Most downloaded biology preprints, since beginning of last month
133,648 results found. For more information, click each entry to expand.
4,085 downloads medRxiv infectious diseases
Peter Horby, Lise Estcourt, Leon Peto, Jonathan R Emberson, Natalie Staplin, Enti Spata, Guilherme Pessoa-Amorim, Mark Campbell, Alistair Roddick, Nigel E Brunskill, Tina George, Daniel Zehnder, Simon Tiberi, Ni Ni Aung, Alison Uriel, John Widdrington, George Koshy, Thomas Brown, Steven Scott, J Kenneth Baillie, Maya H Buch, Lucy C Chappell, Jeremy N Day, Saul N Faust, Thomas Jaki, Katie Jeffery, Edmund Juszczak, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Marion Mafham, David Roberts, Richard Haynes, Martin J Landray
Background: Treatment of COVID-19 patients with plasma containing anti-SARS-CoV-2 antibodies may have a beneficial effect on clinical outcomes. We aimed to evaluate the safety and efficacy of convalescent plasma in patients admitted to hospital with COVID-19. Methods: In this randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) several possible treatments are being compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to receive either usual care plus high titre convalescent plasma or usual care alone. The primary outcome was 28-day mortality. Findings: Between 28 May 2020 and 15 January 2021, 5795 patients were randomly allocated to receive convalescent plasma and 5763 to usual care alone. There was no significant difference in 28-day mortality between the two groups: 1398 (24%) of 5795 patients allocated convalescent plasma and 1408 (24%) of 5763 patients allocated usual care died within 28 days (rate ratio [RR] 1.00; 95% confidence interval [CI] 0.93 to 1.07; p=0.93). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (66% vs. 67%; rate ratio 0.98; 95% CI 0.94-1.03, p=0.50). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of progression to invasive mechanical ventilation or death (28% vs. 29%; rate ratio 0.99; 95% CI 0.93-1.05, p=0.79). Interpretation: Among patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.
4,062 downloads medRxiv infectious diseases
Emma B Hodcroft, Daryl B. Domman, Daniel J. Snyder, Kasopefoluwa Y. Oguntuyo, Maarten Van Diest, Kenneth H. Densmore, Kurt C Schwalm, Jon Femling, Jennifer L. Carroll, Rona S. Scott, Martha M. Whyte, Michael W. Edwards, Noah C. Hull, Christopher G. Kevil, John A. Vanchiere, Benhur Lee, Darrell L Dinwiddie, Vaughn S Cooper, Jeremy P. Kamil
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2). Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021, GISAID data show 499 viral sequences of this variant from the USA. Phylogenetic analyses revealed the independent evolution and spread of at least six distinct Q677H sub-lineages, with first collection dates ranging from mid-August to late November 2020. Four 677H clades from clade 20G (B.1.2), 20A (B.1.234), and 20B (B.1.1.220, and B.1.1.222) each contain roughly 100 or fewer sequenced cases, while a distinct pair of clade 20G clusters are represented by 754 and 298 cases, respectively. Although sampling bias and founder effects may have contributed to the rise of S:677 polymorphic variants, the proximity of this position to the polybasic cleavage site at the S1/S2 boundary are consistent with its potential functional relevance during cell entry, suggesting parallel evolution of a trait that may confer an advantage in spread or transmission. Taken together, our findings demonstrate simultaneous convergent evolution, thus providing an impetus to further evaluate S:677 polymorphisms for effects on proteolytic processing, cell tropism, and transmissibility.
