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13 pages, 817 KiB  
Article
Etiology of Four Waves of the COVID-19 Pandemic in Ukraine according to the SARS-CoV-2 Virus Genome Sequencing Data: A Pilot Study
by Alla Mironenko, Ihor Kravchuk, Larysa Radchenko, Nataliia Teteriuk, Olha Holubka, Liudmyla Bolotova, Mykola Pydiura and Andriy Goy
Microbiol. Res. 2024, 15(2), 994-1006; https://doi.org/10.3390/microbiolres15020065 (registering DOI) - 13 Jun 2024
Abstract
The COVID-19 pandemic in Ukraine, from March 2020 to June 2022, witnessed distinct waves, each characterized by an increase in cases and fatalities. Next-generation sequencing has been used to understand the impact of viral variants on the pandemic situation in Ukraine. We analyzed [...] Read more.
The COVID-19 pandemic in Ukraine, from March 2020 to June 2022, witnessed distinct waves, each characterized by an increase in cases and fatalities. Next-generation sequencing has been used to understand the impact of viral variants on the pandemic situation in Ukraine. We analyzed SARS-CoV-2 genome sequencing data to identify viral variants circulating during each wave. By integrating epidemiological information, we established associations between viral variants and disease spread. The adoption of next-generation sequencing for SARS-CoV-2 surveillance in Ukraine, despite limited resources, yielded adequate and trustworthy results, reflecting the pandemic situation. After the Russian military invasion of Ukraine in February 2022, a large number of refugees crossed the border with neighboring countries. Mutation analysis on sequencing data from Ukraine and Poland was used to estimate the exchange of SARS-CoV-2 variants between the countries during this period. Omicron subvariants detected in both countries were similar. The analysis of SARS-CoV-2 sequences from Poland and Ukraine revealed shared nucleotide mutations that can be used to identify the directions of spreading. Full article
12 pages, 3300 KiB  
Article
Lysophosphatidylcholines Promote Influenza Virus Reproduction through the MAPK/JNK Pathway in PMA-Differentiated THP-1 Macrophages
by Min-Ho Cha, Hee-Jeong Choi and Jin-Yeul Ma
Int. J. Mol. Sci. 2024, 25(12), 6538; https://doi.org/10.3390/ijms25126538 (registering DOI) - 13 Jun 2024
Abstract
Obesity and metabolic syndrome alter serum lipid profiles. They also increase vulnerability to viral infections and worsen the survival rate and symptoms after infection. How serum lipids affect influenza virus proliferation is unclear. Here, we investigated the effects of lysophosphatidylcholines on influenza A [...] Read more.
Obesity and metabolic syndrome alter serum lipid profiles. They also increase vulnerability to viral infections and worsen the survival rate and symptoms after infection. How serum lipids affect influenza virus proliferation is unclear. Here, we investigated the effects of lysophosphatidylcholines on influenza A virus (IAV) proliferation. IAV particles in the culture medium were titrated using extraction-free quantitative PCR, and viral RNA and protein levels were assessed using real-time PCR and Western blot, respectively. RNA sequencing data were analyzed using PCA and heatmap analysis, and pathway analysis was performed using the KEGG mapper and PathIN tools. Statistical analysis was conducted using SPSS21.0. LPC treatment of THP-1 cells significantly increased IAV proliferation and IAV RNA and protein levels, and saturated LPC was more active in IAV RNA expression than unsaturated LPC was. The functional analysis of genes affected by LPCs showed that the expression of genes involved in IAV signaling, such as suppressor of cytokine signaling 3 (SOCS3), phosphoinositide-3-kinase regulatory subunit 3 (PI3K) and AKT serine/threonine kinase 3 (AKT3), Toll-like receptor 7 (TKR7), and interferon gamma receptor 1 (IFNGR1), was changed by LPC. Altered influenza A pathways were linked with MAPK and PI3K/AKT signaling. Treatment with inhibitors of MAPK or PI3K attenuated viral gene expression changes induced by LPCs. The present study shows that LPCs stimulated virus reproduction by modifying the cellular environment to one in which viruses proliferated better. This was mediated by the MAPK, JNK, and PI3K/AKT pathways. Further animal studies are needed to confirm the link between LPCs from serum or the respiratory system and IAV proliferation. Full article
(This article belongs to the Special Issue Lysophosphatidic Acid Signaling in Health and Disease)
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<p>Increase in IAV titer after LPC treatment. (<b>A</b>) Viability of THP-1 macrophages pretreated with different doses of LPCs and exposed to IAV for 24 or 36 h. (<b>B</b>) Number of virus particles released into the culture medium of cells treated with LPCs before IAV infection. Color boxs indicated control (□), IAV (■) and IAV with LPC (▒). (<b>C</b>) Relative quantification of the number of virus particles released into the culture medium at different times after IAV infection of cells pretreated with LPCs for 8 h. (<b>D</b>) Relative amount of viral genome in cells immediately after viral infection. THP-1 macrophages were treated with LPCs at the indicated concentrations for 8 h and then infected with IAV for 2 h. After replacing the medium with fresh medium, cells were incubated for the indicated times. Cell viability was determined using the CCK-8 assay, and IAV titer was detected using RT-qPCR. The data are representative of three independent experiments and are presented as means ± SDs of three independent experiments. Statistical significance was assessed using an unpaired Student <span class="html-italic">t</span>-test. *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.005, * <span class="html-italic">p</span> &lt; 0.05 compared with the values obtained for cells infected with IAV.</p>
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<p>Increase in viral RNA and protein levels by LPCs. (<b>A</b>) Relative expression levels of IAV genes in THP-1 cells treated with different dosages of LPCs. Color boxes indicated control (□), IAV (■) and IAV with LPC (▒). (<b>B</b>) The protein level of IAV proteins in THP-1 cells treated with LPCs. RNA levels were determined using RT-qPCR, and protein expression was detected using Western blotting. Data represent the means ± SDs of three independent experiments. Statistical significance was assessed using an unpaired Student <span class="html-italic">t</span>-test. *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.005, * <span class="html-italic">p</span> &lt; 0.05 compared with the values obtained for cells infected with IAV. M2: matrix-2; M1: matrix-1; PA: polymerase acidic protein; PB1: polymerase basic 1; NP: nucleoprotein; NS1: non-structural protein; PB2: polymerase basic 2; HA: hemagglutinin; NA: neuraminidase.</p>
