Most tweeted biology preprints, last 24 hours
*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.
325 results found. For more information, click each entry to expand.
104 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
The SARS-CoV-2 Delta variant is highly transmissible and contains mutations that confer partial immune escape. We compared RT-PCR cycle threshold (Ct) data from 699 test-positive anterior nasal swab specimens from fully vaccinated (n = 310) or unvaccinated (n=389) individuals. We observed low Ct values (<25) in 212 of 310 fully vaccinated (68%) and 246 of 389 (63%) unvaccinated individuals. Testing a subset of these low-Ct samples revealed infectious SARS-CoV-2 in 15 of 17 specimens (88%) from unvaccinated individuals and 37 of 39 (95%) from vaccinated people. To determine whether infectious virus titers differed in vaccinated and unvaccinated persons, we performed plaque assays on an additional set of 48 samples with Ct <25, finding no difference in infectious virus titer between groups.
96 tweets bioRxiv evolutionary biology
The Japanese wolf (Canis lupus hodophilax Temminck, 1839) was a subspecies of the gray wolf that inhabited the Japanese Archipelago and became extinct 100-120 years ago. In this study, we determined the whole genomes of nine Japanese wolves from the 19th- early 20th centuries and 11 Japanese dogs and analyzed them along with both modern and ancient wolves and dogs. Genomic analyses indicate that the Japanese wolf was a unique subspecies of the gray wolf that was genetically distinct from both modern and ancient gray wolves, lacking gene flow with other gray wolves. A Phylogenetic tree that minimizes the effects of introgression shows that Japanese wolves are closest to the dog monophyletic group among the gray wolves. Moreover, Japanese wolves show significant genetic affinities with East Eurasian dogs. We estimated the level of introgression from the ancestor of the Japanese wolves to the ancestor of East Eurasian dogs that had occurred in the transitional period from the Pleistocene to the Holocene, at an early stage after divergence from West Eurasian dog lineages. Because of this introgression, Japanese wolf ancestry has been inherited by many dogs through admixture between East Eurasian dog lineages. As a result of this heredity, up to 5.5% of modern dog genomes throughout East Eurasia are derived from Japanese wolf ancestry.
68 tweets medRxiv infectious diseases
Background: Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. Methods: We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naive individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naive vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naive vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected. Conclusions: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.
44 tweets medRxiv infectious diseases
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.
35 tweets medRxiv infectious diseases
Charlotte B. Acharya, John Schrom, Anthea M Mitchell, David A Coil, Carina Marquez, Susana Rojas, Chung Yu Wang, Jamin Liu, Genay Pilarowski, Leslie Solis, Elizabeth Georgian, Maya Petersen, Joseph DeRisi, Richard Michelmore, Diane Havlir
We found no significant difference in cycle threshold values between vaccinated and unvaccinated, asymptomatic and symptomatic groups infected with SARS-CoV-2 Delta. Given the substantial proportion of asymptomatic vaccine breakthrough cases with high viral levels, interventions, including masking and testing, should be considered for all in settings with elevated COVID-19 transmission.
33 tweets medRxiv infectious diseases
Lydia Horndler, Pilar Delgado, Salvador Romero-Pinedo, Marina Quesada, Ivaylo Balabanov, Rocio Laguna-Goya, Patricia Almendro-Vazquez, Miguel A Llamas, Manuel Fresno, Estela Paz-Artal, Hisse M. van Santen, Stela Alvarez, Asuncion Olmo, Balbino Alarcon
The rapid development of vaccines to prevent infection by SARS-CoV-2 virus causing COVID-19 makes necessary to compare the capacity of the different vaccines in terms of development of a protective humoral response. Here, we have used a highly sensitive and reliable flow cytometry method to measure the titers of antibodies of the IgG1 isotype in blood of healthy volunteers after receiving one or two doses of the vaccines being administered in Spain. We took advantage of the multiplexed capacity of the method to measure simultaneously the reactivity of antibodies with the S protein of the original strain Wuhan and the variants B.1.1.7 (Alpha), B.1.617.2 (Delta) and B.1.617.1 (Kappa). We found significant differences in the titer of anti-S antibodies produced after a first dose of the vaccines ChAdOx1 nCov-19/AstraZeneca, mRNA-1273/Moderna, BNT162b2/Pfizer-BioNTech and Ad26.COV.S/Janssen. Most important, we found a relative reduction in the reactivity of the sera with the Alpha, Delta and Kappa variants, versus the Wuhan one, after the second boosting immunization. These data allow to make a comparison of different vaccines in terms of anti-S antibody generation and cast doubts about the convenience of repeatedly immunizing with the same S protein sequence.
