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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 140,607 papers from 597,880 authors.

Most downloaded biology preprints, since beginning of last month

135,599 results found. For more information, click each entry to expand.

41: What level of neutralising antibody protects from COVID-19? .
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Posted 11 Mar 2021

What level of neutralising antibody protects from COVID-19? .
5,506 downloads medRxiv infectious diseases

David S. Khoury, Deborah Cromer, Arnold Reynaldi, Timothy E Schlub, Adam K Wheatley, Jennifer A Juno, Kanta Subbarao, Stephen J Kent, James A Triccas, Miles P Davenport

Both previous infection and vaccination have been shown to provide potent protection from COVID-19. However, there are concerns that waning immunity and viral variation may lead to a loss of protection over time. Predictive models of immune protection are urgently needed to identify immune correlates of protection to assist in the future deployment of vaccines. To address this, we modelled the relationship between in vitro neutralisation levels and observed protection from SARS-CoV-2 infection using data from seven current vaccines as well as convalescent cohorts. Here we show that neutralisation level is highly predictive of immune protection. The 50% protective neutralisation level was estimated to be approximately 20% of the average convalescent level (95% CI = 14-28%). The estimated neutralisation level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level (CI = 0.7-13%, p = 0.0004). Given the relationship between in vitro neutralization titer and protection, we then used this to investigate how waning immunity and antigenic variation might affect vaccine efficacy. We found that the decay of neutralising titre in vaccinated subjects over the first 3-4 months after vaccination was at least as rapid as the decay observed in convalescent subjects. Modelling the decay of neutralisation titre over the first 250 days after immunisation predicts a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralisation titres against some SARS-CoV-2 variants of concern are reduced compared to the vaccine strain and our model predicts the relationship between neutralisation and efficacy against viral variants. Our analyses provide an evidence-based prediction of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.

42: On the Generation of Medical Dialogues for COVID-19
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Posted 15 May 2020

On the Generation of Medical Dialogues for COVID-19
5,422 downloads medRxiv health informatics

Wenmian Yang, Guangtao Zeng, Bowen Tan, Zeqian Ju, Subrato Chakravorty, Xuehai He, Shu Chen, Xingyi Yang, Qingyang Wu, Zhou Yu, Eric Xing, Pengtao Xie

Under the pandemic of COVID-19, people experiencing COVID19-related symptoms or exposed to risk factors have a pressing need to consult doctors. Due to hospital closure, a lot of consulting services have been moved online. Because of the shortage of medical professionals, many people cannot receive online consultations timely. To address this problem, we aim to develop a medical dialogue system that can provide COVID19-related consultations. We collected two dialogue datasets - CovidDialog - (in English and Chinese respectively) containing conversations between doctors and patients about COVID-19. On these two datasets, we train several dialogue generation models based on Transformer, GPT, and BERT-GPT. Since the two COVID-19 dialogue datasets are small in size, which bear high risk of overfitting, we leverage transfer learning to mitigate data deficiency. Specifically, we take the pretrained models of Transformer, GPT, and BERT-GPT on dialog datasets and other large-scale texts, then finetune them on our CovidDialog datasets. Experiments demonstrate that these approaches are promising in generating meaningful medical dialogue about COVID-19. But more advanced approaches are needed to build a fully useful dialogue system that can offer accurate COVID-related consultations. The data and code are available at https://github.com/UCSD-AI4H/COVID-Dialogue

43: Erythrocyte Sedimentation Rate in COVID-19 Infections
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Posted 26 Jun 2020

Erythrocyte Sedimentation Rate in COVID-19 Infections
5,254 downloads medRxiv infectious diseases

Wei Zhang, Youshu Yuan, Shucheng Zhang, Can Jin, Linlin Wu, Hong Mei, Chen Miao, Zhixia Jiang, Zhixu He

Objectives To compare the clinical characteristics between the rapid cohort and the normal cohort of erythrocyte sedimentation rate (ESR) in COVID-19 infections, analyze the variables with significant differences, and explore the influencing factors of rapid ESR. Methods Selected a total of 80 patients with ESR detection during hospitalization were measured in 146 patients who received medical observation in concentrated isolation hospital in Guizhou province in China , collected and compared demographic information, epidemiological data, clinical symptoms, laboratory test data and CT image data during the observation between rapid cohort and normal group of ESR. Results By comparison, the proportion of male in the rapid cohort was higher than female. The average age was more than 35 years old, with a large age gap. The proportion of severe and critical patients was more than 26.53% (13/49). However, in the normal cohort the proportion of female was more than male, and the average age was about 8 years lower than the rapid cohort, and the age gap was smaller. The proportion of severe and critical patients was 12.90%, which was less than half of the rapid group. In the two groups, the proportion of clustered cases accounted for more than 50%, and the average number of patients in one family was more than 3. The most common clinical symptoms were cough, sputum, fever, sore throat and weakness of limbs. There were significant differences in ALT, {gamma}-GT and C-reactive protein between the rapid and normal cohort (P<0.05), but no statistically significant in other indicators. Hemoglobin and C-reactive protein have a significant effect on erythrocyte sedimentation rate. Conclusions In this study, we found that ESR is related to Hemoglobin and C-reactive protein.