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<p>Differential expression of viral RNAs according to the type of LPCs. The relative expression levels of IAV genes were determined using RT-qPCR. Data represent the means ± SDs of three independent experiments. Statistical significance was assessed using an unpaired Student <span class="html-italic">t</span>-test. *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.005, * <span class="html-italic">p</span> &lt; 0.05 compared with the values obtained for cells infected with IAV. Color boxes indicated control (□), IAV (■) and IAV with LPCs (▒). M2: matrix-2; M1: matrix-1; PA: polymerase acidic protein; PB1: polymerase basic 1; NP: nucleoprotein; NS1: non-structural protein; PB2: polymerase basic 2; HA: hemagglutinin; NA: neuraminidase.</p>
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<p>RNA expression profiles in THP-1 cells treated with LPCs. (<b>A</b>) PCA of RNA profiles in control cells and cells treated with 40 µM LPCs. (<b>B</b>) Heatmap of genes with a more than twofold expression changes in response to LPCs (<span class="html-italic">p</span> &lt; 0.01). Heatmap was obtained using ClustVis (<a href="https://biit.cs.ut.ee/clustvis/" target="_blank">https://biit.cs.ut.ee/clustvis/</a>; accessed on 2 November 2023). (<b>C</b>) KEGG pathway analysis of 1082 genes with decreased or enhanced expression in response to LPCs.</p>
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<p>Effects of LPCs on influenza A signaling pathways. (<b>A</b>) Genes involved in influenza A signaling pathways and altered by LPC treatment of THP-1 cells. Pink indicates genes of which the expression increased 2-fold upon LPC treatment, respectively. Green and yellow indicate genes with a more than 2- or 1.5-fold decrease in expression upon LPC treatment, respectively. (<b>B</b>) Interaction of pathways linked with influenza A signaling and affected by LPCs. (<b>C</b>) The protein level of p38, JNK, and AKT and their phosphorylated forms in THP-1 cells treated with LPCs. The protein expression was detected using Western blotting. p38: mitogen-activated protein kinase P38 alpha; JNK: C-Jun N-terminal kinase 1; AKT: AKT serine/threonine kinase 1.</p>
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<p>Attenuation of viral gene expression by MAP kinase inhibitor (SB203580), JNK inhibitor, and PI3K inhibitor (LY294002) in LPC-treated THP-1 cells. Relative expression levels of IAV genes were determined using RT-qPCR. Data represent the means ± SDs of three independent experiments. Statistical significance was assessed using an unpaired Student <span class="html-italic">t</span>-test. *** <span class="html-italic">p</span> &lt; 0.001 compared with values obtained for cells infected with IAV, # <span class="html-italic">p</span> &lt; 0.05 compared with values obtained for cells infected with IAV and treated with LPC. Color boxes indicated control (□), IAV (■) and IAV with LPC and inhibitors (▒). M2: matrix-2; M1: matrix-1; PA: polymerase acidic protein; PB1: polymerase basic 1; NP: nucleoprotein; NS1: non-structural protein; PB2: polymerase basic 2; HA: hemagglutinin; NA: neuraminidase.</p>
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12 pages, 1224 KiB  
Article
Protective Effects of Long Double-Stranded RNA with Different CpG Motifs against Miamiensis avidus and Viral Hemorrhagic Septicemia Virus (VHSV) Infections in Olive Flounder (Paralichthys olivaceus)
by Hee-Jae Choi, Da-Yeon Choi, Jung-Jin Park, Hye Jin Jung, Bo-Seong Kim, Sung-Chul Hong, Jun-Hwan Kim and Yue Jai Kang
Fishes 2024, 9(6), 227; https://doi.org/10.3390/fishes9060227 - 13 Jun 2024
Abstract
The South Korean aquaculture industry has incurred considerable production losses due to various infectious diseases. Artificially synthesized polyinosinic–polycytidylic acid (poly I:C), structurally similar to double-stranded RNA (dsRNA) and cytidine–phosphate–guanosine oligodeoxynucleotides, can enhance immune responses and protect against diseases. Here, we investigated dsRNA molecules [...] Read more.
The South Korean aquaculture industry has incurred considerable production losses due to various infectious diseases. Artificially synthesized polyinosinic–polycytidylic acid (poly I:C), structurally similar to double-stranded RNA (dsRNA) and cytidine–phosphate–guanosine oligodeoxynucleotides, can enhance immune responses and protect against diseases. Here, we investigated dsRNA molecules with different cytidine–phosphate–guanosine (CpG) motifs (dsRNA-CpGMix) as fused agents to treat Miamiensis avidus and viral hemorrhagic septicemia virus (VHSV) infection in olive flounders. We further investigated the efficacy of specific sequence motifs in dsRNA in modulating immunostimulatory effects. Fish treated with poly I:C or dsRNA-CpGMix exhibited higher survival rates than the control group. Olive flounder leukocytes stimulated with poly I:C or dsRNA-CpGMix showed increased scuticocidal activity in the presence of inactivated immune sera. dsRNA with CpG motif sequences induced higher resistance against M. avidus and VHSV infections than dsRNA without CpG motif sequences, and the dsRNA-CpGMix group showed upregulated ISG15 or Mx compared to the dsRNA-GFP group. Thus, dsRNA containing CpG motifs can be used as effective immunostimulants to enhance resistance against viral and parasitic diseases in olive flounder. The specific sequences of the CpG motifs in dsRNA may be important for enhancing immune responses and resistance against M. avidus and VHSV infections in olive flounders. Full article
(This article belongs to the Section Fish Pathology and Parasitology)
11 pages, 910 KiB  
Article
Serological and Community Awareness Study of Lumpy Skin Disease in Different Agro-Ecological Zones of Sidama Regional State, Southern Ethiopia
by Nebyou Moje, Adane Seifu, Gizachew Hailegebreal, Dereje Shegu, Serena Montagnaro and Gianmarco Ferrara
Animals 2024, 14(12), 1782; https://doi.org/10.3390/ani14121782 - 13 Jun 2024
Viewed by 68
Abstract
The lumpy skin disease (LSD) vaccination status and epidemiological distribution remain unknown in some parts of Ethiopia, including the Sidama regional state. In this study, a serological survey of LSD was performed using a specific virus neutralization assay in selected districts of the [...] Read more.
