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  • COVID-19
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  • Frontiers in Microbiology

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Yoshihiro Yokoyama; Tomoko Ichiki; Tsukasa Yamakawa; Yoshihisa Tsuji; +5 Authors

    IntroductionPatients with COVID-19 have dysbiosis of the intestinal microbiota with altered metabolites in the stool. However, it remains unclear whether the differences among SARS-CoV-2 variants lead to differences in intestinal microbiota and metabolites. Thus, we compared the microbiome and metabolome changes for each SARS-CoV-2 variant in patients with COVID-19.Materials and methodsWe conducted a multicenter observational study of patients with COVID-19 and performed fecal microbiome, metabolome, and calprotectin analyses and compared the results among the different SARS-CoV-2 variants.ResultsTwenty-one patients with COVID-19 were enrolled and stratified according to the SARS-CoV-2 strain: six with the Alpha, 10 with the Delta, and five with the Omicron variant. Fecal microbiome analysis showed that α-diversity was reduced in the order of the Omicron, Delta, and Alpha variants (p = 0.07). Linear discriminant analysis revealed differences in the abundance of short-chain fatty acid-producing gut microbiota for each SARS-CoV-2 variant. Fecal metabolome analysis showed that the Omicron and Delta variants had markedly reduced propionic and lactic acid levels compared to the Alpha strain (p < 0.05).ConclusionThe intestinal microbiota of patients with COVID-19 varies depending on the SARS-CoV-2 variant. Dysbiosis of the intestinal microbiota due to differences in SARS-CoV-2 variants causes a decrease in intestinal short-chain fatty acids.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Microbi...arrow_drop_down
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    Frontiers in Microbiology
    Article . 2024
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Microbi...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Frontiers in Microbiology
      Article . 2024
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    Authors: Mirjana Novkovic; Bojana Banovic Djeri; Bojan Ristivojevic; Aleksandra Knezevic; +10 Authors

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has been evolving rapidly causing emergence of new variants and health uncertainties. Monitoring the evolution of the virus was of the utmost importance for public health interventions and the development of national and global mitigation strategies. Here, we report national data on the emergence of new variants, their distribution, and dynamics in a 3-year study conducted from March 2020 to the end of January 2023 in the Republic of Serbia. Nasopharyngeal and oropharyngeal swabs from 2,398 COVID-19-positive patients were collected and sequenced using three different next generation technologies: Oxford Nanopore, Ion Torrent, and DNBSeq. In the subset of 2,107 SARS-CoV-2 sequences which met the quality requirements, detection of mutations, assignment to SARS-CoV-2 lineages, and phylogenetic analysis were performed. During the 3-year period, we detected three variants of concern, namely, Alpha (5.6%), Delta (7.4%), and Omicron (70.3%) and one variant of interest—Omicron recombinant “Kraken” (XBB1.5) (&lt;1%), whereas 16.8% of the samples belonged to other SARS-CoV-2 (sub)lineages. The detected SARS-CoV-2 (sub)lineages resulted in eight COVID-19 pandemic waves in Serbia, which correspond to the pandemic waves reported in Europe and the United States. Wave dynamics in Serbia showed the most resemblance with the profile of pandemic waves in southern Europe, consistent with the southeastern European location of Serbia. The samples were assigned to sixteen SARS-CoV-2 Nextstrain clades: 20A, 20B, 20C, 20D, 20E, 20G, 20I, 21J, 21K, 21L, 22A, 22B, 22C, 22D, 22E, and 22F and six different Omicron recombinants (XZ, XAZ, XAS, XBB, XBF, and XBK). The 10 most common mutations detected in the coding and untranslated regions of the SARS-CoV-2 genomes included four mutations affecting the spike protein (S:D614G, S:T478K, S:P681H, and S:S477N) and one mutation at each of the following positions: 5′-untranslated region (5’UTR:241); N protein (N:RG203KR); NSP3 protein (NSP3:F106F); NSP4 protein (NSP4:T492I); NSP6 protein (NSP6: S106/G107/F108 - triple deletion), and NSP12b protein (NSP12b:P314L). This national-level study is the most comprehensive in terms of sequencing and genomic surveillance of SARS-CoV-2 during the pandemic in Serbia, highlighting the importance of establishing and maintaining good national practice for monitoring SARS-CoV-2 and other viruses circulating worldwide.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Microbi...arrow_drop_down
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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
    License: CC BY
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Frontiers in Microbiology
    Article . 2024
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
      License: CC BY
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Frontiers in Microbiology
      Article . 2024
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    Authors: Patricia Buendia; Krystal Fernandez; Castle Raley; Ali Rahnavard; +3 Authors