27 tweets medRxiv infectious diseases
Background Pre-Delta, vaccination reduced SARS-CoV-2 transmission from individuals infected despite vaccination, potentially via reducing viral loads. While vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated individuals infected with Delta question how much vaccination prevents transmission. Methods We performed a retrospective observational cohort study of adult contacts of SARS-CoV-2-infected adult index cases using English contact testing data. We used multivariable Poisson regression to investigate associations between transmission and index case and contact vaccination, and how these vary with Alpha and Delta variants (classified using S-gene detection/calendar trends) and time since second vaccination. Results 54,667/146,243(37.4%) PCR-tested contacts of 108,498 index cases were PCR-positive. Two doses of BNT162b2 or ChAdOx1 vaccines in Alpha index cases were independently associated with reduced PCR-positivity in contacts (aRR, adjusted rate ratio vs. unvaccinated=0.32[95%CI 0.21-0.48] and 0.48[0.30-0.78] respectively). The Delta variant attenuated vaccine-associated reductions in transmission: two BNT162b2 doses reduced Delta transmission (aRR=0.50[0.39-0.65]), more than ChAdOx1 (aRR=0.76[0.70-0.82]). Variation in Ct values (indicative of viral load) explained 7-23% of vaccine-associated transmission reductions. Transmission reductions declined over time post-second vaccination, for Delta reaching similar levels to unvaccinated individuals by 12 weeks for ChAdOx1 and attenuating substantially for BNT162b2. Protection in contacts also declined in the 3 months post-second vaccination. Conclusions Vaccination reduces transmission of Delta, but by less than the Alpha variant. The impact of vaccination decreased over time. Factors other than PCR Ct values at diagnosis are important in understanding vaccine-associated transmission reductions. Booster vaccinations may help control transmission together with preventing infections.
24 tweets medRxiv public and global health
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.
24 tweets bioRxiv bioinformatics
Summary: Studying transcription using single-molecule RNA-FISH (smFISH) is a powerful method to gain insights into gene regulation on a single cell basis, which relies on accurate identification of sub-resolution fluorescent spots in microscopy images. Here we present Radial Symmetry-FISH (RS-FISH), which can robustly and quickly detect even close smFISH spots in two and three dimensions with high precision, allows interactive parameter tuning, and can easily be applied to large sets of images. Availability and implementation: RS-FISH is an open-source implementation written in Java/ImgLib2 and provided as a macro-scriptable Fiji plugin. Source code, tutorial, documentation, and example images are available at: https://github.com/PreibischLab/RadialSymmetryLocalization.
20 tweets bioRxiv neuroscience
Mario de la Fuente Revenga, Bohan Zhu, Christopher A. Guevara, Lynette B Naler, Justin M. Saunders, Zirui Zhou, Rudy Toneatti, Salvador Sierra, Jennifer T. Wolstenholme, Patrick M. Beardsley, George W. Huntley, Chang Lu, Javier Gonzalez-Maeso
Clinical evidence suggests a potential therapeutic effect of classic psychedelics for the treatment of depression. The most outstanding and distinct characteristic is the rapid and sustained antidepressant action with one single exposure to the drug. However, the biological substrates and key mediators of psychedelics enduring action remain unknown. Here, we show that a single administration of the psychedelic DOI produced fast-acting effects on frontal cortex dendritic spine structure and acceleration of fear extinction via the 5-HT2A receptor. Additionally, a single dose of DOI led to changes in chromatin organization particularly at enhancer regions of genes involved in synaptic assembly that stretched for days after the psychedelic exposure. DOI-induced alterations in neuronal epigenome overlapped with genetic loci associated with schizophrenia, depression and attention deficit hyperactivity disorder. Together, these data support the notion that epigenetic-driven changes in synaptic plasticity operate as the mechanistic substrate of psychedelics long-lasting antidepressant action but also warn on the limitations in individuals with underlying risk for psychosis.
