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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 158,252 papers from 662,608 authors.

Most tweeted biology preprints, last 7 days

*There are gaps in historical Twitter data, most notably in spring 2020. This may result in some preprints appearing with less tweets than they should.

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

1: Infection fatality rate of COVID-19 in community-dwelling populations with emphasis on the elderly: An overview
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Posted 13 Jul 2021

Infection fatality rate of COVID-19 in community-dwelling populations with emphasis on the elderly: An overview
256 tweets medRxiv epidemiology

Cathrine Axfors, John Ioannidis

Background: The infection fatality rate (IFR) of Coronavirus Disease 2019 (COVID-19) varies widely according to age and residence status. Purpose: Estimate the IFR of COVID-19 in community-dwelling elderly populations and other age groups from seroprevalence studies. Study protocol: https://osf.io/47cgb. Data Sources: Seroprevalence studies done in 2020 and identified by any of four existing systematic reviews. Study Selection: SARS-CoV-2 seroprevalence studies with [≥]1000 participants aged [≥]70 years that presented seroprevalence in elderly people; aimed to generate samples reflecting the general population; and whose location had available data on cumulative COVID-19 deaths in elderly (primary cutoff [≥]70 years; [≥]65 or [≥]60 also eligible). Data Extraction: We extracted the most fully adjusted (if unavailable, unadjusted) seroprevalence estimates and sampling procedure details. We also extracted age- and residence-stratified cumulative COVID-19 deaths (until 1 week after the seroprevalence sampling midpoint) from official reports, and population statistics, to calculate IFRs corrected for unmeasured antibody types. Sample size-weighted IFRs were estimated for countries with multiple estimates. Secondary analyses examined data on younger age strata from the same studies. Data Synthesis: Twenty-three seroprevalence surveys representing 14 countries were included. Across all countries, the median IFR in community-dwelling elderly and elderly overall was 2.4% (range 0.3%-7.2%) and 5.5% (range 0.3%-12.1%). IFR was higher with larger proportions of people >85 years. Younger age strata had low IFR values (median 0.0027%, 0.014%, 0.031%, 0.082%, 0.27%, and 0.59%, at 0-19, 20-29, 30-39, 40-49, 50-59, and 60-69 years). Limitations: Biases in seroprevalence and mortality data. Conclusions: The IFR of COVID-19 in community-dwelling elderly people is lower than previously reported. Very low IFRs were confirmed in the youngest populations.

2: A Systematic Review of the Protective Effect of Prior SARS-CoV-2 Infection on Repeat Infection
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Posted 29 Aug 2021

A Systematic Review of the Protective Effect of Prior SARS-CoV-2 Infection on Repeat Infection
234 tweets medRxiv infectious diseases

Noah Kojima, Nabin Shrestha, Jeffrey D Klausner

Introduction: We systematically reviewed studies to estimate the risk of SARS-CoV-2 reinfection among those previously infected with SARS-CoV-2. Methods: For this systematic review, we searched scientific publications on PubMed and, the pre-print server, MedRxiv through August 18, 2021. Eligible studies were retrieved on August 18, 2021. We used the following search term on PubMed: (((Cohort Studies [Majr]) AND (COVID-19 [Mesh] OR SARS-CoV-2 [Mesh])) OR Reinfection [Majr]) OR Reinfection [Mesh]. We used the following search term on MedRxiv: Cohort Studies AND COVID-19 OR SARS-CoV-2 AND Reinfection. The search terms were broad to encompass all possibilities for applicable studies. There were no restrictions on the date of publication. Studies that did not describe cohorts with estimates of the risk of SARS-CoV-2 reinfection among those with previous infection were excluded. Studies that included vaccinated participants were either excluded or limited to sub-groups of non-vaccinated individuals. To identify relevant studies with appropriate control groups, we developed the following criteria for studies to be included in the systematic analysis: (1) baseline polymerase chain reaction (PCR) testing, (2) a negative comparison group, (3) longitudinal follow-up, (4) a cohort of human participants, i.e., not a case report or case series, and (5) outcome determined by PCR. The review was conducted following PRISMA guidelines. We assessed for selection, information, and analysis bias, per PRISMA guidelines. Results: We identified 1,392 reports. Of those, 10 studies were eligible for our systematic review. The weighted average risk reduction against reinfection was 90.4% with a standard deviation of 7.7%. Protection against SARS-CoV-2 reinfection was observed for up to 10 months. Studies had potential information, selection, and analysis biases. Conclusions: The protective effect of prior SARS-CoV-2 infection on re-infection is high and similar to the protective effect of vaccination. More research is needed to characterize the duration of protection and the impact of different SARS-CoV-2 variants.

