Search Results (3,209)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a wide range of clinical manifestations modulated by genetic factors. The aim of this study was to identify genetic determinants of severe COVID-19 affecting protein sequence to gain insight into disease pathogenesis. Variants prioritized in two patients requiring lung transplant were tested in the Milan FOGS cohort (487/869 cases/controls), highlighting an independent association between the p.F8S low-frequency variant of interferon alpha receptor 2 gene (IFNAR2) and severe disease (OR = 1.73 [1.24–2.42], p = 0.001), replicated in the COVID-19 Host Genetics Initiative cohort (26,167/2,061,934 cases/controls). In the FOGS cohort, the p.F8S variant was linked to higher circulating IL-6 levels. In keeping, bulk transcriptomic analysis in PBMCs at the peak of infection (n = 57) showed that carriers of the p.F8S variant had upregulation of immune signaling and pathogens response (p < 0.05). Functional flow cytometry experiments in healthy donors (n = 12) revealed that membrane IFNAR2 protein expression was reduced in B lymphocytes, but higher in dendritic cells (p < 0.05). Finally, by interrogating a public scRNAseq resource of PBMC of people with COVID-19, we showed that p.F8S carriers had upregulation of immune pathways specifically in dendritic cells (p < 0.05). These results suggest that the p.F8S variant may influence COVID-19 severity by enhancing adaptive immune response, thereby favoring inflammation. Full article

Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer’s Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection. Full article

SARS-CoV-2, the virus responsible for coronavirus disease COVID-19, is a highly transmissible pathogen that has caused substantial global morbidity and mortality. The ongoing COVID-19 pandemic caused by this virus has had a significant impact on public health and the global economy. One approach to combating COVID-19 is the development of broadly neutralizing antibodies for prevention and treatment. In this work, we performed an in silico ligand-based screening of the PDB database to search for unique anti-SARS-CoV-2 motifs. The collected data were organized and presented in a classified SARS-CoV-2 Ligands Database, categorized based on the number of ligands and structural components of the spike glycoprotein. The database contains 1797 entries related to the structures of the spike glycoprotein (UniProt ID: P0DTC2), including both full-length molecules and their fragments (individual domains and their combinations) with various ligands, such as angiotensin-converting enzyme II and antibodies. The database’s capabilities allow users to explore various datasets according to the research objectives. To search for motifs in the receptor-binding domain (RBD) most frequently involved in antibody binding sites, antibodies were classified into four classes according to their location on the RBD; for each class, special binding motifs are revealed. In the RBD binding sites, specific tyrosine-containing motifs were found. Data obtained may help speed up the creation of new antibody-based therapies, and guide the rational design of next-generation vaccines. Full article

Background: Although the relationship between androgen deprivation therapy (ADT) for prostate cancer (PC) and the biological mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unequivocally unclear, it is possible that exposure to the virus may influence PC evolution by altering TMPRSS2 expression. This study aims to evaluate the long-term oncological outcomes of patients with metastatic PC who were undergoing medical therapy at the time of contracting SARS-CoV-2 and who resumed/continued anticancer treatment after recovery. Methods: We retrospectively evaluated a consecutive series of 151 metastatic PC patients who developed SARS-CoV-2 infection while receiving one active systemic anticancer therapy (125 metastatic castration-resistant PC (mCRPC) patients and 26 metastatic hormone-sensitive PC (mHSPC) patients). We evaluated variables that influence the ability to maintain or resume the ongoing therapy. For the maintained/resumed therapies, we calculated the post-infection overall survival (piOS) and the overall survival (OS). Results: Of the patients, 12.6% died due to SARS-CoV-2 infection, 10.6% recovered from the infection but failed to maintain/resume the ongoing anticancer treatment, and the remaining 76.8% maintained/resumed the treatment after recovery. Hospitalization, duration of infection, and the type of ongoing anticancer agent influenced these treatment changes. In the cohort of mCRPC patients, the median piOS was 32 months, and the median OS was 67.8 months. The median piOS was not achieved in the cohort of mHSPC patients, while the median OS was 122 months. The outcomes of single anticancer agents were in line with those of pivotal trials. Conclusions: Although observed in a highly selected population of PC patients who survived SARS-CoV-2 infection and were able to resume/maintain anticancer therapy, the survival outcomes of this study appear to be in line with those reported in pivotal studies, and SARS-CoV-2 infection does not seem to have adversely affected long-term oncological outcomes. Full article