20 tweets medRxiv infectious diseases
Marc Conrad Shamier, Alma Tostmann, Susanne Bogers, Janet De Wilde, Jeroen IJpelaar, Willemijn Van Der Kleij, Herbert De Jager, Bart Haagmans, Richard Molenkamp, Bas Oude Munnink, Carsten van Rossum, Janette Rahamat-Langendoen, Nannet Van Der Geest, Chantal Bleeker-Rovers, Heiman Wertheim, Marion Koopmans, Corine H Geurts van Kessel
SARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur. We analyzed the virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), using RT-PCR and virus culture. The delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, we demonstrate lower probability of infectious virus detection in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness. We conclude that rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases.
19 tweets medRxiv epidemiology
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.
19 tweets bioRxiv genomics
Mitchell R. Vollger, Xavi Guitart, Philip C. Dishuck, Ludovica Mercuri, William T. Harvey, Ariel Gershman, Mark Diekhans, Arvis Sulovari, Katherine M. Munson, Alexandra M. Lewis, Kendra Hoekzema, David Porubsky, Ruiyang Li, Sergey Nurk, Sergey Koren, Karen H Miga, Adam M. Phillippy, Winston Timp, Mario Ventura, Evan E. Eichler
Despite their importance in disease and evolution, highly identical segmental duplications (SDs) have been among the last regions of the human reference genome (GRCh38) to be finished. Based on a complete telomere-to-telomere human genome (T2T CHM13), we present the first comprehensive view of human SD organization. SDs account for nearly one-third of the additional sequence increasing the genome-wide estimate from 5.4% to 7.0% (218 Mbp). An analysis of 266 human genomes shows that 91% of the new T2T CHM13 SD sequence (68.3 Mbp) better represents human copy number. We find that SDs show increased single-nucleotide variation diversity when compared to unique regions; we characterize methylation signatures that correlate with duplicate gene transcription and predict 182 novel protein-coding gene candidates. We find that 63% (35.11/55.7 Mbp) of acrocentric chromosomes consist of SDs distinct from rDNA and satellite sequences. Acrocentric SDs are 1.75-fold longer (p=0.00034) than other SDs, are frequently shared with autosomal pericentromeric regions, and are heteromorphic among human chromosomes. Comparing long-read assemblies from other human (n=12) and nonhuman primate (n=5) genomes, we use the T2T CHM13 genome to systematically reconstruct the evolution and structural haplotype diversity of biomedically relevant (LPA, SMN) and duplicated genes (TBC1D3, SRGAP2C, ARHGAP11B) important in the expansion of the human frontal cortex. The analysis reveals unprecedented patterns of structural heterozygosity and massive evolutionary differences in SD organization between humans and their closest living relatives.
19 tweets medRxiv hematology
Adolfo Aleman, Oliver Van Oekelen, Bhaskar Upadhyaya, Sarita Agte, Katerina Kappes, Katherine Beach, Komal Srivastava, Charles R Gleason, PVI study group, Bo Wang, Tarek H Mouhieddine, Kevin Tuballes, Daniel Geanon, Zenab Khan, Ana S. Gonzalez-Reiche, Harm van Bakel, Konstantinos Mouskas, Nicole W. Simons, Alexander W Charney, Seunghee Kim-Schulze, Adeeb H Rahman, Emilia M. Sordillo, Florian M Krammer, Carlos Cordon-Cardo, Nina Bhardwaj, Sacha Gnjatic, Miriam Merad, Brian D. Brown, Larysa Sanchez, Ajai Chari, Sundar Jagannath, Viviana Simon, Ania Wajnberg, Samir Parekh
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly effective in healthy individuals. Patients with multiple myeloma (MM) are immunocompromised due to defects in humoral and cellular immunity as well as immunosuppressive therapies. The efficacy after two doses of SARS-CoV-2 mRNA vaccination in MM patients is currently unknown. Here, we report the case of a MM patient who developed a fatal SARS-CoV-2 infection after full vaccination while in remission after B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T treatment. We show that the patient failed to generate antibodies or SARS-CoV-2-specific B and T cell responses, highlighting the continued risk of severe coronavirus disease 2019 (COVID-19) in vaccine non-responders. In the largest cohort of vaccinated MM patients to date, we demonstrate that 15.9% lack SARS-CoV-2 spike antibody response more than 10 days after the second mRNA vaccine dose. The patients actively receiving MM treatment, especially on regimens containing anti-CD38 and anti-BCMA, have lower antibody responses compared to healthy controls. Thus, it is of critical importance to monitor this patient population for serological responses. Non-responders may benefit from ongoing public health measures and from urgent study of prophylactic treatments to prevent SARS-CoV-2 infection.
