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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 140,676 papers from 598,159 authors.

Most downloaded biology preprints, since beginning of last month

135,937 results found. For more information, click each entry to expand.

61: 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.

62: Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants
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Posted 02 Apr 2021

Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants
3,717 downloads medRxiv infectious diseases

Satoshi Ikegame, Mohammed N. A. Siddiquey, Chuan-Tien Hung, Griffin Haas, Luca Brambilla, Kasopefoluwa Y. Oguntuyo, Shreyas Kowdle, Ariel Esteban Vilardo, Alexis Edelstein, Claudia Perandones, Jeremy P. Kamil, Benhur Lee

The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 variants of concern (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that 8 out of 12 (75%) of serum samples from 12 recipients of the Russian Sputnik V Ad26 / Ad5 vaccine showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of emergent SARS-CoV-2 variants may benefit from updated vaccines.

63: A SIMPLE, HOME-THERAPY ALGORITHM TO PREVENT HOSPITALIZATION FOR COVID-19 PATIENTS: A RETROSPECTIVE OBSERVATIONAL MATCHED-COHORT STUDY
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Posted 26 Mar 2021

A SIMPLE, HOME-THERAPY ALGORITHM TO PREVENT HOSPITALIZATION FOR COVID-19 PATIENTS: A RETROSPECTIVE OBSERVATIONAL MATCHED-COHORT STUDY
3,691 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.

64: SARS-CoV-2 infectivity by viral load, S gene variants and demographic factors and the utility of lateral flow devices to prevent transmission
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Posted 05 Apr 2021

SARS-CoV-2 infectivity by viral load, S gene variants and demographic factors and the utility of lateral flow devices to prevent transmission
3,650 downloads medRxiv infectious diseases

Lennard YW Lee, Stefan Rozmanowski, Matthew Pang, Andre Charlett, Charlotte Anderson, Gareth J. Hughes, Matthew Barnard, Leon Peto, Richard Vipond, Alex Sienkiewicz, Susan Hopkins, John Bell, Derrick W Crook, Nick Gent, A Sarah Walker, Tim EA Peto, David W Eyre

Background: How SARS-CoV-2 infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect sensitivity is unknown. Methods: We combined SARS-CoV-2 testing and contact tracing data from England between 01-September-2020 and 28-February-2021. We used multivariable logistic regression to investigate relationships between PCR-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. We used LFD performance to simulate the proportion of cases with a PCR-positive contact expected to be detected using one of four LFDs. Results: 231,498/2,474,066 (9%) contacts of 1,064,004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower Ct values) e.g., 11.7%(95%CI 11.5-12.0%) at Ct=15 and 4.5%(4.4-4.6%) at Ct=30. B.1.1.7 infection increased PCR-positive results by ~50%, (e.g. 1.55-fold, 95%CI 1.49-1.61, at Ct=20). PCR-positive results were most common in household contacts (at Ct=20.1, 8.7%[95%CI 8.6-8.9%]), followed by household visitors (7.1%[6.8-7.3%]), contacts at events/activities (5.2%[4.9-5.4%]), work/education (4.6%[4.4-4.8%]), and least common after outdoor contact (2.9%[2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5%(89.4-89.6%) and 83.0%(82.8-83.1%) of cases with PCR-positive contacts respectively. Conclusions: SARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Those with high viral loads are the most infectious. B.1.1.7 increased transmission by ~50%. The best performing LFDs detect most infectious cases.

65: Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial
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Posted 08 Feb 2021

Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial
3,561 downloads medRxiv primary care research

Sanjay Ramakrishnan, Dan V Nicolau, Beverly Langford, Mahdi Mahdi, Helen Jeffers, Christine Mwasuku, Karolina Krassowska, Robin Fox, Ian Binnian, Victoria Glover, Stephen Bright, Christopher Butler, Jennifer L Cane, Andreas Halner, Philippa C Matthews, Louise E Donnelly, Jodie L Simpson, Jonathan R Baker, Nabil T Fadai, Stefan Peterson, Thomas Bengtsson, Peter J Barnes, Richard E K Russell, Mona Bafadhel

Background Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. Methods We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. Results 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Conclusion Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.