44: SARS-CoV-2 RT-PCR profile in 298 Indian COVID-19 patients : a retrospective observational study
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Posted 20 Jun 2020

SARS-CoV-2 RT-PCR profile in 298 Indian COVID-19 patients : a retrospective observational study
5,010 downloads medRxiv infectious diseases

bisakh bhattacharya, Rohit Kumar, Dr. Ved prakash Meena, Manish Soneja, Saurabh Vig, Vandana Rastogi, Sushma Bhatnagar, Anant Mohan, Naveet Wig

Background: Despite being in the 5th month of pandemic, knowledge with respect to viral dynamics, infectivity and RT-PCR positivity continues to evolve. Aim: To analyse the SARS CoV-2 nucleic acid RT-PCR profiles in COVID-19 patients. Design: It was a retrospective, observational study conducted at COVID facilities under AIIMS, New Delhi. Methods : Patients admitted with laboratory confirmed COVID-19 were eligible for enrolment. Patients with incomplete details, or only single PCR tests were excluded. Data regarding demographic details, comorbidities, treatment received and results of SARS-CoV-2 RT-PCR performed on nasopharyngeal and oropharyngeal swabs, collected at different time points, was retrieved from the hospital records. Results : 298 patients were included, majority were males (75.8%) with mean age of 39.07 years (0.6-88 years). The mean duration from symptom onset to first positive RT-PCR was 4.7 days (SD 3.67), while that of symptom onset to last positive test was 17.83 days (SD 6.22). Proportions of positive RT-PCR tests were 100%, 49%, 24%, 8.7% and 20.6% in the 1st, 2nd, 3rd, 4th & >4 weeks of illness. 12 symptomatic patients had prolonged positive test results even after 3 weeks of symptom onset. Age >= 60 years was associated with prolonged RT-PCR positivity (statistically significant). Conclusion : This study showed that the average period of PCR positivity is more than 2 weeks in COVID-19 patients; elderly patients have prolonged duration of RT-PCR positivity and requires further follow up.

45: SARS-CoV-2 infection risk among unvaccinated is negatively associated with community-level vaccination rates
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Posted 29 Mar 2021

SARS-CoV-2 infection risk among unvaccinated is negatively associated with community-level vaccination rates
5,006 downloads medRxiv infectious diseases

Oren Milman, Idan Yelin, Noga Aharony, Rachel Katz, Esma Herzel, Amir Ben-Tov, Jacob Kuint, Sivan Gazit, Gabriel Chodick, Tal Patalon, Roy Kishony

Mass vaccination has the potential to curb the current COVID-19 pandemic by protecting vaccinees from the disease and possibly lowering the chance of transmission to unvaccinated individuals. The high effectiveness of the widely-administered BNT162b vaccine in preventing not only the disease but also infection suggests a potential for a population-level effect, critical for disease eradication. However, this putative effect is difficult to observe, especially in light of highly fluctuating spatio-temporal epidemic dynamics. Here, analyzing vaccination records and test results collected during a rapid vaccine rollout for a large population from 223 geographically defined communities, we find that the rates of vaccination in each community are highly correlated with a later decline in infections among a cohort of under 16 years old which are unvaccinated. These results provide observational evidence that vaccination not only protects individual vaccinees but also provides cross-protection to unvaccinated individuals in the community.

46: Excess mortality associated with the COVID-19 pandemic among Californians 18-65 years of age, by occupational sector and occupation: March through October 2020
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Posted 22 Jan 2021

Excess mortality associated with the COVID-19 pandemic among Californians 18-65 years of age, by occupational sector and occupation: March through October 2020
4,836 downloads medRxiv occupational and environmental health

Yea-Hung Chen, Maria Glymour, Alicia Riley, John Balmes, Kate Duchowny, Robert Harrison, Ellicott Matthay, Kirsten Bibbins-Domingo