    IntroductionDuring the COVID-19 Delta variant surge, the CLAIRE cross-sectional study sampled saliva from 120 hospitalized patients, 116 of whom had a positive COVID-19 PCR test. Patients received antibiotics upon admission due to possible secondary bacterial infections, with patients at risk of sepsis receiving broad-spectrum antibiotics (BSA).MethodsThe saliva samples were analyzed with shotgun DNA metagenomics and respiratory RNA virome sequencing. Medical records for the period of hospitalization were obtained for all patients. Once hospitalization outcomes were known, patients were classified based on their COVID-19 disease severity and the antibiotics they received.ResultsOur study reveals that BSA regimens differentially impacted the human salivary microbiome and disease progression. 12 patients died and all of them received BSA. Significant associations were found between the composition of the COVID-19 saliva microbiome and BSA use, between SARS-CoV-2 genome coverage and severity of disease. We also found significant associations between the non-bacterial microbiome and severity of disease, with Candida albicans detected most frequently in critical patients. For patients who did not receive BSA before saliva sampling, our study suggests Staphylococcus aureus as a potential risk factor for sepsis.DiscussionOur results indicate that the course of the infection may be explained by both monitoring antibiotic treatment and profiling a patient’s salivary microbiome, establishing a compelling link between microbiome and the specific antibiotic type and timing of treatment. This approach can aid with emergency room triage and inpatient management but also requires a better understanding of and access to narrow-spectrum agents that target pathogenic bacteria.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Microbi...arrow_drop_down
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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
    License: CC BY
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Frontiers in Microbiology
    Article . 2024
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Microbi...arrow_drop_down
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
      License: CC BY
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Frontiers in Microbiology
      Article . 2024
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    Authors: Weimiao Lv; Weimiao Lv; Weimiao Lv; Zichen Li; +6 Authors

    Tunneling nanotubes (TNTs) are actin-rich intercellular conduits that mediate distant cell-to-cell communication and enable the transfer of various cargos, including proteins, organelles, and virions. They play vital roles in both physiological and pathological processes. In this review, we focus on TNTs in different types of viruses, including retroviruses such as HIV, HTLV, influenza A, herpesvirus, paramyxovirus, alphavirus and SARS-CoV-2. We summarize the viral proteins responsible for inducing TNT formation and explore how these virus-induced TNTs facilitate intercellular communication, thereby promoting viral spread. Furthermore, we highlight other virus infections that can induce TNT-like structures, facilitating the dissemination of viruses. Moreover, TNTs promote intercellular spread of certain viruses even in the presence of neutralizing antibodies and antiviral drugs, posing significant challenges in combating viral infections. Understanding the mechanisms underlying viral spread via TNTs provides valuable insights into potential drug targets and contributes to the development of effective therapies for viral infections.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Microbi...arrow_drop_down
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    Frontiers in Microbiology
    Article . 2024
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Microbi...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Frontiers in Microbiology
      Article . 2024
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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    Authors: Gang Liu; Min Zhang; Baolei Wu; Cheng Zhang; +20 Authors

    Several animal models have been used to assist the development of vaccines and therapeutics since the COVID-19 outbreak. Due to the lack of binding affinity of mouse angiotensin-converting enzyme II (ACE2) to the S protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), increasing the susceptibility of mice to SARS-CoV-2 infection was considered in several ways. Here, we generated a COVID-19 mouse model expressing human ACE2 (hACE2) under the control of the CAG promoter. Overexpression of hACE2 did not pose a significant effect on weight growth. After SARS-CoV-2 inoculation, mice showed obvious viral replication and production of inflammation within 7 days, with a gradual decrease in body weight until death. Virological testing found that the virus can replicate in the respiratory system, small intestine, and brain. Additionally, this mouse model was applied to compare two antibody drug candidates, the anti-RBD antibody (MW06) and the mouse CD24-conjugated anti-RBD antibody (mCD24-MW06). Differences in antiviral effects between these two antibodies can be demonstrated in this mouse model when a challenge dose that invalidates the anti-RBD antibody treatment was used. This study provided a new mouse model for studying SARS-CoV-2 pathogenesis and evaluating potential interventions.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Microbi...arrow_drop_down
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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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    Frontiers in Microbiology
    Article . 2024
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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    Authors: Ilana S. Fratty; Ilana S. Fratty; Menucha Jurkowicz; Menucha Jurkowicz; +13 Authors