4,012 downloads medRxiv infectious diseases
Guillaume Butler-Laporte, Tomoko Nakanishi, Vincent Mooser, David R Morrison, Tala Abdullah, Olumide Adeleye, Noor Mamlook, Nofar Kimchi, Zaman Afrasiabi, Nardin Rezk, Annarita Giliberti, Alessandra Renieri, Yiheng Chen, Sirui Zhou, Vincenzo Forgetta, J. Brent Richards
INTRODUCTION: Increased vitamin D levels, as reflected by 25OHD measurements, have been proposed to protect against COVID-19 disease based on in-vitro, observational, and ecological studies. However, vitamin D levels are associated with many confounding variables and thus associations described to date may not be causal. Vitamin D Mendelian randomization (MR) studies have provided results that are concordant with large-scale vitamin D randomized trials. Here, we used two-sample MR to assess evidence supporting a causal effect of circulating 25OHD levels on COVID-19 susceptibility and severity. METHODS AND FINDINGS: Genetic variants strongly associated with 25OHD levels in a genome-wide association study (GWAS) of 443,734 participants of European ancestry (including 401,460 from the UK Biobank) were used as instrumental variables. GWASs of COVID-19 susceptibility, hospitalization, and severe disease from the COVID-19 Host Genetics Initiative were used as outcome GWASs. These included up to 14,134 individuals with COVID-19, and 1,284,876 without COVID-19, from 11 countries. SARS-CoV-2 positivity was determined by laboratory testing or medical chart review. Population controls without COVID-19 were also included in the control groups for all outcomes, including hospitalization and severe disease. Analyses were restricted to individuals of European descent when possible. Using inverse-weighted MR, genetically increased 25OHD levels by one standard deviation on the logarithmic scale had no significant association with COVID-19 susceptibility (OR = 0.97; 95% CI: 0.95, 1.10; P=0.61), hospitalization (OR = 1.11; 95% CI: 0.91, 1.35; P=0.30), and severe disease (OR = 0.93; 95% CI: 0.73, 1.17; P=0.53). We used an additional 6 meta-analytic methods, as well as sensitivity analyses after removal of variants at risk of horizontal pleiotropy and obtained similar results. These results may be limited by weak instrument bias in some analyses. Further, our results do not apply to individuals with vitamin D deficiency. CONCLUSION: In this two-sample MR study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a mean of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials.
4,001 downloads medRxiv infectious diseases
Renato M. Coutinho, Flavia Maria Darci Marquitti, Leonardo Souto Ferreira, Marcelo Eduardo Borges, Rafael Lopes Paixao da Silva, Otavio Canton, Tatiana P. Portella, Silas Poloni Lyra, Caroline Franco, Mateusz M. Plucinski, Fernanda C. Lessa, Antonio D Silva, Roberto A. Kraenkel, Maria Amelia S M Veras, Paulo Inacio Prado
The variant of concern (VOC) P.1 emerged in the Amazonas state (Brazil) in November-2020. It contains a constellation of mutations, ten of them in the spike protein. Consequences of these specific mutations at the population level have been little studied so far, despite the detection of P.1 variant in 26 countries, with local transmission in at least four other countries in the Americas and Europe. Here, we estimate P.1's transmissibility and reinfection using a model-based approach, by fitting data from the Brazilian national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December 2020 to February 2021, when the city was devastated by four times more cases than in the previous peak (April 2020). The new variant was found to be about 2.6 times more transmissible (95\% Confidence Interval (CI): 2.4--2.8) than previous circulating variant(s). The city already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus (estimated as 78\%, CI:73--83\%), and the fitted model attributed 28\% of the cases during the period to reinfections by the variant P.1. Our estimates rank P.1 as the most transmissible among the current identified SARS-CoV-2 VOCs, posing a serious threat and requiring urgent measures to control its global spread.
