Search Results (19,269)

Wastewater surveillance emerged as a critical public health tool during the COVID-19 pandemic, enabling early detection of community-level pathogen circulation independent of clinical testing. Its ability to capture signals from both symptomatic and asymptomatic individuals highlighted the importance of optimizing sampling methodologies to improve sensitivity and reliability. A key question is whether the several-fold increase in SARS-CoV-2 detectability observed when using passive tampon swab sampling compared with paired grab samples also applies to other respiratory viruses, including influenza A (including its avian influenza H5N1 subtype), influenza B, and respiratory syncytial virus (RSV). We collected 24 h passive swab samples with same-day grab samples from Detroit sewersheds, concentrated and purified nucleic acids, and using RT-ddPCR, quantified respiratory syncytial virus, SARS-CoV-2, influenza A, influenza B, and H5N1 influenza A viruses using markers RSV, SC2, InfA, InfB, and H5, respectively. Samples testing positive for H5 (marker for H5N1 influenza A) were further analyzed by targeted PCR and amplicon sequencing. Across three sites, median 24 h swab:grab ratios of virus copies were 7.0 for RSV, 9.2 for SC2, 9.9 for InfA, and 3.6 for InfB. A 239 bp hemagglutinin sequence from a sample with a strong H5 signal (795 copies/10 mL) had 100% identity to avian influenza viruses from Canada geese. Twenty-four-hour swab sampling greatly improves viral detectability across diverse targets and enabled the first confirmed detection of H5 in Detroit wastewater. Combined with magnetic bead purification, the overall sensitivity gain over conventional PEG-NaCl-Qiagen methods is approximately 36-fold, enabling earlier warning of community pathogens than grab samples. By integrating 24 hour passive swab sampling with high-efficiency nucleic acid purification, we expand the sensitivity of wastewater surveillance to enable detection and confirmation of low-abundance pathogens like avian influenza (H5). Full article

Background/Objectives: Individuals with alcohol use disorder (AUD) and tobacco use disorder (TUD) are at increased risk for severe COVID-19 outcomes. However, real-world evidence on vaccine effectiveness (VE) in these populations remains limited, particularly in low- and middle-income countries. This study aimed to evaluate the effectiveness of three or more COVID-19 vaccine doses against mortality in hospitalized patients with AUD and TUD in Brazil. Methods: This retrospective cohort study used data from the SIVEP Gripe database, a national surveillance system of hospitalized COVID-19 cases in Brazil. The study included adults aged ≥18 years with confirmed SARS-CoV 2 infection between February 2020 and June 2025. The intervention was defined as receipt of three or more vaccine doses (fully vaccinated) versus no doses (unvaccinated). Propensity score matching was performed separately for AUD and TUD cohorts. Vaccine effectiveness was estimated using McNemar’s test for paired samples, and the average treatment effect (ATE) and number needed to vaccinate (NNV) were calculated. Results: Among 2,184,723 hospitalized patients, 12,115 had AUD and 45,679 had TUD. After matching, VE against mortality was 42% (95% CI: 27.5–53.5) in the AUD group and 52.6% (95% CI: 46.5–58.1) in the TUD group, compared to 58.5% and 58.9% in their respective non-exposed counterparts. The ATE was consistent across groups (approximately −0.12), and the NNV to prevent one death was 8 (95% CI: 6–15 for AUD; 7–12 for TUD). Conclusions: Although VE was attenuated in individuals with AUD and TUD compared to the general population, the absolute benefit of vaccination remained substantial. Full article