Background Though SARS-CoV-2 outbreaks have been documented in occupational settings and though there is speculation that essential workers face heightened risks for COVID-19, occupational differences in excess mortality have, to date, not been examined. Such information could point to opportunities for intervention, such as workplace modifications and prioritization of vaccine distribution. Methods and findings Using death records from the California Department of Public Health, we estimated excess mortality among Californians 18--65 years of age by occupational sector and occupation, with additional stratification of the sector analysis by race/ethnicity. During the COVID-19 pandemic, working age adults experienced a 22% increase in mortality compared to historical periods. Relative excess mortality was highest in food/agriculture workers (39% increase), transportation/logistics workers (28% increase), facilities (27%) and manufacturing workers (23% increase). Latino Californians experienced a 36% increase in mortality, with a 59% increase among Latino food/agriculture workers. Black Californians experienced a 28% increase in mortality, with a 36% increase for Black retail workers. Asian Californians experienced an 18% increase, with a 40% increase among Asian healthcare workers. Excess mortality among White working-age Californians increased by 6%, with a 16% increase among White food/agriculture workers. Conclusions Certain occupational sectors have been associated with high excess mortality during the pandemic, particularly among racial and ethnic groups also disproportionately affected by COVID-19. In-person essential work is a likely venue of transmission of coronavirus infection and must be addressed through strict enforcement of health orders in workplace settings and protection of in-person workers. Vaccine distribution prioritizing in-person essential workers will be important for reducing excess COVID mortality.

47: An integrated brain-machine interface platform with thousands of channels
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Posted 17 Jul 2019

An integrated brain-machine interface platform with thousands of channels
4,772 downloads bioRxiv neuroscience

Elon Musk, Neuralink

Brain-machine interfaces (BMIs) hold promise for the restoration of sensory and motor function and the treatment of neurological disorders, but clinical BMIs have not yet been widely adopted, in part because modest channel counts have limited their potential. In this white paper, we describe Neuralink’s first steps toward a scalable high-bandwidth BMI system. We have built arrays of small and flexible electrode “threads”, with as many as 3,072 electrodes per array distributed across 96 threads. We have also built a neurosurgical robot capable of inserting six threads (192 electrodes) per minute. Each thread can be individually inserted into the brain with micron precision for avoidance of surface vasculature and targeting specific brain regions. The electrode array is packaged into a small implantable device that contains custom chips for low-power on-board amplification and digitization: the package for 3,072 channels occupies less than (23 × 18.5 × 2) mm3. A single USB-C cable provides full-bandwidth data streaming from the device, recording from all channels simultaneously. This system has achieved a spiking yield of up to 70% in chronically implanted electrodes. Neuralink’s approach to BMI has unprecedented packaging density and scalability in a clinically relevant package.

48: Estimating the early impact of immunization against COVID-19 on deaths among elderly people in Brazil: analyses of secondary data on vaccine coverage and mortality.
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Posted 30 Apr 2021

Estimating the early impact of immunization against COVID-19 on deaths among elderly people in Brazil: analyses of secondary data on vaccine coverage and mortality.
4,669 downloads medRxiv infectious diseases

Cesar G Victora, Marcia C. Castro, Susie Gurzenda, Aluisio JD Barros

ABSTRACT Background Immunization against COVID-19 in Brazil started in January 2021, with health workers and the elderly as the priority groups. We assessed whether there was an impact of immunizations on the mortality of individuals aged 80+ years. Methods By April 22, 2021, 147,454 COVID-19 deaths had been reported to the Brazilian Mortality Information System. Denominators for mortality rates were calculated by correcting population estimates for all-cause deaths reported in 2020. Proportionate mortality at ages 80+ and 90+ years relative to deaths at all ages were calculated, and mortality rate ratios compared these two age groups with individuals aged 0-79 years. Vaccine coverage data were obtained from the Ministry of Health vaccination monitoring website. All results were tabulated by two-week periods from epidemiological weeks 1-14, 2021. Findings As the P.1 variant spread throughout Brazil, the total number of deaths increased over time starting in epidemiological week 9 of 2021. The proportion of all deaths occurring at ages 80+ years was over 25% in weeks 1-6 and declined rapidly to 13.1% in weeks 13-14. Mortality rates were over 13 times higher in the 80+ years age group compared to that of 0-79 year olds up to week 6, and declined to 6.9 times in weeks 13-14. Coronavac accounted for 77.3% and AstraZeneca for 15.9% of all doses administered. Vaccination coverage (first dose) increased rapidly among individuals aged 80+ years, reaching 49.1% in weeks 5-6 and over 90% after week 9. Interpretation Rapid scaling up of vaccination coverage among elderly Brazilians was associated with an important decline in relative mortality compared to younger individuals, in a setting where the P.1 variant predominates. Had mortality rates among the elderly remained proportionate to what was observed up to week 6, an estimated additional 13,824 deaths would have been expected up to week 14.