3,989 downloads bioRxiv immunology
Thandeka Moyo-Gwete, Mashudu Madzivhandila, Zanele Makhado, Frances Ayres, Donald Mhlanga, Brent Oosthuysen, Bronwen Lambson, Prudence Kgagudi, Houriiyah Tegally, Arash Iranzadeh, Deelan Doolabh, Lynn Tyers, Lionel Chinhoyi, Mathilda Mennen, Sango Skelem, Gert Marais, Constantinos Kurt Wibmer, Jinal Bhiman, Veronica Ueckermann, Theresa Rossouw, Michael Boswell, Tulio de Oliveira, Carolyn Williamson, Wendy Burgers, Ntobeko Ntusi, Lynn Morris, Penny Moore
Neutralization escape by SARS-CoV-2 variants, as has been observed in the 501Y.V2 (B.1.351) variant, has impacted the efficacy of first generation COVID-19 vaccines. Here, the antibody response to the 501Y.V2 variant was examined in a cohort of patients hospitalized with COVID-19 in early 2021 - when over 90% of infections in South Africa were attributed to 501Y.V2. Robust binding and neutralizing antibody titers to the 501Y.V2 variant were detected and these binding antibodies showed high levels of cross-reactivity for the original variant, from the first wave. In contrast to an earlier study where sera from individuals infected with the original variant showed dramatically reduced potency against 501Y.V2, sera from 501Y.V2-infected patients maintained good cross-reactivity against viruses from the first wave. Furthermore, sera from 501Y.V2-infected patients also neutralized the 501Y.V3 (P.1) variant first described in Brazil, and now circulating globally. Collectively these data suggest that the antibody response in patients infected with 501Y.V2 has a broad specificity and that vaccines designed with the 501Y.V2 sequence may elicit more cross-reactive responses.
3,969 downloads medRxiv epidemiology
Health officials warn that SARS-CoV-2 vaccines must be uniformly distributed within and among countries if we are to quell the ongoing pandemic. Yet there has been little critical assessment of the underlying reasons for this warning. Here, we explicitly show why vaccine equity is necessary. Perhaps counter-intuitively, we find that vaccine escape mutants are less likely to come from highly vaccinated regions where there is strong selection pressure favoring vaccine escape and more likely to come from neighboring unvaccinated regions where there is no selection favoring escape. Unvaccinated geographic regions thus provide evolutionary reservoirs from which new strains can arise and cause new epidemics within neighboring vaccinated regions and beyond. Our findings have timely implications for vaccine rollout strategies and public health policy. Summary sentenceCalls for vaccine equity are about more than fairness; we show why vaccine equity is critical to ending the COVID pandemic.
3,966 downloads medRxiv infectious diseases
Structured AbstractO_ST_ABSObjectiveC_ST_ABSDetermine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. MethodsStudies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities four weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. ResultsOur analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. DiscussionThese results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.
3,962 downloads medRxiv intensive care and critical care medicine
Ewan C Goligher, Charlotte Ann Bradbury, Bryan J. McVerry, Patrick R. Lawler, Jeffrey S Berger, Michelle N Gong, Marc Carrier, Harmony R Reynolds, Anand Kumar, Alexis F Turgeon, Lucy Z Kornblith, Susan R Kahn, John C Marshall, Keri S Kim, Brett L Houston, Lennie P. G. Derde, Mary Cushman, Tobias Tritschler, Derek C. Angus, Lucas C Godoy, Zoe McQuilten, Bridget-Anne Kirwan, Michael E Farkouh, Maria M Brooks, Roger J. Lewis, Anthony Gordon, Scott Berry, Colin J. McArthur, Matthew D Neal, Judith S Hochman, Steven A Webb, Ryan Zarychanski
Background Thrombosis may contribute to morbidity and mortality in Covid-19. We hypothesized that therapeutic anticoagulation would improve outcomes in critically ill patients with Covid-19. Methods We conducted an open-label, adaptive, multiplatform, randomized, clinical trial. Patients with severe Covid-19, defined as the requirement for organ support with high flow nasal cannula, non-invasive ventilation, invasive ventilation, vasopressors, or inotropes, were randomized to receive therapeutic anticoagulation with heparin or pharmacological thromboprophylaxis as per local usual care. The primary outcome was an ordinal scale combining in-hospital mortality (assigned -1) and days free of organ support to day 21. Results Therapeutic anticoagulation met the pre-defined criteria for futility in patients with severe Covid-19. The primary outcome was available for 1,074 participants (529 randomized to therapeutic anticoagulation and 545 randomized to usual care pharmacological thromboprophylaxis). Median organ support-free days were 3 days (interquartile range -1, 16) in patients assigned to therapeutic anticoagulation and 5 days (interquartile range -1, 16) in patients assigned to usual care pharmacological thromboprophylaxis (adjusted odds ratio 0.87, 95% credible interval (CrI) 0.70-1.08, posterior probability of futility [odds ratio<1.2] 99.8%). Hospital survival was comparable between groups (64.3% vs. 65.3%, adjusted odds ratio 0.88, 95% CrI 0.67-1.16). Major bleeding occurred in 3.1% of patients assigned to therapeutic anticoagulation and 2.4% of patients assigned to usual care pharmacological thromboprophylaxis. Conclusions In patients with severe Covid-19, therapeutic anticoagulation did not improve hospital survival or days free of organ support compared to usual care pharmacological thromboprophylaxis.
