The COVID-19 pandemic has raised concerns about potential links between SARS-CoV-2 infection and autoimmune diseases. This study investigated changes in the incidence rate (IR) of autoimmune diseases among children following the pandemic's onset.

A retrospective cross-sectional study analyzed data from Clalit Health Services, Israel's largest healthcare provider, examining the IR of different autoimmune diseases in children aged 0-18. The study compared pre-pandemic (2019) with pandemic/post-pandemic periods (2020-2023), encompassing a cohort of over 1.5 million children.

Significant IR increases were observed across multiple autoimmune diseases. Rheumatic diseases (Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus, Henoch Schoenlein Purpura (HSP)) showed consistent increases, with HSP demonstrating the most pronounced trend. Endocrine disorders exhibited diverse patterns, with autoimmune thyroid diseases and Type 1 diabetes showing overall increases, while diabetic ketoacidosis exhibited an initial spike followed by a decline. Gastrointestinal diseases displayed heterogeneous patterns; Celiac disease and Ulcerative colitis showed general increases, Crohn's disease showed a downward trend, and autoimmune hepatitis exhibited an initial significant decrease followed by a significant increase. Dermatological conditions, including Psoriasis and Vitiligo, demonstrated consistent elevations throughout 2020-2023. Immune Thrombocytopenia Purpura showed initial decreases followed by significant increases in 2022-2023.

This comprehensive analysis reveals significant changes in pediatric autoimmune disease incidence following the COVID-19 pandemic, suggesting potential associations between SARS-CoV-2 infection and autoimmune dysregulation. The diverse patterns observed across different conditions highlight the complex interplay between viral infection and autoimmunity, emphasizing the need for continued surveillance and investigation of long-term immunological consequences of COVID-19 in pediatric populations.

SARS-CoV-2 remains a severe threat to worldwide public health, particularly as the virus continues to evolve and diversify into variants of concern (VOCs). Among these VOCs, Omicron variants exhibit unique phenotypic traits, such as immune evasion, transmissibility, and severity, due to numerous spike protein mutations and the rapid subvariant evolution. These Omicron subvariants have more than 15 mutations in the receptor-binding domain (RBD), a region of the SARS-CoV-2 spike protein that is important for recognition and binding with the angiotensin-converting enzyme 2 (ACE2) human receptor. To address the impact of these high numbers of Omicron mutations on the binding process, we have developed a novel method to precisely quantify amino acid interactions via the amino acid-amino acid bond pair (AABP). We applied this concept to investigate the interface interactions of the RBD-ACE2 complex in four Omicron Variants (BA.1, BA.2, BA.5, and XBB.1.16) with its Wild Type counterpart. Based on the AABP analysis, we have identified all the sites that are affected by mutation and have provided evidence that unmutated sites are also impacted by mutation. We have calculated that the binding between RBD and ACE2 is strongest in OV BA.1, followed by OV BA.2, WT, OV BA.5, and OV XBB.1.16. We also present the partial charge values for all 311 residues across these five models. Our analysis provides a detailed understanding of changes caused by mutation in each Omicron interface complex.

The COVID-19 pandemic, driven by SARS-CoV-2, has led to a global health crisis, highlighting the virus's unique molecular mechanisms that distinguish it from other respiratory pathogens. It is known that the Hypoxia-Inducible Factor 1α (HIF-1α) activates a complex network of intracellular signaling pathways regulating cellular energy metabolism, angiogenesis, and cell survival, contributing to the wide range of clinical manifestations of COVID-19, including Post-Acute COVID-19 Syndrome (PACS). Emerging evidence suggests that dysregulation of HIF-1α is a key driver of systemic inflammation, silent hypoxia, and pathological tissue remodeling in both the acute and post-acute phases of the disease. This scoping review was conducted following PRISMA-ScR guidelines and registered in INPLASY. It involved a literature search in Scopus and PubMed, supplemented by manual reference screening, with study selection facilitated by Rayyan software. Our analysis clarifies the dual role of HIF-1α, which may either worsen inflammatory responses and viral persistence or support adaptive mechanisms that reduce cellular damage. The potential for targeting HIF-1α therapeutically in COVID-19 is complex, requiring further investigation to clarify its precise role and translational applications. This review deepens the molecular understanding of SARS-CoV-2-induced cellular and tissue dysfunction in hypoxia, offering insights for improving clinical management strategies and addressing long-term sequelae.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), and SARS-CoV-2 has been linked to changes in DNA methylation (DNAm) patterns. Studies focused on post-SARS-CoV-2 infection and DNAm have been mainly carried out among severe COVID-19 cases or without distinguishing the severity of cases. However, investigations into mild and asymptomatic cases after SARS-CoV-2 infection are limited. In this study, we analyzed DNAm patterns of mild and asymptomatic cases seven months after SARS-CoV-2 infection in a household setting by conducting epigenome-wide association studies (EWAS).