66: SARS-CoV-2 antibodies detected in human breast milk post-vaccination
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Posted 02 Mar 2021

SARS-CoV-2 antibodies detected in human breast milk post-vaccination
3,412 downloads medRxiv infectious diseases

Jill K. Baird, Shawn M. Jensen, Walter J. Urba, Bernard A. Fox, Jason R. Baird

Importance: The SARS-CoV-2 pandemic has infected over a hundred million people worldwide, with almost 2.5 million deaths at the date of this publication. In the United States, Pfizer-BioNTech and Moderna vaccines were first administered to the public starting in December 2020, and no lactating women were included in the initial trials of safety/efficacy. Research on SARS-CoV-2 vaccination in lactating women and the potential transmission of passive immunity to the infant through breast milk is needed to guide patients, clinicians and policy makers during the worldwide effort to curb the spread of this virus. Objective: To determine whether SARS-CoV-2 specific immunoglobins are found in breast milk post-vaccination, and to characterize the time course and types of immunoglobulins present. Design:.Prospective cohort study Setting: Providence Portland Medical Center, Oregon, USA Participants: Six lactating women who planned to receive both doses of the Pfizer-BioNTech or Moderna vaccine between December 2020 and January 2021. Breast milk samples were collected pre-vaccination and at 11 additional timepoints, with last sample at 14 days post 2nd dose of vaccine. Exposure: Two doses of Pfizer-BioNTech or Moderna SARS-CoV-2 vaccine. Main Outcome(s) and Measure(s): Levels of SARS-CoV-2 specific IgA and IgG immunoglobulins in breast milk. Results: In this cohort of 6 lactating women who received 2 doses of SARS-CoV-2 vaccine, we observed significantly elevated levels of SARS-CoV-2 specific IgG and IgA antibodies in breast milk beginning at Day 7 after the initial vaccine dose, with an IgG-dominant response. Conclusions and Relevance: We are the first to show that maternal vaccination results in SARS-CoV-2 specific immunoglobulins in breast milk that may be protective for infants.

67: Impairment of T cells' antiviral and anti-inflammation immunities dominates the death from COVID-19
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Posted 29 Apr 2021

Impairment of T cells' antiviral and anti-inflammation immunities dominates the death from COVID-19
3,376 downloads medRxiv infectious diseases

Zhen-su She, Gregory Scholes, Luhao Zhang, Rong Li, Gang Song

Clarifying key factors dominating the immune heterogeneity from non-survivors to survivors is crucial for therapeutics and vaccine developments against COVID-19. The main difficulty is to quantitatively analyze the multi-level clinical data of viral dynamics, immune response, and tissue damages. Here, we adopt top-down modeling to quantify key functional aspects and their dynamical interplays in the virus-immune system battle, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses demonstrates T cells' dominant role in the virus clearance relative to antibodies, especially for mild patients(96.5%). Moreover, the anti-inflammatory responses, namely cytokine inhibition rate and tissue repair rate also have positive correlations with T cell number, and are significantly suppressed in non-survivors. Simulations show that impaired immune functions of T cells leads to greater inflammation (thus dominates the death), explaining the monotonous increase of COVID-19 mortality with age and higher mortality for males. We conclude that T cells play the role of crucial immunity that saves the death from COVID-19, which points out a new direction to advance current prevention and treatment by incorporating the vaccines, drugs and health care activities that aim to improve T cells' number and functions.

68: Facemasks and similar barriers to prevent respiratory illness such asCOVID-19: A rapid systematic review
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Posted 06 Apr 2020

Facemasks and similar barriers to prevent respiratory illness such asCOVID-19: A rapid systematic review
3,366 downloads medRxiv infectious diseases