3,956 downloads medRxiv epidemiology
One of the key questions regarding COVID19 vaccines is whether they can reduce viral shedding. To date, Israel vaccinated substantial parts of the adult population, which enables extracting real world signals. The vaccination rollout started on Dec 20th 2020, utilized mainly the BNT162b2 vaccine, and focused on individuals who are 60 years or older. By now, more than 75% of the individuals of this age group have been at least 14 days after the first dose, compared to 25% of the individuals between ages 40-60 years old. Here, we traced the Ct value distribution of 16,297 positive qPCR tests in our lab between Dec 1st to Jan 31st that came from these two age groups. As we do not have access to the vaccine status of each test, our hypothesis was that if vaccines reduce viral load, we should see a difference in the Ct values between these two age groups in late January but not before. Consistent with this hypothesis, until Jan 15th, we did not find any statistically significant differences in the average Ct value between the groups. In stark contrast, our results in the last two weeks of January show a significant weakening in the average Ct value of 60+ individuals to the 40-60 group. To further corroborate these results, we also used a series nested linear models to explain the Ct values of the positive tests. This analysis favored a model that included an interaction between age and the late January time period, consistent with the effect of vaccination. We then used demographic data and the daily vaccination rates to estimate the effect of vaccination on viral load reduction. Our estimate suggests that vaccination reduces the viral load by 1.6x to 20x in individuals who are positive for SARS-CoV-2. This estimate might improve after more individuals receive the second dose. Taken together, our findings indicate vaccination is not only important for individual's protection but can reduce transmission.
3,931 downloads medRxiv infectious diseases
Victor M Corman, Verena Claudia Haage, Tobias Bleicker, Marie Luisa Schmidt, Barbara Mühlemann, Marta Zuchowski, Wendy Karen Jó Lei, Patricia Tscheak, Elisabeth Möncke-Buchner, Marcel A Müller, Andi Krumbholz, Jan Felix Drexler, Christian Drosten
BackgroundAntigen point of care tests (AgPOCT) can accelerate SARS-CoV-2 testing. As first AgPOCT are becoming available, there is a growing interest in their utility and performance. MethodsHere we compare AgPOCT products by seven suppliers: the Abbott Panbio COVID-19 Ag Rapid Test; the RapiGEN BIOCREDIT COVID-19 Ag; the Healgen(R) Coronavirus Ag Rapid Test Cassette (Swab); the Coris Bioconcept Covid.19 Ag Respi-Strip; the R-Biopharm RIDA(R)QUICK SARS-CoV-2 Antigen; the NAL von minden NADAL COVID19-Ag Test; and the Roche/SD Biosensor SARS-CoV Rapid Antigen Test. Tests were evaluated on recombinant nucleoprotein, cultured endemic and emerging coronaviruses, stored clinical samples with known SARS-CoV-2 viral loads (n=138), stored samples from patients with respiratory agents other than SARS-CoV-2 (n=100), as well as self-sampled swabs from healthy volunteers (n=35). FindingsLimits of detection in six of seven tested products ranged between 2.08 x 106 and 2.88 x 107 copies per swab, the outlier at 1.58 x 1010 copies per swab. Specificities ranged between 98.53% and 100% in five products, with two outliers at 94.85% and 88.24%. False positive results were not associated with any specific respiratory agent. As some of the tested AgPOCT were early production lots, the observed issues with specificity are unlikely to persist. InterpretationThe sensitivity range of most AgPOCT overlaps with viral load figures typically observed during the first week of symptoms, which marks the infectious period in the majority patients. AgPOCTs with a limit of detection that approximates the virus concentration above which patients are infectious may enable shortcuts in decision-making in various areas of healthcare and public health.
