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| Open AccessDistinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion
SARS-CoV-2 evolved into several sublineages harboring different mutations in spike. Here, the authors isolate and characterize nine SARS-CoV-2 variants and show that EG.5.1.3 has highest fitness in nasal epithelial cells, while JN.1 shows lower affinity to ACE2 and higher immune evasion compared to BA.2.86.1.
- Delphine Planas
- , Isabelle Staropoli
- & Olivier Schwartz
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Article
| Open AccessInhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2
Inhibiting SARS-CoV-2 interaction with ACE2 is a promising antiviral strategy. Here, the authors show that exosomes derived from human lung spheroid cells expressing hACE2 accumulate in the lung following prophylactic inhalation to bind and neutralize SARS-CoV-2 and protect mice from SARS-CoV-2-induced disease.
- Zhenzhen Wang
- , Shiqi Hu
- & Ke Cheng
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Article
| Open AccessN6-methyladenosine modification is not a general trait of viral RNA genomes
A comprehensive analysis found no evidence of m6A modifications in the genome of the cytoplasmic RNA viruses CHIKV and DENV, challenging the current notion that m6A modification is a general feature of cytoplasmic RNA viruses.
- Belinda Baquero-Pérez
- , Ivaylo D. Yonchev
- & Juana Díez
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| Open AccessQuantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
SARS-CoV-2 variants with mutations in spike have emerged during the pandemic. Magaret et al. show that in Latin America, efficacy of the Ad26.COV2.S vaccine against moderate to severe–critical COVID-19 varied by sequence features, antibody escape scores, and neutralization impacting features of the SARS-CoV-2 variant.
- Craig A. Magaret
- , Li Li
- & Peter B. Gilbert
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Article
| Open AccessImpact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study
SARS-CoV-2 infection is associated with an increased risk of arterial and venous thrombotic events. Here, the authors investigate the degree to which this association is modified by virus variant and vaccination using electronic health record data for ~18 million adults in England.
- Genevieve I. Cezard
- , Rachel E. Denholm
- & Venexia Walker
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Article
| Open AccessDrivers and impact of the early silent invasion of SARS-CoV-2 Alpha
The SARS-CoV-2 Alpha variant of concern emerged in the UK in late 2020 but spread internationally before it was detected. Here, the authors reconstruct the dynamics of dissemination of this variant out of the UK by combining extent of genomic sequencing, travel volume, and local epidemic dynamics in a Bayesian model.
- Benjamin Faucher
- , Chiara E. Sabbatini
- & Chiara Poletto
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Article
| Open AccessPMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness
Glucose metabolism is crucial for cellular energy regulation and affects the immune response. Here the authors show that nutritional supplementation of mannose may be beneficial during virus infections by rewiring glucose metabolic dysregulation and alleviating inflammatory tissue damage.
- Ronghui Liang
- , Zi-Wei Ye
- & Shuofeng Yuan
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Article
| Open AccessNFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins
The immunobiology regulating the contribution of monocytes to severe COVID-19 immunopathology are not fully understood. Here the authors show that SARS-CoV-2 S1 and NP proteins differentially promote NLRP3/NLRC4 inflammasome activity, differentiation, and T cell-priming function of monocytes.
- Ilya Tsukalov
- , Ildefonso Sánchez-Cerrillo
- & Enrique Martin-Gayo
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Article
| Open AccessComparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States
The optimal frequency of COVID-19 booster vaccination is unclear. Here, the authors use a microsimulation model to assess the impact of different vaccine schedules on severe disease and show that regular boosters have large benefits for older and immunocompromised individuals but less so for younger age groups.
- Hailey J. Park
- , Gregg S. Gonsalves
- & Nathan C. Lo
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Article
| Open AccessSARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle
SARS-CoV-2 uses the host endolysosomal system for replication and egress. Here the authors show that SARS-CoV-2 virulence factor ORF3a localizes to the late endocytic compartments of the host cell to disrupt Rab7 GTP to GDP cycling and block lysosome function in cargo degradation, while activated Rab7 promotes virus replication.