Julii Suzanne Brainard, Natalia Jones, Iain Lake, Lee Hooper, Paul R Hunter

The current pandemic of COVID-19 has lead to conflicting opinions on whether wearing facemasks outside of health care facilities protects against the infection. To better understand the value of wearing facemasks we undertook a rapid systematic review of existing scientific evidence about development of respiratory illness, linked to use of facemasks in community settings. MethodsWe included all study designs. There were 31 eligible studies (including 12 RCTs). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention in 28 studies were performed. Results were reported by design, setting and type of face barrier in primary prevention, and by who wore the facemask (index patient or well contacts) in secondary prevention trials. The preferred outcome was influenza-like illness (ILI) but similar outcomes were pooled with ILI when ILI was unavailable. GRADE quality assessment was based on RCTs with support from observational studies. ResultsWhere specific information was available, most studies reported about use of medical grade (surgical paper masks). In 3 RCTs, wearing a facemask may very slightly reduce the odds of developing ILI/respiratory symptoms, by around 6% (OR 0.94, 95% CI 0.75 to 1.19, I 29%, low-certainty evidence). Greater effectiveness was suggested by observational studies. When both house-mates and an infected household member wore facemasks the odds of further household members becoming ill may be modestly reduced by around 19% (OR 0.81, 95%CI 0.48 to 1.37, I 45%, 5 RCTs, low certainty evidence). The protective effect was very small if only the well person (OR 0.93, 95% CI 0.68 to 1.28, I 11%, 2 RCTs, low uncertainty evidence) or the infected person wore the facemask (very low certainty evidence). DiscussionBased on the RCTs we would conclude that wearing facemasks can be very slightly protective against primary infection from casual community contact, and modestly protective against household infections when both infected and uninfected members wear facemasks. However, the RCTs often suffered from poor compliance and controls using facemasks. Across observational studies the evidence in favour of wearing facemasks was stronger. We expect RCTs to under-estimate the protective effect and observational studies to exaggerate it. The evidence is not sufficiently strong to support widespread use of facemasks as a protective measure against COVID-19. However, there is enough evidence to support the use of facemasks for short periods of time by particularly vulnerable individuals when in transient higher risk situations. Further high quality trials are needed to assess when wearing a facemask in the community is most likely to be protective.

69: Rapid induction of antigen-specific CD4+ T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination
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Posted 22 Apr 2021

Rapid induction of antigen-specific CD4+ T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination
3,346 downloads bioRxiv immunology

Mark M. Painter, Divij Mathew, Rishi R. Goel, Sokratis A. Apostolidis, Ajinkya Pattekar, Oliva Kuthuru, Amy E. Baxter, Ramin Herati, Derek A. Oldridge, Sigrid Gouma, Philip Hicks, Sarah Dysinger, Kendall A Lundgreen, Leticia Kuri-Cervantes, Sharon Adamski, Amanda Hicks, Scott Korte, Josephine R. Giles, Madison E. Weirick, Christopher M. McAllister, Jeanette Dougherty, Sherea Long, Kurt D'Andrea, Jacob T. Hamilton, Michael R. Betts, Paul Bates, Scott E Hensley, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Allison R. Greenplate, E John Wherry

The SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses in healthy individuals following mRNA vaccination. Vaccination induced rapid near-maximal antigen-specific CD4+ T cell responses in all subjects after the first vaccine dose. CD8+ T cell responses developed gradually after the first and second dose and were variable. Vaccine-induced T cells had central memory characteristics and included both Tfh and Th1 subsets, similar to natural infection. Th1 and Tfh responses following the first dose predicted post-boost CD8+ T cell and neutralizing antibody levels, respectively. Integrated analysis of 26 antigen-specific T cell and humoral responses revealed coordinated features of the immune response to vaccination. Lastly, whereas booster vaccination improved CD4+ and CD8+ T cell responses in SARS-CoV-2 naive subjects, the second vaccine dose had little effect on T cell responses in SARS-CoV-2 recovered individuals. Thus, longitudinal analysis revealed robust T cell responses to mRNA vaccination and highlighted early induction of antigen-specific CD4+ T cells.

