Evidence of recurrent selection of mutations commonly found in SARS-CoV-2 variants of concern in viruses infecting immunocompromised patients.
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ABSTRACT:
SUBMITTER: Goes LR
PROVIDER: S-EPMC9362983 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
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Evidence of recurrent selection of mutations commonly found in SARS-CoV-2 variants of concern in viruses infecting immunocompromised patients.
Goes Livia R LR Siqueira Juliana D JD Garrido Marianne M MM Alves Brunna M BM Cicala Claudia C Arthos James J Viola João P B JPB Soares Marcelo A MA
Frontiers in microbiology 20220726
Chronically immunosuppressed patients infected with SARS-CoV-2 often experience prolonged virus shedding, and may pave the way to the emergence of mutations that render viral variants of concern (VOC) able to escape immune responses induced by natural infection or by vaccination. We report herein a SARS-CoV-2<sup>+</sup> cancer patient from the beginning of the COVID-19 pandemic whose virus quasispecies across multiple timepoints carried several immune escape mutations found in more contemporary ...[more]
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Project description:ImportanceThere are limited comparative data on the durability of neutralizing antibody (nAb) responses elicited by messenger RNA (mRNA) vaccines against the SARS-CoV-2 variants of concern (VOCs) in immunocompromised patients and healthy controls.ObjectiveTo assess the humoral responses after vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines.Design, setting, and participantsIn this prospective, longitudinal monocentric comparative effectiveness study conducted at the Lausanne University Hospital, binding IgG anti-spike antibody and nAb levels were measured at 1 week, 1 month, 3 months, and 6 months after vaccination with mRNA-1273 (24.6% of participants) or BNT162b2 (75.3% of participants).InterventionsAll participants received 2 doses of either mRNA-1273 or BNT162b2 vaccines 4 to 6 weeks apart.Main outcomes and measuresThe primary outcome of the study was the persistence of nAb responses against the original, nonvariant SARS-CoV-2 (2019-nCoV) and different VOCs at 6 months after vaccination. Key secondary outcomes were associations of the type of mRNA vaccine, the underlying disease, and the treatment with the response to vaccination.ResultsAmong the 841 participants enrolled between January 14 and August 8, 2021, the patient population comprised 637 participants (mean [SD] age, 61.8 [13.7] years; 386 [60.6%] female), and the healthy control population comprised 204 participants (mean [SD] age, 45.9 [12.0] years; 144 [70.6%] female). There were 399 patients with solid cancers, 101 with hematologic cancers, 38 with solid organ transplants, 99 with autoimmune diseases, and 204 healthy controls. More than 15 000 nAb determinations were performed against the original, nonvariant 2019-nCoV and the Alpha, Beta, Gamma, and Delta variants. The proportions of nAbs and their titers decreased in all study groups at 6 months after vaccination, with the greatest decreases for the Beta and Delta variants. For Beta, the proportion decreased to a median (SE) of 39.2% (5.5%) in those with hematologic cancers, 44.8% (2.7%) in those with solid cancers, 23.1% (8.3%) in those with solid organ transplants, and 22.7% (4.8%) in those with autoimmune diseases compared with 52.1% (4.2%) in healthy controls. For Delta, the proportions decreased to 41.8% (5.6%) in participants with hematologic cancer, 51.9% (2.7%) in those with solid cancers, 26.9% (8.7%) in those with solid organ transplants, and 30.7% (5.3%) in those with autoimmune diseases compared with 56.9% (4.1%) healthy controls. Neutralizing antibody titers decreased 3.5- to 5-fold between month 1 and month 6, and the estimated duration of response was greater and more durable among those participants vaccinated with mRNA-1273. In participants with solid cancers, the estimated duration of nAbs against the Beta variant was 221 days with mRNA-1273 and 146 days with BNT162b2, and against the Delta variant, it was 226 days with mRNA-1273 and 161 with BNT162b2. The estimated duration of nAbs in participants with hematologic cancers was 113 and 127 days against Beta and Delta variants, respectively.Conclusions and relevanceThis comparative effectiveness study suggests that approximately half of patients with hematologic cancers and solid cancers, about 70% of patients with solid organ transplants or autoimmune diseases, and 40% of healthy controls have lost nAbs against the circulating VOCs at 6 months after vaccination. These findings may be helpful for developing the best boosting vaccination schedule especially in immunocompromised patients.