The lumpy skin disease (LSD) vaccination status and epidemiological distribution remain unknown in some parts of Ethiopia, including the Sidama regional state. In this study, a serological survey of LSD was performed using a specific virus neutralization assay in selected districts of the Sidama regional state representing three agroecological zones from September 2021 to June 2022. Moreover, an assessment of community awareness and LSD vaccine-related problems was conducted using a questionnaire. Our results showed an overall animal and herd level seroprevalence of 40.8% (95%CI = 35.8, 45.8) and 81% (95%CI = 77, 85), respectively. High and low seroprevalence were observed in lowland (48%) and highland (28%) areas, although they were not statistically significant. However, risk factors such as management systems and breeds showed substantial differences in their LSD prevalence. The results obtained through the questionnaire showed that a small portion of respondents (29.2%) know about LSD and vaccinate their cattle (23.3%) against this disease. Only 20.8% of the respondents stated that there was LSD occurrence in their vaccinated cattle. In conclusion, both qualitative and quantitative study results showed the need for intervention in terms of community-based awareness creation about LSD clinical signs and vaccination advantages together with the frequently updated information on LSD prevalence. Full article
(This article belongs to the Collection Cattle Diseases)
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<p>Map of the study area from different administrative hierarchies created by using QGIS 3.36.3.</p>
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20 pages, 685 KiB  
Systematic Review
Characteristics of Nontyphoid Salmonella Isolated from Human, Environmental, Animal, and Food Samples in Burkina Faso: A Systematic Review and Meta-Analysis
by Kuan Abdoulaye Traore, Abdoul Rachid Aboubacar-Paraiso, Soutongnooma Caroline Bouda, Jean Bienvenue Ouoba, Assèta Kagambèga, Pierre Roques and Nicolas Barro
Antibiotics 2024, 13(6), 556; https://doi.org/10.3390/antibiotics13060556 - 13 Jun 2024
Viewed by 73
Abstract
Salmonella is one of the world’s leading causes of zoonotic and foodborne illnesses. Recently, antimicrobial resistance (AMR) has become one of the most critical challenges to public health and food safety. Herein, we employed a meta-analysis to determine the pooled prevalence and spatiotemporal [...] Read more.
Salmonella is one of the world’s leading causes of zoonotic and foodborne illnesses. Recently, antimicrobial resistance (AMR) has become one of the most critical challenges to public health and food safety. Herein, we employed a meta-analysis to determine the pooled prevalence and spatiotemporal distribution of serovars and antimicrobial resistance in NTS in Burkina Faso. To find eligible articles, a comprehensive literature search of PubMed, African Journals Online, ScienceDirect, Google Scholar, and the gray literature (university libraries) in Burkina was conducted for the period from 2008 to 2020. Studies meeting the inclusion criteria were selected and assessed for risk of bias. To assess the temporal and spatial relationships between serotypes and resistant strains from humans, animals, food, and the environment, a random-effects statistical model meta-analysis was carried out using the Comprehensive Meta-Analysis Version 3.0 program. The NTS prevalence rates were 4.6% (95% CI: 3–7) and 20.1% (95% CI: 6.6–47.4) in humans and animals, respectively, and 16.8% (95% CI: 10.5–25.8) and 15.6% (95% CI: 8.2–27.5) in food and the environment, respectively. Most NTS serovars were S. Derby, reported both in food and animals, and S. Typhimurium, reported in humans, while S. Croft II, S. Jodpur II, and S. Kentucky were the most prevalent in the environment. NTS isolates were highly resistant to erythromycin, amoxicillin, cefixime, and cephalothin, with a pooled prevalence of multidrug resistance of 29% (95% CI: 14.5–49.5). The results of this review show a high diversity of Salmonella serotypes, as well as high antibiotic resistance in Salmonella isolates from animal, human, food, and environmental samples in Burkina, calling for a consolidated “One Health” approach to better understand the drivers of pathogen emergence, spread, and antimicrobial resistance, as well as the formulation of intervention measures needed to limit the risk associated with the disease. Full article
19 pages, 949 KiB  
Review
MASLD-Related HCC: A Comprehensive Review of the Trends, Pathophysiology, Tumor Microenvironment, Surveillance, and Treatment Options
by Yuming Shi, Erfan Taherifard, Ali Saeed and Anwaar Saeed
Curr. Issues Mol. Biol. 2024, 46(6), 5965-5983; https://doi.org/10.3390/cimb46060356 (registering DOI) - 13 Jun 2024
Viewed by 54
Abstract
Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, [...] Read more.
Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, with MASLD replacing the hepatitis B virus as the primary contributor to new cases of HCC. MASLD-related HCC exhibits distinct characteristics compared to viral HCC, including unique immune cell profiles resulting in an overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, MASLD-related HCC is frequently identified in older age groups and among individuals with cardiometabolic comorbidities. Additionally, a greater percentage of MASLD-related HCC cases occur in noncirrhotic patients compared to those with viral etiologies, hindering early detection. However, the current clinical practice guidelines lack specific recommendations for the screening of HCC in MASLD patients. The evolving landscape of HCC management offers a spectrum of therapeutic options, ranging from surgical interventions and locoregional therapies to systemic treatments, for patients across various stages of the disease. Despite ongoing debates, the current evidence does not support differences in optimal treatment modalities based on etiology. In this study, we aimed to provide a comprehensive overview of the current literature on the trends, characteristics, clinical implications, and treatment modalities for MASLD-related HCC. Full article
(This article belongs to the Special Issue Tumorigenesis and Tumor Microenvironment)
28 pages, 6709 KiB  
Article
Epidemiological and Genetic Characteristics of Respiratory Viral Coinfections with Different Variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
by Ivelina Trifonova, Neli Korsun, Iveta Madzharova, Ivailo Alexiev, Ivan Ivanov, Viktoria Levterova, Lyubomira Grigorova, Ivan Stoikov, Dean Donchev and Iva Christova
Viruses 2024, 16(6), 958; https://doi.org/10.3390/v16060958 (registering DOI) - 13 Jun 2024
Viewed by 101
Abstract
This study aimed to determine the incidence and etiological, seasonal, and genetic characteristics of respiratory viral coinfections involving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Between October 2020 and January 2024, nasopharyngeal samples were collected from 2277 SARS-CoV-2-positive patients. Two multiplex approaches were [...] Read more.