- Kshitiz Walia
- , Abhishek Sharma
- & Amit Tuli
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Article
| Open AccessNeuronal miR-9 promotes HSV-1 epigenetic silencing and latency by repressing Oct-1 and Onecut family genes
Here, the authors identify neuron-specific miR-9 that potentially blocks HSV-1 neuronal replication by targeting host OCT-1 and ONECUT transcription factors involved in epigenetic activation of HSV-1 productive-cycle genes. Thus miR-9 promotes viral epigenetic silencing and latent infection in neurons.
- Yue Deng
- , Yuqi Lin
- & Dongli Pan
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Article
| Open AccessFrequency, kinetics and determinants of viable SARS-CoV-2 in bioaerosols from ambulatory COVID-19 patients infected with the Beta, Delta or Omicron variants
SARS-CoV-2 can be spread by aerosols. Here the authors show that between 50-60% of ambulatory COVID-19 patients exhale culturable virus and that this is associated with lower neutralizing antibody titers and suppression of immune related transcriptomic pathways.
- S. Jaumdally
- , M. Tomasicchio
- & K. Dheda
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Article
| Open AccessTransmission and dynamics of mother-infant gut viruses during pregnancy and early life
Gut ecosystem colonization impacts lifelong health. Here, authors track mother-infant gut viruses over time, reveal feeding’s influence on early viral colonization, and demonstrate the co-transmission of bacteriophages and bacteria from mothers to infants.
- Sanzhima Garmaeva
- , Trishla Sinha
- & Alexandra Zhernakova
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Article
| Open AccessInequalities in healthcare use during the COVID-19 pandemic
An indirect impact of the COVID-19 pandemic was a decline in healthcare utilisation for other conditions. Here, the authors quantify this decline in the Netherlands and show that impacts were greater for individuals with lower household income, females, older people, and those with a migrant background.
- Arun Frey
- , Andrea M. Tilstra
- & Mark D. Verhagen
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Article
| Open AccessExploring the gut DNA virome in fecal immunochemical test stool samples reveals associations with lifestyle in a large population-based study
Here, the authors use fecal immunochemical test (FIT) samples from around 1000 individuals to characterize their gut virome, showing a diverse viral community, indicative of the individual lifestyle (smoking, fiber consumption and physical activity), thus highlighting FIT samples as a useful alternative for virome analyses.
- Paula Istvan
- , Einar Birkeland
- & Trine B. Rounge
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Article
| Open AccessAltered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein
New variants of SARS-CoV-2 virus can evolve such that antibodies that recognised previous versions are not able to recognise newer versions. Here the authors characterise antibody binding to the XBB.1.5 variant and how antibodies and T cells from persons infected with earlier versions of SARS-CoV-2 are able to recognise and/or bind to the XBB.1.5 spike protein.
- Dhiraj Mannar
- , James W. Saville
- & Sriram Subramaniam
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Article
| Open AccessDispersion patterns of SARS-CoV-2 variants Gamma, Lambda and Mu in Latin America and the Caribbean
Genomic surveillance has been important for tracking the evolution and spread of SARS-CoV-2. Here, the authors analyse ~300,000 SARS-CoV-2 genomes from two years of sequencing in the Latin America and Caribbean regions and describe the emergence and spread of different lineages over time.
- Tiago Gräf
- , Alexander A. Martinez
- & Juliana Almeida Leite
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Article
| Open AccessCoordinated inflammatory responses dictate Marburg virus control by reservoir bats
The authors show pro-inflammatory responses are needed for Marburg virus control in its natural bat reservoir, and that if reduced, humanlike disease and shedding results, suggesting that natural immunomodulatory stressors may increase spillover risk.
- Jonathan C. Guito
- , Shannon G. M. Kirejczyk
- & Jonathan S. Towner
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Article
| Open AccessHuman cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells
Human cytomegalovirus (HCMV) is a ubiquitous pathogen associated with morbidity and mortality in the immunocompromised or immunonaive context. Here the authors show that HCMV exploits STING signalling and subverts the interferon response to support infection of monocyte derive dendritic cells.