49: The World Mortality Dataset: Tracking excess mortality across countries during the COVID-19 pandemic
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Posted 29 Jan 2021

The World Mortality Dataset: Tracking excess mortality across countries during the COVID-19 pandemic
4,618 downloads medRxiv epidemiology

Ariel Karlinsky, Dmitry Kobak

Comparing the impact of the COVID-19 pandemic between countries or across time is difficult because the reported numbers of cases and deaths can be strongly affected by testing capacity and reporting policy. Excess mortality, defined as the increase in all-cause mortality relative to the recent average, is widely considered as a more objective indicator of the COVID-19 death toll. However, there has been no central, frequently-updated repository of the all-cause mortality data across countries. To fill this gap, we have collected weekly, monthly, or quarterly all-cause mortality data from 77 countries, openly available as the regularly-updated World Mortality Dataset. We used this dataset to compute the excess mortality in each country during the COVID-19 pandemic. We found that in the worst-affected countries the annual mortality increased by over 50%, while in several other countries it decreased by over 5%, presumably due to lockdown measures decreasing the non-COVID mortality. Moreover, we found that while some countries have been reporting the COVID-19 deaths very accurately, many countries have been underreporting their COVID-19 deaths by an order of magnitude or more. Averaging across the entire dataset suggests that the world's COVID-19 death toll may be at least 1.6 times higher than the reported number of confirmed deaths.

50: State-wise estimates of current hospital beds, intensive care unit (ICU) beds and ventilators in India: Are we prepared for a surge in COVID-19 hospitalizations?
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Posted 18 Jun 2020

State-wise estimates of current hospital beds, intensive care unit (ICU) beds and ventilators in India: Are we prepared for a surge in COVID-19 hospitalizations?
4,477 downloads medRxiv health policy

Geetanjali Kapoor, Stephanie Hauck, Aditi Sriram, Jyoti Joshi, Emily Schueller, Isabel Frost, Ruchita Balasubramanian, Ramanan Laxminarayan, Arindam Nandi

Background The rapid spread of COVID-19 globally has prompted policymakers to evaluate the capacity of health care infrastructure in their communities. Many hard-hit localities have witnessed a large influx of severe cases that strained existing hospitals. As COVID-19 spreads in India, it is essential to evaluate the country's capacity to treat severe cases. Methods We combined data on public and private sector hospitals in India to produce state level estimates of hospital beds, ICU beds, and mechanical ventilators. Based on the number of public sector hospitals from the 2019 National Health Profile (NHP) of India and the relative proportions of public and private health care facilities from the National Sample Survey (NSS) 75th round (2017-2018), we estimated capacity in each Indian state and union territory (UT). We assumed that 5% of all hospital beds were ICU beds and that 50% of ICU beds were equipped with ventilators. Results We estimated that India has approximately 1.9 million hospital beds, 95,000 ICU beds and 48,000 ventilators. Nationally, resources are concentrated in the private sector (hospital beds: 1,185,242 private vs 713,986 public; ICU beds: 59,262 private vs 35,699 public; ventilators: 29,631 private vs. 17,850 public). Our findings suggest substantial variation in available resources across states and UTs. Conclusion Some projections shave suggested a potential need for approximately 270,000 ICU beds in an optimistic scenario, over 2.8 times the estimated number of total available ICU beds in India. Additional resources will likely be required to accommodate patients with severe COVID-19 infections in India.

51: mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
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Posted 19 Jan 2021

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
4,425 downloads bioRxiv immunology

Zijun Wang, Fabian Schmidt, Yiska Weisblum, Frauke Muecksch, Christopher O Barnes, Shlomo Finkin, Dennis Schaefer-Babajew, Melissa Cipolla, Christian Gaebler, Jenna A Lieberman, Thiago Y. Oliveira, Zhi Yang, Morgan E. Abernathy, Kathryn E. Huey-Tubman, Arlene Hurley, Martina Turroja, Kamille A West, Kristie Gordon, Katrina G Millard, Victor Ramos, Justin Da Silva, Jianliang Xu, Robert A Colbert, Roshni Patel, Juan P. Dizon, Cecille Unson-O'Brien, Irina Shimeliovich, Anna Gazumyan, Marina Caskey, Pamela Bjorkman, Rafael Casellas, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected nearly 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease-2019 (COVID-19) including two novel mRNA-based vaccines. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S), receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

52: A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates
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Posted 08 Sep 2020

A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates
4,414 downloads bioRxiv immunology