We identified DNAm changes at 42 CpG sites associated with anti-SARS-CoV-2 antibody levels. We additionally report EWAS between COVID-19 cases and controls, with the case status being confirmed by either an antibody test or a PCR test. The EWAS with an antibody test case definition identified 172 CpG sites to be differentially methylated, while the EWAS with a PCR test case definition identified 502 CpG sites. Two common sites, namely cg17126990 (annotated to AFAP1L2) and cg25483596 (annotated to PC), were identified to be hypermethylated across the three EWAS. Both CpG sites have been reported to be involved in molecular pathways after SARS-CoV-2 infection. While AFAP1L2 has been found to be upregulated after SARS-CoV-2 infection, the pyruvate carboxylase (PC) activity seems to be affected by SARS-CoV-2 infection resulting in changes to the host cell metabolism. Additionally, an EWAS to assess persistent health restrictions among PCR-confirmed cases showed 40 CpG sites to be differentially methylated.

We detected associations between DNAm in individuals who had asymptomatic and mild SARS-CoV-2 infections as compared to their household controls. These findings contribute to our understanding of the molecular consequences of SARS-CoV-2 infection observed months after infection.

The recent surge of COVID-19 cases has raised concerns about its potential long-term effects on cognitive function. This review explores the growing body of research investigating the link between COVID-19 infection and cognitive impairment. Studies employing observational, longitudinal, and case-control designs reveal a concerning prevalence of cognitive impairment in survivors, affecting domains like attention, memory, executive function, and processing speed. The persistence of these deficits for months after the initial infection highlights the potential for long-term consequences. While the precise mechanisms remain under investigation, potential contributing factors include neuroinflammation, hypoxia, and psychological effects. Limitations within the current research landscape necessitate further investigation into the long-term trajectory of cognitive decline, the potential for intervention and recovery, and the role of vaccination in mitigating these effects. Understanding the multifaceted nature of this issue is crucial for developing effective strategies to ensure optimal cognitive health outcomes for COVID-19 survivors.

Metabolic modeling is essential for understanding the mechanistic bases of cellular metabolism in various organisms, from microbes to humans, and the design of fitter microbial strains. Metabolic networks focus on the overall fluxes through biochemical reactions that implicitly rely on several biochemical processes, such as active or diffusive uptake (or export) of nutrients (or metabolites), enzymatic turnover of metabolites, and metal-cofactor enzyme interactions. Despite independent progress in biomolecular simulations, they have yet to be integrated to inform metabolic models. We explore the evolution of computational metabolic modeling approaches, starting with flux balance analysis, dynamic, kinetic delineations of metabolic shifts in single organisms within cells and across tissues, and mutually informing, community-level modeling frameworks and provide a narrative to tie in biomolecular simulations and machine learning predictions to usher the new phase of structure-guided synthetic biology applications. These additions and prospective novel ones are likely to open hitherto untapped paradigms for optimizing/understanding metabolic pathways toward improving bioproduction of protein and small molecule products with downstream applications in health, environment, energy, and sustainability.