Background/Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to pose a significant global health challenge due to its high transmissibility and potential for severe clinical outcomes. Early identification of patients at risk of hospitalization is essential for effective triage in emergency departments and for the optimal allocation of healthcare resources. Methods: This prospective study included 84 patients aged over 18 years who presented to the emergency department on 23 December 2020, with suspected SARS-CoV-2 infection. Initially, 100 patients were evaluated, and 16 were excluded based on predefined exclusion criteria. The mean age of the participants was 53.65 ± 13.62 years, and 39 (46.4%) were women. Results: At admission, the mean signal peptide, CUB domain, EGF (SCUBE-1) level among SARS-CoV-2 patients was 0.16 ± 0.08 ng/mL. There was no significant difference in SCUBE-1 levels between patient and control groups (n = 59 vs. 25), but levels differed significantly between hospitalized and home-treated patients (n = 37 vs. 22; p = 0.001). Neutrophil count (p = 0.001) and NLR (p = 0.010) were higher in patients than controls and also higher in hospitalized than home-treated patients (p = 0.003 and p = 0.015). ROC analysis revealed that SCUBE-1 predicted hospitalization with 84.6% sensitivity and 88.9% specificity. A positive correlation was observed between SCUBE-1 levels and length of hospital stay (p = 0.007, r = 0.554), with a median stay of 9.0 (5.0–11.0) days. Conclusions: SCUBE-1 levels were significantly associated with disease severity in SARS-CoV-2 patients and may serve as a promising biomarker to support clinical decision-making for hospitalization versus home-based management. Full article

The overlapping circulation of influenza (Flu), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; SC2), and respiratory syncytial virus (RSV) continues to challenge clinical laboratories, particularly in settings with limited automation and fragmented healthcare coverage. This study expanded the CDC Flu-SC2 assay by incorporating a laboratory-developed test (LDT) for RSV A/B detection into a fully automated quadruplex RT-qPCR (LDRA) on the Panther Fusion^® Open Access™ system. The design, based on more than 8000 RSV genomic sequences targeting the conserved M gene, achieved optimal amplification efficiencies (97–105%) and full multiplex compatibility. Analytical assessment established limits of detection between 9.6 and 37.8 copies per reaction, absence of cross-reactivity with 30 respiratory pathogens, and inclusivity for 32 viral variants. Commutability and diagnostic performance among the LDRA, CE IVD-marked Allplex™ SARS-CoV-2/FluA/FluB/RSV, and US IVD-marked Panther Fusion^® SARS-CoV-2/Flu A/B/RSV Assays were evaluated using 405 nasopharyngeal UTM-preserved swabs. The LDRA demonstrated excellent concordance (overall agreement ≥ 98%, κ > 0.95), strong diagnostic accuracy, and reliable detection of mixed infections. This quadruplex provides a fully automated, rapid, and accurate solution for the simultaneous detection of influenza A, influenza B, SARS-CoV-2, and RSV viruses, enhancing molecular diagnostic capacity and supporting equitable, timely clinical decision-making in middle-income healthcare systems such as that of the Dominican Republic. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global COVID-19 pandemic, which led to hundreds of millions of human infections and more than seven million deaths worldwide. Major variants of concern, particularly the Omicron variant and its associated subvariants, can escape the vaccines developed so far to target previous strains/subvariants. Therefore, effective vaccines that broadly neutralize different Omicron subvariants and show good protective efficacy are needed to prevent further spread of Omicron. The spike (S) protein, including its receptor-binding domain (RBD), is a key vaccine target. Methods: Here, we designed a unique mRNA vaccine encoding Omicron-KP.3 RBD based on RBD-truncated S protein backbone of an earlier Omicron subvariant EG.5 (KP3 mRNA), and evaluated its stability, immunogenicity, neutralizing activity, and protective efficacy in a mouse model. Results: Our data showed that the nucleoside-modified, lipid nanoparticle-encapsulated mRNA vaccine was stable at various temperatures during the period of detection. In addition, the vaccine elicited potent antibody responses with broadly neutralizing activity against multiple Omicron subvariants, including KP.2, KP.3, XEC, and NB.1.8.1. This mRNA vaccine protected immunized transgenic mice from challenge with SARS-CoV-2 Omicron-KP.3. Immune serum also protected against subsequent virus challenge, with the level of protection associating positively with the serum neutralizing antibody titer. Conclusions: Taken together, the data presented herein suggest that this newly designed mRNA vaccine has potential against current and future Omicron subvariants. Full article