    IntroductionFollowing the significant decrease in SARS-CoV-2 cases worldwide, Israel, as well as other countries, have again been faced with a rise in seasonal influenza. This study compared circulating influenza A and B in hospitalized patients in Israel with the influenza strains in the vaccine following the 2021–2022 winter season which was dominated by the omicron variant.MethodsNasopharyngeal samples of 16,325 patients were examined for the detection of influenza A(H1N1)pdm09, influenza A(H1N1)pdm09 and influenza B. Phylogenetic trees of hemagglutinin were then prepared using sanger sequencing. Vaccine immunogenicity was also performed using the hemagglutination inhibition test.ResultsOf the 16,325 nasopharyngeal samples collected from hospitalized patients between September 2021 (Week 40) and April 2023 (Week 15), 7.5% were found to be positive for influenza. Phylogenetic analyses show that in the 2021–2022 winter season, the leading virus subtype was influenza A(H3N2), belonging to clade 3C.2a1b.2a.2. However, the following winter season was dominated by influenza A(H1N1)pdm09, which belongs to clade 6B.aA.5a.2. The circulating influenza A(H1N1)pdm09 strain showed a shift from the vaccine strain, while the co-circulating influenza A(H3N2) and influenza B strains were similar to those of the vaccine. Antigenic analysis coincided with the sequence analysis.DiscussionInfluenza prevalence during 2022–2023 returned to typical levels as seen prior to the emergence of SARS-CoV-2, which may suggest a gradual viral adaptation to SARS-CoV-2 variants. Domination of influenza A(H1N1)pdm09 was observed uniquely in Israel compared to Europe and USA and phylogenetic and antigenic analysis showed lower recognition of the vaccine with the circulating influenza A(H1N1)pdm09 in Israel compared to the vaccine.

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    Frontiers in Microbiology
    Article . 2024
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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    Authors: Rui Yang; Rui Yang; Xin Guan; Ziguang Niu; +9 Authors

    IntroductionThe Omicron variant has rapidly spread throughout the world compared to the Delta variant and poses a great threat to global healthcare systems due to its immune evasion and rapid spread. Sex has been identified as a factor significantly associated with COVID-19 mortality, but it remains unclear which clinical indicators could be identified as risk factors in each sex group and which sex-specific risk factors might shape the worse clinical outcome, especially for Omicrons. This study aimed to confirm the relationship between sex and the progression of the Omicron variant and to explore its sex-biased risk factors.MethodsWe conducted a retrospective study including 1,132 hospitalized patients with the COVID-19 Omicron variant from 5 December 2022 to 25 January 2023 at Shanghai General Hospital, and the medical history data and clinical index data of the inpatients for possible sex differences were compared and analyzed. Then, a sex-specific Lasso regression was performed to select the variables significantly associated with critical illness, including intensive care unit admission, invasive mechanical ventilation, or death. A logistic regression was used to construct a sex-specific predictive model distinctively for the critical illness outcome using selected covariates.ResultsAmong the collected 115 clinical indicators, up to 72 showed significant sex differences, including the difference in merit and the proportion of people with abnormalities. More importantly, males had greater critical illness (28.4% vs. 19.9%) and a significantly higher intensive care unit occupancy (20.96% vs. 14.49%) and mortality (13.2% vs. 4.9%), and males over 80 showed worse outcomes than females. Predictive models (AUC: 0.861 for males and 0.898 for females) showed 12 risk factors for males and 10 for females. Through a comprehensive sex-stratified analysis of a large cohort of hospitalized Omicron-infected patients, we identified the specific risk factors for critical illness by developing prediction models.DiscussionSex disparities and the identified risk factors should be considered, especially in the personalized prevention and treatment of the COVID-19 Omicron variant.