This study aimed to determine the incidence and etiological, seasonal, and genetic characteristics of respiratory viral coinfections involving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Between October 2020 and January 2024, nasopharyngeal samples were collected from 2277 SARS-CoV-2-positive patients. Two multiplex approaches were used to detect and sequence SARS-CoV-2, influenza A/B viruses, and other seasonal respiratory viruses: multiplex real-time polymerase chain reaction (PCR) and multiplex next-generation sequencing. Coinfections of SARS-CoV-2 with other respiratory viruses were detected in 164 (7.2%) patients. The most common co-infecting virus was respiratory syncytial virus (RSV) (38 cases, 1.7%), followed by bocavirus (BoV) (1.2%) and rhinovirus (RV) (1.1%). Patients ≤ 16 years of age had the highest rate (15%) of mixed infections. Whole-genome sequencing produced 19 complete genomes of seasonal respiratory viral co-pathogens, which were subjected to phylogenetic and amino acid analyses. The detected influenza viruses were classified into the genetic groups 6B.1A.5a.2a and 6B.1A.5a.2a.1 for A(H1N1)pdm09, 3C.2a1b.2a.2a.1 and 3C.2a.2b for A(H3N2), and V1A.3a.2 for the B/Victoria lineage. The RSV-B sequences belonged to the genetic group GB5.0.5a, with HAdV-C belonging to type 1, BoV to genotype VP1, and PIV3 to lineage 1a(i). Multiple amino acid substitutions were identified, including at the antibody-binding sites. This study provides insights into respiratory viral coinfections involving SARS-CoV-2 and reinforces the importance of genetic characterization of co-pathogens in the development of therapeutic and preventive strategies. Full article
27 pages, 636 KiB  
Article
Determining Factors Influencing Filipinos’ Behavioral Protection against COVID: Integrating Extended Protection Motivation Theory, Theory of Planned Behavior, and Ergonomic Appraisal
by Ma. Janice J. Gumasing, Frankern Luis S. Malabuyoc, Ardvin Kester S. Ong and Charmine Sheena Saflor
COVID 2024, 4(6), 771-797; https://doi.org/10.3390/covid4060052 (registering DOI) - 13 Jun 2024
Viewed by 109
Abstract
This study examined the perceived protective behavior of Filipinos towards COVID-19. It utilized the extended protection motivation theory (PMT) and theory of planned behavior (TPB) models with the integration of ergonomic appraisal, applying partial least square structural equation modeling (PLS-SEM) to determine the [...] Read more.
This study examined the perceived protective behavior of Filipinos towards COVID-19. It utilized the extended protection motivation theory (PMT) and theory of planned behavior (TPB) models with the integration of ergonomic appraisal, applying partial least square structural equation modeling (PLS-SEM) to determine the factors affecting the protective behavior of Filipinos against COVID-19. A questionnaire was developed and distributed to 3000 Filipino citizens to measure the factors and their relationships. Results showed that understanding COVID-19 significantly influences the Filipinos’ perceived virus severity and vulnerability. In turn, perceived severity, self-efficacy, attitude, and subjective norms were the significant factors that affected the behavioral intention, impacting protective behavior. In addition, cognitive and macro ergonomics have been found to be the factors that influence the protective behavior of Filipinos against COVID-19. Thus, the study’s findings can be used as a framework for developing pandemic response initiatives that aim to inform and educate Filipinos, especially those who do not have the privilege of accessing information. Lastly, the outcome of this study can be used as a theoretical framework for future researchers who aim to conduct a study in a similar discipline. Full article
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<p>Conceptual framework.</p>
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8 pages, 1219 KiB  
Article
A Novel Cryptic Virus Isolated from Galphimia spp. in Mexico
by Dianella Iglesias, Kristian Stevens, Ashutosh Sharma and Alfredo Diaz-Lara
Pathogens 2024, 13(6), 504; https://doi.org/10.3390/pathogens13060504 - 13 Jun 2024
Viewed by 141
Abstract
Galphimia spp. is a plant employed in traditional medicine in Mexico because of its anxiolytic and sedative effects. Viruses have been associated with different alterations in plants, although asymptomatic agents (i.e., cryptic viruses) are also known. High-throughput sequencing (HTS) allows for the detection [...] Read more.
Galphimia spp. is a plant employed in traditional medicine in Mexico because of its anxiolytic and sedative effects. Viruses have been associated with different alterations in plants, although asymptomatic agents (i.e., cryptic viruses) are also known. High-throughput sequencing (HTS) allows for the detection of pathogenic and non-pathogenic viral agents in plants, including potential novel viruses. The aim of this study was to investigate the presence of viral agents in two populations of Galphimia spp. by HTS. Sequencing was conducted on an Illumina NextSeq 550 platform, and a putative novel virus was identified. Two contigs showed homology to partitiviruses, and these encoded the RNA-dependent RNA polymerase and coat protein. These proteins showed the highest identities with orthologs in the recently discovered Vitis cryptic virus. A phylogenetic analysis of both RNAs showed that the new virus clusters into the monophyletic genus Deltapartitivirus along with other plant-infecting viruses. The result of the HTS analysis was validated by conventional RT-PCR and Sanger sequencing. A novel virus was discovered in a symptomless Galphimia spp. plant and tentatively named the Galphimia cryptic virus (GCV). This is the first virus discovered in medicinal plants in Mexico. Full article
(This article belongs to the Section Viral Pathogens)
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<p>Asymptomatic leaves in <span class="html-italic">Galphimia</span> spp. plants. (<b>a</b>), Guanajuato population; (<b>b</b>), Morelos population.</p>
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<p>Proposed near-complete genome organization of Galphimia cryptic virus (GCV). (<b>a</b>), RNA molecules and corresponding genes are presented as gray boxes. (<b>b</b>), fold coverage of aligned reads for the two RNA sequences. Numbers represent nucleotide position in the virus genome.</p>
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<p>Phylogenetic trees showing the relationship of Galphimia cryptic virus with other members of the <span class="html-italic">Partitiviridae</span> family. The evolutionary history was inferred using amino acid sequence of the (<b>a</b>), RNA-dependent RNA polymerase and (<b>b</b>), coat protein. The human picobirna virus was included as outgroup. GenBank accession numbers are provided.</p>
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15 pages, 1296 KiB  
Article
Comprehensive Summary of Safety Data on Nirsevimab in Infants and Children from All Pivotal Randomized Clinical Trials
by Vaishali S. Mankad, Amanda Leach, Yue Chang, Ulrika Wählby Hamrén, Alexandre Kiazand, Robert J. Kubiak, Therese Takas, Tonya Villafana and Manish Shroff
Pathogens 2024, 13(6), 503; https://doi.org/10.3390/pathogens13060503 - 13 Jun 2024
Viewed by 126
Abstract
Background: Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their [...] Read more.
