Chronic shedding of a SARS-CoV-2 Alpha variant in wastewater

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 13, 2024

Central Michigan University (CMU) participated in a state-wide SARS-CoV-2 wastewater monitoring program since 2021. Wastewater samples were collected from on-campus sites and nine off-campus treatment plants servicing small metropolitan rural communities. genome copies quantified using droplet digital PCR results reported to the health department.

Language: Английский

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The effects of amino acid substitution of spike protein and genomic recombination on the evolution of SARS-CoV-2

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: July 25, 2023

Over three years’ pandemic of 2019 novel coronavirus disease (COVID-19), multiple variants and subvariants have emerged successively, outcompeted earlier become predominant. The sequential emergence reflects the evolutionary process mutation-selection-adaption severe acute respiratory syndrome 2 (SARS-CoV-2). Amino acid substitution/insertion/deletion in spike protein causes altered viral antigenicity, transmissibility, pathogenicity SARS-CoV-2. Early pandemic, D614G mutation conferred virus with advantages over previous increased it also laid a conservative background for subsequent substantial mutations. role genomic recombination evolution SARS-CoV-2 raised increasing concern occurrence recombinants such as Deltacron, XBB.1.5, XBB.1.9.1, XBB.1.16 late phase pandemic. Co-circulation different co-infection immunocompromised patients accelerate recombinants. Surveillance variations, particularly recombination, is essential to identify ongoing changes genome antigenic epitopes thus leads development new vaccine strategies interventions.

Language: Английский

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Review: The Landscape of Antiviral Therapy for COVID-19 in the Era of Widespread Population Immunity and Omicron-Lineage Viruses

Clinical Infectious Diseases, Journal Year: 2023, Volume and Issue: 78(4), P. 908 - 917

Published: Nov. 9, 2023

Abstract The goals of coronavirus disease 2019 (COVID-19) antiviral therapy early in the pandemic were to prevent severe disease, hospitalization, and death. As these outcomes have become infrequent age widespread population immunity, objectives shifted. For general population, COVID-19–directed should decrease symptom severity duration minimize infectiousness, for immunocompromised individuals, reduce persistent infection. increased recognition virologic rebound following ritonavir-boosted nirmatrelvir (NMV/r) lack randomized controlled trial data showing benefit acute respiratory syndrome 2 (SARS-CoV-2) infection standard-risk, vaccinated individuals remain major knowledge gaps. Here, we review selected agents immunomodulators currently available or late-stage clinical trials use outpatients. We do not antibody products, convalescent plasma, systemic corticosteroids, IL-6 inhibitors, Janus kinase that Food Drug Administration approval emergency authorization are appropriate

Language: Английский

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Duration of SARS-CоV-2 virus shedding in COVID-19 patients with HIV infection

HIV Infection and Immunosuppressive Disorders, Journal Year: 2025, Volume and Issue: 16(4), P. 99 - 106

Published: Feb. 14, 2025

The aim: to describe the duration of SARS-CoV-2 virus shedding in patients with HIV infection and identify factors associated prolonged viral shedding. Materials methods: a prospective study, clinical laboratory characteristics COVID-19 were compared 170 patients, titers neutralizing antibodies SARSCoV-2 identified 68 patients; pathogen genotyping was performed 36 patients. Statistical analysis carried out using IBM SPSS Statistics package. Results discussion: there no significant differences varying severity grade COVID-19; negative relationship between titer revealed. In 35.9% (61 persons), persistence lasted for more than 21 days, this group characterized by an unfavorable course absence ART, significantly lower CD4 cell values higher load blood. Virus shown be longer B.1.1 strain versus other gene variants. Mutations Spike protein that increase infectious ability reduce its sensitivity found 4 Conclusion: did not affect infection. Long-term discovered severe immunodeficiency (CD4<200 cl/μl) ART. Patients pose epidemiological risk regard developing new mutational variants pathogen.

Language: Английский

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In Vitro Combinatorial Activity of Direct Acting Antivirals and Monoclonal Antibodies against the Ancestral B.1 and BQ.1.1 SARS-CoV-2 Viral Variants

Published: Jan. 3, 2024

Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection, however no clinical trial data are available and combined use direct acting antivirals (DAA) monoclonal antibodies (mAb) has been reported only anecdotally. To assess cooperative effects dual drug combinations vitro, we used a VERO E6 cell based vitro system with ancestral B.1 or highly divergent BQ.1.1 virus to test pairwise licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) active metabolite molnupiravir (EIDD-1931) as well combination RDV four mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested susceptible virus). According SynergyFinder 3.0 summary weighted scores, all had an additive effect. Within DAA/DAA combinations, paired scores variants were comparable. In post-hoc analysis weighting synergy by concentrations, several cases synergistic detected at specific both for RDV/mAb combinations. This was supported confirmation experiments showing more than linear shift effective concentration (IC50) increasing concentrations companion drug, although effect prominent but minimal null These results support which should further investigated animal models before introduction into clinic.

