic curve of day 0 up to day 20 after tocilizumab initiation. A population pharmacokinetic model with parallel linear and non-linear clearance was developed and validated. Average AUC0-inf 1st DOSE was 938 [+/-190] ug/mL*days. Tocilizumab half-life was estimated to be 4.15 [+/-0.24] days. All patients had tocilizumab exposure above 1 ug/ml for at least 15 days. Conclusion This study provides evidence to support a fixed dose of 600 mg tocilizumab in COVID-19 MESHD patients. Furthermore our findings suggest that alternative cost saving regimens with even lower doses are likely to be as effective as the current 8 mg/kg recommendation.

    Prevalence and source analysis of COVID-19 MESHD misinformation of 138 countries

    Authors: Md. Sayeed Al-Zaman

    doi:10.1101/2021.05.08.21256879 Date: 2021-05-12 Source: medRxiv

    This study analyzed 9,657 pieces of misinformation that originated in 138 countries and fact-checked by 94 organizations. Collected from Poynter Institute's official website and following a quantitative content analysis method along with descriptive statistical analysis, this research produces some novel insights regarding COVID-19 MESHD misinformation. The findings show that India (15.94%), the US (9.74%), Brazil (8.57%), and Spain (8.03%) are the four most misinformation-affected countries. Based on the results, it is presumed that the prevalence of COVID-19 MESHD misinformation can have a positive association with the COVID-19 MESHD situation. Social media (84.94%) produces the highest amount of misinformation, and the internet (90.5%) as a whole is responsible for most of the COVID-19 MESHD misinformation. Moreover, Facebook alone produces 66.87% misinformation among all social media platforms. Of all countries, India (18.07%) produced the highest amount of social media misinformation, perhaps thanks to the country's higher internet penetration rate, increasing social media consumption, and users' lack of internet literacy. On the other hand, countries like Turkey, the US, Brazil, and the Philippines where either political control over media is intense or political conservatism is apparent, experienced a higher amount of misinformation from mainstream media, political figures, and celebrities. Although the prevalence of misinformation was the highest in March 2020, given the present trends, it may likely to increase slightly in 2021.

    Insights into genetic factors contributing to variability in SARS-CoV-2 susceptibility and COVID-19 MESHD disease severity

    Authors: Matteo D'Antonio; - The COVID-19 Host Genetics Initiative; Timothy D. Arthur; Jennifer P. Nguyen; Hiroko Matsui; Agnieszka D'Antonio-Chronowska; Kelly A. Frazer

    doi:10.1101/2021.05.10.21256423 Date: 2021-05-12 Source: medRxiv

    Variability in SARS-CoV-2 susceptibility and COVID-19 MESHD disease severity between individuals is partly due to genetic factors. Here, we applied colocalization to compare summary statistics for 16 GWASs from the COVID-19 MESHD Host Genetics Initiative to investigate similarities and differences in their genetic signals. We identified 9 loci associated with susceptibility (one with two independent GWAS signals; one with an ethnicity-specific signal), 14 associated with severity (one with two independent GWAS signals; two with ethnicity-specific signals) and one harboring two discrepant GWAS signals (one for susceptibility; one for severity). Utilizing colocalization we also identified 45 GTEx tissues that had eQTL(s) for 18 genes strongly associated with GWAS signals in eleven loci (1-4 genes per locus). Some of these genes showed tissue-specific altered expression and others showed altered expression in up to 41 different tissue types. Our study provides insights into the complex molecular mechanisms underlying inherited predispositions to COVID-19 MESHD-disease phenotypes.

    A Simple Mathematical MESHD Tool to Help Distribute Doses of Two-Dose Covid-19 MESHD Vaccines among Non-Immunized and Partly-Immunized Population