3: Necessity of COVID-19 Vaccination in Previously Infected Individuals: A Retrospective Cohort Study
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Posted 04 Jun 2021

Necessity of COVID-19 Vaccination in Previously Infected Individuals: A Retrospective Cohort Study
171 tweets medRxiv infectious diseases

Nabin Shrestha, Patrick C. Burke, Amy S. Nowacki, Paul Terpeluk, Steven M. Gordon

Background: There are good reasons to expect natural infection to provide protection against future infection with SARS-CoV-2. The purpose of this study was to evaluate the necessity of COVID-19 vaccination in persons previously infected with SARS-CoV-2. Methods: Employees of the Cleveland Clinic Health System working in Ohio on Dec 16, 2020, the day COVID-19 vaccination was started, were included. Any subject who tested positive for SARS-CoV-2 at least 42 days earlier was considered previously infected. One was considered vaccinated 14 days after receipt of the second dose of a SARS-CoV-2 mRNA vaccine. The cumulative incidence of SARS-CoV-2 infection over the next four months, among previously infected subjects who received the vaccine, was compared with those of previously infected subjects who remained unvaccinated, previously uninfected subjects who received the vaccine, and previously uninfected subjects who remained unvaccinated. Results: Among the 52238 included employees, 1220 (47%) of 2579 previously infected subjects received the vaccine, compared with 29461 (59%) of 49659 not previously infected. The cumulative incidence of SARS-CoV-2 infection did not differ among previously infected unvaccinated subjects, previously infected subjects who were vaccinated, and previously uninfected subjects who were vaccinated, and was much lower than that of previously uninfected subjects who remained unvaccinated. Not one of the 1359 previously infected subjects who remained unvaccinated had a SARS-CoV-2 infection over the duration of the study. Conclusion: Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination, and vaccines can be safely prioritized to those who have not been infected before.

4: Shedding of Infectious SARS-CoV-2 Despite Vaccination when the Delta Variant is Prevalent - Wisconsin, July 2021
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Posted 31 Jul 2021

Shedding of Infectious SARS-CoV-2 Despite Vaccination when the Delta Variant is Prevalent - Wisconsin, July 2021
169 tweets medRxiv infectious diseases

Kasen K Riemersma, Brittany E Grogan, Amanda Kita-Yarbro, Peter Halfmann, Anna Kocharian, Kelsey R Florek, Ryan Westergaard, Allen Bateman, Gunnar E Jeppson, Yoshihiro Kawaoka, David H O'Connor, Thomas C Friedrich, Katarina M Grande

SARS-CoV-2 variant B.1.617.2 (delta) is associated with higher viral loads [1] and increased transmissibility relative to other variants, as well as partial escape from polyclonal and monoclonal antibodies [2]. The emergence of the delta variant has been associated with increasing case counts and test-positivity rates, indicative of rapid community spread. Since early July 2021, SARS-CoV-2 cases in the United States have increased coincident with delta SARS-CoV-2 becoming the predominant lineage nationwide [3]. Understanding how and why the virus is spreading in settings where there is high vaccine coverage has important public health implications. It is particularly important to assess whether vaccinated individuals who become infected can transmit SARS-CoV-2 to others. In Wisconsin, a large local contract laboratory provides SARS-CoV-2 testing for multiple local health departments, providing a single standard source of data using the same assay to measure virus burdens in test-positive cases. This includes providing high-volume testing in Dane County, a county with extremely high vaccine coverage. These PCR-based tests provide semi-quantitative information about the viral load, or amount of SARS-CoV-2 RNA, in respiratory specimens. Here we use this viral load data to compare the amount of SARS-CoV-2 present in test-positive specimens from people who self-report their vaccine status and date of final immunization, during a period in which the delta variant became the predominant circulating variant in Wisconsin. We find no difference in viral loads when comparing unvaccinated individuals to those who have vaccine "breakthrough" infections. Furthermore, individuals with vaccine breakthrough infections frequently test positive with viral loads consistent with the ability to shed infectious viruses. Our results, while preliminary, suggest that if vaccinated individuals become infected with the delta variant, they may be sources of SARS-CoV-2 transmission to others.

5: Effectiveness of the Single-Dose Ad26.COV2.S COVID Vaccine
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Posted 12 Sep 2021

Effectiveness of the Single-Dose Ad26.COV2.S COVID Vaccine
94 tweets medRxiv infectious diseases

Jennifer M. Polinski, Andrew R. Weckstein, Michael Batech, Carly Kabelac, Tripthi Kamath, Raymond Harvey, Sid Jain, Jeremy A. Rassen, Najat Khan, Sebastian Schneeweiss