| S-EPMC8914885 | biostudies-literature
Project description:Ever since their discovery just about 56 years ago in the cultivated mushroom Agaricus bisporus, many more viruses infecting fungi have been identified in a wide range of fungal taxa. With mostly being asymptomatic, especially the ones that are detrimental to their phytopathogenic hosts are intensively studied due to their considerable importance in developing novel plant protection measures. Contrary to the rapid accumulation of notable data on viruses of plant pathogenic microfungi, much less information have hitherto been obtained in regards to the viruses whose hosts are macrofungi. According to the current literature, only more than 80 distinct viruses bearing either linear dsRNA or linear positive sense ssRNA genome and infecting a total number of 34 macrofungal species represented with four Ascomycota and 30 Basidiomycota have been identified so far. Among these 34 macrofungal species, 14 are cultivated edible and wild edible mushroom species. According to the 10th ICTV (International Committee on Taxonomy of Viruses) Report, macrofungal viruses with linear dsRNA genome are classified into five families (Partitiviridae, Totiviridae, Chrysoviridae, Endornaviridae and Hypoviridae) and macrofungal viruses with linear positive sense ssRNA genome are classified into seven families (Betaflexiviridae, Gammaflexiviridae, Barnaviridae, Narnaviridae, Virgaviridae, Benyviridae and Tymoviridae). In this review, following a brief overview of some general characteristics of fungal viruses, an up to date knowledge on viruses infecting macrofungal hosts were presented by summarizing the previous, recent and prospective studies of the field.
| S-EPMC5877858 | biostudies-literature
Project description:Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014-2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.
| S-EPMC5087998 | biostudies-literature
Project description:BackgroundWhether or not a mutant allele in a population is under selection is an important issue in population genetics, and various neutrality tests have been invented so far to detect selection. However, detection of negative selection has been notoriously difficult, partly because negatively selected alleles are usually rare in the population and have little impact on either population dynamics or the shape of the gene genealogy. Recently, through studies of genetic disorders and genome-wide analyses, many structural variations were shown to occur recurrently in the population. Such "recurrent mutations" might be revealed as deleterious by exploiting the signal of negative selection in the gene genealogy enhanced by their recurrence.ResultsMotivated by the above idea, we devised two new test statistics. One is the total number of mutants at a recurrently mutating locus among sampled sequences, which is tested conditionally on the number of forward mutations mapped on the sequence genealogy. The other is the size of the most common class of identical-by-descent mutants in the sample, again tested conditionally on the number of forward mutations mapped on the sequence genealogy. To examine the performance of these two tests, we simulated recurrently mutated loci each flanked by sites with neutral single nucleotide polymorphisms (SNPs), with no recombination. Using neutral recurrent mutations as null models, we attempted to detect deleterious recurrent mutations. Our analyses demonstrated high powers of our new tests under constant population size, as well as their moderate power to detect selection in expanding populations. We also devised a new maximum parsimony algorithm that, given the states of the sampled sequences at a recurrently mutating locus and an incompletely resolved genealogy, enumerates mutation histories with a minimum number of mutations while partially resolving genealogical relationships when necessary.ConclusionsWith their considerably high powers to detect negative selection, our new neutrality tests may open new venues for dealing with the population genetics of recurrent mutations as well as help identifying some types of genetic disorders that may have escaped identification by currently existing methods.
| S-EPMC3661350 | biostudies-literature
Project description:Human noggin (NOG) is a responsible gene for multiple synostosis syndrome (SYNS1) and proximal symphalangism (SYM1), two conditions that are recently known to be within a wider range of clinical manifestations of stapes ankylosis with symphalangism. This study was performed to determine the range of phenotype caused by NOG mutations, using Japanese patients with various phenotypes including sporadic inherited SYM1, dominantly inherited SYM1, stapes ankylosis with broad thumb and toes (Teunissen and Cremer syndrome). In addition, 33 patients with typical otosclerosis (without symphalangism) were studied. Direct sequencing analysis disclosed three novel mutations of the NOG gene in three SYM1 families. None of the otosclerosis patients without symphalangism had NOG mutations, indicating that NOG mutations may be restrictively found within patients with various skeletal abnormalities. These results together with the literature review indicated that there are no clear genotype-phenotype correlations for NOG mutations. With regard to surgical outcome, most of the patients in these three families with NOG mutations showed remarkable air-bone gap recovery after stapes surgery. Molecular genetic testing is useful to differentiate syndromic stapes ankylosis from otosclerosis, and even mild skeletal anomalies can be a diagnostic indicator of NOG-associated disease.