Long coronavirus disease 2019 (COVID-19)-a postacute consequence of severe acute respiratory syndrome coronavirus 2 infection-manifests with a broad spectrum of relapsing and remitting or persistent symptoms as well as varied levels of organ damage, which may be asymptomatic or present as acute events such as heart attacks or strokes and recurrent infections, hinting at complex underlying pathogenic mechanisms. Central to these symptoms is vascular dysfunction rooted in thrombotic endothelialitis. We review the scientific evidence that widespread endothelial dysfunction (ED) leads to chronic symptomatology. We briefly examine the molecular pathways contributing to endothelial pathology and provide a detailed analysis of how these cellular processes underpin the clinical picture. Noninvasive diagnostic techniques, such as flow-mediated dilation and peripheral arterial tonometry, are evaluated for their utility in identifying ED. We then explore mechanistic, cellular-targeted therapeutic interventions for their potential in treating ED. Overall, we emphasize the critical role of cellular health in managing Long COVID and highlight the need for early intervention to prevent long-term vascular and cellular dysfunction.

Coronavirus disease 2019 (COVID-19) changed the practice of medicine, and various anti-contagion restrictions were implemented worldwide.

This study aimed to evaluate the annual trend in the incidence of otologic diseases during the COVID-19 pandemic and determine the influence of social restrictions on these diseases.

We retrospectively reviewed the number of patients treated for otologic diseases, particularly those associated with infectious pathophysiology, and the total number of patients in the otolaryngology departments at three tertiary referral centers in South Korea.

The number of patients who underwent ventilation tube insertion due to persistent otitis media with effusion (OME) significantly decreased (raw number: -37.1%, incidence: -2.04‰) after the onset of the COVID-19 pandemic. However, a sharp increase was observed in 2023 (raw number: +42.9%, incidence: +1.63‰) when the pandemic officially ended. The number of patients newly diagnosed with sudden sensorineural hearing loss (SSNHL) gradually increased during the pandemic period.

Restrictive measures to control COVID-19 spread positively influenced the reduction in the incidence of OME. Whether COVID-19 is a direct risk factor for SSNHL remains uncertain, but the potential impact of the virus itself or the COVID-19 vaccine on the auditory system appears to exist.

Sleep disorders that involve circadian rhythm disruption and sleep-disordered breathing (SDB) such as obstructive sleep apnea (OSA) are closely linked to respiratory infections. SDB leads to a proinflammatory state due to intermittent hypoxia, sleep fragmentation, increased oxidative stress, and elevation of inflammatory mediators such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and C-reactive protein (CRP). Furthermore, inflammatory mediator levels correlate with SDB severity, especially in people with OSA. Nocturnal microaspiration, gastroesophageal reflux, and associated comorbidities (e.g., obesity) increase the risk of community-acquired pneumonia, viral infections such as SARS-CoV-2, respiratory complications, and death. OSA has been associated with post-COVID syndrome. It also increases the risk of postoperative complications in both adults and children. Circadian rhythm disorders such as insomnia predispose to immune disorders and increase the risk of infection. Chronic conditions such as bronchiectasis, with or without concomitant cystic fibrosis, can lead to structural sleep changes and increase the risk of OSA due to chronic cough, arousals, aspirations, hypoxia, upper airway edema, and overexpression of proinflammatory cytokines. The protective effect of treatment for sleep disorders against respiratory infection is currently unknown. However, in people presenting with respiratory infection, it is important to test for SDB to prevent complications.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) can damage the endothelium and increase arterial stiffness, potentially leading to adverse cardiovascular events. In parallel, systemic inflammation in COVID-19 also impacts endothelial function. Angiotensin-converting enzyme 2 (ACE2) promotes vasodilation and anti-inflammatory effects, but also facilitates SARS-CoV-2 entry into human cells. Thus, concerns have been raised about the use of RAAS inhibitors (RAASi) in COVID-19 patients due to potential ACE2 upregulation. However, the clinical significance of increased plasma ACE2 (sACE2) in RAASi-treated COVID-19 patients remains unclear. Methods: This prospective, single-centre study evaluated RAASi, sACE2, and vascular function in acutely ill patients with COVID-19 in comparison with acutely ill patients without COVID-19. Adult emergency department patients with confirmed or suspected COVID-19 were enrolled and underwent pulse wave velocity, ankle brachial index, and sACE2 measurements. Results: In the 152 included patients (50% female, median age 62 years, 68% COVID-19 positive), the sACE2 values were slightly higher in the COVID-19 (0.485 [0.364-1.329]) than in the non-COVID-19 subgroup (0.458 [0.356-1.138]; p = 0.70). No significant differences in sACE2 were observed between patients with and without RAASi, regardless of COVID-19 status. Pulse wave velocity values differed significantly between groups (p = 0.015). Conclusions: In emergency department patients, sACE2 was upregulated in COVID-19 patients, probably due to oxidative stress and inflammation. RAASi did not increase sACE2, but may have protective effects against inflammation. Elevated sACE2 appeared to have a beneficial effect on arterial stiffness in all patients. These findings support continued RAASi therapy in COVID-19 patients to protect against chronic inflammation and apoptosis.