- Bibiana Costa
- , Jennifer Becker
- & Ulrich Kalinke
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Article
| Open AccessPersistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection
The long-term health consequences of COVID-19 infection are not fully understood. In this retrospective cohort study from Hong Kong, the authors describe changes in the risk of various clinical outcomes including all-cause mortality for one year following COVID-19 infection and how they vary by vaccination status.
- Ivan Chun Hang Lam
- , Ran Zhang
- & Eric Yuk Fai Wan
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Article
| Open AccessNucleocapsid protein-specific monoclonal antibodies protect mice against Crimean-Congo hemorrhagic fever virus
There are limited treatment options for infection with Crimean-Congo hemorrhagic fever virus in humans. Here, the authors show that a monoclonal antibody targeting the highly conserved viral nucleocapsid protein provides protective effects in a mouse model of infection.
- Aura R. Garrison
- , Vanessa Moresco
- & Joseph W. Golden
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Article
| Open AccessPrior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection
Flavivirus infection or vaccination can induce cross-reactive immune responses. Here, the authors show how previous immunization with the tick-borne encephalitis virus vaccine affects the immune response to the yellow fever vaccine, suggesting that the yellow fever vaccine virus conceals epitopes shared with other flaviviruses in flavivirus-naive but not flavivirus-pre-exposed individuals.
- Antonio Santos-Peral
- , Fabian Luppa
- & Simon Rothenfusser
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Article
| Open AccessRandomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients
In this clinical trial, the authors show that a 5-day molnupiravir treatment reduces SARS-CoV-2 viral load in at-risk outpatients by day 5 but mostly fails to clear virus, leads to lower spike antibody response by day 14 and higher virus mutation rates.
- Joseph F. Standing
- , Laura Buggiotti
- & Francis Yongblah
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Article
| Open AccessGlobal evaluation of lineage-specific human papillomavirus capsid antigenicity using antibodies elicited by natural infection
Human Papillomaviruses (HPV) are classified in lineages based on their sequence. Here, the authors test neutralizing activity of sera from naturally infected women against vaccine-preventable HPV variants, delineating lineage-specific antibody responses.
- Gathoni Kamuyu
- , Filomeno Coelho da Silva
- & Simon Beddows
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Article
| Open AccessStructure of the recombinant RNA polymerase from African Swine Fever Virus
Pilotto and colleagues produce recombinant and catalytically active RNA polymerase (RNAP) from African Swine Fever Virus. Cryo-EM structures of RNAP with closed and open clamp conformations are presented along with in vitro transcription assays, yielding distinct functional conclusions.
- Simona Pilotto
- , Michal Sýkora
- & Finn Werner
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Article
| Open AccessPrefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge
Broadly protective vaccines are needed to combat current and future human coronaviruses. Here the authors use structure-based design to engineer spike S2-only antigens that provide partial protection from sarbecovirus challenge in mice.
- Ching-Lin Hsieh
- , Sarah R. Leist
- & Jason S. McLellan
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Article
| Open AccessDemographic and Clinical Factors Associated With SARS-CoV-2 Spike 1 Antibody Response Among Vaccinated US Adults: the C4R Study
The antibody response to COVID-19 vaccines varies among individuals. Here the authors find that older age, male sex, smoking, higher BMI, vaccine type, and certain comorbidities are associated with lower anti-S1 antibody levels after COVID-19 vaccinations, indicating that certain groups might benefit from higher frequency or doses of vaccination.
- John S. Kim
- , Yifei Sun
- & Elizabeth C. Oelsner
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Article
| Open AccessHijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus
The oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) is known to reprogram cellular metabolism. Here, Wan et al show that viral Cyclin exploits host nucleotide synthesis and glycolysis to support KSHV pathogenesis.
- Quanyuan Wan
- , Leah Tavakoli
- & Jun Zhao
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Article
| Open AccessBroad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine
Evolution of SARS-CoV-2 and emergence of other sarbecoviruses are of potential concern. Here, the authors designed a trivalent spike-protein-nanoparticle vaccine that elicits neutralizing antibodies and protects female hamsters against challenges with SARS-CoV-2-like and SARS-CoV-1-like coronaviruses.