The COVID-19 pandemic has profoundly affected societies around the world. Although the emergency phase of coronavirus disease 2019 (COVID-19) has ended, the threat it poses remains persistent. This review aims to clarify the mechanisms of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection to support effective management of the disease. A central focus is the host cellular response to the viral infection, with particular emphasis on the role of cytokines. Cytokines play a dual role in antiviral defense: they contribute to the inhibition of viral replication and facilitate the clearance of pathogens, yet dysregulated cytokine responses can result in severe immunopathology. Interferons (type I, type II, and type III) and other cytokines are pivotal in activating intracellular antiviral mechanisms and in orchestrating the recruitment of immune cells through extracellular signaling. Effective immune responses to viral infections are governed not only by primary immune cells—such as dendritic cells, T lymphocytes, and B lymphocytes—but also by the local cytokine milieu shaped by infected and neighboring cells. Given the presence of endogenous inhibitors and autoantibodies in vivo, it is essential to evaluate the functional activity of cytokines in clinical samples. We propose a novel approach to quantify biologically active cytokine levels. Full article

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated not only with respiratory illness but also with profound vascular and coagulation disturbances. Long COVID (LC) is characterized by persistent symptoms such as fatigue, dyspnea, cognitive impairment, and palpitations. Mechanistically, SARS-CoV-2 induces direct endothelial injury, promotes a pro-inflammatory cytokine milieu, and activates platelets, leading to immunothrombosis and impaired fibrinolysis. Consequently, patients exhibit microthrombosis, elevated plasma D-dimer, fibrinogen dysregulation, and persistent hypercoagulability. Clinically, this translates into an increased risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, as well as arterial thrombotic events such as myocardial infarction and stroke, which may persist months after acute infection. Understanding the interplay between endothelial injury, inflammation, and coagulation is crucial for risk stratification and the development of preventive and therapeutic strategies. We conducted a systematic narrative review of the literature, including human clinical and mechanistic studies identified through PubMed, Scopus and Web of Science up to 30 September 2025. This review synthesizes current evidence on vascular complications in LC, highlighting endothelial dysfunction as a central pathophysiological nexus linking the acute phase of SARS-CoV-2 infection with chronic LC manifestations. Full article

The coronavirus disease 2019 (COVID-19) pandemic remains a significant public health threat globally with significant socio-economic impacts. People living with human immunodeficiency virus (HIV) (PLWH) have a high risk of severe outcomes of COVID-19 due to immunosuppression. Clinical manifestation of COVID-19 in HIV patients largely remains unclear. We carried out a pilot study to investigate the clinical laboratory data and circulating cytokines in PLWH infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Tatarstan, Russia. Serum samples were collected from three groups: PLWH with COVID-19 (PLWH/COVID-19), COVID-19-only, and uninfected controls. We found an increased risk of severe COVID-19 in PLWH/COVID-19 patients compared to COVID-19-only. Four fatal cases were in PLWH/COVID-19, while there was no fatality in COVID-19-only. Pro-inflammatory cytokines, such as IL-5, IL-6, IL-9, and IL-15, were elevated in PLWH/COVID-19 compered to COVID-19-only. These preliminary findings highlight the potential for more severe COVID-19 in PLWH/COVID-19 where pro-inflammatory cytokines could play pathogenic role. Full article