18 tweets medRxiv epidemiology
Objectives: Establishing the rate of post-vaccination cardiac myocarditis in the 12-15 and 16-17-year-old population in the context of their COVID-19 hospitalization risk is critical for developing a vaccination recommendation framework that balances harms with benefits for this patient demographic. Design, Setting and Participants: Using the Vaccine Adverse Event Reporting System (VAERS), this retrospective epidemiological assessment reviewed reports filed between January 1, 2021, and June 18, 2021, among adolescents ages 12-17 who received mRNA vaccination against COVID-19. Symptom search criteria included the words myocarditis, pericarditis, and myopericarditis to identify children with evidence of cardiac injury. The word troponin was a required element in the laboratory findings. Inclusion criteria were aligned with the CDC working case definition for probable myocarditis. Stratified cardiac adverse event (CAE) rates were reported for age, sex and vaccination dose number. A harm-benefit analysis was conducted using existing literature on COVID-19-related hospitalization risks in this demographic. Main outcome measures: 1) Stratified rates of mRNA vaccine-related myocarditis in adolescents age 12-15 and 16-17; and 2) harm-benefit analysis of vaccine-related CAEs in relation to COVID-19 hospitalization risk. Results: A total of 257 CAEs were identified. Rates per million following dose 2 among males were 162.2 (ages 12-15) and 94.0 (ages 16-17); among females, rates were 13.0 and 13.4 per million, respectively. For boys 12-15 without medical comorbidities receiving their second mRNA vaccination dose, the rate of CAE is 3.7-6.1 times higher than their 120-day COVID-19 hospitalization risk as of August 21, 2021 (7-day hospitalizations 1.5/100k population) and 2.6-4.3-fold higher at times of high weekly hospitalization risk (2.1/100k), such as during January 2021. For boys 16-17 without medical comorbidities, the rate of CAE is currently 2.1-3.5 times higher than their 120-day COVID-19 hospitalization risk, and 1.5-2.5 times higher at times of high weekly COVID-19 hospitalization. Conclusions: Post-vaccination CAE rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence. Further research into the severity and long-term sequelae of post-vaccination CAE is warranted. Quantification of the benefits of the second vaccination dose and vaccination in addition to natural immunity in this demographic may be indicated to minimize harm.
17 tweets bioRxiv neuroscience
Ingrid H.C.H.M. Philippens, Kinga P. Boszormenyi, Jacqueline A. Wubben, Zahra C Fagrouch, Nikki van Driel, Amber Q. Mayenburg, Diana Lozovagia, Eva Roos, Bernadette Schurink, Marianna Bugiani, Ronald E Bontrop, Jinte Middeldorp, Willy M Bogers, Lioe-Fee de Geus-Oei, Jan A.M. Langermans, Marieke A Stammes, Babs E Verstrepen, Ernst J Verschoor
SARS-CoV-2 may cause acute respiratory disease, but the infection can also initiate neurological symptoms. Here we show that SARS-CoV-2 infection causes brain inflammation in the macaque model. An increased metabolic activity in the pituitary gland of two macaques was observed by longitudinal positron emission tomography-computed tomography (PET-CT). Post-mortem analysis demonstrated infiltration of T-cells and activated microglia in the brain, and viral RNA was detected in brain tissues from one animal. We observed Lewy bodies in brains of all rhesus macaques. These data emphasize the virus' capability to induce neuropathology in this nonhuman primate model for SARS-CoV-2 infection. As in humans, Lewy body formation is an indication for the development of Parkinson's disease, this data represents a warning for potential long-term neurological effects after SARS-CoV-2 infection.