Importance: Vaccination against the SARS-CoV-2 virus is critical to control the pandemic. Randomized trials demonstrated efficacy of the single-dose Ad26.COV2.S COVID vaccine but data on longer-term protection in clinical practice and effectiveness against variants are needed. Objective: To assess the effectiveness of Ad26.COV2.S in preventing COVID infections and COVID-related hospitalizations in clinical practice, the longer-term stability of its protective effect and effectiveness against Delta variants. Design: Cohort study of newly Ad26.COV2.S-vaccinated and unvaccinated individuals. Setting: U.S. insurance claims data through July 2021. Participants: Individuals 18 years and older newly vaccinated with Ad26.COV2.S and up to 10 unvaccinated individuals matched exactly by age, sex, date, location, comorbidity index plus 17 COVID-19 risk factors via propensity score (PS) matching. Intervention: Vaccination with Ad26.COV2.S versus no vaccination. Main outcomes: We estimated vaccine effectiveness (VE) for observed COVID-19 infection and COVID-19-related hospitalization, nationwide and stratified by age, immunocompromised status, calendar time, and states with high incidence of the Delta variant. We corrected VE estimates for under-recording of vaccinations in insurance data. Results: Among 390,517 vaccinated and 1,524,153 matched unvaccinated individuals, VE was 79% (95% CI, 77% to 80%) for COVID-19 and 81% (79% to 84%) for COVID-19-related hospitalizations. VE was stable over calendar time. Among states with high Delta variant incidence, VE during June/July 2021 was 78% (73% to 82%) for infections and 85% (73% to 91%) for hospitalizations. VE for COVID-19 was higher in individuals <50 years (83%; 81% to 85%) and lower in immunocompromised patients (64%; 57% to 70%). All estimates were corrected for under-recording; uncorrected VE was 69% (67% to 71%) and 73% (69% to 76%), for COVID-19 and COVID-19-related hospitalization, respectively. Conclusions: These non-randomized data across U.S. clinical practices show high and stable vaccine effectiveness of Ad26.COV2.S over time before the Delta variant emerged to when the Delta variant was dominant.

6: Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine
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Posted 28 Jul 2021

Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine
60 tweets medRxiv infectious diseases

Stephen J. Thomas, Edson D Moreira, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, John L Perez, Gonzalo Pérez Marc, Fernando P. Polack, Cristiano Zerbini, Ruth Bailey, Kena A. Swanson, Xia Xu, Satrajit Roychoudhury, Kenneth Koury, Salim Bouguermouh, Warren V. Kalina, David Cooper, Robert W Frenck, Laura L. Hammitt, Özlem Türeci, Haylene Nell, Axel Schaefer, Serhat Ünal, Qi Yang, Paul Liberator, Dina B Tresnan, Susan Mather, Philip R. Dormitzer, Uğur Şahin, William C. Gruber, Kathrin U. Jansen, C4591001 Clinical Trial Group

Background: BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. BNT162b2 is highly efficacious against COVID-19 and is currently authorized for emergency use or conditional approval worldwide. At the time of authorization, data beyond 2 months post-vaccination were unavailable. Methods: In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy study, 44,165 [&ge;]16-year-old participants and 2,264 12-15-year-old participants were randomized to receive 2 doses, 21 days apart, of 30 g BNT162b2 or placebo. Study endpoints reported here are vaccine efficacy (VE) against laboratory-confirmed COVID-19 and safety data, both up to 6 months post-vaccination. Results: BNT162b2 continued to be safe and well tolerated. Few participants had adverse events leading to study withdrawal. VE against COVID-19 was 91% (95% CI 89.0-93.2) through up to 6 months of follow-up, among evaluable participants and irrespective of previous SARS-CoV-2 infection. VE of 86%-100% was seen across countries and in populations with diverse characteristics of age, sex, race/ethnicity, and COVID-19 risk factors in participants without evidence of previous SARS-CoV-2 infection. VE against severe disease was 97% % (95% CI 80.3-99.9). In South Africa, where the SARS-CoV-2 variant of concern, B.1.351 (beta), was predominant, 100% (95% CI 53.5, 100.0) VE was observed. Conclusion: With up to 6 months of follow-up and despite a gradually declining trend in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing COVID-19. (ClinicalTrials.gov number, NCT04368728)

7: Antigen identification and high-throughput interaction mapping by reprogramming viral entry
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Posted 20 Sep 2021

Antigen identification and high-throughput interaction mapping by reprogramming viral entry
47 tweets bioRxiv immunology

Connor S Dobson, Anna N Reich, Stephanie Gaglione, Blake E Smith, Ellen J Kim, Jiayi Dong, Larance Ronsard, Vintus Okonkwo, Daniel Lingwood, Michael Dougan, Stephanie K Dougan, Michael E Birnbaum

Deciphering immune recognition is critical for understanding a broad range of diseases and for the development of effective vaccines and immunotherapies. Efforts to do so are limited by a lack of technologies capable of simultaneously capturing the complexity of adaptive immune receptor repertoires and the landscape of potential antigens. To address this, we present RAPTR (Receptor-Antigen Pairing by Targeted Retroviruses). RAPTR combines viral pseudotyping and molecular engineering approaches to enable one-pot library on library interaction screens by displaying antigens on the surface of lentiviruses and encoding their identity in the viral genome. Antigen-specific viral infection of cells allows readout of both antigen and receptor identities via single-cell sequencing. The resulting system is modular, scalable, and compatible with any cell type, making it easily implemented. These techniques provide a suite of new tools for targeted viral entry, molecular engineering, and interaction screens with broad potential applications.