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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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    Frontiers in Microbiology
    Article . 2024
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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    Authors: Gayatri Gogoi; Gayatri Gogoi; Sarangthem Dinamani Singh; Emon Kalyan; +11 Authors

    Wastewater-based epidemiology (WBE) has been used for monitoring infectious diseases like polio, hepatitis, etc. since the 1940s. It is also being used for tracking the SARS-CoV-2 at the population level. This article aims to compile and assess the information for the qualitative and quantitative detection of the SARS-CoV-2 in wastewater. Based on the globally published studies, we highlight the importance of monitoring SARS-CoV-2 presence/detection in the wastewater and concurrently emphasize the development of early surveillance techniques. SARS-CoV-2 RNA sheds in the human feces, saliva, sputum and mucus that ultimately reaches to the wastewater and brings viral RNA into it. For the detection of the virus in the wastewater, different detection techniques have been optimized and are in use. These are based on serological, biosensor, targeted PCR, and next generation sequencing for whole genome sequencing or targeted amplicon sequencing. The presence of the SARS-CoV-2 RNA in wastewater could be used as a potential tool for early detection and devising the strategies for eradication of the virus before it is spread in the community. Additionally, with the right and timely understanding of viral behavior in the environment, an accurate and instructive model that leverages WBE-derived data may be created. This might help with the creation of technological tools and doable plans of action to lessen the negative effects of current viral epidemics or future potential outbreaks on public health and the economy. Further work toward whether presence of viral load correlates with its ability to induce infection, still needs evidence. The current increasing incidences of JN.1 variant is a case in point for continued early detection and surveillance, including wastewater.

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    Frontiers in Microbiology
    Article . 2024
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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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    Authors: Shailender Negi; Diksha; Deepjyoti Kalita; Neeraj Ranakoti; +5 Authors

    India had faced three waves throughout the Coronavirus disease 2019 (COVID-19) pandemic, which had already impacted economic lives and affected the healthcare setting and infrastructure. The widespread impacts have inspired researchers to look for clinical indicators of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prognosis. Cyclic threshold values have been used to correlate the viral load in COVID-19 patients and for viral transmission. In light of this correlation, a retrospective study was conducted to assess the trend of viral load in clinical and demographic profiles across the three waves. Data of a total of 11,125 COVID-19-positive patients were obtained, which had a Ct value of &lt;35. We stratified Ct values as follows: under 25 (high viral load), 25–30 (moderate viral load), and over 30 (low viral load). We found a significantly high proportion of patients with high viral load during the second wave. A significantly high viral load across the symptomatic and vaccinated populations was found in all three waves, whereas a significantly high viral load across age groups was found only in the first wave. With the widespread availability of real-time PCR and the limited use of genomic surveillance, the Ct value and viral load could be a suitable tool for population-level monitoring and forecasting.

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    Frontiers in Microbiology
    Article . 2024
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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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    Authors: Davide Mangioni; Davide Mangioni; Valeria Fox; Paola Saltini; +22 Authors

    BackgroundGroup A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in 2022 a sharp increase of GAS was reported globally.MethodsGAS strains collected in 09/2022–03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed. Clinical/epidemiological data were combined with whole-genome sequencing to: (i) define resistome/virulome, (ii) identify putative transmission chains, (iii) explore associations between emm-types and clinical severity.ResultsTwenty-eight isolates were available, 19/28 (67.9%) from adults and 9/28 (32.1%) from pediatric population. The criteria for iGAS were met by 19/28 cases (67.9%), of which 11/19 (39.3%) met the further criteria for severe-iGAS. Pediatric cases were mainly non-invasive infections (8/9, 88.9%), adult cases were iGAS and severe-iGAS in 18/19 (94.7%) and 10/19 (52.6%), respectively. Thirteen emm-types were detected, the most prevalent being emm1 and emm12 (6/28 strains each, 21.4%). Single nucleotide polymorphism (SNP) analysis of emm1.0 and emm12.0 strains revealed pairwise SNP distance always &gt;10, inconsistent with unique transmission chains. Emm12.0-type, found to almost exclusively carry virulence factors speH and speI, was mainly detected in children and in no-iGAS infections (55.6 vs. 5.3%, p = 0.007 and 66.7 vs. 0.0%, p &lt; 0.001, respectively), while emm1.0-type was mainly detected in severe-iGAS (0.0 vs. 45.5%, p = 0.045).ConclusionsThis study showed that multiple emm-types contributed to a 2022/2023 GAS infection increase in two hospitals in Milan, with no evidence of direct transmission chains. Specific emm-types could be associated with disease severity or invasiveness. Overall, these results support the integration of classical epidemiological studies with genomic investigation to appropriately manage severe infections and improve surveillance.