The impact of physical health conditions on coronavirus disease of 2019 (COVID-19) severity in World Trade Center disaster-exposed populations remains understudied. We examined the association of type, number and diagnosis time of pre-existing health conditions with COVID-19 severity, using the WTC Health Registry (WTCHR). We analyzed 3568 WTCHR enrollees with self-reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a 2021 follow-up survey. COVID-19 severity was measured by self-reported symptom duration (<2, 2–4, and >4 weeks) and hospitalization (hospitalized versus not). Pre-existing gastroesophageal reflux disease (GERD), respiratory conditions, cardiovascular conditions, and diabetes were self-reported and categorized into four groups (no diagnosis, post-9/11, pre-9/11, and undefinable). We used multinomial logistic regression and binary logistic regression to analyze the association of comorbidities with COVID-19 symptom duration and hospitalization, respectively, adjusting for post-traumatic stress disorder and demographic factors. Analysis was also conducted separately by enrollee type: rescue and recovery workers (RRW) vs. community members (non-RRW). Having all four health conditions post-9/11 was associated with longer symptom duration after SARS-CoV-2 infection (>4 weeks) among RRW (AOR: 2.66, 95% CI: 1.03–6.87). Reporting a post-9/11 respiratory condition was associated with an increased risk of being hospitalized among RRW and an increased risk of longer symptom duration (>4 weeks) among non-RRW. While post-9/11 diabetes was associated with an increased risk of longer symptom duration among RRW, post-9/11 GERD and pre-9/11 cardiovascular conditions were associated with an increased risk of longer symptom duration and being hospitalized among non-RRW, respectively. The impact of certain health conditions on COVID-19 severity varied across enrollee types and time of diagnosis. Given the lasting health impacts of 9/11-related exposures, targeted medical surveillance and proactive healthcare interventions are critical for mitigating the risk of severe COVID-19 illness in this population. Full article

The escalating global crisis of antimicrobial-resistant (AMR) bacterial infections, along with the continuous threat of viral outbreaks, poses a serious risk to public health worldwide and underscores the urgent need for innovative therapeutic strategies. In this study, mesoporous silica nanoparticles (MSNs) were successfully synthesized and subsequently functionalized with copper to impart broad-spectrum antimicrobial activity. The oxidation state of copper on the MSN surface was modulated through thermal treatments, allowing the evaluation of its influence on antimicrobial efficacy. The modified MSNs were tested against key bacterial pathogens, including Escherichia coli and Staphylococcus aureus, achieving complete bactericidal activity after 2 h of exposure to E. coli. Moreover, as well as influenza A (H1N1) pdm09, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and MS2 bacteriophage (MS2) were evaluated, reaching an efficiency higher than 80%, 90%, and 97%, respectively. The results indicated that copper-modified MSNs exhibit potent antibacterial and antiviral activity, highlighting their potential as an antibiotic-free alternative for preventing microbial infections while mitigating the development of AMR bacteria. Full article