Annette B. Vogel, Isis Kanevsky, Ye Che, Kena A. Swanson, Alexander Muik, Mathias Vormehr, Lena M Kranz, Kerstin C. Walzer, Stephanie Hein, Alptekin Güler, Jakob Loschko, Mohan S. Maddur, Kristin Tompkins, Journey Cole, Bonny G. Lui, Thomas Ziegenhals, Arianne Plaschke, David Eisel, Sarah C. Dany, Stephanie Fesser, Stephanie Erbar, Ferdia Bates, Diana Schneider, Bernadette Jesionek, Bianca Sänger, Ann-Kathrin Wallisch, Yvonne Feuchter, Hanna Junginger, Stefanie A. Krumm, André P. Heinen, Petra Adams-Quack, Julia Schlereth, Christoph Kröner, Shannan Hall-Ursone, Kathleen Brasky, Matthew C. Griffor, Seungil Han, Joshua A. Lees, Ellene H. Mashalidis, Parag V. Sahasrabudhe, Charles Y. Tan, Danka Pavliakova, Guy Singh, Camila Fontes-Garfias, Michael Pride, Ingrid L. Scully, Tara Ciolino, Jennifer Obregon, Michal Gazi, Ricardo Carrion, Kendra J. Alfson, Warren V. Kalina, Deepak Kaushal, Pei-Yong Shi, Thorsten Klamp, Corinna Rosenbaum, Andreas N. Kuhn, Özlem Türeci, Philip R. Dormitzer, Kathrin U. Jansen, Ugur Sahin

To contain the coronavirus disease 2019 (COVID-19) pandemic, a safe and effective vaccine against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is urgently needed in quantities sufficient to immunise large populations. In this study, we report the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the BNT162b2 vaccine candidate. BNT162b2 contains an LNP-formulated nucleoside-modified mRNA that encodes the spike glycoprotein captured in its prefusion conformation. After expression of the BNT162b2 coding sequence in cells, approximately 20% of the spike molecules are in the one-RBD ‘up’, two-RBD ‘down’ state. Immunisation of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralisation titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralising geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+ and IFNγ+ CD8+ T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunised rhesus macaques from infectious SARS-CoV-2 challenge. BNT162b2 is currently being evaluated in a global, pivotal Phase 2/3 trial ([NCT04368728][1]). ### Competing Interest Statement U.S. and O.T. are management board members and employees at BioNTech SE (Mainz, Germany); K.C.W., B.G.L., D.S., B.J., T.K. and C.R. are employees at BioNTech SE; A.B.V., A.M., M.V., L.M.K., S.He., A.G., T.Z., A.P., D.E., S.C.D., S.F., S.E., F.B., B.S., A.W., Y.F., H.J., S.A.K., A.P.H., P.A., J.S., C.K., and A.N.K. are employees at BioNTech RNA Pharmaceuticals GmbH (Mainz, Germany); A.B.V., A.M., K.C.W., A.G., S.F., A.N.K and U.S. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccine; A.B.V., A.M., M.V., L.M.K., K.C.W., S.He., B.G.L., A.P., D.E., S.C.D., S.F., S.E., D.S., B.J., B.S., A.P.H., P.A., J.S., C.K., T.K., C.R., A.N.K., O.T. and U.S. have securities from BioNTech SE; I.K., Y.C., K.A.S., J.L., M.M., K.T., M.C.G., S.H., J.A.L.,E.H.M., P.V.S., C.Y.T., D.P., G.S., M.P., I.L.S., T.C., J.O., W.V.K., P.R.D. and K.U.J. are employees of Pfizer and may hold stock options; C.F.-G. and P.-Y.S. received compensation from Pfizer to perform neutralisation assays; J.C., S.H.-U, K.B., R.C., jr., K.J.A. and D.K., are employees of Southwest National Primate Research Center, which received compensation from Pfizer to conduct the animal challenge work; no other relationships or activities that could appear to have influenced the submitted work. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04368728&atom=%2Fbiorxiv%2Fearly%2F2020%2F09%2F08%2F2020.09.08.280818.atom

53: Effective gene expression prediction from sequence by integrating long-range interactions
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Posted 08 Apr 2021

Effective gene expression prediction from sequence by integrating long-range interactions
4,411 downloads bioRxiv genomics

Ziga Avsec, Vikram Agarwal, Daniel Visentin, Joseph R. Ledsam, Agnieszka Grabska-Barwinska, Kyle R. Taylor, Yannis Assael, John Jumper, Pushmeet Kohli, David R Kelley

The next phase of genome biology research requires understanding how DNA sequence encodes phenotypes, from the molecular to organismal levels. How noncoding DNA determines gene expression in different cell types is a major unsolved problem, and critical downstream applications in human genetics depend on improved solutions. Here, we report substantially improved gene expression prediction accuracy from DNA sequence through the use of a new deep learning architecture called Enformer that is able to integrate long-range interactions (up to 100 kb away) in the genome. This improvement yielded more accurate variant effect predictions on gene expression for both natural genetic variants and saturation mutagenesis measured by massively parallel reporter assays. Notably, Enformer outperformed the best team on the critical assessment of genome interpretation (CAGI5) challenge for noncoding variant interpretation with no additional training. Furthermore, Enformer learned to predict promoter-enhancer interactions directly from DNA sequence competitively with methods that take direct experimental data as input. We expect that these advances will enable more effective fine-mapping of growing human disease associations to cell-type-specific gene regulatory mechanisms and provide a framework to interpret cis-regulatory evolution. To foster these downstream applications, we have made the pre-trained Enformer model openly available, and provide pre-computed effect predictions for all common variants in the 1000 Genomes dataset.