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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Yoshihiro Yokoyama; Tomoko Ichiki; Tsukasa Yamakawa; Yoshihisa Tsuji; +5 Authors

    IntroductionPatients with COVID-19 have dysbiosis of the intestinal microbiota with altered metabolites in the stool. However, it remains unclear whether the differences among SARS-CoV-2 variants lead to differences in intestinal microbiota and metabolites. Thus, we compared the microbiome and metabolome changes for each SARS-CoV-2 variant in patients with COVID-19.Materials and methodsWe conducted a multicenter observational study of patients with COVID-19 and performed fecal microbiome, metabolome, and calprotectin analyses and compared the results among the different SARS-CoV-2 variants.ResultsTwenty-one patients with COVID-19 were enrolled and stratified according to the SARS-CoV-2 strain: six with the Alpha, 10 with the Delta, and five with the Omicron variant. Fecal microbiome analysis showed that α-diversity was reduced in the order of the Omicron, Delta, and Alpha variants (p = 0.07). Linear discriminant analysis revealed differences in the abundance of short-chain fatty acid-producing gut microbiota for each SARS-CoV-2 variant. Fecal metabolome analysis showed that the Omicron and Delta variants had markedly reduced propionic and lactic acid levels compared to the Alpha strain (p < 0.05).ConclusionThe intestinal microbiota of patients with COVID-19 varies depending on the SARS-CoV-2 variant. Dysbiosis of the intestinal microbiota due to differences in SARS-CoV-2 variants causes a decrease in intestinal short-chain fatty acids.

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    Authors: Mirjana Novkovic; Bojana Banovic Djeri; Bojan Ristivojevic; Aleksandra Knezevic; +10 Authors

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has been evolving rapidly causing emergence of new variants and health uncertainties. Monitoring the evolution of the virus was of the utmost importance for public health interventions and the development of national and global mitigation strategies. Here, we report national data on the emergence of new variants, their distribution, and dynamics in a 3-year study conducted from March 2020 to the end of January 2023 in the Republic of Serbia. Nasopharyngeal and oropharyngeal swabs from 2,398 COVID-19-positive patients were collected and sequenced using three different next generation technologies: Oxford Nanopore, Ion Torrent, and DNBSeq. In the subset of 2,107 SARS-CoV-2 sequences which met the quality requirements, detection of mutations, assignment to SARS-CoV-2 lineages, and phylogenetic analysis were performed. During the 3-year period, we detected three variants of concern, namely, Alpha (5.6%), Delta (7.4%), and Omicron (70.3%) and one variant of interest—Omicron recombinant “Kraken” (XBB1.5) (&lt;1%), whereas 16.8% of the samples belonged to other SARS-CoV-2 (sub)lineages. The detected SARS-CoV-2 (sub)lineages resulted in eight COVID-19 pandemic waves in Serbia, which correspond to the pandemic waves reported in Europe and the United States. Wave dynamics in Serbia showed the most resemblance with the profile of pandemic waves in southern Europe, consistent with the southeastern European location of Serbia. The samples were assigned to sixteen SARS-CoV-2 Nextstrain clades: 20A, 20B, 20C, 20D, 20E, 20G, 20I, 21J, 21K, 21L, 22A, 22B, 22C, 22D, 22E, and 22F and six different Omicron recombinants (XZ, XAZ, XAS, XBB, XBF, and XBK). The 10 most common mutations detected in the coding and untranslated regions of the SARS-CoV-2 genomes included four mutations affecting the spike protein (S:D614G, S:T478K, S:P681H, and S:S477N) and one mutation at each of the following positions: 5′-untranslated region (5’UTR:241); N protein (N:RG203KR); NSP3 protein (NSP3:F106F); NSP4 protein (NSP4:T492I); NSP6 protein (NSP6: S106/G107/F108 - triple deletion), and NSP12b protein (NSP12b:P314L). This national-level study is the most comprehensive in terms of sequencing and genomic surveillance of SARS-CoV-2 during the pandemic in Serbia, highlighting the importance of establishing and maintaining good national practice for monitoring SARS-CoV-2 and other viruses circulating worldwide.