70: Previous COVID-19 infection but not Long-COVID is associated with increased adverse events following BNT162b2/Pfizer vaccination
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Posted 22 Apr 2021

Previous COVID-19 infection but not Long-COVID is associated with increased adverse events following BNT162b2/Pfizer vaccination
3,338 downloads medRxiv infectious diseases

Rachael Kathleen Raw, Clive Kelly, Jon Rees, Caroline Wroe, David Robert Chadwick

Recent evidence suggests individuals with a history of COVID-19 are more likely to experience Adverse Events (AEs) following vaccination. A survey of 974 healthcare staff found that those with prior positive SARS-CoV-2 PCR and/or antibody results, reported more moderate/severe AEs, than those without past infection, particularly systemic symptoms, as did those with features of long COVID.

71: INO-4800 DNA Vaccine Induces Neutralizing Antibodies and T cell Activity Against Global SARS-CoV-2 Variants
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Posted 14 Apr 2021

INO-4800 DNA Vaccine Induces Neutralizing Antibodies and T cell Activity Against Global SARS-CoV-2 Variants
3,255 downloads bioRxiv immunology

Viviane M Andrade, Aaron Christensen-Quick, Joseph Agnes, Jared Tur, Charles Reed, Richa Kalia, Idania Marrero, Dustin Elwood, Katherine Schultheis, Mansi Purwar, Emma Reuschel, Trevor McMullan, Patrick Pezzoli, Kim Kraynyak, Albert Sylvester, Mammen P Mammen, Pablo Tebas, J Joseph Kim, David B Weiner, Trevor R.F. Smith, Stephanie J Ramos, Laurent M Humeau, Jean D Boyer, Kate E. Broderick

Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with broadened host specificity, pathogenicity, and immune evasion to vaccine induced immunity. Here we compared humoral and cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFN{gamma} T cell responses were fully maintained against all variants tested.

72: Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7
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Posted 26 Jan 2021

Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7
3,174 downloads bioRxiv immunology

Pengfei Wang, Manoj S. Nair, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D. Kwong, Barney Graham, John R Mascola, Jennifer Y Chang, Michael T. Yin, Magdalena E Sobieszczyk, Christos A Kyratsous, Lawrence Shapiro, Zizhang Sheng, Yaoxing Huang, David D Ho

The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody (mAb) therapeutics have received emergency use authorization, with more in the pipeline. Furthermore, multiple vaccine constructs have shown promise, including two with ~95% protective efficacy against COVID-19. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK and B.1.351 in South Africa is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

73: COVID-19 and Mental Health: A Study of its Impact on Students
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Posted 11 Aug 2020

COVID-19 and Mental Health: A Study of its Impact on Students
3,135 downloads medRxiv health informatics

Kshipra Moghe, Disha Kotecha, Manjusha Patil

The purpose of this study was to identify and analyse the personal, social and psychological impact of COVID - 19 on the mental health of students of age group 16 to 25. A response from N= 351 students (from the most affected state in India), provided a comparative analysis based on the gender, and background to understand the pattern in issues related to mental health during the pandemic. The results show that female students are more concerned about health, and future, and are more prone to psychological issues like feelings of uncertainty, helplessness and outbursts than male students. Urban students population is more mentally affected than their rural counterparts, however time spent on the internet is almost the same despite the difference in infrastructure and resources. Also, there is an increase in need for solitude, being withdrawn and self-harm in male students require attention. A shift in perception from seeing family as a source of support to that of a restriction is indicated, although the benefits of a collectivistic society are undisputed. The results indicate that there is overall increased awareness about mental health among the student population and with programs/strategies focusing on background and gender, a significant improvement is attainable.

74: False positives in reverse transcription PCR testing for SARS-CoV-2
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Posted 01 May 2020

False positives in reverse transcription PCR testing for SARS-CoV-2
3,083 downloads medRxiv epidemiology

Andrew N Cohen, Bruce Kessel, Michael G Milgroom

Contrary to the practice during previous epidemics, with COVID-19 health authorities have treated a single positive result from a PCR-based test as confirmation of infection, irrespective of signs, symptoms and exposure. This is based on a widespread belief that positive results in these tests are highly reliable. However, evidence from external quality assessments and real-world data indicate enough a high enough false positive rate to make positive results highly unreliable over a broad range of scenarios. This has clinical and case management implications, and affects an array of epidemiological statistics, including the asymptomatic ratio, prevalence, and hospitalization and death rates, as well as epidemiologic models. Steps should be taken to raise awareness of false positives and reduce their frequency. The most important immediate action is to check positive results with additional tests, at least when prevalence is low.