Background: Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to <35 weeks’ gestational age [wGA]); Phase 3 MELODY (NCT03979313; healthy infants born ≥35 wGA); and Phase 2/3 MEDLEY (NCT03959488; infants with congenital heart disease [CHD] and/or chronic lung disease of prematurity [CLD] or born ≤35 wGA). Methods: Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab. Results: The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment. Conclusions: A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities. Full article
(This article belongs to the Special Issue Recent Advances in Pediatric Infectious Diseases)
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<p>Overall summary of AEs through 360 days post-dose in (<b>A</b>) healthy term and preterm infants ≥ 29 wGA (includes infants from Phase 2b weighing &lt; 5 kg and the full MELODY enrollment cohort) and palivizumab-eligible infants at higher risk of severe RSV disease from the MEDLEY trial, including (<b>B</b>) preterm infants ≤ 35 weeks 0 days GA without CLD or CHD, (<b>C</b>) infants with CHD/CLD (all entering their first RSV season), and (<b>D</b>) children with CHD/CLD entering their second RSV season (before the second season, children with CHD/CLD randomized to nirsevimab in the first season received a single IM dose of 200 mg nirsevimab followed by 4× once-monthly IM doses of placebo [nirsevimab/nirsevimab], and those randomized to palivizumab in the first season were re-randomized 1:1 to either a single IM dose of 200 mg nirsevimab followed by 4× once-monthly IM doses of placebo [palivizumab/nirsevimab] or 5× once-monthly IM doses of palivizumab [15 mg/kg per dose; palivizumab/palivizumab]). Participants with multiple events in the same category were counted once in that category; participants with events in &gt;1 category were counted once in each category. (a) Defined as death, life-threatening, requiring inpatient hospitalization, prolongation of existing hospitalization, persistent or significant disability/incapacity, important medical event, or congenital anomaly/birth defect. (b) Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening; Grade 5: fatal. (c) Included immediate type I hypersensitivity reactions (including anaphylaxis), immune complex disease, and thrombocytopenia. Abbreviations: AE, adverse event; CHD, congenital heart disease; CLD, chronic lung disease of prematurity; GA, gestational age; IM, intramuscular; RSV, respiratory syncytial virus; wGA, weeks’ gestational age.</p>
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22 pages, 4569 KiB  
Article
Spontaneous Lethal Outbreak of Influenza A Virus Infection in Vaccinated Sows on Two Farms Suggesting the Occurrence of Vaccine-Associated Enhanced Respiratory Disease with Eosinophilic Lung Pathology
by Wencke Reineking, Isabel Hennig-Pauka, Ludger Schröder, Ulf Höner, Elena Schreiber, Lukas Geiping, Simon Lassnig, Marta C. Bonilla, Marion Hewicker-Trautwein and Nicole de Buhr
Viruses 2024, 16(6), 955; https://doi.org/10.3390/v16060955 (registering DOI) - 13 Jun 2024
Viewed by 186
Abstract
Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six vaccinated, spontaneously deceased sows revealed IAV infection and enhanced neutrophilic bronchopneumonia with unexpectedly large numbers of [...] Read more.
Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six vaccinated, spontaneously deceased sows revealed IAV infection and enhanced neutrophilic bronchopneumonia with unexpectedly large numbers of infiltrating eosinophils. The purpose of this study was to characterize these lung lesions with special emphasis on the phenotypes of inflammatory cells, the presence of eosinophilic peroxidase (EPO), and neutrophil extracellular traps (NETs). The number of Sirius red-stained eosinophils was significantly higher in the lungs of IAV-infected sows compared to healthy pigs, indicating a migration of eosinophils from blood vessels into the lung tissue stimulated by IAV infection. The detection of intra- and extracellular EPO in the lungs suggests its contribution to pulmonary damage. The presence of CD3+ T lymphocytes, CD20+ B lymphocytes, and Iba-1+ macrophages indicates the involvement of cell-mediated immune responses in disease progression. Furthermore, high numbers of myeloperoxidase-positive cells were detected. However, DNA-histone-1 complexes were reduced in IAV-infected sows, leading to the hypothesis that NETs are not formed in the IAV-infected sows. In conclusion, our findings in the lungs of IAV-infected vaccinated sows suggest the presence of so far unreported field cases of vaccine-associated enhanced respiratory disease. Full article
(This article belongs to the Special Issue Advances in Animal Influenza Virus Research: Third Edition)
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<p>Morphological findings in IAV-infected sows. (<b>A</b>,<b>C</b>): Accentuated around bronchi and larger vessels, there was a marked infiltration of neutrophilic and eosinophilic granulocytes as well as lower numbers of macrophages and lymphocytes (*). Multifocally, pronounced edema was present. Hematoxylin and eosin. Bar: 500 μm. (<b>B</b>,<b>D</b>): The presence of eosinophils was confirmed by the Sirius red stainability of numerous granulocytes (*). Sirius red. Bar: 500 μm.</p>
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<p>Detection of NETs in lung tissue. (<b>A</b>) Representative pictures of immunofluorescence microscopy are shown (blue = DNA (Hoechst), green = DNA-histone-1-complexes, red = MPO). The right image is a magnification from the left image, and the arrowhead marks a NET fiber. The scale bar in all images represents 50 µm. (<b>B</b>) Stained lung slices of three to six animals per group were analyzed from two technical runs per animal. Images were analyzed using ImageJ (version 1.5.4) software to determine the percentage of mean fluorescence of the green (DNA-histone-1-complex) and magenta (MPO) signals based on the blue signal (nuclei). The means from the technical runs were calculated and used for statistics. Per animal, 10 immunofluorescence microscopy images were analyzed in each technical run (control n = 6, IAV n = 3, VAERD n = 6 animals). A high intensity of MPO signals was detectable in the lungs of VAERD sows. Data were analyzed with ordinary one-way ANOVA followed by Dunnett’s multiple comparisons test and are presented with mean ± SD (* <span class="html-italic">p</span> ≤ 0.05, ** <span class="html-italic">p</span> ≤ 0.01).</p>