3,925 downloads medRxiv infectious diseases
A distinctive feature of the roll out of vaccination against SARS-CoV-2 virus in the UK was the decision to delay the timing of the second injection till 12 weeks after the first. The logic behind this is to protect more people sooner and so reduce the total number of severe infections, hospitalisations, and deaths. This decision caused criticism from some quarters due in part to a belief that a single injection may not give adequate immunity. A recent paper based on Israel s experience of vaccination suggested that a single dose may not provide adequate protection. Here we extract the primary data from the Israeli paper and then estimate the incidence per day for each day after the first injection and also estimate vaccine effectiveness for each day from day 13 to day 24. We used a pooled estimate of the daily incidence rate during days 1 to 12 as the counterfactual estimate of incidence without disease and estimated confidence intervals using Monte Carlo modelling. After initial injection case numbers increased to day 8 before declining to low levels by day 21. Estimated vaccine effectiveness was pretty much 0 at day 14 but then rose to about 90% at day 21 before levelling off. The cause of the initial surge in infection risk is unknown but may be related to people being less cautious about maintaining protective behaviours as soon as they have the injection. What our analysis shows is that a single dose of vaccine is highly protective, although it can take up to 21 days to achieve this. The early results coming from Israel support the UK policy of extending the gap between doses by showing that a single dose can give a high level of protection.
3,916 downloads medRxiv epidemiology
Objectives: The epidemiology of post-COVID syndrome (PCS) is currently undefined. We quantified rates of organ-specific impairment following recovery from COVID-19 hospitalisation compared with those in a matched control group, and how the rate ratio (RR) varies by age, sex, and ethnicity. Design: Observational, retrospective, matched cohort study. Setting: NHS hospitals in England. Participants: 47,780 individuals (mean age 65 years, 55% male) in hospital with COVID-19 and discharged alive by 31 August 2020, matched to controls on demographic and clinical characteristics. Outcome measures: Rates of hospital readmission, all-cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney and liver diseases until 30 September 2020. Results: Mean follow-up time was 140 days for COVID-19 cases and 153 days for controls. 766 (95% confidence interval: 753 to 779) readmissions and 320 (312 to 328) deaths per 1,000 person-years were observed in COVID-19 cases, 3.5 (3.4 to 3.6) and 7.7 (7.2 to 8.3) times greater, respectively, than in controls. Rates of respiratory, diabetes and cardiovascular events were also significantly elevated in COVID-19 cases, at 770 (758 to 783), 127 (122 to 132) and 126 (121 to 131) events per 1,000 person-years, respectively. RRs were greater for individuals aged <70 than [≥]70 years, and in ethnic minority groups than the White population, with the biggest differences observed for respiratory disease: 10.5 [9.7 to 11.4] for <70 years versus 4.6 [4.3 to 4.8] for [≥]70 years, and 11.4 (9.8 to 13.3) for Non-White versus 5.2 (5.0 to 5.5) for White. Conclusions: Individuals discharged from hospital following COVID-19 face elevated rates of multi-organ dysfunction compared with background levels, and the increase in risk is neither confined to the elderly nor uniform across ethnicities. The diagnosis, treatment and prevention of PCS require integrated rather than organ- or disease-specific approaches. Urgent research is required to establish risk factors for PCS.