- Peter J. Halfmann
- , Kathryn Loeffler
- & Ravi S. Kane
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Article
| Open AccessEvaluating vector competence for Yellow fever in the Caribbean
Yellow fever is a public health threat in the Americas but has not recently been reported in the Caribbean despite presence of the mosquito vector Aedes aegypti. Here, the authors show through experimental infection that populations of Aedes aegypti from the Caribbean and surrounding areas are competent of yellow fever transmission.
- Gaelle Gabiane
- , Chloé Bohers
- & Anna-Bella Failloux
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Article
| Open AccessT-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms
Endogenous retroviruses (ERV) can induce immune responses and the control of these viruses uses immune mechanisms also involved in autoimmunity. Here, the authors characterize the control of ERVs in mice and show age-associated B cell control and nucleic acid sensing TLR pathway involvement.
- Eileen Rauch
- , Timm Amendt
- & Philipp Yu
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Article
| Open AccessComparative effectiveness of alternative intervals between first and second doses of the mRNA COVID-19 vaccines
The optimal timing between first and second mRNA COVID-19 vaccine doses has not been established. Here, the authors use electronic health record data from Georgia, USA in a target trial emulation study to estimate vaccine effectiveness against infection for different dose intervals.
- Kayoko Shioda
- , Alexander Breskin
- & Elizabeth T. Rogawski McQuade
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Article
| Open AccessTherapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets
Measles virus infection causes immunosuppression and it’s unclear whether this can be prevented by antivirals. Here, using a canine distemper virus ferret model, the authors show that measles-like immune amnesia and lethal exacerbated respiratory disease after consecutive respiratory virus infections can be mitigated by oral antiviral therapy initiated at the onset of primary clinical signs.
- Robert M. Cox
- , Josef D. Wolf
- & Richard K. Plemper
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Article
| Open AccessVirological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant
XBB.1.5 of SARS-CoV-2 is a descendant of XBB.1 and has mutations in spike and ORF8, making it more infectious to humans. Here, the authors examined in detail the differences in virological properties of the two variants.
- Tomokazu Tamura
- , Takashi Irie
- & Takasuke Fukuhara
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Article
| Open AccessDrug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor
There is a need for effective antiviral drugs against RSV infection. Conducting an RSV repurposing screen using the ReFRAME library Sake et al. identify lonafarnib as an RSV fusion protein inhibitor, characterize its binding site within the viral protein and show its antiviral effects in a mouse model.
- Svenja M. Sake
- , Xiaoyu Zhang
- & Thomas Pietschmann
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Article
| Open AccessContribution of climate change to the spatial expansion of West Nile virus in Europe
West Nile Virus is emerging as an important pathogen in Europe, likely driven by recent climate and land-use changes. Here, the authors estimate the extent of the climate change-driven impact by modelling the change in West Nile Virus ecological suitability across the continent in the absence of climate change.
- Diana Erazo
- , Luke Grant
- & Simon Dellicour
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Article
| Open AccessSkin muscle is the initial site of viral replication for arboviral bunyavirus infection
Here, the authors provide evidence that, unlike other arboviruses, the initial site of orthobunyavirus replication is the panniculus carnosus muscle layer within the skin. However, virus infection does not damage or kill these cells, allowing them to produce virus over a longer period of time.
- Christine A. Schneider
- , Jacqueline M. Leung
- & Karin E. Peterson
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Article
| Open AccessA phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome
Invariant natural killer T (iNKT) cells recognize abnormal cells, but their T cell receptor is not variable and kill cancerous or infected target cells without MHC I restriction. Here, the authors show that in a clinical trial, donor-unrestricted allogeneic iNKT cells could be safely administered to human COVID-19 patients suffering from acute respiratory distress syndrome and trigger an anti-inflammatory response.