Background/Objectives: SARS-CoV-2 is the causative agent of COVID-19, an infectious viral respiratory disease with human-to-human transmission. Current molecular understanding of how hosts respond to infection by respiratory viral pathogens in general and to SARS-CoV-2 in particular is still a research field under development. The activation levels of various host pathways are dependent on several variables, including the host tissue compartment. Methods: In this work, Illumina RNA sequencing was performed to assess the transcriptional host response to SARS-CoV-2 infection using COVID-19 PCR testing nasopharyngeal (NP) swab remnants from twenty infected and nine non-infected individuals. Results: Differential gene expression (DGE) analysis identified 182 overexpressed genes, with strong enrichment in innate immune and viral response genes. This included a significant induction of IFIH1/MDA5, a pattern recognition receptor (PRR) gene participating in the initial sensing of viral RNAs and subsequent cascade activation of interferon (IFN) and IFN-stimulated genes (ISGs). Interestingly, we observed different levels of concordance with previous similar studies and a significant induction of RIG1 and TLR3, two PRR genes encoding proteins that function to upregulate IFN and ISGs, but which are not normally identified as differentially expressed genes (DEGs). Finally, the overexpression of MX1, a well-characterized biomarker of viral infection; IFIT1, one of the top upregulated genes; and OAS1, OAS2 and OAS3, genes with a molecular function, 2-5-oligoadenylate synthase activity, identified as enriched in the DGE analyses, was confirmed by RT-qPCR. Conclusions: This study provides insights into upper respiratory tract responses to SARS-CoV-2 infections and identifies a set of differentially expressed genes (DEGs) with potential as candidates for further investigations as viral infection biomarkers. Full article

Background: Hematological patients have a high risk of developing severe COVID-19 (37%). Most mRNA vaccine trials in hematological patients showed a low immunogenicity after two doses, while long-term data are scarce. Methods: In this monocentric retrospective observational study, we evaluated humoral and T cell-mediated immune responses in 230 hematological patients after three doses of the Pfizer-BioNTech mRNA COVID-19 vaccine. Patients were stratified by age, disease type/state, prior COVID-19 infection, and treatment status and regimens (anti-CD20 monoclonal antibodies, BTK and BCL-2 inhibitors, and treatment line). Antibody titer to SARS-CoV-2 was assessed by electrochemiluminescence immunoassay and T cell response by QuantiFERON interferon-γ release assay (IGRA). Data were analyzed using univariate (Fisher’s exact test) and Firth’s bias-reduced penalized-likelihood logistic regression. Results: A robust humoral response was observed with 91.55% of patients developing anti-spike antibodies (GMT 988.83 U/mL). Anti-CD20-bendamustine treatment was associated with a significantly lower antibody positivity compared to untreated subjects. Prior COVID-19 infection significantly boosted both antibody positivity (95.9% vs. 85.2%) and GMT (847.02 U/mL vs. 258.79 U/mL). Conversely, T cell response was suboptimal (36.1% positive), particularly in anti-CD20-bendamustine-treated and multi-treated patients (27.1%), but highest in those treated with BTK inhibitors (50%). Multivariable logistic regression analysis linked multiple treatments to lower T cell response. Following vaccination, 29.1% of patients contracted SARS-CoV-2, but only 0.89% developed severe COVID-19. Conclusions: Three doses of mRNA vaccine elicit a strong humoral but a low T cell response, as detected by IGRA, in hematological patients. These findings underscore the importance of completing vaccination before initiating immunosuppressive therapies. Full article

Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as Long COVID, affects millions worldwide and is characterized by persistent fatigue, reduced immune fitness, and mood disturbances. The aim of the current study was to identify if immune fitness, mood, fatigue, and quality of life prior to SARS-CoV-2 infection could predict PASC fatigue severity. A retrospective cross-sectional survey was conducted among 299 Dutch PASC patients. Participants completed validated measures of immune fitness, fatigue (assessed with both the Fatigue Severity Scale and a single-item scale), mood (including stress, anxiety, depression, hostility, loneliness, and happiness) and quality of life for the three months prior to SARS-CoV-2 infection. The same assessments were made for the month before survey completion (i.e., during PASC). Correlational and regression analyses were conducted to identify possible predictors of PASC fatigue severity. Participants were predominantly female (90%): mean age 44.1 (SD 11.2) years. Both assessments of PASC fatigue did not correlate significantly with the prior SARS-CoV-2 assessments of immune fitness, fatigue, mood, and quality of life. The regression analyses revealed no significant predictors for PASC fatigue severity. In conclusion, immune fitness, fatigue, mood and quality of life prior to SARS-CoV-2 infection were not identified as independent predictors of PASC fatigue severity. Full article

Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic profoundly disrupted global respiratory virus circulation, with sharp declines during 2020–2021, followed by a resurgence after the relaxation of public health measures. In South America, post-pandemic respiratory virus dynamics remain insufficiently characterized, particularly in ecologically diverse regions. Arequipa, a high-altitude city in southern Peru, has unique environmental conditions, including marked seasonal temperature variability, that may influence viral transmission. Methods: We performed a cross-sectional analysis of 21,784 nasopharyngeal swabs collected from symptomatic patients at four major hospitals between June 2021 and September 2023. All samples were tested for SARS-CoV-2 by RT-qPCR. Because routine screening for other respiratory viruses was implemented only in SARS-CoV-2-negative cases during the study period, a subset of SARS-CoV-2-negative samples was subsequently analyzed for influenza A virus (IAV), influenza B virus (IBV), and respiratory syncytial virus (RSV) using VIASURE assays. Viral circulation patterns were evaluated by year, month, and epidemiological week. Meteorological data were obtained from the SENAMHI–La Pampilla station. Logistic regression models were used to assess epidemiological and climatic predictors of viral detection. Results: SARS-CoV-2 positivity declined from 20.0% in 2021 to 8.8% in 2023. Conversely, detection of other respiratory viruses among SARS-CoV-2-negative samples increased from 0.8% in 2021 to 29.0% in 2023 (p < 0.01). Temporal increases in detection were observed during 2022–2023, particularly for IAV and RSV. In exploratory analyses, calendar year and relative humidity were associated with IAV and RSV detection, while age and temperature variables were associated with IBV. Conclusions: Climatic and demographic variables were associated with changes in viral detection for IAV, IBV, and RSV during the post-pandemic transition period in Arequipa. These findings describe patterns of viral detection within SARS-CoV-2-negative symptomatic patients and should be interpreted as surveillance-based observations rather than population-level estimates. Strengthened integrated epidemiological and genomic surveillance will be essential for vaccine planning and outbreak preparedness in the post-pandemic era. Full article

Background: COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally licensed COVID-19 vaccines. Methods: The potential public health and economic impact of mRNA-1283 in adults ≥ 60 years and high-risk adults aged 18–59 years was modeled versus no vaccination and originally licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with a 1-year time horizon. COVID-19 burden reflected two full post-pandemic seasons. Vaccine efficacy versus mRNA-1273 was based on pivotal phase 3 NextCOVE trial data; efficacy versus BNT162b2 was derived from an indirect treatment comparison. The economically justifiable price (EJP) of mRNA-1283 versus no vaccination and price premiums over existing vaccines were determined at a willingness-to-pay threshold of €50,000/quality-adjusted life-year (QALY) gained. Results: Without COVID-19 vaccination, an estimated 460,000 infections, 23,800 hospitalizations, and 5300 deaths would occur. With current coverage, mRNA-1283 was estimated to prevent 68,000 infections, 5400 hospitalizations, and 1200 deaths, saving 9667 QALYs and over €66.5 million in treatment costs. The EJP was €238 versus no vaccination. Compared with mRNA-1273 and BNT162b2, mRNA-1283 was estimated to prevent additional burden (e.g., 1309 and 1679 hospitalizations, respectively) and was cost-effective at an incremental EJP of €62 versus mRNA-1273 and €80 versus BNT162b2. Conclusions: The results support continued COVID-19 vaccination to mitigate the ongoing health and societal burden of SARS-CoV-2 in the Netherlands. The comparative analyses indicate that mRNA-1283 may be associated with substantial health benefits over originally licensed mRNA vaccines; consequently, its use may further improve health outcomes and economic efficiency within COVID-19 vaccination programs. Full article