3,857 downloads medRxiv infectious diseases
Fredy Suter, Elena Consolaro, Stefania Pedroni, Chiara Moroni, Elena Pasto, Maria Vittoria Paganini, Grazia Prevettoni, Umberto Cantarelli, Nadia Rubis, Norberto Perico, Annalisa Perna, Tobia Peracchi, Piero Ruggenenti, Giuseppe Remuzzi
Background. Effective simple, home-treatment algorithms implemented on the basis of a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalization of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health care providers. Methods. This academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians from October 2020 to January 2021 according to the proposed recommendation algorithm with those of 90 age-, sex-, and comorbidities- matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalization. Analyses were by intention-to-treat. Findings. All patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the recommended schedule cohort and 14 [7-30] days in the matched control cohort (p=0.033). Minor symptoms persisted in a lower percentage of patients in the recommended than in the control cohort (23.3% versus 73.3%, respectively, p<0.0001) and for a shorter period (p=0.0107). Two patients in the recommended cohort were hospitalized compared to 13 (14.4%) controls (Log-rank test, p=0.0038). Prevention algorithm abated the days and cumulative costs of hospitalization by >90% (from 481 to 44 days and from 296 to 28 thousand Euros, respectively. 1.2 patients had to be treated to save one hospitalization event. Interpretation. Implementation of an early, home-treatment algorithm failed to accelerate recovery from major symptoms of COVID-19, but almost blunted the risk of hospitalization and related treatment costs.
3,814 downloads medRxiv pediatrics
There is increasing evidence that adult patients diagnosed with acute COVID-19 suffer from Long COVID initially described in Italy. To date, data on Long COVID in children are lacking. We assessed persistent symptoms in pediatric patients previously diagnosed with COVID-19. More than a half reported at least one persisting symptom even after 120 days since COVID-19, with 42.6% being impaired by these symptoms during daily activities. Symptoms like fatigue, muscle and joint pain, headache , insomnia, respiratory problems and palpitations were particularly frequent, as also described in adults. The evidence that COVID-19 can have long-term impact children as well, including those with asymptomatic/paucisymptomatic COVID-19, highlight the need for pediatricians, mental health experts and policy makers of implementing measures to reduce impact of the pandemic on child s health.
3,801 downloads bioRxiv cell biology
Nathan H. Cho, Keith C Cheveralls, Andreas-David Brunner, Kibeom Kim, Andre C. Michaelis, Preethi Raghavan, Hirofumi Kobayashi, Laura Savy, Jason Y. Li, Hera Canaj, James Y.S. Kim, Edna M. Setwart, Christian Gnann, Frank McCarthy, Joana P. Cabrera, Rachel M. Brunetti, Bryant B. Chhun, Greg Dingle, Marco Y. Hein, Bo Huang, Shalin B. Mehta, Jonathan S. Weissman, Rafael Gomez-Sjoberg, Daniel N Itzhak, Loic Alain Royer, Matthias Mann, Manuel Leonetti
Elucidating the wiring diagram of the human cell is one of the central goals of the post-genomic era. Here, we integrate genome engineering, confocal imaging, mass spectrometry and data science to systematically map protein localization in live cells and protein interactions under endogenous expression conditions. For this, we generated a library of 1,311 CRISPR-edited cell lines harboring fluorescent tags that also serve as handles for affinity capture, and applied a new machine learning framework to encode the interaction and localization profiles of each protein. Our approach provides a data-driven description of the molecular and spatial networks that organize the human proteome. We show that unsupervised clustering of these networks delineates functional groups and facilitates biological discovery, while hierarchical analyses uncover the core features that template cellular architecture. Furthermore, we discover that localization signatures are remarkably predictive of protein function, and often contain enough information to identify molecular interactions. Paired with a fully interactive website (opencell.czbiohub.org), OpenCell is a resource for the quantitative cartography of human cellular organization.