Background/Objectives: Quantitative computed tomography (CT) metrics are widely used to assess pulmonary involvement and to predict short-term severity in coronavirus disease 2019 (COVID-19). However, it remains unclear whether baseline artificial intelligence (AI)-based quantitative high-resolution computed tomography (HRCT) metrics of pneumonia burden provide incremental prognostic value for in-hospital composite adverse outcomes beyond routine clinical factors, or whether these imaging-derived markers carry any exploratory signal for long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection among hospitalized patients. Most existing imaging studies have focused on diagnosis and acute-phase prognosis, leaving a specific knowledge gap regarding AI-based quantitative HRCT correlates of early deterioration and subsequent reinfection in this population. To evaluate whether combining deep learning-derived, quantitative, HRCT features and clinical factors improve prediction of in-hospital composite adverse events and to explore their association with long-term reinfection in patients with COVID-19 pneumonia. Methods: In this single-center retrospective study, we analyzed 236 reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients who underwent baseline HRCT. Median follow-up durations were 7.65 days for in-hospital outcomes and 611 days for long-term outcomes. A pre-trained, adaptive, artificial-intelligence-based, prototype model (Siemens Healthineers) was used for pneumonia analysis. Inflammatory lung lesions were automatically segmented, and multiple quantitative metrics were extracted, including opacity score, volume and percentage of opacities and high-attenuation opacities, and mean Hounsfield units (HU) of the total lung and opacity. Patients were stratified based on receiver operating characteristic (ROC)-derived optimal thresholds, and multivariable Cox regression was used to identify predictors of the composite adverse outcome (intensive care unit [ICU] admission or all-cause death) and SARS-CoV-2 reinfection, defined as a second RT-PCR-confirmed episode of COVID-19 occurring ≥90 days after initial infection. Results: The composite adverse outcome occurred in 38 of 236 patients (16.1%). Higher AI-derived opacity burden was significantly associated with poorer outcomes; for example, opacity score cut-off of 5.5 yielded an area under the ROC curve (AUC) of 0.71 (95% confidence interval [CI] 0.62–0.79), and similar performance was observed for the volume and percentage of opacities and high-attenuation opacities (AUCs up to 0.71; all p < 0.05). After adjustment for age and comorbidities, selected HRCT metrics—including opacity score, percentage of opacities, and mean HU of the total lung (cut-off −662.38 HU; AUC 0.64, 95% CI 0.54–0.74)—remained independently associated with adverse events. Individual predictors demonstrated modest discriminatory ability, with C-indices of 0.59 for age, 0.57 for chronic obstructive pulmonary disease (COPD), 0.62 for opacity score, 0.63 for percentage of opacities, and 0.63 for mean total-lung HU, whereas a combined model integrating clinical and imaging variables improved prediction performance (C-index = 0.68, 95% CI: 0.57–0.80). During long-term follow-up, RT-PCR–confirmed reinfection occurred in 18 of 193 patients (9.3%). Higher baseline CT-derived metrics—particularly opacity score and both volume and percentage of high-attenuation opacities (percentage cut-off = 4.94%, AUC 0.69, 95% CI 0.60–0.79)—showed exploratory associations with SARS-CoV-2 reinfection. However, this analysis was constrained by the very small number of events (n = 18) and wide confidence intervals, indicating substantial statistical uncertainty. In this context, individual predictors again showed only modest C-indices (e.g., 0.62 for procalcitonin [PCT], 0.66 for opacity score, 0.66 for the volume and 0.64 for the percentage of high-attenuation opacities), whereas the combined model achieved an apparent C-index of 0.73 (95% CI 0.64–0.83), suggesting moderate discrimination in this underpowered exploratory reinfection sample that requires confirmation in external cohorts. Conclusions: Fully automated, deep learning-derived, quantitative HRCT parameters provide useful prognostic information for early in-hospital deterioration beyond routine clinical factors and offer preliminary, hypothesis-generating insights into long-term reinfection risk. The reinfection-related findings, however, require external validation and should be interpreted with caution given the small number of events and limited precision. In both settings, combining AI-based imaging and clinical variables yields better risk stratification than either modality alone. Full article

Background: Rapid and high-throughput diagnostic methods are essential for controlling the spread of infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lateral flow immunoassay (LFIA) strips provide a cost-effective and user-friendly platform for point-of-care testing. However, the sensitivity of conventional LFIA kits is often limited by the performance of their detection probes. This study reports a highly sensitive LFIA strip for detecting the SARS-CoV-2 nucleocapsid (NP) protein using platinum-decorated poly(2-vinylpyridine) nanoparticles (Pt-P2VPs) as probes. Methods: Monoclonal antibodies against SARS-CoV-2 NP were conjugated with Pt-P2VPs and incorporated into LFIA strips. The test line was coated with anti–SARS-CoV-2 NP monoclonal antibody, and the control line with goat anti-mouse IgG. Recombinant proteins, viral strains, and nasopharyngeal swab specimens from patients were used to evaluate assay performance, with reverse transcription polymerase chain reaction (RT-PCR) as the reference standard. Diagnostic accuracy was assessed using nonparametric statistical tests. Results: Pt-P2VP-based LFIA strips enabled sensitive detection of recombinant NP and inactivated SARS-CoV-2, with minimal cross-reactivity. In 200 clinical specimens (100 PCR-negative and 100 PCR-positive), the assay achieved 74% sensitivity and 100% specificity, with strong correlation to viral RNA load. Compared with conventional LFIA kits, Pt-P2VP strips demonstrated superior sensitivity at lower viral loads. Conclusions: Pt-P2VPs represent a promising probe material for enhancing LFIA performance and may facilitate the development of rapid, sensitive, and scalable immunoassays for infectious disease diagnostics in biomedical applications. Full article