8: Impact of SARS-CoV-2 variant on the severity of maternal infection and perinatal outcomes: Data from the UK Obstetric Surveillance System national cohort.
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Posted 25 Jul 2021

Impact of SARS-CoV-2 variant on the severity of maternal infection and perinatal outcomes: Data from the UK Obstetric Surveillance System national cohort.
39 tweets medRxiv obstetrics and gynecology

Nicola Vousden, Rema Ramakrishnan, Kathryn Bunch, Edward Morris, Nigel Simpson, Christopher Gale, Patrick O'Brien, Maria Quigley, Peter Brocklehurst, Jennifer J Kurinczuk, Marian Knight

Background In the UK, the Alpha variant of SARS-CoV-2 became dominant in late 2020, rapidly succeeded by the Delta variant in May 2021. The aim of this study was to compare the impact of these variants on severity of maternal infection and perinatal outcomes within the time-periods in which they predominated. Methods This national, prospective cohort study collated data on hospitalised pregnant women with symptoms of confirmed SARS-CoV-2 infection and compared the severity of infection and perinatal outcomes across the Wildtype (01/03/20-30/11/20), Alpha (01/12/20-15/05/21) and Delta dominant periods (16/05/21-11/07/21), using multivariable logistic regression. Findings Of 3371 pregnant women, the proportion that experienced moderate to severe infection significantly increased between Wildtype and Alpha periods (24.4% vs. 35.8%; aOR1.75 95%CI 1.48-2.06), and between Alpha and Delta periods (35.8% vs. 45.0%; aOR1.53, 95%CI 1.07-2.17). Compared to the Wildtype period, symptomatic women admitted in the Alpha period were more likely to require respiratory support (27.2% vs. 20.3%, aOR1.39, 95%CI 1.13-1.78), have pneumonia (27.5% vs. 19.1%, aOR1.65, 95%CI 1.38-1.98) and be admitted to intensive care (11.3% vs. 7.7%, aOR1.61, 95%CI 1.24-2.10). Women admitted during the Delta period had further increased risk of pneumonia (36.8% vs. 27.5%, aOR1.64 95%CI 1.14-2.35). No fully vaccinated pregnant women were admitted between 01/02/2021 when vaccination data collection commenced and 11/07/2021. The proportion of women receiving pharmacological therapies for SARS-CoV-2 management was low, even in those critically ill. Interpretation SARS-CoV-2 infection during Alpha and Delta dominant periods was associated with more severe infection and worse pregnancy outcomes compared to the Wildtype infection, which itself increased risk compared to women without SARS-CoV-2 infection.1 Clinicians need to be aware and implement COVID-specific therapies in keeping with national guidance. Urgent action to tackle vaccine misinformation and policy change to prioritise uptake in pregnancy is essential. Funding National Institute for Health Research HS&DR Programme (11/46/12).

9: SARS-CoV-2 mRNA vaccine elicits a potent adaptive immune response in the absence of IFN-mediated inflammation observed in COVID-19
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Posted 21 Apr 2021

SARS-CoV-2 mRNA vaccine elicits a potent adaptive immune response in the absence of IFN-mediated inflammation observed in COVID-19
35 tweets medRxiv infectious diseases

Ellie N Ivanova, Joseph C Devlin, Terild B Buus, Akiko Koide, Amber Cornelius, Marie I Samanovic, Alberto Herrera, Eleni Mimitou, Chenzhen Zhang, Ludovic Desvignes, Niels Odum, Peter Smibert, Robert Ulrich, Mark J Mulligan, Shohei Koide, Kelly V Ruggles, Ramin Sedaghat Herati, Sergei B Koralov

Both SARS-CoV-2 infection and vaccination elicit potent immune responses, but the durability and scope of immune responses remain to be elucidated. Here, we performed multimodal single-cell profiling of peripheral blood of patients with acute COVID-19 and healthy volunteers before and after receiving the SARS-CoV-2 BNT162b2 mRNA vaccine to compare the immune responses elicited by the virus and by the vaccine. Phenotypic and transcriptional profiling of immune cells, coupled with reconstruction of B and T cell receptor repertoires, enabled us to characterize and compare the host responses to the virus and to defined viral antigens. In COVID-19 patients, immune responses were characterized by a highly augmented interferon response which was largely absent in vaccine recipients. Increased interferon signaling likely contributed to the dramatic upregulation of cytotoxic genes in the peripheral T cells and innate-like lymphocytes observed in COVID-19 patients. Analysis of B and T cell repertoires revealed that while the majority of clonal lymphocytes in COVID-19 patients were effector cells, in vaccine recipients clonal expansion was primarily restricted to circulating memory cells. Taken together, our analysis of immune responses to the mRNA vaccine reveals that despite the lack of dramatic inflammation observed during infection, the vaccine elicits a robust adaptive immune response.

10: Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome
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Posted 06 Mar 2020

Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome
35 tweets medRxiv infectious diseases

Yang Yang, Chenguang Shen, Jinxiu Li, Jing Yuan, Minghui Yang, Fuxiang Wang, Guobao Li, Yanjie Li, Li Xing, Ling Peng, Jinli Wei, Mengli Cao, Haixia Zheng, Weibo Wu, Rongrong Zou, Delin Li, Zhixiang Xu, Haiyan Wang, Mingxia Zhang, Zheng Zhang, Lei Liu, Yingxia Liu

The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report biomarkers that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, providing novel therapeutic targets and strategy.