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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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    Frontiers in Microbiology
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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    Authors: Patricia Buendia; Krystal Fernandez; Castle Raley; Ali Rahnavard; +3 Authors

    IntroductionDuring the COVID-19 Delta variant surge, the CLAIRE cross-sectional study sampled saliva from 120 hospitalized patients, 116 of whom had a positive COVID-19 PCR test. Patients received antibiotics upon admission due to possible secondary bacterial infections, with patients at risk of sepsis receiving broad-spectrum antibiotics (BSA).MethodsThe saliva samples were analyzed with shotgun DNA metagenomics and respiratory RNA virome sequencing. Medical records for the period of hospitalization were obtained for all patients. Once hospitalization outcomes were known, patients were classified based on their COVID-19 disease severity and the antibiotics they received.ResultsOur study reveals that BSA regimens differentially impacted the human salivary microbiome and disease progression. 12 patients died and all of them received BSA. Significant associations were found between the composition of the COVID-19 saliva microbiome and BSA use, between SARS-CoV-2 genome coverage and severity of disease. We also found significant associations between the non-bacterial microbiome and severity of disease, with Candida albicans detected most frequently in critical patients. For patients who did not receive BSA before saliva sampling, our study suggests Staphylococcus aureus as a potential risk factor for sepsis.DiscussionOur results indicate that the course of the infection may be explained by both monitoring antibiotic treatment and profiling a patient’s salivary microbiome, establishing a compelling link between microbiome and the specific antibiotic type and timing of treatment. This approach can aid with emergency room triage and inpatient management but also requires a better understanding of and access to narrow-spectrum agents that target pathogenic bacteria.

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    Frontiers in Microbiology
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    Frontiers in Microbiology
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
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    Authors: Weimiao Lv; Weimiao Lv; Weimiao Lv; Zichen Li; +6 Authors

    Tunneling nanotubes (TNTs) are actin-rich intercellular conduits that mediate distant cell-to-cell communication and enable the transfer of various cargos, including proteins, organelles, and virions. They play vital roles in both physiological and pathological processes. In this review, we focus on TNTs in different types of viruses, including retroviruses such as HIV, HTLV, influenza A, herpesvirus, paramyxovirus, alphavirus and SARS-CoV-2. We summarize the viral proteins responsible for inducing TNT formation and explore how these virus-induced TNTs facilitate intercellular communication, thereby promoting viral spread. Furthermore, we highlight other virus infections that can induce TNT-like structures, facilitating the dissemination of viruses. Moreover, TNTs promote intercellular spread of certain viruses even in the presence of neutralizing antibodies and antiviral drugs, posing significant challenges in combating viral infections. Understanding the mechanisms underlying viral spread via TNTs provides valuable insights into potential drug targets and contributes to the development of effective therapies for viral infections.

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    Frontiers in Microbiology
    Article . 2024
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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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      Frontiers in Microbiology
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    Authors: Gang Liu; Min Zhang; Baolei Wu; Cheng Zhang; +20 Authors

    Several animal models have been used to assist the development of vaccines and therapeutics since the COVID-19 outbreak. Due to the lack of binding affinity of mouse angiotensin-converting enzyme II (ACE2) to the S protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), increasing the susceptibility of mice to SARS-CoV-2 infection was considered in several ways. Here, we generated a COVID-19 mouse model expressing human ACE2 (hACE2) under the control of the CAG promoter. Overexpression of hACE2 did not pose a significant effect on weight growth. After SARS-CoV-2 inoculation, mice showed obvious viral replication and production of inflammation within 7 days, with a gradual decrease in body weight until death. Virological testing found that the virus can replicate in the respiratory system, small intestine, and brain. Additionally, this mouse model was applied to compare two antibody drug candidates, the anti-RBD antibody (MW06) and the mouse CD24-conjugated anti-RBD antibody (mCD24-MW06). Differences in antiviral effects between these two antibodies can be demonstrated in this mouse model when a challenge dose that invalidates the anti-RBD antibody treatment was used. This study provided a new mouse model for studying SARS-CoV-2 pathogenesis and evaluating potential interventions.

