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Vaccines Jun 2024Endemic SARS-CoV-2 infections still burden the healthcare system and represent a considerable threat to vulnerable patient cohorts, in particular immunocompromised (IC)...
Retrospective, Observational Analysis on the Impact of SARS-CoV-2 Variant Omicron in Hospitalized Immunocompromised Patients in a German Hospital Network-The VISAGE Study.
AIMS
Endemic SARS-CoV-2 infections still burden the healthcare system and represent a considerable threat to vulnerable patient cohorts, in particular immunocompromised (IC) patients. This study aimed to analyze the in-hospital outcome of IC patients with severe SARS-CoV-2 infection in Germany.
METHODS
This retrospective, observational study, analyzed administrative data from inpatient cases ( = 146,324) in 84 German Helios hospitals between 1 January 2022 and 31 December 2022 with regard to in-hospital outcome and health care burden in IC patients during the first 12 months of Omicron dominance. As the primary objective, in-hospital outcomes of patients with COVID-19-related severe acute respiratory infection (SARI) were analyzed by comparing patients with ( = 2037) and without IC diagnoses ( = 14,772). Secondary analyses were conducted on IC patients with ( = 2037) and without COVID-19-related SARI ( = 129,515). A severe in-hospital outcome as a composite endpoint was defined per the WHO definition if one of the following criteria were met: intensive care unit (ICU) treatment, mechanical ventilation (MV), or in-hospital death.
RESULTS
In total, 12% of COVID-related SARI cases were IC patients, accounting for 15% of ICU admissions, 15% of MV use, and 16% of deaths, resulting in a higher prevalence of severe in-hospital courses in IC patients developing COVID-19-related SARI compared to non-IC patients (Odds Ratio, OR = 1.4, < 0.001), based on higher in-hospital mortality (OR = 1.4, < 0.001), increased need for ICU treatment (OR = 1.3, < 0.001) and mechanical ventilation (OR = 1.2, < 0.001). Among IC patients, COVID-19-related SARI profoundly increased the risk for severe courses (OR = 4.0, < 0.001).
CONCLUSIONS
Our findings highlight the vulnerability of IC patients to severe COVID-19. The persistently high prevalence of severe outcomes in these patients in the Omicron era emphasizes the necessity for continuous in-hospital risk assessment and monitoring of IC patients.
PubMed: 38932363
DOI: 10.3390/vaccines12060634 -
Vaccines Jun 2024Porcine reproductive and respiratory syndrome (PRRS) remains a formidable challenge for the global pig industry. Caused by PRRS virus (PRRSV), this disease primarily... (Review)
Review
Porcine reproductive and respiratory syndrome (PRRS) remains a formidable challenge for the global pig industry. Caused by PRRS virus (PRRSV), this disease primarily affects porcine reproductive and respiratory systems, undermining effective host interferon and other immune responses, resulting in vaccine ineffectiveness. In the absence of specific antiviral treatments for PRRSV, vaccines play a crucial role in managing the disease. The current market features a range of vaccine technologies, including live, inactivated, subunit, DNA, and vector vaccines, but only modified live virus (MLV) and killed virus (KV) vaccines are commercially available for PRRS control. Live vaccines are promoted for their enhanced protective effectiveness, although their ability to provide cross-protection is modest. On the other hand, inactivated vaccines are emphasized for their safety profile but are limited in their protective efficacy. This review updates the current knowledge on PRRS vaccines' interactions with the host interferon system, and other immunological aspects, to assess their current status and evaluate advents in PRRSV vaccine development. It presents the strengths and weaknesses of both live attenuated and inactivated vaccines in the prevention and management of PRRS, aiming to inspire the development of innovative strategies and technologies for the next generation of PRRS vaccines.
PubMed: 38932335
DOI: 10.3390/vaccines12060606 -
Vaccines May 2024At times of pandemics, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the situation demands rapid development and production...