    Authors: Aanandita Kapoor; Krishan Mohan Kapoor

    doi:10.1101/2021.05.10.21256978 Date: 2021-05-12 Source: medRxiv

    Background: Full immunization with two doses of Covid vaccine has been found to be a critical factor in preventing morbidity and mortality from the Covid-19 MESHD infection. However, due to the shortage of vaccines, a significant portion of the population is not getting vaccination in many countries. Also, the distribution of vaccine doses between prospective first dose recipient and second dose recipient is not uniformly planned, as seen in India's various states and union territories. It is recommended to give second vaccine doses within 4-8 weeks to first dose recipients for both the approved vaccines in India; hence the judicious distribution between non-immunized and partly immunized populations is essential. Managing the Covid-19 MESHD vaccination drive in an area with a large number of single-dose recipients compared to a smaller number of fully immunized people can become a huge administrative challenge. Therefore, this study was conducted to assess the number of people covered under the Covid vaccination drive in India and analyze the state-wise distribution of vaccines among the non-immunized and partly immunized population. Methods: The Covid 19 vaccination data till 7th may, 2021 was taken from the website of the Ministry of Health and Family Welfare, Govt of India. From the data available of the number of doses injected, other figures like the total number of people vaccinated, people with two doses of vaccine or full immunization (FI), and those with a single dose of vaccine or partial immunization (PI) were found. The percentage of the fully immunized and partly immunized population was also found. A ratio between fully immunized and partly immunized individuals (FI: PI) was proposed as a guide to monitor the progress of the vaccination and future dose distribution of two-dose Covid-19 MESHD vaccines among partly immunized (PI) and non-immunized (NI) population. Results: In India, till 7 May 2021, 16,49,73,058 doses of Covid-19 MESHD vaccines have been injected. A total of 13,20,87,824 people received these vaccine doses, with 9,92,02,590 people getting a single dose or were partly immunized (PI), and 3,28,85,234 got two doses each or were fully immunized (FI). Among the states, Tripura and Andhra Pradesh had the highest FI: PI (Fully Immunized: Partly Immunized) ratio of 0.86 and 0.52, followed by Tamil Nadu, Arunachal Pradesh, and West Bengal with figures of 0.48. 0.47 and 0.47, respectively. Telangana and Punjab had the lowest FI: PI ratio among the states at 0.2 each, with Chhattisgarh, Madhya Pradesh, and Haryana following at 0.21. 0.23 and 0.23, respectively. These values are much lower than the national average of 0.33 in India. Conclusion: The FI: PI ratio could help governments decide how to use scarce vaccine resources among first-time and second-time recipients. This simple mathematical tool could ensure full immunization status to maximum people within the recommended 4-8 week time window after the first dose to avoid a large population group with partly immunized status.

    Plasmodium infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein

    Authors: Sarah Lapidus; Feimei Liu; Arnau Casanovas-Massana; Yile Dai; John D. Huck; Carolina Lucas; Jon Klein; Renata B. Filler; Madison S. Strine; Mouhamad Sy; Awa B. Deme; Aida S. Badiane; Baba Dieye; Ibrahima Mbaye Ndiaye; Younous Diedhiou; Amadou Moctar Mbaye; Cheikh Tidiane Diagne; Inés Vigan-Womas; Alassane Mbengue; Bacary D. Sadio; Moussa M. Diagne; Adam J. Moore; Khadidiatou Mangou; Fatoumata Diallo; Seynabou D. Sene; Mariama N. Pouye; Rokhaya Faye; Babacar Diouf; Nivison Nery Jr; Federico Costa; Mitermayer Reis; M. Catherine Muenker; Daniel Z. Hodson; Yannick Mbarga; Ben Z. Katz; Jason R. Andrews; Melissa Campbell; Ariktha Srivathsan; Kathy Kamath; Elisabeth Baum-Jones; Ousmane Faye; Amadou Alpha Sall; Juan Carlos Quintero Vélez; Michael Cappello; Michael Wilson; Choukri Ben-Mamoun; Fabrice A. Somé; Roch K. Dabiré; Carole Else Eboumbou Moukoko; Jean Bosco Ouédraogo; Yap Boum II; John Shon; Daouda Ndiaye; Adam Wisnewski; Sunil Parikh; Akiko Iwasaki; Craig B. Wilen; Albert I. Ko; Aaron M. Ring; Amy K. Bei

    doi:10.1101/2021.05.10.21256855 Date: 2021-05-12 Source: medRxiv

    Individuals with acute malaria infection MESHD generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein PROTEIN and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein PROTEIN-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria MESHD-endemic countries.