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<p>Comparison of eosinophilic count in the different study groups. (<b>A</b>,<b>E</b>): In IAV-infected sows, numerous eosinophils (arrows) are present within the mucosa and submucosal tissues. Neutrophils are occasionally present within the mucosa (arrowhead). No Sirius red stain was observed in neutrophils ((<b>E</b>); arrowhead). (<b>B</b>,<b>F</b>): The IAV-infected younger pigs have scattered eosinophils (arrows) within the alveolar septa. (<b>C</b>,<b>G</b>): Low numbers of eosinophils (arrows) are also present within the submucosal tissue and alveolar septa of the APP-infected group. The majority of intraluminal cells were confirmed as neutrophils (arrowheads) by their lack of Sirius red staining (<b>G</b>). (<b>D</b>,<b>H</b>): Single eosinophils (arrows) were present in the alveolar septa of healthy control pigs. ((<b>A</b>–<b>D</b>): Hematoxylin-eosin; (<b>E</b>–<b>H</b>): Sirius red stain). Bars: 100 μm.</p>
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<p>Quantification of Sirius red-positive cells. Increased numbers of Sirius red-positive cells were detected within the IAV-infected sows compared to younger IAV-infected pigs as well as APP-infected pigs and healthy controls. Statistical analysis showed significant differences between the IAV-infected sows compared to healthy controls and APP pigs, but not to the younger IAV-infected group. Min-to-max Box-and-Whisker plot. Kruskal–Wallis test with subsequent Dunn’s test for multiple comparisons. *, <span class="html-italic">p</span> ≤ 0.05; **, <span class="html-italic">p</span> ≤ 0.01; SR, Sirius red; +, mean count of cells.</p>
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<p>Detection of eosinophilic peroxidase (EPO) in porcine lung tissue. EPO was detected intracellularly within eosinophils in areas of high eosinophilic count (arrows). In addition, a perivascular and/or peribronchiolar extracellular immunolabeling for EPO was detected in all four groups. (<b>A</b>): IAV-infected sows; (<b>B</b>): younger IAV-infected pigs; (<b>C</b>): APP-infected pigs; (<b>D</b>): healthy control pigs. Indirect immunohistochemistry with 3,3′-diaminobenzidine as chromogen. Bars: 500 μm.</p>
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<p>Semiquantitative analysis of mononuclear cells and influenza A nucleoprotein. (<b>A</b>): CD3-positive T lymphocytes were present in moderate to high numbers within all examined sections. A slight increase in T lymphocytes was noted in the IAV-infected sows (VAERD). (<b>B</b>): Low to moderate numbers of CD20-positive B lymphocytes were detected accentuated in the BALT areas within all groups. (<b>C</b>): Iba-1-positive cells were increased in all disease groups compared to the healthy controls. No differences were noted between the different disease groups. (<b>D</b>): Scattered immunoreactivity for influenza A nucleoprotein (IAV score) was detected in three fattening pigs. (<b>A</b>–<b>D</b>): Min-to-max Box-and-Whisker-plot. APP, <span class="html-italic">Actinobacillus pleuropneumoniae</span>; IAV, Influenza A infected young pigs; VAERD, IAV-infected sows.</p>
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8 pages, 1392 KiB  
Communication
Human Lung Mast Cells as a Possible Reservoir for Coronavirus: A Novel Unrecognized Mechanism for SARS-CoV-2 Immune-Mediated Pathology
by Rebecca Praetzel and Chris Kepley
Int. J. Mol. Sci. 2024, 25(12), 6511; https://doi.org/10.3390/ijms25126511 (registering DOI) - 13 Jun 2024
Viewed by 128
Abstract
The pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health concern. Cell entry of SARS-CoV-2 depends on viral spike (S) proteins binding to cellular receptors (ACE2) and their subsequent priming by host cell proteases (TMPRSS2). Assessing effects of viral-induced host [...] Read more.
The pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health concern. Cell entry of SARS-CoV-2 depends on viral spike (S) proteins binding to cellular receptors (ACE2) and their subsequent priming by host cell proteases (TMPRSS2). Assessing effects of viral-induced host response factors and determining which cells are used by SARS-CoV-2 for entry might provide insights into viral transmission, add clarity to the virus’ pathogenesis, and possibly reveal therapeutic targets. Mast cells (MCs) are ubiquitously expressed tissue cells that act as immune sentinels given their ability to react specifically to pathogens at environmental interfaces, such as in the lung. Several lines of evidence suggest a critical role for MCs in SARS-CoV-2 infections based on patients’ mediator profiles, especially the “cytokine storm” responsible for most morbidity and mortality. In this pilot study, we demonstrated that human lung MCs (n = 3 donors) are a source of renin and that they upregulate the membrane receptor for SARS-CoV-2 (ACE2) as well as the protease required for cellular entry (TMPRSS2) under certain conditions. We hypothesized that infection of human MCs with SARS-CoV-2 may be a heretofore-unrecognized mechanism of viral pathogenesis, and further studies are required to assess this question. Full article
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<p>Human lung MCs as a source of renin. Human lung MCs (1 × 10<sup>6</sup>) were treated with (grey) or without (black) IFN (10 ng/mL) for 24 h, washed, and challenged with optimal concentrations of activator, and the amount ANG I formed (renin activity, pg/mL/h) was determined using a kit from ALPCO according to their instructions (mean ± SEM; <span class="html-italic">n</span> = 3; * <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Human lung mast cells expression of SARS-CoV-2 receptors ACE2 and TMPRSS following a cytokine or FcεRI challenge. Mast cells were purified and treated with IFN-α2 (10 ng/mL) or Fab’<sub>2</sub> of anti-FcεRI Ab (2 μg/mL) for 24 h. Surface expression was performed using mouse anti-human primary Abs followed by Fc-specific, FITC-conjugated anti-mouse Abs and FACs. Each condition was assessed in duplicate using non-specific mouse IgG (MOPC) as a negative control. Bars indicate SD, * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.005.</p>
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<p>A potential unrecognized mechanism for SARS-CoV-2 replication and pathogenesis. In (<b>A</b>), SARS-CoV infects the host, inducing increases in IFN levels (<b>B</b>). The increase in lung IFN induces upregulation of ACE2 and TMPRSS2 on MCs (<b>C</b>). Lung MCs are now primed to be infected by the virus (<b>D</b>). This allows for further propagation of the virus and the alteration and/or release of potent MC mediators.</p>
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10 pages, 1564 KiB  
Article
Hepatitis B Virus Genotypes and Subgenotypes Circulating in Infected Residents in a Country with High Vaccination Rate
by Carolina Silva, Diogo Ramos, Miriam Quina and Elizabeth Pádua
Viruses 2024, 16(6), 954; https://doi.org/10.3390/v16060954 (registering DOI) - 13 Jun 2024
Viewed by 111
Abstract
Despite the availability of a vaccine against hepatitis B virus (HBV), this infection still causes public health problems, particularly in susceptible populations. In Portugal, universal free vaccination started in 1994, and most HBV infections are diagnosed in immigrants from high-prevalence countries. Our aim [...] Read more.