At times of pandemics, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the situation demands rapid development and production timelines of safe and effective vaccines for delivering life-saving medications quickly to patients. Typical biologics production relies on using the lengthy and arduous approach of stable single-cell clones. Here, we used an alternative approach, a stable cell pool that takes only weeks to generate compared to a stable single-cell clone that needs several months to complete. We employed the membrane, envelope, and highly immunogenic spike proteins of SARS-CoV-2 to produce virus-like particles (VLPs) using the HEK293-F cell line as a host system with an economical transfection reagent. The cell pool showed the stability of protein expression for more than one month. We demonstrated that the production of SARS-CoV-2 VLPs using this cell pool was scalable up to a stirred-tank 2 L bioreactor in fed-batch mode. The purified VLPs were properly assembled, and their size was consistent with the authentic virus. Our particles were functional as they specifically entered the cell that naturally expresses ACE-2. Notably, this work reports a practical and cost-effective manufacturing platform for scalable SARS-CoV-2 VLPs production and chromatographic purification.
PubMed: 38932290
DOI: 10.3390/vaccines12060561 -
Viruses Jun 2024Since it was first reported in 2013, the NADC30-like PRRSV has been epidemic in China. Hubei Province is known as China's key hog-exporting region. To understand the...
Since it was first reported in 2013, the NADC30-like PRRSV has been epidemic in China. Hubei Province is known as China's key hog-exporting region. To understand the prevalence and genetic variation of PRRSV, herein, we detected and analyzed 317 lung tissue samples from pigs with respiratory disease in Hubei Province, and demonstrated that the NADC30-like strain was the second-most predominant strain during 2017-2018, following the highly pathogenic PRRSV (HP-PRRSV). Additionally, we isolated a new NADC30-like PRRSV strain, named CHN-HB-2018, which could be stably passaged in Marc-145 cells. Genetic characterization analysis showed that compared with the NADC30 strain, the CHN-HB-2018 strain had several amino acid variations in glycoprotein (GP) 3, GP5, and nonstructural protein 2 (NSP2). Moreover, the CHN-HB-2018 strain showed a unique 5-amino acid (aa) deletion in NSP2, which has not previously been reported. Gene recombination analysis identified the CHN-HB-2018 strain as a potentially recombinant PRRSV of the NADC30-like strain and HP-PRRSV. Animal experiments indicated that the CHN-HB-2018 strain has a mild pathogenicity, with no mortality and only mild fever observed in piglets. This study contributes to defining the evolutionary characteristics of PRRSV and its molecular epidemiology in Hubei Province, and provides a potential candidate strain for PRRSV vaccine development.
Topics: Porcine respiratory and reproductive syndrome virus; Animals; Swine; Porcine Reproductive and Respiratory Syndrome; China; Phylogeny; Virulence; Genome, Viral; Recombination, Genetic; Genetic Variation; Lung
PubMed: 38932283
DOI: 10.3390/v16060993 -
Viruses Jun 2024The epidemiology of different respiratory viral infections is believed to be affected by prior viral infections in addition to seasonal effects. This PROSPERO-registered... (Meta-Analysis)
Meta-Analysis Review
The epidemiology of different respiratory viral infections is believed to be affected by prior viral infections in addition to seasonal effects. This PROSPERO-registered systematic review identified 7388 studies, of which six met our criteria to answer the question specifically. The purpose of this review was to compare the prevalence of sequential viral infections in those with previously documented positive versus negative swabs. The pooled prevalence of sequential viral infections over varying periods from 30-1000 days of follow-up was higher following a negative respiratory viral swab at 0.15 than following a positive swab at 0.08, indicating the potential protective effects of prior respiratory viral infections. However, significant heterogeneity and publication biases were noted. There is some evidence, albeit of low quality, of a possible protective effect of an initial viral infection against subsequent infections by a different virus, which is possibly due to broad, nonspecific innate immunity. Future prospective studies are needed to validate our findings.
Topics: Humans; Respiratory Tract Infections; Virus Diseases; Cross Protection; Prevalence
PubMed: 38932273
DOI: 10.3390/v16060982 -
Viruses Jun 2024This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric...
This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric patients. The study collected data on patients aged between 0 and 18 years, diagnosed with acute SARS-CoV-2 infection, admitted to a pediatric tertiary hospital between 1 March 2020 and 28 February 2023. This study included 1677 patients. Neurological manifestations were noted in 10% (n = 168) of patients with a median age of 3.2 years (interquartile range: 1-11.92). Neurological manifestations were significantly associated with the pandemic waves ( = 0.006) and age groups ( < 0.001). Seizures were noted in 4.2% of cases and reached an increasing frequency over time ( = 0.001), but were not associated with age groups. Febrile seizures accounted for the majority of seizures. Headache was reported in 2.6% of cases and had similar frequencies across the pandemic waves and age groups. Muscular involvement was noted in 2% of cases, reached a decreasing frequency over time ( < 0.001), and showed different frequencies among the age groups. Neurological manifestations of acute SARS-CoV-2 infection exhibit distinct patterns, depending on the pandemic wave and patient age group. The Wuhan and Omicron waves involved the nervous system more often than the other waves.