11: 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
32 tweets 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.

12: Brain imaging before and after COVID-19 in UK Biobank
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Posted 15 Jun 2021

Brain imaging before and after COVID-19 in UK Biobank
29 tweets medRxiv neurology

Gwenaëlle Douaud, Soojin Lee, Fidel Alfaro-Almagro, Christoph Arthofer, Chaoyue Wang, Paul McCarthy, Frederik Lange, Jesper L.R. Andersson, Ludovica Griffanti, Eugene Duff, Saad Jbabdi, Bernd Taschler, Anderson M. Winkler, Thomas E. Nichols, Rory Collins, Paul M. Matthews, Naomi Allen, Karla Miller, Stephen M. Smith

There is strong evidence for brain-related pathologies in COVID-19, some of which could be a consequence of viral neurotropism, or of neuroinflammation following viral infection. Most brain imaging studies have focused on qualitative, gross pathology in moderate to severe cases, most typically carried out on hospitalised patients. It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, in a quantitative and automated manner, and whether this can reveal possible mechanisms for the spread of the disease. UK Biobank scanned over 40,000 participants before the start of the COVID-19 pandemic, making it possible in 2021 to invite back hundreds of previously-imaged participants for a second imaging visit. Here, we studied the possible brain changes associated with the coronavirus infection using multimodal MRI data from 785 adult participants (aged 51-81) from the UK Biobank COVID-19 re-imaging study, including 401 adult participants who tested positive for SARS-CoV-2 infection between their two scans. We used structural, diffusion and functional brain scans from before and after infection, to compare longitudinal changes between these 401 SARS-CoV-2 cases and 384 controls who had either tested negative to rapid antibody testing or had no COVID-19 medical and public health record, and who were matched to the cases for age, sex, ethnicity and interval between scans. The controls and cases did not differ in blood pressure, body mass index, diabetes diagnosis, smoking, alcohol consumption, or socio-economic status. Using both hypothesis-driven and exploratory approaches, with false discovery rate multiple comparison correction, we identified respectively 68 and 67 significant longitudinal effects associated with SARS-CoV-2 infection in the brain, including, on average: (i) a more pronounced reduction in grey matter thickness and contrast in the lateral orbitofrontal cortex (min P=1.7x10-4, r=-0.14) and parahippocampal gyrus (min P=2.7x10-4, r=-0.13), (ii) a relative increase of diffusion indices, a marker of tissue damage, in the regions of the brain functionally-connected to the piriform cortex, anterior olfactory nucleus and olfactory tubercle (min P=2.2x10-5, r=0.16), and (iii) greater reduction in global measures of brain size and increase in cerebrospinal fluid volume suggesting an additional diffuse atrophy in the infected participants (min P=4.0x10-6, r=-0.17). When looking over the entire cortical surface, these grey matter thickness results covered the parahippocampal gyrus and the lateral orbitofrontal cortex, and extended to the anterior insula and anterior cingulate cortex, supramarginal gyrus and temporal pole. The increase of a diffusion index (mean diffusivity) meanwhile could be seen voxel-wise mainly in the medial and lateral orbitofrontal cortex, the anterior insula, the anterior cingulate cortex and the amygdala. These results were not altered after excluding cases who had been hospitalised. We further compared hospitalised (n=15) and non-hospitalised (n=386) infected participants, resulting in similar findings to the larger cases vs control group comparison, with, in addition, a marked reduction of grey matter thickness in fronto-parietal and temporal regions (all FDR-significant, min P=4.0x10-6). The 401 SARS-CoV-2 infected participants also showed larger cognitive decline between the two timepoints in the Trail Making Test compared with the controls (both FDR-significant, min P=1.0x10-4, r=0.17; and still FDR-significant after excluding the hospitalised patients: min P=1.0x10-4, r=0.17), with the duration taken to complete the alphanumeric trail correlating post hoc with the cognitive and olfactory-related crus II of the cerebellum (FDR-significant, P=2.0x10-3, r=-0.19), which was also found significantly atrophic in the SARS-CoV-2 participants (FDR-significant, P=6.1x10-5, r=-0.14). Our findings thus relate to longitudinal abnormalities in limbic cortical areas with direct neuronal connectivity to the primary olfactory system. Unlike in post hoc cross-sectional studies, the availability of pre-infection imaging data mitigates to some extent the issue of pre-existing risk factors or clinical conditions being misinterpreted as disease effects. We were therefore able to demonstrate that the regions of the brain that showed longitudinal differences post-infection did not already show any difference between (future) cases and controls in their initial, pre-infection scans. These brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease -- or of the virus itself -- via olfactory pathways (a possible entry point of the virus to the central nervous system being via the olfactory mucosa), or of neuroinflammatory events due to the infection, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, for instance after improvement of the hyposmic symptoms, or whether these are effects that will persist in the long term, remains to be investigated with additional follow up.