- Terese C. Hammond
- , Marco A. Purbhoo
- & Mark A. Exley
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Article
| Open AccessThe host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
The cellular RNA polymerase II C-terminal domain is known to support transcription of influenza virus mRNAs. Here, Krischuns et al. use cell-based and in vitro approaches to demonstrate that it also plays a role in replication of the viral genome.
- Tim Krischuns
- , Benoît Arragain
- & Nadia Naffakh
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Article
| Open AccessIsolation and characterization of a pangolin-borne HKU4-related coronavirus that potentially infects human-DPP4-transgenic mice
Pangolins are a potential reservoir for viruses with cross-species infection potential. Here, the authors characterize a HKU4-related coronavirus isolated from pangolin and demonstrate its ability to infect human cell lines as well as its potential to infect transgenic mice expressing the human receptor DPP4.
- Luo-Yuan Xia
- , Zhen-Fei Wang
- & Wu-Chun Cao
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Article
| Open AccessAn intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission
In this study, the authors evaluated the protective capacity of a mucosal, live-attenuated SARS-CoV-2 vaccine and show that it induces systemic and mucosal humoral immunity, protects from clinical disease symptoms, and prevents virus transmission in hamsters more efficiently than an intramuscular mRNA vaccine.
- Julia M. Adler
- , Ricardo Martin Vidal
- & Jakob Trimpert
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Article
| Open AccessA Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection
Here the authors show that a Gamma-based subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants including Omicron, induces cellular immune responses, and protects mice from infection with Omicron BA.5 SARS-CoV-2.
- Lorena M. Coria
- , Juan Manuel Rodriguez
- & Juliana Cassataro
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Article
| Open AccessRisk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population
The factors influencing risk of reinfection with SARS-CoV-2 are poorly understood. Here, the authors use data from the UK COVID-19 Infection Survey, a community based longitudinal study, to assess characteristics of ~45,000 reinfections compared to initial infections.
- Jia Wei
- , Nicole Stoesser
- & Chris Cunningham
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Article
| Open AccessSelective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats
The ecology of Ebola virus (EBOV) is still largely unclear. Here, the authors show that Angolan freetailed bats are selectively permissive to EBOV infection, but not to other filoviruses, and demonstrate EBOV placental tissue tropism indicating potential horizontal and vertical transmission between conspecifics.
- S. A. Riesle-Sbarbaro
- , G. Wibbelt
- & A. Kurth
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Article
| Open AccessDimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.
- Peter Sandercock
- , Janet Darbyshire
- & Martin J. Landray
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Article
| Open AccessOmicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue
Shi and Li et al. show that SARS-CoV-2 Omicron subvariants have increased capacity to infect primary human nasal tissue using a distinct entry route that depends on matrix metalloproteinases as opposed to TMPRSS2 used by previous variants, which enables evasion from antiviral factors.
- Guoli Shi
- , Tiansheng Li
- & Alex A. Compton
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Article
| Open AccessHumoral profiles of toddlers and young children following SARS-CoV-2 mRNA vaccination
Nziza et al. profile anti-SARS-CoV-2 antibody responses in infants and toddlers after mRNA vaccination and demonstrate a strong functional activation of humoral immunity in this age group when compared with adults and naturally infected children.
- Nadège Nziza
- , Yixiang Deng
- & Lael M. Yonker
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Article
| Open AccessThe cryo-EM structure of homotetrameric attachment glycoprotein from langya henipavirus
In this work, the authors report the full-length structure of the attachment glycoprotein from Langya Henipavirus, which could enhance the understanding of emerging Henipavirus and provide important clues for vaccine development in the future.
- Yingying Guo
- , Songyue Wu
- & Renhong Yan
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Article
| Open AccessHuman coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice
The origin of SARS-CoV-2 cross-reactive T cells in unexposed humans is unclear. Here, the authors use HLA transgenic mouse models of sequential infections with human coronavirus OC43 and SARSCoV-2 and show that OC43 elicits cross-protective immunity against SARS-CoV-2, which partially depends on CD4 + T cells.
- Rúbens Prince dos Santos Alves
- , Julia Timis
- & Sujan Shresta
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