Despite the availability of a vaccine against hepatitis B virus (HBV), this infection still causes public health problems, particularly in susceptible populations. In Portugal, universal free vaccination started in 1994, and most HBV infections are diagnosed in immigrants from high-prevalence countries. Our aim was to assess the pattern of HBV genotypes/subgenotypes in samples collected between 2017 and 2021 from a convenience sample of 70 infected residents in Portugal. The HBV pol/HBsAg region was amplified and sequenced, allowing the analysis of RT sequences submitted to phylogenetic analysis and mutations assessment. A total of 37.1% of samples were from native Portuguese, aged 25–53 years (mean: 36.7 years), and the remaining samples were from individuals born outside of Portugal. A high diversity of HBV was identified: subgenotypes A1–A3 in 41.0% (16/39); D1, D3, and D4 in 30.7% (12/39); E in 23.1% (9/39); and F4 in 2.6% (1/39). Besides genotypes A and D, Portuguese were also infected with genotypes E and F, which are prevalent in Africa and South America, respectively. Resistance mutations in RT sequences were not found. The findings provide valuable insights for updating the HBV molecular epidemiology in Portugal. However, successful strategies to prevent and control the infection are still needed in the country, especially among susceptible and vulnerable populations. Full article
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<p>Phylogenetic neighbor-joining tree of HBV sequences based on the alignment of 733 nucleotides of the P/HBsAg region along with 37 reference sequences from HBV genotypes and subgenotypes. The sequences under analysis are highlighted: native Portuguese with ● and individuals born outside of Portugal with ▲. Reference sequences are represented by the accession number and HBV subgenotype. The scale bar indicates the number of substitutions per site.</p>
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<p>Amino acid alignment of the sequences under study for the reverse transcriptase (RT) region of the HBV genome. The first line contains the reference sequence used for the drug resistance testing. The analyzed positions are delimited by rectangles. The amino acids corresponding to triplets where one nucleotide could not be determined are marked with an “X” and all amino acid coding hypotheses were evaluated.</p>
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19 pages, 4389 KiB  
Article
Exploring the Complexity of the Human Respiratory Virome through an In Silico Analysis of Shotgun Metagenomic Data Retrieved from Public Repositories
by Talya Conradie, Jose A. Caparros-Martin, Siobhon Egan, Anthony Kicic, Sulev Koks, Stephen M. Stick and Patricia Agudelo-Romero
Viruses 2024, 16(6), 953; https://doi.org/10.3390/v16060953 (registering DOI) - 13 Jun 2024
Viewed by 124
Abstract
Background: Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various viruses and bacteria colonize the respiratory tract without causing disease, potentially influencing respiratory diseases’ pathogenesis. Nevertheless, our understanding of respiratory microbiota [...] Read more.
Background: Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various viruses and bacteria colonize the respiratory tract without causing disease, potentially influencing respiratory diseases’ pathogenesis. Nevertheless, our understanding of respiratory microbiota is limited by technical constraints, predominantly focusing on bacteria and neglecting crucial populations like viruses. Despite recent efforts to improve our understanding of viral diversity in the human body, our knowledge of viral diversity associated with the human respiratory tract remains limited. Methods: Following a comprehensive search in bibliographic and sequencing data repositories using keyword terms, we retrieved shotgun metagenomic data from public repositories (n = 85). After manual curation, sequencing data files from 43 studies were analyzed using EVEREST (pipEline for Viral assEmbly and chaRactEriSaTion). Complete and high-quality contigs were further assessed for genomic and taxonomic characterization. Results: Viral contigs were obtained from 194 out of the 868 FASTQ files processed through EVEREST. Of the 1842 contigs that were quality assessed, 8% (n = 146) were classified as complete/high-quality genomes. Most of the identified viral contigs were taxonomically classified as bacteriophages, with taxonomic resolution ranging from the superkingdom level down to the species level. Captured contigs were spread across 25 putative families and varied between RNA and DNA viruses, including previously uncharacterized viral genomes. Of note, airway samples also contained virus(es) characteristic of the human gastrointestinal tract, which have not been previously described as part of the lung virome. Additionally, by performing a meta-analysis of the integrated datasets, ecological trends within viral populations linked to human disease states and their biogeographical distribution along the respiratory tract were observed. Conclusion: By leveraging publicly available repositories of shotgun metagenomic data, the present study provides new insights into viral genomes associated with specimens from the human respiratory tract across different disease spectra. Further studies are required to validate our findings and evaluate the potential impact of these viral communities on respiratory tract physiology. Full article
(This article belongs to the Special Issue Virus Bioinformatics 2024)
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<p>The bibliographic search and data collection strategy used. A flow diagram depicting the two search strategies used for data collection, with the blue arrows representing search strategy 1, and orange arrows representing search strategy 2.</p>
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<p>The study-filtering strategy used. The flow diagram graphically represents the search strategy employed to identify relevant sequence data from public repositories. The number of studies excluded at each filtering step and the reasons for excluding these bioprojects are also indicated. A final 43 studies were identified that matched the selection criteria and were used for analysis in the present study.</p>
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<p>The distribution of eukaryotic viral contigs and bacteriophage contigs captured through EVEREST. (<b>A</b>) A pie chart depicting the 1414 captured contigs assigned to taxonomy, from which 1193 (84%) were identified as bacteriophages (red), and 221 (16%) were identified as eukaryotic viruses (blue). (<b>B</b>) Baltimore classification of viral contigs. The bar plot summarizes the number of eukaryote virus (blue) and bacteriophage (red) contigs within the indicated Baltimore classes, including those that could not be classified (unclassified).</p>
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<p>The distribution of taxonomic classification following the lowest common ancestor method included in EVEREST. (<b>A</b>) A bar plot showing the number of eukaryotic (blue) and bacteriophage (red) viral contigs classified at the indicated taxonomy ranks. (<b>B</b>). Taxonomic classification at the family level. The bar plots represent the 25 families identified among the bacteriophage (red) and eukaryotic (blue) viral contigs.</p>
