Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are ...urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.
The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa
. It has since spread to many countries and is expected to rapidly become dominant worldwide. The ...lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development
, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose.
Abstract
At the end of 2020, several new variants of SARS-CoV-2—designated variants of concern—were detected and quickly suspected to be associated with a higher transmissibility and possible escape ...of vaccine-induced immunity. In Belgium, this discovery has motivated the initiation of a more ambitious genomic surveillance program, which is drastically increasing the number of SARS-CoV-2 genomes to analyse for monitoring the circulation of viral lineages and variants of concern. In order to efficiently analyse the massive collection of genomic data that are the result of such increased sequencing efforts, streamlined analytical strategies are crucial. In this study, we illustrate how to efficiently map the spatio-temporal dispersal of target mutations at a regional level. As a proof of concept, we focus on the Belgian province of Liège that has been consistently sampled throughout 2020, but was also one of the main epicenters of the second European epidemic wave. Specifically, we employ a recently developed phylogeographic workflow to infer the regional dispersal history of viral lineages associated with three specific mutations on the spike protein (S98F, A222V and S477N) and to quantify their relative importance through time. Our analytical pipeline enables analysing large data sets and has the potential to be quickly applied and updated to track target mutations in space and time throughout the course of an epidemic.
•There are few reported studies on the occurrence of SARS-CoV-2 co-infection.•Whole-genome sequencing allows identification of SARS-CoV-2 variants causing coinfection.•Genomic evidence of ...co-infection with the Omicron and Delta variants is reported.
On November 24, 2021, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant assigned to the lineage B.1.1.529 (Omicron) was first reported to the World Health Organization from South Africa. Despite the co-circulation of several SARS-CoV-2 variants, co-infection by different variants is not commonly identified. Here, we report two cases of SARS-CoV-2 co-identifications with the Omicron and Delta variants.
We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus-infected patients. We studied the relationship between KIR-human leukocyte antigen (HLA) ...combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4-003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4-003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.
Ebolaviruses pose a substantial threat to wildlife populations and to public health in Africa. Evolutionary analyses of virus genome sequences can contribute significantly to elucidate the origin of ...new outbreaks, which can help guide surveillance efforts. The reconstructed between-outbreak evolutionary history of Zaire ebolavirus so far has been highly consistent. By removing the confounding impact of population growth bursts during local outbreaks on the free mixing assumption that underlies coalescent-based demographic reconstructions, we find-contrary to what previous results indicated-that the circulation dynamics of Ebola virus in its animal reservoir are highly uncertain. Our findings also accentuate the need for a more fine-grained picture of the Ebola virus diversity in its reservoir to reliably infer the reservoir origin of outbreak lineages. In addition, the recent appearance of slower-evolving variants is in line with latency as a survival mechanism and with bats as the natural reservoir host.
Background Hydroxychloroquine and chloroquine have been used for hospitalized coronavirus disease 2019 patients because of their antiviral and anti-inflammatory function. However, little research has ...been published on the impact of the immunomodulatory effect of (hydroxy)chloroquine on humoral immunity. Case presentation We report a case of symptomatic severe acute respiratory syndrome coronavirus 2 reinfection, diagnosed 141 days after the first episode, in a 56-year-old man of Black African origin treated with hydroxychloroquine for lupus erythematosus. No anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies could be detected 127 days after the initial episode of coronavirus disease 2019. Conclusions The treatment with hydroxychloroquine probably explains the decreased immune response with negative serology and subsequent reinfection in our patient. As humoral immunity is crucial to fight a severe acute respiratory syndrome coronavirus 2 infection, the use of (hydroxy)chloroquine is likely to have a detrimental effect on the spread of the virus. This case emphasizes that more needs to be learned about the role of antibodies in protecting against severe acute respiratory syndrome coronavirus 2 (re)infection and the role of (hydroxy)chloroquine on humoral immunity. Keywords: SARS-CoV-2, COVID-19, Reinfection, Hydroxychloroquine, Lupus, Case report
Abstract
Since the start of the COVID-19 pandemic, an unprecedented number of genomic sequences of SARS-CoV-2 have been generated and shared with the scientific community. The unparalleled volume of ...available genetic data presents a unique opportunity to gain real-time insights into the virus transmission during the pandemic, but also a daunting computational hurdle if analyzed with gold-standard phylogeographic approaches. To tackle this practical limitation, we here describe and apply a rapid analytical pipeline to analyze the spatiotemporal dispersal history and dynamics of SARS-CoV-2 lineages. As a proof of concept, we focus on the Belgian epidemic, which has had one of the highest spatial densities of available SARS-CoV-2 genomes. Our pipeline has the potential to be quickly applied to other countries or regions, with key benefits in complementing epidemiological analyses in assessing the impact of intervention measures or their progressive easement.
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