The SARS-CoV-2 spike protein interacts with ACE2, a key receptor within the renin-angiotensin-aldosterone system (RAAS), which plays a critical role in maintaining vascular homeostasis, regulating blood pressure, and modulating inflammation. An observational study analyzed the gene expression profiles of RAAS receptors and associated miRNAs in 88 hospitalized COVID-19 patients and 20 healthy controls, comparing the acute and post-acute phases to assess their impact on disease severity and recovery. Our findings revealed an association between reduced MAS1 expression in both advanced age (P = 0.03) and the need for oxygen supplementation (P = 0.04). Additionally, reduced ACE expression was associated with worse mortality outcomes (P = 0.01). Notably, ACE2 and TMPRSS2 expression was significantly decreased (P < 0.0001) in individuals requiring oxygen supplementation and in those with diabetes mellitus during both the acute and post-COVID-19 phases, further highlighting the impact of these conditions on RAAS. The miRNA analysis revealed significant downregulation of miR-200c (P = 0.005), miR-let-7 (P = 0.01), and miR-122 (P = 0.03) in acute-phase COVID-19 patients. This dysregulation contributes to the inflammatory response and highlights the interaction between viral entry and immune regulation. These results underscore the significance of the ACE2/Ang-(1-7)/MAS1 axis in inflammation regulation and suggest that targeting this pathway may have therapeutic potential. Our study provides valuable insights into the molecular mechanisms of COVID-19 pathogenesis and identifies the modulation of RAAS receptors and miRNAs as promising biomarkers for disease severity and potential therapeutic interventions. CLINICAL TRIAL: Not applicable.

Infection with SARS-CoV-2, the virus responsible for COVID-19, can lead to a range of physical symptoms and mental health challenges, including stress, anxiety, and depression. These effects are particularly pronounced in hospitalized patients, likely due to the virus's direct and indirect impact on the nervous system. Gut dysbiosis, an imbalance in the gut microbiome, has been implicated in immune dysfunction and chronic inflammation in COVID-19 patients. However, the interactions between gut microbiome composition and the physical and mental symptoms of COVID-19 remain incompletely understood.

We investigated the association between physical and mental symptoms, cytokine profiles, and gut microbiota composition in 124 hospitalized COVID-19 patients. We collected data on demographics, COVID-19 severity, and mental health indicators (stress, anxiety, and depression). Gut microbiome profiling was performed using full-length 16 S rRNA gene sequencing to evaluate microbial diversity and composition.

COVID-19 severity was categorized as low (27.4%), moderate (29.8%), or critical (42.8%). Common symptoms included fever (66.1%) and cough (55.6%), while somatic symptoms (27.3%), anxiety (27.3%), depressive symptoms (39%), and stress (80.5%) were frequently self-reported. Elevated interleukin-6 levels in severe cases highlighted systemic inflammation, reduced gut bacterial diversity, particularly among women and obese patients, correlated with higher disease severity. Notably, the genus Mitsuokella was associated with increased physical symptoms and mental distress, while Granulicatella was linked to critical illness.