| S-EPMC3532604 | biostudies-literature
Project description:BackgroundMonoclonal antibodies (mAb) targeting SARS-CoV-2 are predominantly less effective against Omicron variants. Immunocompromised patients often experience prolonged viral shedding and are therefore at increased risk for viral escape mutations, when mAbs are used as monotherapy.MethodsIn an observational, prospective cohort, 57 patients infected with Omicron variants receiving sotrovimab alone or in combination with remdesivir were followed. The study endpoints were a decrease in SARS-CoV-2-RNA <106 copies/ml in nasopharyngeal swabs at day 21 and the emergence of resistance mutations at days 7, 14, and 21 after sotrovimab administration. All SARS-CoV-2 samples were analyzed by whole-genome sequencing, individual variants within the quasispecies were subsequently quantified and further characterized by a pseudovirus neutralization assay.Results47/57 patients (82.5%) were infected with Omicron/BA.1 and 10/57 (17.5%) with Omicron/BA.2. The vast majority of patients (43/57, 75.4%) were immunodeficient, predominantly due to immunosuppression after organ transplantation or hematologic malignancies. 21 days after sotrovimab administration, 12/43 (27.9%) of immunodeficient patients had prolonged viral shedding compared to 1/14 (7.1%) immunocompetent patients (p = 0.011). Longitudinal sequencing revealed that 14/43 (32.6%) immunodeficient patients had in part Omicron-specific viral spike protein mutations (e.g., P337S and/or E340D/V) that substantially reduced susceptibility to sotrovimab in a pseudovirus neutralization assay. Combination therapy with remdesivir significantly reduced the selection of escape variants.ConclusionsImmunocompromised patients face a considerable risk of prolonged viral shedding and emergence of escape mutations after early therapy with sotrovimab. These findings underscore the importance of careful monitoring and the need to conduct dedicated clinical trials for this patient population.
| S-EPMC9619606 | biostudies-literature
Project description:Intense transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Africa might promote emergence of variants. We describe 10 SARS-CoV-2 lineages in Benin during early 2021 that harbored mutations associated with variants of concern. Benin-derived SARS-CoV-2 strains were more efficiently neutralized by antibodies derived from vaccinees than patients, warranting accelerated vaccination in Africa.
| S-EPMC8544961 | biostudies-literature
Project description:Quantification of Spike cleavage across different Sars-Cov2 variants by partial reaction monitoring mass spectrometry
2022-02-22 | PXD027641 | Pride
Project description:Genome wide DNA methylation profiling of 4 cell populations purified from paediatic bronchoalveolar lavage samples. The cell types profiled are alveolar macrophages, granulocytes, lymphocytes and alveolar epithelial cells. Fluorescence-activated single cell sorting was used to purify the cell populations of interest using previously described methods (Shanthikumar, AJRCMB, 2020 ;63(2):152-159). Genome wide DNA methylation profiling was performed via the EPICArray. These data can be used for reference based deconvolution of cell proportion of bronchoalveolar lavage samples. DNA extracted from raw BAL (n=6) was also profiled using the EPICArray, allowing for validation of reference based deconvulution.
2021-10-09 | GSE185556 | GEO
Project description:The marine diatom Guinardia delicatula is a cosmopolitan species that dominates seasonal blooms in the English Channel and the North Sea. Several eukaryotic parasites are known to induce the mortality of this key-stone species. Here, we report the isolation and the characterization of the first viruses that infect G. delicatula. Viruses were isolated from the Western English Channel (SOMLIT-ASTAN station) during the late summer bloom decline of G. delicatula. A combination of laboratory approaches revealed that these lytic viruses (GdelRNAV) are small untailed particles of 35-38 nm in diameter that replicated in the host cytoplasm where both unordered particles and crystalline arrays were formed. GdelRNAV displayed a linear single-stranded RNA genome of ~9 kb, including two open reading frames encoding for replication and structural polyproteins. Phylogenetic relationships based on the RNA-dependent-RNA-polymerase gene marker showed that GdelRNAV were new members of the Bacillarnavirus, a monophyletic genus belonging to the order Picornavirales. GdelRNAV were specific to several strains of G. delicatula, they were produced rapidly (< 12h) and in numbers (9.34 x 104 virions per host cell). We recorded a substantial delay (72 h) between virions release and host cell lysis. Our analysis points to variable viral susceptibilities of the host during the early exponential growth phase. Interestingly, we consistently failed to isolate viruses during spring and early summer while G. delicatula developed rapid and massive blooms. While our study suggests that viruses do contribute to the decline of G. delicatula late summer bloom, they may not be the primary mortality agents during the remaining blooms at SOMLIT-ASTAN. Future studies should focus on the relative contribution of the viral and eukaryotic pathogens to the control of Guinardia blooms to understand the fate of these prominent organisms in marine systems.
2019-01-30 | PXD010967 | Pride