Search Results (19,273)

This case-control study investigated the association between polymorphisms in the dedicator of cytokinesis 2 (DOCK2) gene and susceptibility to COVID-19 in a Mexican population. Methods: Genotyping of five single-nucleotide polymorphisms (SNPs) in the DOCK2 gene (rs9307 A/G, rs1045176 G/T, rs1045168 C/T, rs2112703 A/C, and rs2287727 A/C) was performed using TaqMan assays in 248 COVID-19 patients and 288 healthy controls. Results: No significant differences were observed in the allelic or genotypic distributions of rs1045176 G/T and rs2287727 A/C between cases and controls. However, under multiple genetic inheritance models (co-dominant, dominant, recessive, heterozygous, and additive), the rs9307 A, rs1045168 C, and rs2112703 A alleles were significantly associated with a reduced risk of COVID-19 (p < 0.05). Furthermore, sub-analyses stratified by genotype in COVID-19 patients revealed that the rs9307 AA, rs1045168 CC, and rs2112703 AA genotypes correlated with altered plasma concentrations of lactic acid dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and ferritin. Conclusions: The DOCK2 SNPs rs9307 A/G, rs1045168 C/T, and rs2112703 A/C are associated with decreased susceptibility to COVID-19 in this population and influence plasma levels of LDH, ALT, AST, and ferritin, suggesting a potential role in disease pathogenesis and severity. Full article

Background: COVID-19 is primarily a respiratory disease, but increasing evidence suggests possible oral and maxillofacial complications. This study presents a case series of post-COVID maxillary osteonecrosis (PC-RONJ) cases from western Romania and explores the possible association between SARS-CoV-2 infection, its treatment, and this complication. Methods: We conducted a multicenter retrospective case series of two patients with recent PCR-confirmed SARS-CoV-2 infection who subsequently developed maxillary osteonecrosis (ONC) between 2021 and 2023. Clinical examination, CT imaging (including 3D reconstructions), and ENT assessment were used to assess the severity of the disease. All medical records were reviewed to identify comorbidities, details of COVID-19 treatment, and the appearance of maxillofacial symptoms. Results: Both patients had been hospitalized for severe COVID-19 and treated according to the national protocol with systemic corticosteroids, oxygen therapy, anticoagulation, and antivirals. CT scans revealed marked osteolytic destruction of the maxilla and maxillary sinus walls, with extension toward adjacent facial bones. Microbiological analysis revealed a complex polymicrobial profile, including Gram-positive and Gram-negative bacteria as well as opportunistic fungal species, consistent with a chronic biofilm-associated infectious process. Patients received surgical treatment, followed by local care and, in both cases, prosthetic rehabilitation with maxillary obturators, which improved speech, chewing, and oral function. Conclusions: This case series suggests a possible association between severe COVID-19, its treatment, and subsequent maxillary osteonecrosis in susceptible patients; however, the small number of cases precludes causal inference. To our knowledge, this is the first Romanian report describing such cases in patients without prior antiresorptive therapy. These findings highlight the need for careful use of systemic corticosteroids and vigilant post-recovery monitoring of maxillofacial complications. Further studies are required to clarify the underlying mechanisms and risk factors. Full article

The redox mechanisms of RAW 264.7 macrophages exposed to 2.45 GHz RF-EMF at subthermal specific absorption rates and to lipopolysaccharide (LPS) and/or the SARS-CoV-2 spike protein (CSP) were investigated. To this end, cellular responses (lysosomal and mitochondrial activity, nitric oxide (NO) production, and cell survival/death) were measured after 6, 24, and 48 h. Selective loss of viability in cells exposed to RF and LPS was observed at 6 h, consistent with early defects in membrane permeability. Lysosomal activity was significantly enhanced in cells treated with RF + LPS. Mitochondrial activity decreased in cells exposed to RF + LPS at 6 h and increased in cells treated with RF + CPS/LPS. Cell viability decreased greatly in cells treated with LPS and CSP + LPS after 24, particularly after 48 h. Nitrite levels peaked in non-irradiated cells treated with RF + LPS and in CSP + LPS at 24 h and decreased in irradiated cells after 48 h. Irradiation affected selection of the death mode: apoptosis decreased or remained unchanged in cells subjected to any of the treatments, while necrosis increased in cells treated with CPS, LPS, or both for 48 h. The combination of RF-EMF and infectious agents reprogrammed the interaction between mitochondria/lysosomes/nitric oxide (NO)/cell death in macrophages in a time- and stimulus-dependent manner. Full article

The m⁶A RNA methylation pathway plays a critical role in host antiviral defense. Host cells employ m⁶A readers such as YTHDF2 to regulate viral RNA fate through diverse mechanisms, including degradation, translational control, and immune recognition. However, we found that YTHDF2 is essential for SARS-CoV-2 replication, suggesting that a virus may exploit this host machinery to its advantage. Through integrative RNA-proteome analysis, we identified the SARS-CoV-2 nucleocapsid (N) transcript as the most heavily m⁶A-modified viral transcript and a direct interactor of YTHDF2. The N protein forms a complex with YTHDF2 in the cytoplasm and redirects this host RNA decay machinery toward host antiviral transcripts. N suppresses ISG15, IFIT1, MX1 and pro-inflammatory cytokines in a largely YTHDF2-dependent manner, an effect that is lost in YTHDF2-knockout cells. These findings reveal a viral immune evasion strategy wherein a viral protein actively hijacks an m⁶A reader to silence antiviral gene expression, establishing the N-YTHDF2 axis as a therapeutic target against SARS-CoV-2 and other coronaviruses. Full article

Background and Objectives: Healthcare workers are at heightened risk of SARS-CoV-2 infection. Understanding the duration and protective value of vaccine-induced immunity is critical to inform booster strategies. This study investigates longitudinal dynamics of anti-SARS-CoV-2 receptor-binding domain IgG (anti-RBD IgG) antibodies and their association with infection risk among vaccinated healthcare workers. Materials and Methods: A prospective cohort study was conducted at Vilnius University Hospital Santaros Klinikos, Lithuania. A total of 1778 healthcare workers who completed a primary COVID-19 vaccination series were followed. Blood samples were collected every three months to measure anti-RBD IgG levels. Participants also received up to three booster doses. COVID-19 was identified by PCR, antigen tests, or positive anti-nucleocapsid IgG. For serologically detected cases, infection timing was assigned to the interval between study visits. Antibody dynamics were analyzed across vaccination stages, time, age groups, and circulating SARS-CoV-2 variants. Results: Anti-RBD IgG titers peaked in the first quarter after primary vaccination (mean 7904 AU/mL), declined sharply by quarters 2–3, and rose substantially after booster doses. Following the first booster, titers increased to ~12,598 AU/mL in quarter 1 and continued rising through quarter 3. The highest levels were observed after the second booster (24,456 AU/mL in Q1), followed by gradual decline. A high-titer plateau persisted from quarters 6 to 9 (~21,000 AU/mL), followed by decline in quarters 10–11 and partial rebound in Q12. Approximately 49.6% of participants experienced COVID-19 during follow-up. Antibody response patterns were similar across age groups, with only minor transient differences. Conclusions: COVID-19 booster doses significantly enhance and prolong humoral immunity in healthcare workers compared with the primary vaccination series. However, antibody waning over time emphasizes the need for timely boosters, particularly during periods of variant circulation. These findings support continued booster vaccination and monitoring of long-term immune protection, although anti-RBD IgG should be interpreted as a surrogate marker of humoral rather than overall immunity. Full article

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