3,776 downloads bioRxiv neuroscience
Eren Sezener, Agnieszka Grabska-Barwinska, Dimitar Kostadinov, Maxime Beau, Sanjukta Krishnagopal, David Budden, Marcus Hutter, Joel Veness, Matthew Botvinick, Claudia Clopath, Michael Hausser, Peter Latham
The dominant view in neuroscience is that changes in synaptic weights underlie learning. It is unclear, however, how the brain is able to determine which synapses should change, and by how much. This uncertainty stands in sharp contrast to deep learning, where changes in weights are explicitly engineered to optimize performance. However, the main tool for doing that, backpropagation, is not biologically plausible, and networks trained with this rule tend to forget old tasks when learning new ones. Here we introduce the Dendritic Gated Network (DGN), a variant of the Gated Linear Network, which offers a biologically plausible alternative to backpropagation. DGNs combine dendritic "gating" (whereby interneurons target dendrites to shape neuronal response) with local learning rules to yield provably efficient performance. They are significantly more data efficient than conventional artificial networks and are highly resistant to forgetting, and we show that they perform well on a variety of tasks, in some cases better than backpropagation. The DGN bears similarities to the cerebellum, where there is evidence for shaping of Purkinje cell responses by interneurons. It also makes several experimental predictions, one of which we validate with in vivo cerebellar imaging of mice performing a motor task.
3,776 downloads medRxiv oncology
Background: Recent researches reported the impact of the coronavirus disease 2019 (COVID - 19) pandemic on the clinical practice of specific type cancers. The aim of this study was to reveal the impact of the COVID-19 outbreak on the clinical practice of various cancers. Methods: We included hospitalized patients aged 18 years or older diagnosed between July 2018 and June 2020 with one of the top 12 most common cancers in Japan (colon/rectum, lung, gastric, breast, bladder & urinary tract, pancreas, non-Hodgkin lymphoma, liver, prostate, esophagus, uterus, and gallbladder & biliary tract) using Diagnostic Procedure Combination data, an administrative database in Japan. The intervention was defined April 2020 based on a declaration of emergency from Japanese government. The change volume of number of monthly admissions with each cancer was tested by interrupted time series (ITS) analysis, and monthly cases with radical surgery or chemotherapy for each cancer were descripted. Results: 403,344 cases were included during the study period. The most common cancer was colon/rectum (20.5%), followed by lung (17.5%). In almost cancer cases, the number of admissions decreased in May 2020. In particular, colorectal, lung, gastric, breast, uterine, or esophageal cancer cases decreased by over 10%. The number of admissions with surgery or chemotherapy decreased in colorectal, lung, gastric, breast, uterine, or esophageal cancer. ITS analysis indicated that cases with gastric or esophageal cancer were affected more than other type of cancer. Conclusions: The COVID-19 outbreak has a negative impact on the number of admission cases with cancer; the magnitude of impact varied by cancer diagnosis.
3,705 downloads medRxiv infectious diseases
The current epidemic of COVID-19 is unparalleled in recent history as are the social distancing interventions that have led to a significant halt on the economic and social life of so many countries. However, there is very little empirical evidence about which social distancing measures have the most impact. We report a quasi-experimental study of the impact of various interventions for control of the outbreak. Data on case numbers and deaths were taken from the daily published figures by the European Centre for Disease Control and dates of initiation of various control strategies from the Institute of Health Metrics and Evaluation website and published sources. Our complementary analyses were modelled in R using Bayesian generalised additive mixed models (GAMM) and in Stata using multi-level mixed effects regression models. From both sets of modelling, we found that closure of education facilities, prohibiting mass gatherings and closure of some non-essential businesses were associated with reduced incidence whereas stay at home orders and closure of all non-businesses was not associated with any independent additional impact. Our results could help inform strategies for coming out of lockdown.