54: Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers - a Danish cohort study
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Posted 09 Mar 2021

Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers - a Danish cohort study
4,248 downloads medRxiv epidemiology

Ida Rask Moustsen-Helms, Hanne-Dorthe Emborg, Jens Nielsen, Katrine Finderup Nielsen, Tyra Krause, Kaare Molbak, Karina Lauenborg Moeller, Ann-Sofie Nicole Berthelsen, Palle Valentiner-Branth

Abstract Background At the end of 2020, Denmark launched an immunization program against SARS-CoV-2. The Danish health authorities prioritized persons currently living in long-term care facilities (LTCF residents) and frontline healthcare workers (HCW) as the first receivers of vaccination. Here we present preliminary population based vaccine effectiveness (VE) estimates in these two target groups. Methods The study was designed as a retrospective registry- and population-based observational cohort study including all LTCF residents and all HWC. The outcome was a polymerase chain reaction confirmed SARS-CoV-2, and VE was estimated for different periods following first and second dose. We used Poisson and Cox regressions to estimate respectively crude and calendar time-adjusted VE for the BNT162b2 mRNA Covid-19 Vaccine from Pfizer/BioNTech with 95% confidence intervals (CI) for vaccinated versus unvaccinated. Results A total of 39,040 LTCF residents (median age at first dose; 84 years, Interquartile range (IQR): 77-90) and 331,039 HCW (median age at first dose; 47 years, IQR: 36-57) were included. Among LTCF residents, 95.2% and 86.0% received first and second dose from 27 December 2020 until 18 February 2021, for HWC the proportion was 27.8% and 24.4%. During a median follow-up of 53 days , there were 488 and 5,663 confirmed SARS-CoV-2 cases in the unvaccinated groups, whereas there were 57 and 52 in LTCF residents and HCW within the first 7 days after the second dose and 27 and 10 cases beyond seven days of second dose. No protective effect was observed for LTCF residents after first dose. In HCW, VE was 17% (95% CI; 4-28) in the > 14 days after first dose (before second dose). Furthermore, the VE in LTCF residents at day 0-7 of second dose was 52% (95% CI; 27-69) and 46% (95% CI; 28-59) in HCW. Beyond seven days of second dose, VE increased to 64% (95% CI; 14-84) and 90% (95% CI; 82-95) in the two groups, respectively. Conclusion The results were promising regarding the VE both within and beyond seven days of second vaccination with the BNT162b2 mRNA Covid-19 Vaccine currently used in many countries to help mitigate the global SARS-CoV-2 pandemic. Impact of the research: So far, observational studies of the real-word effectiveness of the mRNA Vaccine BNT162b2 has been limited to the period after the administration of the first dose. This is the first report to date to present vaccine effectiveness (VE) estimates after the second BNT162b2 mRNA Covid-19 Vaccine. We estimated a VE of 52% and 46% in LTCF residents and HCW within seven days, which increased to 64% and 90% in the two groups respectively beyond seven days of immunization. These findings supports maintaining a two-dose schedule of the BNT162b2 mRNA Covid-19 Vaccine.

55: Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response
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Posted 10 Mar 2021

Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response
4,119 downloads bioRxiv microbiology

Long Chi Nguyen, Dongbo Yang, Vlad Nicolaescu, Thomas Best, Shaonong Chen, J. Brent Friesen, Nir Drayman, Adil Mohamed, Christopher Dann, Diane Silva, Haley Gula, Krysten A. Jones, J. Michael Millis, Bryan C. Dickinson, Savas Tay, Scott A Oakes, Guido F. Pauli, David O. Meltzer, Glenn Randall, Marsha Rich Rosner

The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARS-CoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population. This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.