Topics: Humans; COVID-19; Child, Preschool; Child; Male; Female; Infant; SARS-CoV-2; Adolescent; Nervous System Diseases; Headache; Infant, Newborn; Seizures, Febrile; Seizures; Pandemics
PubMed: 38932259
DOI: 10.3390/v16060967 -
Viruses Jun 2024This study aimed to determine the incidence and etiological, seasonal, and genetic characteristics of respiratory viral coinfections involving severe acute respiratory...
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.
Topics: Humans; Coinfection; SARS-CoV-2; COVID-19; Middle Aged; Adult; Female; Male; Adolescent; Phylogeny; Child, Preschool; Child; Aged; Young Adult; Infant; Respiratory Tract Infections; Rhinovirus; Influenza A virus; Respiratory Syncytial Virus, Human; Nasopharynx; Whole Genome Sequencing; China; Seasons; Aged, 80 and over; Genome, Viral; Influenza B virus
PubMed: 38932250
DOI: 10.3390/v16060958 -
Viruses Jun 2024Influenza 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...
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.
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.
Topics: Animals; Swine; Lung; Swine Diseases; Orthomyxoviridae Infections; Female; Influenza Vaccines; Influenza A virus; Disease Outbreaks; Eosinophils; Extracellular Traps; Vaccination; Eosinophil Peroxidase
PubMed: 38932247
DOI: 10.3390/v16060955 -
Viruses Jun 2024Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various...
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.
Topics: Humans; Metagenomics; Virome; Genome, Viral; Respiratory System; Viruses; Metagenome; Computer Simulation; Phylogeny; Computational Biology; Microbiota; Bacteriophages
PubMed: 38932245
DOI: 10.3390/v16060953 -
Viruses Jun 2024Porcine hemagglutinating encephalomyelitis virus (PHEV) replicates in the upper respiratory tract and tonsils of pigs. Using an air-liquid interface porcine respiratory...
Transcriptome Analysis in Air-Liquid Interface Porcine Respiratory Epithelial Cell Cultures Reveals That the Betacoronavirus Porcine Encephalomyelitis Hemagglutinating Virus Induces a Robust Interferon Response to Infection.
Porcine hemagglutinating encephalomyelitis virus (PHEV) replicates in the upper respiratory tract and tonsils of pigs. Using an air-liquid interface porcine respiratory epithelial cells (ALI-PRECs) culture system, we demonstrated that PHEV disrupts respiratory epithelia homeostasis by impairing ciliary function and inducing antiviral, pro-inflammatory cytokine, and chemokine responses. This study explores the mechanisms driving early innate immune responses during PHEV infection through host transcriptome analysis. Total RNA was collected from ALI-PRECs at 24, 36, and 48 h post inoculation (hpi). RNA-seq analysis was performed using an Illumina Hiseq 600 to generate 100 bp paired-end reads. Differential gene expression was analyzed using DeSeq2. PHEV replicated actively in ALI-PRECs, causing cytopathic changes and progressive mucociliary disruption. Transcriptome analysis revealed downregulation of cilia-associated genes such as , , , , and , and acidic sialomucin . PHEV also activated antiviral signaling pathways, significantly increasing the expression of interferon-stimulated genes (, , , and ) and chemokine genes ( and ), highlighting inflammatory regulation. This study contributes to elucidating the molecular mechanisms of the innate immune response to PHEV infection of the airway epithelium, emphasizing the critical roles of the mucociliary, interferon, and chemokine responses.
Topics: Animals; Swine; Gene Expression Profiling; Epithelial Cells; Interferons; Betacoronavirus 1; Immunity, Innate; Virus Replication; Coronavirus Infections; Cytokines; Transcriptome; Respiratory Mucosa; Swine Diseases; Cells, Cultured; Deltacoronavirus
PubMed: 38932231
DOI: 10.3390/v16060939