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Posted 19 Sep 2021

28 tweets bioRxiv neuroscience

Ekaterina O Morozova, Peter Newstein, Eve Marder

What features are important for circuit robustness? Reciprocal inhibition is a building block in many circuits. We used dynamic clamp to create reciprocally inhibitory circuits from GM neurons of the crab stomatogastric ganglion by injecting artificial synaptic and hyperpolarization-activated inward (H) currents. In "release", the active neuron controls the off/on transitions. In "escape", the inhibited neuron controls the transitions. We characterized the robustness of escape and release circuits to alterations in circuit parameters, temperature, and neuromodulation. Escape circuits rely on tight correlations between synaptic and H conductances to generate bursting but are resilient to temperature increase. Release circuits are robust to variations in synaptic and H conductances but fragile to temperature increase. The modulatory current (IMI) restores oscillations in release circuits but has little effect in escape. Thus, the same perturbation can have dramatically different effects depending on the circuits' mechanism of operation that may not be observable from circuit output.

14: Competing Health Risks Associated with the COVID-19 Pandemic and Response: A Scoping Review
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Posted 08 Jan 2021

Competing Health Risks Associated with the COVID-19 Pandemic and Response: A Scoping Review
28 tweets medRxiv epidemiology

Stefan Baral, Amrita Rao, Jean Olivier Twahirwa Rwema, Carrie Lyons, Muge Cevik, Anna E. Kågesten, Daouda Diouf, Annette H Sohn, Refilwe Phaswana-Mafuya, Adeeba Kamarulzaman, Gregorio Millett, Julia L Marcus, Sharmistha Mishra

BackgroundCOVID-19 has rapidly emerged as a global public health threat with infections recorded in nearly every country. Responses to COVID-19 have varied in intensity and breadth, but generally have included domestic and international travel limitations, closure of non-essential businesses, and repurposing of health services. While these interventions have focused on testing, treatment, and mitigation of COVID-19, there have been reports of interruptions to diagnostic, prevention, and treatment services for other public health threats. We conducted a scoping review to characterize the impact of COVID-19 on HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition. MethodsA scoping literature review was completed using searches of PubMed and preprint servers (medRxiv/bioRxiv) from January 1st to October 31st, 2020, using Medical Subject Headings (MeSH) terms related to SARS-CoV-2 or COVID-19 and HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition. Empiric studies reporting original data collection and mathematical models were included, and available data synthesized by region. Studies were excluded if they were not written in English. ResultsA total of 1604 published papers and 205 preprints met inclusion criteria, including 8.2% (132/1604) of published studies and 10.2% (21/205) of preprints: 7.3% (68/931) on HIV, 7.1% (24/339) on tuberculosis, 11.6% (26/224) on malaria, 7.8% (13/166) on sexual and reproductive health, and 12.1% (16/132) on malnutrition. Thematic results were similar across competing health risks, with substantial indirect effects of the COVID-19 pandemic and response on diagnostic, prevention, and treatment services for HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition. DiscussionCOVID-19 emerged in the context of existing public health threats that result in millions of deaths every year. Thus, effectively responding to COVID-19 while minimizing the negative impacts of COVID-19 necessitates innovation and integration of existing programs that are often siloed across health systems. Inequities have been a consistent driver of existing health threats; COVID-19 has worsened disparities, reinforcing the need for programs that address structural risks. Data reviewed here suggest that effective strengthening of health systems should include investment in public health with adequate funding to ensure continuity of care for emergent and existing public health threats.

15: Infectious SARS-CoV-2 in Exhaled Aerosols and Efficacy of Masks During Early Mild Infection
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Posted 13 Aug 2021

Infectious SARS-CoV-2 in Exhaled Aerosols and Efficacy of Masks During Early Mild Infection
27 tweets medRxiv infectious diseases

Oluwasanmi Oladapo Adenaiye, Jianyu Lai, P. Jacob Bueno de Mesquita, Filbert H. Hong, Somayeh Youssefi, Jennifer Rebecca German, S.-H. Sheldon Tai, Barbara Jean Albert, Maria Schanz, Stuart Weston, Jun Hang, Christian K. Fung, Hye Kyung Chung, Kristen K. Coleman, Nicolae Sapoval, Todd J Treangen, Irina Maljkovic Berry, Kristin E. Mullins, Matthew Frieman, Tianzhou Ma, Donald K. Milton, University of Maryland StopCOVID Research Group

Background: SARS-CoV-2 epidemiology implicates airborne transmission; mask source-control efficacy for, variant impact on, and infectiousness of aerosols are not well understood. Methods: We recruited COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. We quantified and sequenced viral RNA, cultured virus, and assayed sera for anti-spike and anti-receptor binding domain antibodies. Results: We enrolled 61 participants with active infection, May 2020 through April 2021. Among 49 seronegative cases (mean days post onset 3.8 {+/-}2.1), we detected SARS-CoV-2 RNA in 45% of fine ([&ge;]5 m), 31% of coarse (>5 m) aerosols, and 65% of fomite samples overall and in all samples from four alpha variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols. The alpha variant was associated with a 43-fold (95% CI, 6.6 to 280-fold) increase in fine aerosol viral RNA that remained a significant 18-fold (95% CI, 3.4 to 92-fold) increase adjusting for viral RNA in saliva, in mid-turbinate swabs, and other potential confounders. Two fine aerosol samples, collected days 2-3 post illness onset, while participants wore masks, were culture-positive. Conclusion: SARS-CoV-2 is evolving toward more efficient airborne transmission and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.