Background/Objectives: Optimal specimen collection is essential for accurate diagnostic tests for upper airway infections. Rapid antigen diagnostic tests (RDTs) are commonly used for SARS-CoV-2 testing, yet the optimal sampling depth remains unclear. This study aimed to compare the diagnostic sensitivity and patient discomfort associated with two nasal swab depths: 2 cm (anterior nasal) and 4 cm (proposed mid-turbinate). Methods: In this randomized, paired clinical trial conducted at a public COVID-19 test center in Copenhagen, Denmark, 309 adults presenting for SARS-CoV-2 RT-PCR testing were enrolled. Each participant underwent bilateral nasal sampling using RDTs: one nostril with a 2 cm swab and the other with a 4 cm swab, randomized by side. RT-PCR from oropharyngeal swabs served as the reference standard. Discomfort was rated using a 10-point visual analog scale (VAS). Results: Among the 309 participants, 57 (18.4%) tested positive for SARS-CoV-2 by RT-PCR. RDT sensitivity was 62.1% (95% CI: 48.4–74.5%) for 2 cm swabs and 70.2% (95% CI: 56.6–81.6%) for 4 cm swabs, a non-significant difference (p = 0.34). Among symptomatic individuals, sensitivity increased to 74.4% (2 cm) and 86.0% (4 cm), though the difference also remained non-significant (p = 0.17). Discomfort scores were significantly higher for the 4 cm swab (mean VAS: 5.2) compared to 2 cm (mean VAS: 3.8; p < 0.001). Conclusions: While not statistically significant, deeper mid-turbinate swabbing (4 cm) showed higher diagnostic sensitivity than anterior nasal swabbing (2 cm), especially in symptomatic individuals. However, this came at the cost of increased discomfort. These findings highlight the importance of balancing diagnostic performance and patient tolerability in pandemic testing strategies. The study contributes valuable evidence to inform future guideline development, particularly regarding swab technique, test accuracy, and feasibility in clinical and public health settings. Full article

Surface plasmon resonance (SPR) is a label-free, real-time biosensing technology with high sensitivity for the detection of biomolecular interactions. This review highlights recent advances in SPR biosensors for the detection of SARS-CoV-2. First, we outline design strategies, especially advanced plasmonic nanostructures and precise surface functionalization, that improve the specificity and binding affinity to viral targets. Next, we cover signal amplification methods, such as nanoparticle conjugation and plasmonic photothermal effects, which enhance the sensitivity for low-abundance viral components. Subsequently, we conducted a comparative analysis of SPR biosensors alongside traditional and emerging detection approaches for SARS-CoV-2, elucidating their individual merits and drawbacks. We also discuss how machine learning improves data interpretation and diagnostic accuracy. Finally, we discuss the current challenges and future development directions, particularly for clinical diagnostics, epidemic monitoring, and public health security. These advances support faster, more reliable, and accessible diagnostics for current and future viral outbreaks. Full article

The onset of the COVID-19 pandemic prompted the rapid development and deployment of novel strategies and methodologies to manage the dissemination of microorganisms. Understanding the crucial role that contaminated surfaces play in the spread of viruses highlights the importance of having effective cleaning and disinfection protocols in place for inanimate objects. A variety of antimicrobial agents have shown strong effectiveness against the SARS-CoV-2 virus. Various factors can impact on the performance of these agents. As a result, technologies utilizing ozone’s microbicidal effects have been developed or improved for cleaning indoor areas, surfaces, and materials, despite ozone’s diverse uses being known for years. Ozone offers the advantage of adaptability for both gaseous and aqueous use, depending on the nature of the decontaminated surfaces. Moreover, ozone-infused water is ecologically benign, possesses microbial-fighting capabilities, and synergistically reinforces the biocidal action of other chemical disinfectants. This review aims to summarize the efforts dedicated to harnessing gaseous and aqueous ozone as a valuable means to eliminate the SARS-CoV-2 virus from environments, surfaces, clinical equipment, and office supplies. This review sourced evidence-based articles from electronic databases, including MEDLINE (via PubMed), EMBASE, the Cochrane Library (CENTRAL), and preprint repositories. The findings illustrated that ozone could serve as an additional tool for curbing the proliferation of COVID-19 and other viral infections. Additionally, we elucidated the operational attributes of ozone, the variables that influence its disinfection potency, and the mechanisms of its virucidal action. Notably, this review does not encompass the disinfection of the COVID-19 virus in wastewater. Full article