56: Interim Report: Safety And Immunogenicity Of An Inactivated Vaccine Against Sars-Cov-2 In Healthy Chilean Adults In A Phase 3 Clinical Trial
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Posted 01 Apr 2021

Interim Report: Safety And Immunogenicity Of An Inactivated Vaccine Against Sars-Cov-2 In Healthy Chilean Adults In A Phase 3 Clinical Trial
4,104 downloads medRxiv infectious diseases

Susan M Bueno, Katia Abarca, Pablo A Gonzalez, Nicolas M S Galvez, Jorge A Soto, Luisa F Duarte, Barbara M Schultz, Gaspar A Pacheco, Liliana A Gonzalez, Yaneisi Vasquez, Mariana Rios, Felipe Melo-Gonzalez, Daniela Rivera-Perez, Carolina Iturriaga, Marcela Urzua, Angelica Dominguez, Catalina A Andrade, Roslye V Berrios, Gisela Canedo-Marroquin, Camila Covian, Daniela Moreno-Tapia, Farides Saavedra, Omar P Vallejos, Paulina Donato, Pilar Espinoza, Daniela Fuentes, Marcela Gonzalez, Paula Guzman, Paula Munoz-Venturelli, Carlos M Perez, Marcela Potin, alvaro Rojas, Rodrigo Fasce, Jorge Fernandez, Judith Mora, Eugenio Ramirez, Aracelly Gaete-Argel, Aaron Oyarzun-Arrau, Fernando Valiente-Echeverria, Ricardo Soto-Rifo, Daniela Weiskopf, Alessandro Sette, Gang Zeng, Weining Meng, Jose V Gonzalez-Aramundiz, Alexis M Kalergis

Background: The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. Methods: This is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov (NCT04651790). Findings: The recruitment of participants occurred between November 27th, 2020, until January 9th, 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were over 60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the over 60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the over 60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The over 60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants over 60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-gamma; upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. Interpretation: Immunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-gamma upon recognition of SARS-CoV-2 antigens. Funding: Ministry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

57: An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity
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Posted 05 Apr 2021

An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity
4,079 downloads bioRxiv microbiology

Chihiro Motozono, Mako Toyoda, Jiri Zahradnik, Terumasa Ikeda, Akatsuki Saito, Toong Seng Tan, Isaac Ngare, Hesham Nasser, Izumi Kimura, Keiya Uriu, Yusuke Kosugi, Shiho Torii, Akiko Yonekawa, Nobuyuki Shimono, Yoji Nagasaki, Rumi Minami, Takashi Toya, Noritaka Sekiya, Takasuke Fukuhara, Yoshiharu Matsuura, Gideon Schreiber, The Genotype to Phenotype Japan (G2P-Japan) consortium, So Nakagawa, Takamasa Ueno, Kei Sato

During the current SARS-CoV-2 pandemic that is devastating the modern societies worldwide, many variants that naturally acquire multiple mutations have emerged. Emerging mutations can affect viral properties such as infectivity and immune resistance. Although the sensitivity of naturally occurring SARS-CoV-2 variants to humoral immunity has recently been investigated, that to human leukocyte antigen (HLA)-restricted cellular immunity remains unaddressed. Here we demonstrate that two recently emerging mutants in the receptor binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429) and Y453F (in B.1.298), can escape from the HLA-24-restricted cellular immunity. These mutations reinforce the affinity to viral receptor ACE2, and notably, the L452R mutation increases protein stability, viral infectivity, and potentially promotes viral replication. Our data suggest that the HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes, and the escape from cellular immunity can be a further threat of the SARS-CoV-2 pandemic.

58: Are vaccines safe in patients with Long COVID? A prospective observational study.
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Posted 12 Mar 2021

Are vaccines safe in patients with Long COVID? A prospective observational study.
4,038 downloads medRxiv infectious diseases

David T Arnold, Alice Milne, Emma Samms, Louise Stadon, Nick A Maskell, Fergus W Hamilton

Introduction: Although the efficacy of SARS-CoV-2 vaccination to prevent symptomatic COVID-19 is well established, there are no published studies on the impact on symptoms in patients with Long Covid. Anecdotal reports have suggested both a potential benefit and worsening of symptoms post vaccination with the uncertainty leading to some vaccine hesitancy amongst affected individuals. Methods: Patients initially hospitalised with COVID-19 were prospectively recruited to an observational study with clinical follow-up at 3 months (June-July 2020) and 8 months (Dec 2020-Jan 2021) post-admission. Participants who received the Pfizer-BioNTech (BNT162b2) or Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccine between January to February 2021 were identified and matched 2:1 (in terms of 8-month symptoms) with participants from the same cohort who were unvaccinated. All were re-assessed at 1 month post vaccination (or matched timepoint for unvaccinated cohort). Validated quality of life (SF-36), mental wellbeing (WEMWBS) and ongoing symptoms were assessed at all timepoints. Formal statistical analysis compared the effect of vaccination on recent quality of life using baseline symptoms, age, and gender in linear regression. Results: Forty-four vaccinated participants were assessed at a median of 32 days (IQR 20-41) post vaccination with 22 matched unvaccinated participants. Most were highly symptomatic of Long Covid at 8 months (82% in both groups had at least 1 persistent symptom), with fatigue (61%), breathlessness (50%) and insomnia (38%) predominating. There was no significant worsening in quality-of-life or mental wellbeing metrics pre versus post vaccination. Nearly two-thirds (n=27) reported transient (<72hr duration) systemic effects (including fever, myalgia and headache). When compared to matched unvaccinated participants from the same cohort, those who had receive a vaccine had a small overall improvement in Long Covid symptoms, with a decrease in worsening symptoms (5.6% vaccinated vs 14.2% unvaccinated) and increase in symptom resolution (23.2% vaccinated vs 15.4% unvaccinated) (p=0.035). No difference in response was identified between Pfizer-BioNTech or Oxford-AstraZeneca vaccines. Conclusions: Receipt of vaccination with either an mRNA or adenoviral vector vaccine was not associated with a worsening of Long Covid symptoms, quality of life, or mental wellbeing. Individuals with prolonged COVID-19 symptoms should receive vaccinations as suggested by national guidance.