    Reinfection by the SARS-CoV-2 P.1 HGNC variant in blood donors in Manaus, Brazil

    Authors: Carlos A. Prete Jr.; Lewis F Buss; Claudia M. M. Abrahim; Tassila Salomon; Myuki A. E. Crispim; Marcio K. Oikawa; Renata Buccheri; Eduard Grebe; Allyson G. da Costa; Nelson A. Fraiji; Maria do P. S. S. Carvalho; Neal Alexander; Nuno R. Faria; Christopher Dye; Vitor H. Nascimento; Michael Paul Busch; Ester C. Sabino

    doi:10.1101/2021.05.10.21256644 Date: 2021-05-12 Source: medRxiv

    The city of Manaus, north Brazil, was stricken by a severe epidemic of SARS-Cov-2 in March 2020, reaching a seroprevalence of 76% by October 2020. Nevertheless, in late November an abrupt increase in hospitalizations and deaths hit Manaus, causing higher number of deaths compared to the first epidemic wave. It has been hypothesized that virus lineages circulating in the second wave, namely the P.1 HGNC variant of concern first detected in early December in Manaus, could be better at evading immunity generated in response to previous infection with other lineages. In order to estimate the reinfection rate during the resurgence of SARS-CoV-2 in Manaus, we tested serial samples from 238 unvaccinated repeat blood donors using a SARS-CoV-2 anti-N IgG chemiluminescence microparticle assay. Blood donors were divided into six groups that reflected the inferred sequence of infection and reinfection with non- P.1 HGNC and P.1 HGNC variants. We assumed that reinfections induce a recrudescence (or boosting) of plasma anti-N IgG antibody levels, yielding a V-shaped time series of antibody reactivity levels. We infer that 16.9% (95% CI [9.48%, 28.5%]) of all presumed P.1 HGNC infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections (defined by considering the time period when the antibody levels are expected to grow after recovery and the range of half-lives for antibody waning after seroconversion), these percentages increase respectively to 25.8% (95% CI [16.7%, 37.4%]), and 31.0% (95% CI [21.4%, 42.5%]). Our data suggest that reinfection due to P.1 HGNC is common and more frequent than what has been detected by traditional epidemiologic, molecular and genomic surveillance of clinical cases.

    Who should get vaccinated first? An effective network information-driven priority vaccination strategy

    Authors: Dong Liu; Chi K. Tse; Rosa Ho Man Chan; Choujun Zhan

    doi:10.1101/2021.05.10.21256999 Date: 2021-05-12 Source: medRxiv

    Approval of emergency use of the Novel Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) vaccines in many countries has brought hope to ending the COVID-19 pandemic MESHD sooner. Considering the limited vaccine supply in the early stage of COVID-19 MESHD vaccination programs in most countries, a highly relevant question to ask is: who should get vaccinated first? In this article we propose a network information-driven vaccination strategy where a small number of people in a network (population) are categorized, according to a few key network properties, into priority groups. Using a network-based SEIR model for simulating the pandemic progression, the network information-driven vaccination strategy is compared with a random vaccination strategy. Results for both large-scale synthesized networks and real social networks have demonstrated that the network information-driven vaccination strategy can significantly reduce the cumulative number of infected individuals and lead to a more rapid containment of the pandemic. The results provide insight for policymakers in designing an effective early-stage vaccination plan.

    Comparative sensitivity evaluation for 122 CE-marked SARS-CoV-2 antigen rapid tests

    Authors: Heinrich Scheiblauer; Angela Filomena; Andreas Nitsche; Andreas Puyskens; Victor Corman; Christian Drosten; Katrin Zwirglmaier; Constanze Lange; Petra Emmerich; Michael Mueller; Olivia Knauer; Micha Nuebling

    doi:10.1101/2021.05.11.21257016 Date: 2021-05-12 Source: medRxiv

    Abstract Objective Independent evaluation of the sensitivity of CE-marked SARS-CoV-2 antigen rapid diagnostic tests (Ag RDT) offered in Germany. Method The sensitivity of 122 Ag RDT was adressed using a common evaluation panel. Minimum sensitivity of 75% for panel members with CT<25 HGNC was used for differentiation of devices eligible for reimbursement in in the German healthcare system. Results The sensitivity of different SARS-CoV-2 Ag RDT varied over a wide range. The sensitivity limit of 75% for panel members with CT <25 was met by 96 of the 122 tests evaluated; 26 tests exhibited lower sensitivity, few of which were completely failing. Some devices exhibited high sensitivity, e.g. 100% for CT<30 HGNC. Conclusion This comparative evaluation succeeded to distinguish less sensitive from better performing Ag RDT. Most of the Ag RDT evaluated appear to be suitable for fast identification of acute infections MESHD associated with high viral loads. Market access of SARS-CoV-2 Ag RDT should be based on minimal requirements for sensitivity and specificity.