Language: Английский

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In Vitro Combinatorial Activity of Direct Acting Antivirals and Monoclonal Antibodies against the Ancestral B.1 and BQ.1.1 SARS-CoV-2 Viral Variants

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 168 - 168

Published: Jan. 23, 2024

Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection; however, no clinical trial data are available, and combined use direct-acting antivirals (DAA) monoclonal antibodies (mAb) has been reported only anecdotally. To assess cooperative effects dual drug combinations vitro, we used a VERO E6 cell-based vitro system with ancestral B.1 or highly divergent BQ.1.1 virus to test pairwise licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) active metabolite molnupiravir (EIDD-1931) as well combination RDV four mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested susceptible virus). According SynergyFinder 3.0 summary weighted scores, all had an additive effect. Within DAA/DAA combinations, paired scores variants were comparable. In post hoc analysis weighting synergy by concentrations, several cases synergistic detected at specific both for RDV/mAb combinations. This was supported confirmation experiments showing more than linear shift drug-effective concentration (IC50) increasing concentrations companion drug, although effect prominent minimal null These results support which should further investigated animal models before introduction into clinic.

Language: Английский

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Antiviral combination treatment strategies for SARS-CoV-2 infection in immunocompromised patients

Current Opinion in Infectious Diseases, Journal Year: 2024, Volume and Issue: 37(6), P. 506 - 517

Published: Oct. 23, 2024

Purpose of review The purpose this is to report the available evidence regarding use combination regimens antivirals and/or antibody-based therapy in treatment SARS-CoV-2 immunocompromised patients. Recent findings Literature search identified 24 articles, excluding single case reports, which included mainly patients with hematological malignancies B-cell depletion. Data were divided based on timing and reason for administration treatment, that is, early prevent progression severe COVID-19 prolonged or relapsed infection. We described treated populations, duration composition treatment. briefly addressed new options we proposed an algorithm management infection affected by malignancies. Summary Combination seems effective (73–100%) well tolerated (<5% reported bradycardia, hepatotoxicity, neutropenia) strategy treating prolonged/relapsed infections host, although its optimal cannot be defined currently evidence. role as at a high risk disease/persistent shedding requires further from comparison monotherapy, even though efficacy was combinations plus mAbs previous viral variants.

Language: Английский

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Current Progress in Genomic and Genetic Research on Human Viral Diseases

Frontiers research topics, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

it is a pioneering approach to the world of academia, radically improving way scholarly research managed.The grand vision Frontiers where all people have an equal opportunity seek, share and generate knowledge.Frontiers provides immediate permanent online open access its publications, but this alone not enough realize our goals. journal seriesThe series multi-tier interdisciplinary set openaccess, journals, promising paradigm shift from current review, selection dissemination processes in academic publishing.All journals are driven by researchers for researchers; therefore, they constitute service community.At same time, operates on revolutionary invention, tiered publishing system, initially addressing specific communities scholars, gradually climbing up broader public understanding, thus serving interests lay society, too. Dedication qualityEach article landmark highest quality, thanks genuinely collaborative interactions between authors review editors, who include some world's best academicians.Research must be certified peers before entering stream knowledge that may eventually reach -and shape society; only applies most rigorous unbiased reviews.Frontiers revolutionizes freely delivering outstanding research, evaluated with no bias both social point view.By applying advanced information technologies, catapulting into new generation.

Language: Английский

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Limited Short-Term Evolution of SARS-CoV-2 RNA-Dependent RNA Polymerase under Remdesivir Exposure in Upper Respiratory Compartments

Viruses, Journal Year: 2024, Volume and Issue: 16(10), P. 1511 - 1511

Published: Sept. 24, 2024

Background: The extent of the SARS-CoV-2 short-term evolution under Remdesivir (RDV) exposure and whether it varies across different upper respiratory compartments are not fully understood. Methods: Patients hospitalized for COVID-19, with or without RDV therapy, were enrolled completed up to three visits, in which they provided specimens from four compartments. Near full-length genome sequences obtained viral RNA, standard lineage variant assignments performed, mutations RNA-dependent RNA polymerase (RdRp) region—the target gene—were detected compared between participants RDV, compartments, within versus a larger sequence dataset. statistical analysis used generalized linear mixed-effects model. Results: A total 139 37 out 44 (84%) participants. genotyping success varied ranged 42% oropharyngeal 67% nasopharyngeal showed improvement higher loads. No RdRp known be associated resistance identified, 34 at 32 amino acid positions that as RDV-associated, there was no evidence any associations exposure, compartment, time. At least 1 these all participants, some differed Conclusions: This study highlighted genomic stability hosts suggests lack over contributes our understanding dynamics.

Language: Английский

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Wastewater sequencing from a rural community enables identification of widespread adaptive mutations in a SARS-CoV-2 Alpha variant

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Abstract Background Central Michigan University (CMU) participated in a state-wide wastewater monitoring program starting 2021. One rural site consistently produced higher concentrations of SARS-CoV-2 genome copies. Samples from this were sequenced retrospectively and exclusively contained derivative Alpha variant lineage B.1.1.7 that shed the same for 20-28 months. Results Complete reconstruction each open reading frame (ORF) alignment to an early clinical isolate identified novel mutations selected non-structural (nsp1, nsp2, nsp3, nsp4, nsp5/3CLpro, nsp6, RdRp, nsp15, nsp16, ORF3a, ORF6, ORF7a, ORF7b) structural genes (Spike, M, N). These rare have not accumulated samples worldwide. Mutational analysis revealed divergence reference sequence over time. We present on available models discuss potential role these during chronic infection. Conclusions This study further supports small treatment plants can enhance resolution events facilitate viral genomes due relative lack contaminating sequences identifies may be associated with infections.

Language: Английский

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