59: Detection and characterization of the SARS-CoV-2 lineage B.1.526 in New York
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Posted 15 Feb 2021

Detection and characterization of the SARS-CoV-2 lineage B.1.526 in New York
4,030 downloads bioRxiv bioinformatics

Anthony P. West, Joel O. Wertheim, Jade C. Wang, Tetyana I. Vasylyeva, Jennifer L. Havens, Moinuddin A. Chowdhury, Edimarlyn Gonzalez, Courtney E. Fang, Steve S. Di Lonardo, Scott Hughes, Jennifer L. Rakeman, Henry H Lee, Christopher O Barnes, Priyanthi N.P. Gnanapragasam, Zhi Yang, Christian Gaebler, Marina Caskey, Michel C. Nussenzweig, Jennifer R Keeffe, Pamela J Bjorkman

Wide-scale SARS-CoV-2 genome sequencing is critical to tracking viral evolution during the ongoing pandemic. Variants first detected in the United Kingdom, South Africa, and Brazil have spread to multiple countries. We developed the software tool, Variant Database (VDB), for quickly examining the changing landscape of spike mutations. Using VDB, we detected an emerging lineage of SARS-CoV-2 in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This lineage was first sequenced in late November 2020 when it represented <1% of sequenced coronavirus genomes that were collected in New York City (NYC). By February 2021, genomes from this lineage accounted for ~32% of 3288 sequenced genomes from NYC specimens. Phylodynamic inference confirmed the rapid growth of the B.1.526 lineage in NYC, notably the sub-clade defined by the spike mutation E484K, which has outpaced the growth of other variants in NYC. Pseudovirus neutralization experiments demonstrated that B.1.526 spike mutations adversely affect the neutralization titer of convalescent and vaccinee plasma, indicating the public health importance of this lineage.

60: Features of C-reactive protein in COVID-19 patients within various period: a cohort study
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Posted 27 Oct 2020

Features of C-reactive protein in COVID-19 patients within various period: a cohort study
3,789 downloads medRxiv infectious diseases

Guoxin Huang, Gaojing Qu, Hui Yu, Meiling Zhang, Xiaoming Song, Lei Chen, Haoming Zhu, Yunfu Wang, Bin Pei

BACKGROUNDCoronavirus disease 2019 (COVID-19) has been declared as a threat to the global. Due to the lack of efficient treatments, indicators were urgently needed during the evolvement of disease to analyze the illness and prognosis and prevent the aggravation of COVID-19. METHODSAll laboratory confirmed COVID-19 patients hospitalized in Xiangyang No.1 Peoples Hospital were included. Patients general information, clinical type, CRP value and outcome were collected. CRP values of all patients during disease course from different initial time were analyzed. RESULTSThe 131 enrolled patients were 50.13{+/-}17.13 years old. All cases underwent 724 tests of CRP since symptom onset, 53.18% of the test results were abnormal and the median value was 9.52(2.63-34.10) mg/L. The first median value on the day 8 from exposure onset was 39.08(11.92-47.89) mg/L then fluctuated around it until the day 28. The CRP median increased from 15.93 mg/L to 41.44 mg/L and then decreased to 18.26 mg/L before transformation of severe type, and then increased to 62.25 mg/L on the transforming date. Conversely, the CRP median increased from 56.17 mg/L 102.75 mg/L before transformation of critical type but decreased to 68.68 mg/L on the transforming date. The changes of CRP median over time before death ranged from 77.77 mg/L to 133.52 mg/L. CONCLUSIONSCRP increased before symptom onset and substantially increased during the early-to-mid stage (especially early stage), which was different from other virus-infected diseases. The changes of CRP before the transformation of clinical type was inconsistent with the aggravating of illness. And the CRP maintained over 100.00 mg/L prompted poor prognosis.

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