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<p>Genome quality assessment of the viral contigs and taxonomic characterization of the complete and high-quality genomes. (<b>A</b>) Bar plots represent the distribution of the 1842 contigs classified based on their quality as determined by CheckV [<a href="#B34-viruses-16-00953" class="html-bibr">34</a>]. Blue bars represent viral genomes, while red bars represent proviruses. (<b>B</b>) Bar plots representing the number of complete (red) and high-quality (blue) genomes that were assigned at each taxonomic rank. (<b>C</b>) Bar plots representing the number of complete (red) or high-quality (blue) viral genomes that were assigned to the indicated viral families.</p>
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<p>An overview of the viral contigs recovered from the bioprojects analyzed in this study grouped by taxonomic viral families. The scatter plot shows the correlation between GC content and viral contig size. Density plots of viral families on the top and right sides represent contig size and GC content, respectively.</p>
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<p>(<b>A</b>–<b>F</b>) A projection of the samples included in this study in the two first components of the PCA model. (<b>A</b>) A biplot showing the PCA score plot and the loading plot. The left and bottom axes represent the PCA scores of the samples, and the top and right axes indicate how strong each feature (vector) influences the principal components. Vectors represent features with at least a 0.6 correlation coefficient with any of the two first components of the PCA model, and their project values on each principal component indicates how much weight they have on those specific components of the PCA model. The unclassified family within Caudovirales is negatively correlated with component 1 and represents the major source of variation along this component. Conversely, <span class="html-italic">Siphoviridae</span> exhibit a positive correlation with component 1. Distribution across component 2 is mostly driven by <span class="html-italic">Siphoviridae</span> (positive correlation) and to a lesser extent by the unclassified family within Caudovirales. For each PCA graph, dots represent individual samples. Samples are labelled based on whether they were obtained from adults (blue) or children (orange) (<b>B</b>), whether they were obtained from healthy individuals (orange) or individuals with disease (blue) (<b>C</b>), whether they were obtained from the lower (blue) or upper (orange) respiratory tract (<b>D</b>), the specific respiratory pathology (<b>E</b>), or the type of specimen used to sample the airways (<b>F</b>). ARI: acute respiratory infection; CF: cystic fibrosis; LTR: lung transplant recipient; BAL: bronchoalveolar lavage; NPS: nasopharyngeal swabs; NSA: nasopharyngeal aspirates.</p>
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<p>Shannon index diversity of viral families identified in lung samples. (<b>A</b>–<b>E</b>) Box plots displaying the comparison in alpha viral diversity between samples from the upper and lower respiratory tract (<b>A</b>), between samples collected from adults and children (<b>B</b>), between samples obtained from healthy controls or individuals with disease (<b>C</b>), between samples obtained from patients with different respiratory pathologies and healthy controls (<b>D</b>), and between bronchoalveolar lavage fluid and other type of specimens from the respiratory tract (<b>E</b>). Red dots represent individual datapoints. Only groups containing more than three datapoints were included in these analyses. The density plots (shaded blue area) represent the probability distribution for each data group. Differences between the indicated groups were evaluated using a Wilcoxon rank sum test and the resulting <span class="html-italic">p</span>-values are indicated in each panel. In A and B, notches in the boxplot represent the 95% confidence interval for the median. In D and E, <span class="html-italic">p</span>-values were corrected using the Bonferroni method. ARI: acute respiratory infection; LTR: lung transplant recipient; BAL: bronchoalveolar lavage; NSA: nasopharyngeal aspirates; NPS: nasopharyngeal swabs.</p>
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18 pages, 628 KiB  
Systematic Review
ANCA-Positive Small-Vessel Vasculitis Following SARS-CoV-2 Vaccination—A Systematic Review
by Kinga Łysak, Agata Walulik, Michał Błaszkiewicz and Krzysztof Gomułka
Vaccines 2024, 12(6), 656; https://doi.org/10.3390/vaccines12060656 (registering DOI) - 13 Jun 2024
Viewed by 305
Abstract
As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged, including new-onset antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV). We systematically reviewed new-onset AAV following COVID-19 vaccination case reports [...] Read more.
As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged, including new-onset antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV). We systematically reviewed new-onset AAV following COVID-19 vaccination case reports and case series published in three databases before January 2024 following PRISMA guidelines to understand the characteristics of possible causal relationships or coincidences. In total, 404 articles were screened respectively by title, abstracts, and full-texts. Thirty-four papers fulfilled the inclusion criteria and have been analyzed, covering 44 patients with new-onset AAV after COVID-19 vaccination with no prior history of COVID-19 infection. Data regarding patients’ metrics, comorbidities, vaccination characteristics, symptoms, diagnostics, treatment, and outcomes were investigated and summarized. The cohort consisted predominantly of females. AAV diagnosis was confirmed via biopsy, with renal dysfunction as a prevailing manifestation. In most cases, the first symptoms of AAV developed after the second dose; moreover, Pfizer-BioNTech was the most frequently administered vaccine among the analyzed cohort. Primary treatment involved glucocorticoid therapy, with a mostly favourable response. This systematic review aims to raise awareness among clinicians in the field regarding this rare but possible complication, to promote the prompt recognition and diagnosis of de novo ANCA-positive small-vessel vasculitis in timely association with SARS-CoV-2 vaccination. Full article
(This article belongs to the Special Issue COVID-19 Vaccine-Associated Autoimmune Diseases and Disorders)
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<p>The PRISMA searching strategy flow chart.</p>
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<p>Charts present proportions of selected results.</p>
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<p>Charts presenting the contributions of individual systems in symptoms manifestation (<b>a</b>) and treatment used (<b>b</b>).</p>
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