75: SARS-CoV-2 immune evasion by variant B.1.427/B.1.429
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Posted 01 Apr 2021

SARS-CoV-2 immune evasion by variant B.1.427/B.1.429
3,081 downloads bioRxiv immunology

Matthew McCallum, Jessica Bassi, Anna De Marco, Alex Chen, Alexandra C. Walls, Julia di Iulio, M. Alejandra Tortorici, Mary-Jane Navarro, Chiara Silacci-Fregni, Christian Saliba, Maria Agostini, Dora Pinto, Katja Culap, Siro Bianchi, Stefano Jaconi, Elisabetta Cameroni, John E Bowen, Sasha W Tiles, Matteo Samuele Pizzuto, Sonja Bernasconi Guastalla, Giovanni Bona, Alessandra Franzetti Pellanda, Christian Garzoni, Wesley C Van Voorhis, Laura E. Rosen, Gyorgy C Snell, Amalio Telenti, Herbert W Virgin, Luca Piccoli, Davide Corti, David Veesler

SARS-CoV-2 entry is mediated by the spike (S) glycoprotein which contains the receptor-binding domain (RBD) and the N-terminal domain (NTD) as the two main targets of neutralizing antibodies (Abs). A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429) was originally detected in California and is currently spreading throughout the US and 29 additional countries. It is unclear whether antibody responses to SARS-CoV-2 infection or to the prototypic Wuhan-1 isolate-based vaccines will be impacted by the three B.1.427/B.1.429 S mutations: S13I, W152C and L452R. Here, we assessed neutralizing Ab responses following natural infection or mRNA vaccination using pseudoviruses expressing the wildtype or the B.1.427/B.1.429 S protein. Plasma from vaccinated or convalescent individuals exhibited neutralizing titers, which were reduced 3-6 fold against the B.1.427/B.1.429 variant relative to wildtype pseudoviruses. The RBD L452R mutation reduced or abolished neutralizing activity of 14 out of 35 RBD-specific monoclonal antibodies (mAbs), including three clinical-stage mAbs. Furthermore, we observed a complete loss of B.1.427/B.1.429 neutralization for a panel of mAbs targeting the N-terminal domain due to a large structural rearrangement of the NTD antigenic supersite involving an S13I-mediated shift of the signal peptide cleavage site. These data warrant closer monitoring of signal peptide variants and their involvement in immune evasion and show that Abs directed to the NTD impose a selection pressure driving SARS-CoV-2 viral evolution through conventional and unconventional escape mechanisms.

76: Integrated analysis of multimodal single-cell data
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Posted 12 Oct 2020

Integrated analysis of multimodal single-cell data
3,078 downloads bioRxiv genomics

Yuhan Hao, Stephanie Hao, Erica Andersen-Nissen, William M. Mauck, Shiwei Zheng, Andrew Butler, Maddie J. Lee, Aaron J. Wilk, Charlotte Darby, Michael Zagar, Paul Hoffman, Marlon Stoeckius, Efthymia Papalexi, Eleni Mimitou, Jaison Jain, Avi Srivastava, Tim Stuart, Lamar B. Fleming, Bertrand Yeung, Angela J. Rogers, M. Juliana McElrath, Catherine A. Blish, Raphael Gottardo, Peter Smibert, Rahul Satija