16: Risk of Myocarditis from COVID-19 Infection in People Under Age 20: A Population-Based Analysis
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Posted 27 Jul 2021

Risk of Myocarditis from COVID-19 Infection in People Under Age 20: A Population-Based Analysis
27 tweets medRxiv public and global health

Mendel E Singer, Ira B. Taub, David C. Kaelber

Background There have been recent reports of myocarditis (including myocarditis, pericarditis or myopericarditis) as a side-effect of mRNA-based COVID-19 vaccines, particularly in young males. Less information is available regarding the risk of myocarditis from COVID-19 infection itself. Such data would be helpful in developing a complete risk-benefit analysis for this population. Methods A de-identified, limited data set was created from the TriNetX Research Network, aggregating electronic health records from 48 mostly large U.S. Healthcare Organizations (HCOs). Inclusion criteria were a first COVID-19 diagnosis during the April 1, 2020 - March 31, 2021 time period, with an outpatient visit 1 month to 2 years before, and another 6 months to 2 years before that. Analysis was stratified by sex and age (12-17, 12-15, 16-19). Patients were excluded for any prior cardiovascular condition. Primary outcome was an encounter diagnosis of myocarditis within 90 days following the index date. Rates of COVID-19 cases and myocarditis not identified in the system were estimated and the results adjusted accordingly. Wilson score intervals were used for 95% confidence intervals due to the very low probability outcome. Results For the 12-17-year-old male cohort, 6/6,846 (0.09%) patients developed myocarditis overall, with an adjusted rate per million of 876 cases (Wilson score interval 402 - 1,911). For the 12-15 and 16-19 male age groups, the adjusted rates per million were 601 (257 - 1,406) and 561 (240 - 1,313). For 12-17-year-old females, there were 3 (0.04%) cases of myocarditis of 7,361 patients. The adjusted rate was 213 (73 - 627) per million cases. For the 12-15- and 16-19-year-old female cohorts the adjusted rates per million cases were 235 (64 - 857) and 708 (359 - 1,397). The outcomes occurred either within 5 days (40.0%) or from 19-82 days (~60.0%). Conclusions Myocarditis (or pericarditis or myopericarditis) from primary COVID19 infection occurred at a rate as high as 450 per million in young males. Young males infected with the virus are up 6 times more likely to develop myocarditis as those who have received the vaccine.

17: The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses
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Posted 06 May 2021

The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses
26 tweets medRxiv infectious diseases

F. Konstantin Föhse, Büsranur Geckin, Gijs Overheul, Josephine van de Maat, Gizem Kilic, Ozlem Bulut, Helga Dijkstra, Heidi Lemmers, S. Andrei Sarlea, Maartje Reijnders, Jacobien Hoogerwerf, Jaap ten Oever, Elles Simonetti, Frank L van de Veerdonk, Leo A.B. Joosten, Bart L. Haagmans, Reinout van Crevel, Yang Li, Ronald P. van Rij, Corine GeurtsvanKessel, Marien I. de Jonge, Jorge Domínguez-Andrés, Mihai G. Netea

The mRNA-based BNT162b2 vaccine from Pfizer/BioNTech was the first registered COVID-19 vaccine and has been shown to be up to 95% effective in preventing SARS-CoV-2 infections. Little is known about the broad effects of the new class of mRNA vaccines, especially whether they have combined effects on innate and adaptive immune responses. Here we confirmed that BNT162b2 vaccination of healthy individuals induced effective humoral and cellular immunity against several SARS-CoV-2 variants. Interestingly, however, the BNT162b2 vaccine also modulated the production of inflammatory cytokines by innate immune cells upon stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli. The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination, while fungi-induced cytokine responses were stronger. In conclusion, the mRNA BNT162b2 vaccine induces complex functional reprogramming of innate immune responses, which should be considered in the development and use of this new class of vaccines.

18: Self-reported real-world safety and reactogenicity of COVID-19 vaccines: An international vaccine-recipient survey.
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Posted 08 Mar 2021

Self-reported real-world safety and reactogenicity of COVID-19 vaccines: An international vaccine-recipient survey.
25 tweets medRxiv public and global health

Alexander G. Mathioudakis, Murad Ghrew, Andrew Ustianowski, Shazaad Ahmad, Ray Borrow, Lida Pieretta Papavasileiou, Dimitrios Petrakis, Nawar Diar Bakerly