    Quantifying the potential for dominant spread of SARS-CoV-2 variant B.1.351 in the United States

    Authors: Pratha Sah; Thomas N Vilches; Affan Shoukat; Abhishek Pandey; Meagan C Fitzpatrick; Seyed M Moghadas; Alison P. Galvani

    doi:10.1101/2021.05.10.21256996 Date: 2021-05-12 Source: medRxiv

    Recent evidence suggests that the SARS-CoV-2 variant B.1.351 exhibits partial immune evasion to antibodies generated by natural infection or vaccination. We used a dynamic transmission model to evaluate whether this variant could become dominant in the United States given mounting vaccination coverage and other circulating variants. In the presence of the B.1.1.7 variant, we show that B.1.351 is unlikely to become dominant even when all fully vaccinated individuals return to their pre-pandemic behavior. However, an improved selection advantage of B.1.351 arising from a combination of increased transmission and immune escape could drive this variant to dominance as early as July 2021 and fuel a resurgence of cases and hospitalizations. Our study underscores the urgency for continued rollout of the current generation of vaccines despite the emergence of immune escape variants.

    Cohort-based surveillance of SARS-CoV2 transmission mirrors infection rates at the population level: a one-year longitudinal study

    Authors: Christine Klein; Max Borsche; Alexander Balck; Bandik Foeh; Johann Rahmoeller; Elke Peters; Jan Knickmann; Miranda Lane; Eva-Juliane Vollstedt; Susanne A. Elsner; Nadja Kaeding; Susanne Hauswaldt; Tanja Lange; Jennifer E. Hundt; Alexander Mischnik; Stefan Niemann; Florian Maurer; Susanne Homolka; Laura Paulowski; Jan Kramer; Christoph Twesten; Christian Sina; Gabriele Gillessen-Kaesbach; Hauke Busch; Marc Ehlers; Stefan Taube; Jan Rupp; Alexander Katalinic

    doi:10.1101/2021.05.10.21256966 Date: 2021-05-12 Source: medRxiv

    Background More than one year into the COVID-19 pandemic MESHD, important data gaps remain on longitudinal prevalence of SARS-CoV-2 infection MESHD at the population level and in defined risk groups, efficacy of specific lockdown measures, and on (cost-)effective surveillance. Methods The ELISA (Luebeck Longitudinal Investigation of SARS-CoV-2 Infection MESHD) study invited adult inhabitants (n=~300,000) from the Luebeck area (Northern Germany) and enrolled 3051 participants (~1%); 1929 population-matched and 1645 with high-exposure based on profession. The one-year study period (03/2020-02/2021) covered massive influx of tourism in the summer, rise of infection rates in the fall/winter 2020/2021, and two lockdowns. Participants were screened seven times for SARS-CoV-2 infection MESHD using PCR and antibody testing and monitored with an app-based questionnaire (n=~91,000). Results Cohort (56% female; mean age: 45.6 years) retention was 75%-98%; 92 persons (3.5%) were antibody- and/or PCR-positive. Seropositivity was almost 2-fold higher in men and increased risk detected in several high-exposure groups (highest for nurses, followed by police, army, firemen, and students). In May 2020, 92% of the infections were missed by PCR testing; by February 2021, only 29% remained undiagnosed. Contact to COVID-19 MESHD-affected was the most relevant risk factor. Other factors, such as frequent use of public transportation, shopping, close contacts at work, and extensive tourism in the summer did not impact infection MESHD rates. Conclusions We i) provide a model for effective, regional surveillance; ii) identify infection risk factors informing public health measures; iii) demonstrate that easing of lockdown measures appears safe at times of low prevalence in the presence of continuous monitoring.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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