17 tweets medRxiv infectious diseases
F. Konstantin Föhse, Büsranur Geckin, Gijs J. 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 H Geurts van Kessel, 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.
16 tweets bioRxiv evolutionary biology
Hybridization and subsequent genetic introgression are now known to be common features of the histories of many species, including our own. Following hybridization, selection often purges introgressed DNA genome-wide. While mate choice can prevent hybridization in the first place, it is also known to play an important role in post-zygotic selection against hybrids, and thus the purging of introgressed DNA. However, this role is usually thought of as a direct one: a mating preference for conspecifics reduces the sexual fitness of hybrids, reducing the transmission of introgressed ancestry. Here, we explore a second, indirect role of mate choice as a barrier to gene flow. Under assortative mating, parents covary in their ancestry, causing ancestry to be "bundled" in their offspring and later generations. This bundling effect increases ancestry variance in the population, enhancing the efficiency with which post-zygotic selection purges introgressed DNA. Using whole-genome simulations, we show that the bundling effect can comprise a substantial portion of mate choice's overall effect as a post-zygotic barrier to gene flow, and that it is driven by ancestry covariances between and within maternally and paternally inherited genomes. We derive a simple method for estimating the impact of the bundling effect from standard measures of assortative mating. Applying this method to data from a diverse set of hybrid zones, we find that the bundling effect increases the purging of introgressed DNA by between 1.2-fold (in a baboon system with weak assortative mating) and 14-fold (in a swordtail system with strong assortative mating). Thus, the bundling effect of mate choice contributes substantially to the genetic isolation of species.
16 tweets bioRxiv microbiology
The Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) presents here a global collection of 15,211 Mycobacterium tuberculosis clinical isolates, all of which have undergone whole genome sequencing and have had their minimum inhibitory concentrations to 13 antitubercular drugs measured. The isolates represent five major M. tuberculosis lineages originating from 23 countries across four continents. 6,814 isolates were found resistant to at least one drug, including 2,129 samples fully satisfy the clinical definitions of RR/MDR, pre-XDR or XDR. Resistance status to eight antitubercular drugs can be accurately predicted using a genetic mutation catalogue for over 90% of the isolates. Furthermore, we show the presence of suspected resistance conferring mutations for isolates resistant to the newly introduced drugs bedaquiline, clofazimine, delamanid and linezolid. Finally, a case study of rifampicin mono-resistance is presented to showcase how this compendium could be used to advance our genetic understanding of rare resistance phenotypes and evaluate the likely performance of a widely used molecular diagnostic tool. It is hoped that this compendium, the largest M. tuberculosis matched phenotypic and genotypic dataset to date, will facilitate and inspire new research projects for years to come.
14 tweets medRxiv infectious diseases
Robert L Atmar, Kirsten E. Lyke, Meagan E Deming, Lisa A. Jackson, Angela R. Branche, Hana M. El Sahly, Christina A. Rostad, Judith M Martin, Christine Johnston, Richard E Rupp, Mark J Mulligan, Rebecca C Brady, Robert W Frenck, Martin Backer, Angelica C Kottkamp, Tara M Babu, Kumaravel Rajakumar, Srilatha Edupuganti, David Dobryzynski, Christine M. Posavad, Janet I Archer, Sonja Crandon, Seema U Nayak, Daniel Szydlo, Jillian Zemanek, Clara P Dominguez Islas, Elizabeth R. Brown, Mehul S Suthar, M. Juliana McElrath, Adrian B. McDermott, Sarah E O'Connell, David C. Montefiori, Amanda Eaton, Kathleen M. Neuzil, David S Stephens, Paul C. Roberts, John Beigel
Background: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. Methods: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-mcg, Janssen Ad26.COV2.S 5x1010 virus particles, or Pfizer-BioNTech BNT162b2 30-mcg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29. Results: 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 154 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations. Conclusion: Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.
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