Background: The safety of COVID-19 vaccines has been demonstrated in selected populations in recent studies, but more data in specific groups is needed to inform vaccine choice and health policy. Objectives: An international, online survey was conducted to compare the safety, tolerability and reactogenicity of available COVID-19 vaccines in different recipient groups. Methods: This survey was launched in February 2021, for 11 days. Recipients of a first COVID-19 vaccine dose [&ge;]7 days prior to survey completion were eligible. The incidence and severity of vaccination side effects were assessed. Results: Survey was completed by 2,002 respondents, of whom 26.6% had prior COVID-19 infection (68.8% laboratory confirmed). Prior COVID-19 infection was associated with increased risk of any side effect (risk ratio 1.08, 95% confidence intervals [1.05-1.11]), fever (2.24 [1.86-2.70]), breathlessness (2.05 [1.28-3.29]), flu-like illness (1.78 [1.51-2.10]), fatigue (1.34 [1.20-1.49]) and local reactions (1.10 [1.06-1.15]). It was also associated with increased risk of severe side effects, leading to hospital care (1.56 [1.14-2.12]). While mRNA vaccines were associated with a higher incidence of any side effect (1.06 [1.01-1.11]) compared to viral vector-based vaccines, these were generally milder (p<0.001), mostly local reactions. Importantly, mRNA vaccine-recipients reported considerably lower incidence of systemic reactions (RR<0.6) including anaphylaxis, swelling, flu-like illness, breathlessness and fatigue, and of side effects requiring hospital care (0.42 [0.31-0.58]). Conclusion: For the first time, our study links prior COVID-19 illness with increased incidence of vaccination side effects and demonstrates that mRNA vaccines cause milder, less frequent systemic side effects, but more local reactions.

19: Phylogenomic systematics of the spotted skunks (Carnivora, Mephitidae, Spilogale): Additional species diversity and Pleistocene climate change as a major driver of diversification
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Posted 25 Oct 2020

Phylogenomic systematics of the spotted skunks (Carnivora, Mephitidae, Spilogale): Additional species diversity and Pleistocene climate change as a major driver of diversification
23 tweets bioRxiv evolutionary biology

Molly M. McDonough, Adam W Ferguson, Robert C. Dowler, Matthew Gompper, Jesus Maldonado

Four species of spotted skunks (Carnivora, Mephitidae, Spilogale ) are currently recognized: Spilogale angustifrons, S. gracilis, S. putorius, and S. pygmaea . Understanding species boundaries within this group is critical for effective conservation given that regional populations or subspecies (e.g., S. p. interrupta ) have experienced significant population declines. Further, there may be currently unrecognized diversity within this genus as some taxa (e.g., S. angustifrons ) and geographic regions (e.g., Central America) never have been assessed using DNA sequence data. We analyzed species limits and diversification patterns in spotted skunks using multilocus nuclear (ultraconserved elements) and mitochondrial (whole mitogenomes and single gene analysis) data sets from broad geographic sampling representing all currently recognized species and subspecies. We found a high degree of genetic divergence among Spilogale that reflects seven distinct species and eight unique mitochondrial lineages. Initial divergence between S. pygmaea and all other Spilogale occurred in the Early Pliocene (~ 5.0 million years ago) which was followed by subsequent diversification of the remaining Spilogale into an eastern and western lineage during the Early Pleistocene (~1.5 million years ago). These two lineages experienced temporally coincident patterns of diversification at ~0.66 and ~0.35 million years ago into two and ultimately three distinct evolutionary units, respectively. Diversification was confined almost entirely within the Pleistocene during a timeframe characterized by alternating glacial-interglacial cycles, with the origin of this diversity occurring in northeastern Mexico and the southwestern United States of America. Mitochondrial-nuclear discordance was recovered across three lineages in geographic regions consistent with secondary contact, including a distinct mitochondrial lineage confined to the Sonoran Desert. Our results have direct consequences for conservation of threatened populations, or species, as well as for our understanding of the evolution of delayed implantation in this enigmatic group of small carnivores. ### Competing Interest Statement The authors have declared no competing interest.

20: The Vaccination Threshold for SARS-CoV-2 Depends on the Indoor Setting and Room Ventilation
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Posted 29 Jul 2021

The Vaccination Threshold for SARS-CoV-2 Depends on the Indoor Setting and Room Ventilation
23 tweets medRxiv infectious diseases

Alex Mikszewski, Luca Stabile, Giorgio Buonanno, Lidia Morawska

Background: Effective vaccines are now available for SARS-CoV-2 in the second year of the COVID-19 pandemic, but there remains significant uncertainty surrounding the necessary vaccination rate to safely lift occupancy controls in public buildings and return to pre-pandemic norms. The aim of this paper is to estimate setting-specific vaccination thresholds for SARS-CoV-2 to prevent sustained community transmission using classical principles of airborne contagion modeling. We calculated the airborne infection risk in three settings, a classroom, prison cell block, and restaurant, at typical ventilation rates, and then the expected number of infections resulting from this risk at varying levels of occupant susceptibility to infection. Results: We estimate the vaccination threshold for control of SARS-CoV-2 to range from a low of 40% for a mechanically ventilation classroom to a high of 85% for a naturally ventilated restaurant. Conclusions: If vaccination rates are limited to a theoretical minimum of approximately two-thirds of the population, enhanced ventilation above minimum standards for acceptable air quality is needed to reduce the frequency and severity of SARS-CoV-2 superspreading events in high-risk indoor environments.

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