Given the rapid mutation and high transmissibility of coronaviruses, especially SARS-CoV-2, comparative genomic studies are crucial for understanding viral evolution, transmission dynamics, and therapeutic development. In prior work, we analyzed and compared the spectral distribution patterns of various k-mer subsets across 920 genome sequences, spanning from primates to prokaryotes. This revealed an evolutionary mechanism in genome sequences, indicating the presence of both CG and TA-specific selection modes. In the present study, we further investigate the specific selection modes in coronavirus genomic sequences by examining the intrinsic distribution rules of 32 XYi 6-mer subset spectra. Our results show that coronavirus genomes exhibit only the CG-specific selection mode, with no evidence of TA-specific selection. Using the CG-specific selection mode, we identified CG1 6-mers as the fundamental subset underlying coronavirus genome evolution. To validate the CG1 subset, we constructed phylogenetic relationships for a set of coronaviruses and SARS-CoV-2 variant genomes. Comparative analysis confirmed that the resulting phylogenetic relationships align more closely with established knowledge. This study thus provides a theoretical framework for inferring phylogenetic relationships at the whole-genome level. Full article

Background/Objective: This study is a cross-sectional investigation of long-term immune responses measured at different time intervals after COVID-19 infections, vaccinations, or combined exposure. The focus is on immune reactivity against recombinant spike (S) and nucleocapsid (N) protein antigens. Materials and Methods: Serum antibody levels were assessed up to four to four and a half years after infection or immunization, including virus-specific immunoglobulin G (IgG), IgA and IgM antibodies, as well as neutralizing antibodies against the S-protein. Cellular immunity was assessed by analyzing peripheral blood mononuclear cells (PBMC; n = 43 in first cohort, n = 32 in second cohort), including T-helper memory and cytotoxic subsets, and cytokine production after in vitro stimulation with recombinant SARS-CoV-2 proteins. A multiplex cytokine assay was used to analyze effector and regulatory immune responses. Results: Virus-specific IgG antibodies persisted for years after exposure to SARS-CoV-2, with IgG against the receptor-binding domain (RBD) correlating most strongly with neutralizing activity. Vaccinated individuals demonstrated higher IgA responses, whereas antibodies to the N-protein were associated with previous infection. No IgM antibodies were detected in any subjects, suggesting an immune response based on memory rather than ongoing infection. PBMCs from individuals with a history of both COVID-19 exposure and vaccination exhibited enhanced responsiveness, characterized by increased frequencies of memory T cells compared to vaccination alone. Stimulating with the S-protein induces higher cytokine production, including IFN-gamma, TNF-alfa, and IL-12(p70), compared with stimulation by the N-protein. Cytokines such as IL-10 and TGF-beta are also elevated, suggesting immune regulation rather than persistent inflammation. Conclusions: SARS-CoV-2 infection and vaccination are associated with persistent humoral and cellular immune responses detectable several years after exposure. Individuals with hybrid immunity exhibit broader and functionally enhanced immune reactivity, indicating more robust long-term immune memory. Future studies should focus on the long-term consequences of hybrid immunity and optimize other vaccine strategies, including recombinant antigen vaccines. Full article