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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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    Frontiers in Microbiology
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      Frontiers in Microbiology
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      Frontiers in Microbiology
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    Authors: Ilana S. Fratty; Ilana S. Fratty; Menucha Jurkowicz; Menucha Jurkowicz; +13 Authors

    IntroductionFollowing the significant decrease in SARS-CoV-2 cases worldwide, Israel, as well as other countries, have again been faced with a rise in seasonal influenza. This study compared circulating influenza A and B in hospitalized patients in Israel with the influenza strains in the vaccine following the 2021–2022 winter season which was dominated by the omicron variant.MethodsNasopharyngeal samples of 16,325 patients were examined for the detection of influenza A(H1N1)pdm09, influenza A(H1N1)pdm09 and influenza B. Phylogenetic trees of hemagglutinin were then prepared using sanger sequencing. Vaccine immunogenicity was also performed using the hemagglutination inhibition test.ResultsOf the 16,325 nasopharyngeal samples collected from hospitalized patients between September 2021 (Week 40) and April 2023 (Week 15), 7.5% were found to be positive for influenza. Phylogenetic analyses show that in the 2021–2022 winter season, the leading virus subtype was influenza A(H3N2), belonging to clade 3C.2a1b.2a.2. However, the following winter season was dominated by influenza A(H1N1)pdm09, which belongs to clade 6B.aA.5a.2. The circulating influenza A(H1N1)pdm09 strain showed a shift from the vaccine strain, while the co-circulating influenza A(H3N2) and influenza B strains were similar to those of the vaccine. Antigenic analysis coincided with the sequence analysis.DiscussionInfluenza prevalence during 2022–2023 returned to typical levels as seen prior to the emergence of SARS-CoV-2, which may suggest a gradual viral adaptation to SARS-CoV-2 variants. Domination of influenza A(H1N1)pdm09 was observed uniquely in Israel compared to Europe and USA and phylogenetic and antigenic analysis showed lower recognition of the vaccine with the circulating influenza A(H1N1)pdm09 in Israel compared to the vaccine.

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    Frontiers in Microbiology
    Article . 2024
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    Frontiers in Microbiology
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      Frontiers in Microbiology
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    Authors: Rui Yang; Rui Yang; Xin Guan; Ziguang Niu; +9 Authors

    IntroductionThe Omicron variant has rapidly spread throughout the world compared to the Delta variant and poses a great threat to global healthcare systems due to its immune evasion and rapid spread. Sex has been identified as a factor significantly associated with COVID-19 mortality, but it remains unclear which clinical indicators could be identified as risk factors in each sex group and which sex-specific risk factors might shape the worse clinical outcome, especially for Omicrons. This study aimed to confirm the relationship between sex and the progression of the Omicron variant and to explore its sex-biased risk factors.MethodsWe conducted a retrospective study including 1,132 hospitalized patients with the COVID-19 Omicron variant from 5 December 2022 to 25 January 2023 at Shanghai General Hospital, and the medical history data and clinical index data of the inpatients for possible sex differences were compared and analyzed. Then, a sex-specific Lasso regression was performed to select the variables significantly associated with critical illness, including intensive care unit admission, invasive mechanical ventilation, or death. A logistic regression was used to construct a sex-specific predictive model distinctively for the critical illness outcome using selected covariates.ResultsAmong the collected 115 clinical indicators, up to 72 showed significant sex differences, including the difference in merit and the proportion of people with abnormalities. More importantly, males had greater critical illness (28.4% vs. 19.9%) and a significantly higher intensive care unit occupancy (20.96% vs. 14.49%) and mortality (13.2% vs. 4.9%), and males over 80 showed worse outcomes than females. Predictive models (AUC: 0.861 for males and 0.898 for females) showed 12 risk factors for males and 10 for females. Through a comprehensive sex-stratified analysis of a large cohort of hospitalized Omicron-infected patients, we identified the specific risk factors for critical illness by developing prediction models.DiscussionSex disparities and the identified risk factors should be considered, especially in the personalized prevention and treatment of the COVID-19 Omicron variant.

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    Frontiers in Microbiology
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    Frontiers in Microbiology
    Article . 2024
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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    Authors: Gayatri Gogoi; Gayatri Gogoi; Sarangthem Dinamani Singh; Emon Kalyan; +11 Authors