The simultaneous measurement of multiple modalities, known as multimodal analysis, represents an exciting frontier for single-cell genomics and necessitates new computational methods that can define cellular states based on multiple data types. Here, we introduce "weighted-nearest neighbor analysis", an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of hundreds of thousands of human white blood cells alongside a panel of 228 antibodies to construct a multimodal reference atlas of the circulating immune system. We demonstrate that integrative analysis substantially improves our ability to resolve cell states and validate the presence of previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets, and to interpret immune responses to vaccination and COVID-19. Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets, including paired measurements of RNA and chromatin state, and to look beyond the transcriptome towards a unified and multimodal definition of cellular identity. Availability: Installation instructions, documentation, tutorials, and CITE-seq datasets are available at http://www.satijalab.org/seurat ### Competing Interest Statement In the past three years, RS has worked as a consultant for Bristol-Myers Squibb, Regeneron, and Kallyope, and served as an SAB member for ImmunAI, Apollo Life Sciences GmbH, Nanostring and the NYC Pandemic Response Lab. R.G. has received consulting income from Juno Therapeutics, Takeda, Infotech Soft, Celgene, Merck and has received research support from Janssen Pharmaceuticals and Juno Therapeutics, and declares ownership in CellSpace Biosciences. PS is a co-inventor of a patent related to this work. BZY is an employee at BioLegend Inc., which is the exclusive licensee of the New York Genome Center patent application related to this work.

77: Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination
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Posted 05 Mar 2021

Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination
2,999 downloads medRxiv infectious diseases

Lisa Müller, Marcel Andrée, Wiebke Moskorz, Ingo Drexler, Lara Walotka, Ramona Grothmann, Johannes Ptok, Jonas Hillebrandt, Anastasia Ritchie, Denise Rabl, Philipp Niklas Ostermann, Rebekka Robitzsch, Sandra Hauka, Andreas Walker, Christopher Menne, Ralf Grutza, Jörg Timm, Ortwin Adams, Heiner Schaal

BackgroundThe SARS-CoV-2 pandemic has led to the development of various vaccines. Real-life data on immune responses elicited in the most vulnerable group of vaccinees over 80 years old is still underrepresented despite the prioritization of the elderly in vaccination campaigns. MethodsWe conducted a cohort study with two age groups, young vaccinees below the age of 60 and elderly vaccinees over the age of 80, to compare their antibody responses to the first and second dose of the BNT162b2 COVID-19 vaccination. ResultsWhile the majority of participants in both groups produced specific IgG antibody titers against SARS-CoV-2 spike protein, titers were significantly lower in elderly participants. Although the increment of antibody levels after the second immunization was higher in elderly participants, the absolute mean titer of this group remained lower than the <60 group. After the second vaccination, 31.3 % of the elderly had no detectable neutralizing antibodies in contrast to the younger group, in which only 2.2% had no detectable neutralizing antibodies. ConclusionOur data suggests that lower frequencies of neutralizing antibodies after BNT162b2 vaccination in the elderly population may require earlier revaccination to ensure strong immunity and protection against infection.

78: Altered Smell and Taste: anosmia, parosmia and the long impact of Covid-19
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Posted 30 Nov 2020

Altered Smell and Taste: anosmia, parosmia and the long impact of Covid-19
2,990 downloads medRxiv infectious diseases

Duika L Burges Watson, Miglena Campbell, Claire Hopkins, Barry Smith, Chris Kelly, Vincent Deary

Abstract Background: Qualitative olfactory (smell) dysfunctions are a common side effect of post-viral illness and known to impact on quality of life and health status. Evidence is emerging that taste and smell loss are common symptoms of Covid-19 that may emerge and persist long after initial infection. The aim of the present study was to document the impact of post Covid-19 alterations to taste and smell. Methods: We conducted passive and active thematic analysis of user-generated text from 9000 users of the AbScent Covid-19 Smell and Taste Loss moderated Facebook support group from March 24 to 30th September 2020. Results: Participants reported difficulty understanding, explaining and managing altered taste and smell; a lack of interpersonal and professional explanation or support; altered eating; appetite loss, weight change; loss of pleasure in food, eating and social engagement; altered intimacy and an altered relationship to self and others. Conclusions: Our findings suggest altered taste and smell with Covid-19 lead to a severe disruption to daily living that impacts on psychological well-being and health. Moreover, this impact is broad, spanning flavour perception; desire and ability to eat and prepare food; weight gain, loss and nutritional sufficiency; emotional wellbeing; professional practice; intimacy; social bonding and erosion of peoples very sense of reality. Our findings should inform the training, assessment and treatment practices of health care professionals working with long Covid.