Background: Patients with kidney failure requiring dialysis experience a high burden of vaccine-preventable diseases, and vaccine hypo-responsiveness is a key contributor. Uraemic toxins and gut dysbiosis are potential causes of hypo-responsiveness. Aim: This study aimed to determine whether uraemic toxin concentrations or gut dysbiosis are associated with vaccine response in haemodialysis patients. Methods: This was a single centre, observational cohort study of maintenance dialysis patients receiving a conventional 2-dose primary COVID-19 vaccination course. Demographic, clinical and vaccination data were collected from the eMR. Vaccine response (Elecsys Anti-SARS-CoV-2 immunoassay), serum uraemic toxin concentrations (indoxyl sulphate, p-cresyl sulphate, and trimethylamine N-oxide by liquid chromatography), and stool microbiome (16S rRNA gene sequencing) were measured 8 weeks after the second dose of vaccine. Results: Forty participants (43% female, mean age 66 years; 59% Caucasian) were included, 70% of whom were classified as a vaccine responder. Antibiotic exposure, prednisolone use and lymphopenia were significantly associated with hypo-responsiveness. Microbiome profiling identified differences in beta diversity between responders and non-responders, positively correlated with short-chain fatty acid producers (Parabacteriodes) and negatively with pathobionts (Escherichia/Shigella). Differential abundance analysis identified lower levels of Tyzzerella, Gemmiger, and Hungatella and higher levels of Turicibacter in vaccine responders. Total uraemic toxin burden and individual toxin concentrations did not differ between responders and hypo-responders (all p > 0.05). Stratification by low versus high/very high toxin burden groupings was not associated with response (p > 0.99). Conclusions: Differences in gut microbial composition were observed between vaccine responder groups, while uraemic toxin concentrations were not associated with vaccine responsiveness. These findings suggest gut microbiota composition may contribute to vaccine hypo-responsiveness in individuals receiving dialysis and warrant further investigation in larger mechanistic studies. Full article

Background: Myocarditis is an uncommon but recognized adverse event following mRNA COVID-19 vaccination, with risk varying by age, sex, dose number, and vaccine product. Clarifying the magnitude of risk, clinical course, and recovery—relative to myocarditis following SARS-CoV-2 infection—is essential for risk–benefit assessment and public health guidance. Methods: We performed a systematic PubMed and Embase search (January 2020–December 2024) and synthesized cohort, registry, and surveillance data on myocarditis incidence and outcomes following mRNA COVID-19 vaccination. Outcomes included incidence, observed-to-expected (OE) or incidence rate (IRRs) ratios, hospitalization, and short-term recovery. Study selection followed PRISMA 2020 systematic review guidelines. Results: Myocarditis following mRNA COVID-19 vaccination was identified as a rare adverse event, most commonly occurring after the second dose and in younger male individuals. Across multiple cohort and registry-based studies, cases were generally mild and self-limited, with most patients recovering without complication. In contrast, myocarditis following SARS-CoV-2 infection was consistently associated with more severe outcomes, including higher rates of hospitalization and mortality. Conclusions: Vaccine-associated myocarditis is rare, typically mild, and self-limited, with excellent short-term recovery; vaccinated individuals also exhibit lower odds of in-hospital death and intubation. In contrast, infection-associated myocarditis is more frequent and severe. Overall, the benefit–risk profile of mRNA vaccination remains strongly favorable. Full article

COVID-19 perturbs the renin-angiotensin system (RAAS) and inflammatory pathways, shaping disease severity. Soluble ACE2 (sACE2) and angiotensin II (Ang II) are central regulators of vascular and immune homeostasis. We profiled plasma from COVID-19 patients and controls using ELISA, together with 48 cytokine profiling and clinical data. Both sACE2 and Ang II were significantly elevated in patients. Increased Ang II was associated with oxygen supplementation and dyspnea, and negatively correlated with IL-3, whereas sACE2 correlated with IL-13 and FGF. Comorbidities modulated cytokine expression: diabetes mellitus was linked to reduced LIF and MCP-1, hypertension to decreased LIF and increased IP-10, and obesity to elevated IL-12p70. Age correlated with TNF and HGF, and reduced oxygen saturation was associated with lower LIF. These findings reveal that acute COVID-19 disrupts RAAS and amplifies immune dysregulation, with Ang II emerging as a pivotal mediator of respiratory compromise and inflammatory imbalance, underscoring its potential as a biomarker and therapeutic relevance. Full article