    Wastewater-based epidemiology (WBE) has been used for monitoring infectious diseases like polio, hepatitis, etc. since the 1940s. It is also being used for tracking the SARS-CoV-2 at the population level. This article aims to compile and assess the information for the qualitative and quantitative detection of the SARS-CoV-2 in wastewater. Based on the globally published studies, we highlight the importance of monitoring SARS-CoV-2 presence/detection in the wastewater and concurrently emphasize the development of early surveillance techniques. SARS-CoV-2 RNA sheds in the human feces, saliva, sputum and mucus that ultimately reaches to the wastewater and brings viral RNA into it. For the detection of the virus in the wastewater, different detection techniques have been optimized and are in use. These are based on serological, biosensor, targeted PCR, and next generation sequencing for whole genome sequencing or targeted amplicon sequencing. The presence of the SARS-CoV-2 RNA in wastewater could be used as a potential tool for early detection and devising the strategies for eradication of the virus before it is spread in the community. Additionally, with the right and timely understanding of viral behavior in the environment, an accurate and instructive model that leverages WBE-derived data may be created. This might help with the creation of technological tools and doable plans of action to lessen the negative effects of current viral epidemics or future potential outbreaks on public health and the economy. Further work toward whether presence of viral load correlates with its ability to induce infection, still needs evidence. The current increasing incidences of JN.1 variant is a case in point for continued early detection and surveillance, including wastewater.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Microbi...arrow_drop_down
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    Frontiers in Microbiology
    Article . 2024
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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    Authors: Shailender Negi; Diksha; Deepjyoti Kalita; Neeraj Ranakoti; +5 Authors

    India had faced three waves throughout the Coronavirus disease 2019 (COVID-19) pandemic, which had already impacted economic lives and affected the healthcare setting and infrastructure. The widespread impacts have inspired researchers to look for clinical indicators of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prognosis. Cyclic threshold values have been used to correlate the viral load in COVID-19 patients and for viral transmission. In light of this correlation, a retrospective study was conducted to assess the trend of viral load in clinical and demographic profiles across the three waves. Data of a total of 11,125 COVID-19-positive patients were obtained, which had a Ct value of &lt;35. We stratified Ct values as follows: under 25 (high viral load), 25–30 (moderate viral load), and over 30 (low viral load). We found a significantly high proportion of patients with high viral load during the second wave. A significantly high viral load across the symptomatic and vaccinated populations was found in all three waves, whereas a significantly high viral load across age groups was found only in the first wave. With the widespread availability of real-time PCR and the limited use of genomic surveillance, the Ct value and viral load could be a suitable tool for population-level monitoring and forecasting.

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    Frontiers in Microbiology
    Article . 2024
    Data sources: DOAJ
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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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    Authors: Davide Mangioni; Davide Mangioni; Valeria Fox; Paola Saltini; +22 Authors

    BackgroundGroup A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in 2022 a sharp increase of GAS was reported globally.MethodsGAS strains collected in 09/2022–03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed. Clinical/epidemiological data were combined with whole-genome sequencing to: (i) define resistome/virulome, (ii) identify putative transmission chains, (iii) explore associations between emm-types and clinical severity.ResultsTwenty-eight isolates were available, 19/28 (67.9%) from adults and 9/28 (32.1%) from pediatric population. The criteria for iGAS were met by 19/28 cases (67.9%), of which 11/19 (39.3%) met the further criteria for severe-iGAS. Pediatric cases were mainly non-invasive infections (8/9, 88.9%), adult cases were iGAS and severe-iGAS in 18/19 (94.7%) and 10/19 (52.6%), respectively. Thirteen emm-types were detected, the most prevalent being emm1 and emm12 (6/28 strains each, 21.4%). Single nucleotide polymorphism (SNP) analysis of emm1.0 and emm12.0 strains revealed pairwise SNP distance always &gt;10, inconsistent with unique transmission chains. Emm12.0-type, found to almost exclusively carry virulence factors speH and speI, was mainly detected in children and in no-iGAS infections (55.6 vs. 5.3%, p = 0.007 and 66.7 vs. 0.0%, p &lt; 0.001, respectively), while emm1.0-type was mainly detected in severe-iGAS (0.0 vs. 45.5%, p = 0.045).ConclusionsThis study showed that multiple emm-types contributed to a 2022/2023 GAS infection increase in two hospitals in Milan, with no evidence of direct transmission chains. Specific emm-types could be associated with disease severity or invasiveness. Overall, these results support the integration of classical epidemiological studies with genomic investigation to appropriately manage severe infections and improve surveillance.

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    Frontiers in Microbiology
    Article . 2024 . Peer-reviewed
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    Frontiers in Microbiology
    Article . 2024
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      Frontiers in Microbiology
      Article . 2024 . Peer-reviewed
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      Frontiers in Microbiology
      Article . 2024
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