3,700 downloads medRxiv infectious diseases
Jean-Claude Tardif, Nadia Bouabdallaoui, Philippe L L'Allier, Daniel Gaudet, Binita Shah, Michael H Pillinger, Jose Lopez-Sendon, Protasio da Luz, Lucie Verret, Sylvia Audet, Jocelyn Dupuis, Andre Y Denault, Martin Pelletier, Philippe A Tessier, Sarah Samson, Denis Fortin, Jean-Daniel Tardif, David Busseuil, Elisabeth Goulet, Chantal Lacoste, Anick Dubois, Avni Y Joshi, David D Waters, Priscilla Hsue, Norman E Lepor, Frederic Lesage, Nicolas Sainturet, Eve Roy-Clavel, Zohar Bassevitch, Andreas Orfanos, Jean C Gregoire, Lambert Busque, Christian Lavallee, Pierre-Olivier Hetu, Jean-Sebastien Paquette, Sylvie Levesque, Marieve Cossette, Anna Nozza, Malorie Chabot-Blanchet, Marie-Pierre Dube, Marie-Claude Guertin, Guy Boivin
Background Evidence suggests the role of an inflammatory storm in COVID-19 complications. Colchicine is an orally administered, anti-inflammatory medication beneficial in gout, pericarditis and coronary disease. Methods We performed a randomized, double-blind trial involving non-hospitalized patients with COVID-19 diagnosed by polymerase chain reaction (PCR) testing or clinical criteria. The patients were randomly assigned to receive colchicine (0.5 mg twice daily for 3 days and once daily thereafter) or placebo for 30 days. The primary efficacy endpoint was the composite of death or hospitalization for COVID-19. Results A total of 4488 patients were enrolled. The primary endpoint occurred in 4.7% of the patients in the colchicine group and 5.8% of those in the placebo group (odds ratio, 0.79; 95.1% confidence interval (CI), 0.61 to 1.03; P=0.08). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 4.6% and 6.0% of patients in the colchicine and placebo groups, respectively (odds ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04). In these patients with PCR-confirmed COVID-19, the odds ratios were 0.75 (95% CI, 0.57 to 0.99) for hospitalization due to COVID-19, 0.50 (95% CI, 0.23 to 1.07) for mechanical ventilation, and 0.56 (95% CI, 0.19 to 1.66) for death. Serious adverse events were reported in 4.9% and 6.3% in the colchicine and placebo groups (P=0.05); pneumonia occurred in 2.9% and 4.1% of patients (P=0.02). Diarrhea was reported in 13.7% and 7.3% in the colchicine and placebo groups (P<0.0001). Conclusion Among non-hospitalized patients with COVID-19, colchicine reduces the composite rate of death or hospitalization. (COLCORONA ClinicalTrials.gov number: NCT04322682)
3,683 downloads medRxiv nutrition
BackgroundCOVID-19 has emerged as a global pandemic, affecting nearly 104 million people worldwide as of February 4th 2021. In previous published studies, the association between the mean Vit D status of each country and COVID-19 infection rate, and mortality among the adult population in European countries was examined. The aim of this study was to re-examine the relationship between the Vit D status of each country and COVID-19 infection, recovery, and mortality using updated data and a different methodological approach. MethodsInformation only form the last decade on Vit D concentration/deficiency for each country was retrieved through literature search on PubMed(R) database. As of February, 4th 2021, COVID-19 infections and mortalities per one million population as well as total recoveries were extracted from the Worldometer website. The association between vitamin D deficiency and COVID-19 infection, recovery, and mortality were explored using correlation coefficients and scatterplots. FindingsThe prevalence of vitamin D deficiency among European countries ranged from 6.0 (Finland) to 75.5% (Turkey), with several countries facing more than 50% of vitamin D deficiency among their population. Non-significant correlations were observed between the number of COVID-19 infections (r=0.190; p=0.374), recoveries (rs=0.317, p=0.131), and mortalities (r=0.129; p=0.549) per one million population, with the prevalence of vitamin D deficiency. InterpretationPrevalence of vitamin D deficiency was not significantly associated with either number of infections, recoveries or mortality rate of COVID-19 among European countries. Thus, it is an important parameter to be considered when implementing preventive measures to face COVID-19. FundingNone
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