79: Acceptance and Attitudes Toward COVID-19 Vaccines: A Cross-Sectional Study from Jordan
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Posted 24 Dec 2020

Acceptance and Attitudes Toward COVID-19 Vaccines: A Cross-Sectional Study from Jordan
2,895 downloads medRxiv health policy

Tamam El-Elimat, Mahmoud M. AbuAlSamen, Basima A. Almomani, Nour A. Al-Sawalha, Feras Q. Alali

BackgroundVaccines are effective interventions that can reduce the high burden of diseases globally. However, public vaccine hesitancy is a pressing problem for public health authorities. With the availability of COVID-19 vaccines, little information is available on the public acceptability and attitudes towards the COVID-19 vaccines in Jordan. This study aimed to investigate the acceptability of COVID-19 vaccines and its predictors in addition to the attitudes towards these vaccines among public in Jordan. MethodsAn online, cross-sectional, and self-administered questionnaire was instrumentalized to survey adult participants from Jordan on the acceptability of COVID-19 vaccines. Logistic regression analysis was used to find the predictors of COVID-19 vaccines acceptability. ResultsA total of 3,100 participants completed the survey. The public acceptability of COVID-19 vaccines was fairly low (37.4%) in Jordan. Males (OR=2.488, 95CI%=1.834-3.375, p<.001) and those who took the seasonal influenza vaccine (OR=2.036, 95CI%=1.306-3.174, p=.002) were more likely to accept Covid-19 vaccines. Similarly, participants who believed that vaccines are generally safe (OR=9.258, 95CI%=6.020-14.237, p<.001) and those who were willing to pay for vaccines (OR=19.223, 95CI%=13.665-27.042, p<.001), once available, were more likely to accept the COVID-19 vaccines. However, those above 35 years old (OR=0.376, 95CI%=0.233-0.607, p<.001) and employed participants (OR=0.542, 95CI%=0.405-0.725, p<.001) were less likely to accept the COVID-19 vaccines. Moreover, participants who believed that there was a conspiracy behind COVID-19 (OR=0.502, 95CI%=0.356- 0.709, p<.001) and those who do not trust any source of information on COVID-19 vaccines (OR=0.271, 95CI%=0.183 - 0.400, p<.001), were less likely to have acceptance towards them. The most trusted sources of information on COVID-19 vaccines were healthcare providers. ConclusionSystematic interventions are required by public health authorities to reduce the levels of vaccines hesitancy and improve their acceptance. We believe these results and specifically the low rate of acceptability is alarming to Jordanian health authorities and should stir further studies on the root causes and the need of awareness campaigns. These interventions should take the form of reviving the trust in national health authorities and structured awareness campaigns that offer transparent information about the safety and efficacy of the vaccines and the technology that was utilized in their production.

80: Compositional perturbation autoencoder for single-cell response modeling
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Posted 15 Apr 2021

Compositional perturbation autoencoder for single-cell response modeling
2,882 downloads bioRxiv bioinformatics

Mohammad Lotfollahi, Anna Klimovskaia, Carlo De Donno, Yuge Ji, Ignacio L. Ibarra, F. Alexander Wolf, Nafissa Yakubova, Fabian J Theis, David Lopez-Paz

Recent advances in multiplexing single-cell transcriptomics across experiments are enabling the high throughput study of drug and genetic perturbations. However, an exhaustive exploration of the combinatorial perturbation space is experimentally unfeasible, so computational methods are needed to predict, interpret and prioritize perturbations. Here, we present the Compositional Perturbation Autoencoder (CPA), which combines the interpretability of linear models with the flexibility of deep-learning approaches for single-cell response modeling. CPA encodes and learns transcriptional drug response across different cell types, doses, and drug combinations. The model produces easy-to-interpret embeddings for drugs and cell types, allowing drug similarity analysis and predictions for unseen dosages and drug combinations. We show CPA accurately models single-cell perturbations across compounds, dosages, species, and time. We further demonstrate that CPA predicts combinatorial genetic interactions of several types, implying it captures features that distinguish different interaction programs. Finally, we demonstrate CPA allows in-silico generation of 5,329 missing combinations (97.6% of all possibilities) with diverse genetic interactions. We envision our model will facilitate efficient experimental design by enabling in silico response prediction at the single-cell level.

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