Our findings reveal significant associations between mental health status, systemic inflammation, and gut dysbiosis in hospitalized COVID-19 patients. These results indicate the potential for microbiome-targeted therapies to mitigate psychological and physical complications and improve recovery outcomes in this population.

Particulate matter 2.5 (PM2.5) pollution and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are the greatest environmental health issues worldwide. Several statistics revealed the significant positive correlation between the morbidity of coronavirus disease-19 (COVID-19) and the levels of air pollution. Nevertheless, there is no direct experimental evidence to indicate the effect of PM2.5 exposure on SARS-CoV-2 infection. The objective of this study was to evaluate whether the infection of SARS-CoV-2 affected by PM2.5 through angiotensin-converting enzyme II (ACE2) expression enhances and investigate the function of ACE2 in lung injury induced by PM2.5. An animal model of PM2.5-induced lung injury was established using wild-type (WT, C57BL/6), human ACE2 transgenic (K18-hACE2 TG), and murine ACE2 gene knockout (mACE2 KO) mice. The results indicate that PM2.5 exposure facilitates SARS-CoV-2 infection through inducing ACE2 expression in vitro (10 μg/mL) and in vivo (6.25 mg/kg/day in 50 μL saline). The levels of ACE, inflammatory cytokines, and mitogen-activated protein kinase (MAPK) proteins in WT, K18-hACE TG and mACE2 KO mice were significantly increased after PM2.5 instillation. The severest PM2.5-induced lung damage was observed in mACE2 KO mice. In summary, ACE2 plays a double-edged sword role in lung injury, PM2.5 exposure contributed to SARS-CoV-2 infection through inducing ACE2 expression, but ACE2 also protected pulmonary inflammation from PM2.5 challenge.

COVID-19, caused by the SARS-CoV-2 virus, is not only characterized by respiratory symptoms but is also associated with a wide range of systemic complications, including significant hematologic abnormalities. This is a comprehensive review of the current literature, using PubMed and Google Scholar, on the pathophysiology and incidence of thromboembolic events in COVID-19 patients and thromboprophylaxis. COVID-19 infection induces a prothrombotic state in patients through the dysregulation of the renin-angiotensin-aldosterone system (RAAS), endothelial dysfunction, elevated von Willebrand factor (vWF), and a dysregulated immune response involving the complement system and neutrophil extracellular traps (NETs). As a result, thromboembolic complications have emerged in COVID-19 cases, occurring more frequently in severe cases and hospitalized patients. These thrombotic events affect both venous and arterial circulation, with increased incidences of deep venous thrombosis (DVT), pulmonary embolism (PE), systemic arterial thrombosis, and myocardial infarction (MI). While DVT and PE are more common, the literature highlights the potential lethal consequences of arterial thromboembolism (ATE). This review also briefly examines the ongoing discussions regarding the use of anticoagulants for the prevention of thrombotic events in COVID-19 patients. While theoretically promising, current studies have yielded varied outcomes: Some suggest potential benefits, whereas others report an increased risk of bleeding events among hospitalized patients. Therefore, further large-scale studies are needed to assess the efficacy and safety of anticoagulants for thromboprophylaxis in COVID-19 patients.

The clinical consequences of coronavirus infection in elite judokas with exercise-induced bronchoconstriction (EIB) are unclear. We aimed to determine potential respiratory function abnormalities and recovery in athletes with and without EIB after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

Retrospective cohort study.

Türkiye Olympic Preparation Centre.

This retrospective study analyzed data collected from 25 consecutive elite judokas diagnosed with and without EIB and SARS-CoV-2 infection, routinely followed at an Olympic Sports Center between September 2020 and 2021.

Respiratory muscle strength and pulmonary function data were collected before and up to 90 days after SARS-CoV-2 infection.

Measurements included maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC ratio, and peak expiratory flow (PEF).

Infected athletes with EIB had more markedly reduced respiratory muscle strength and pulmonary function than those without EIB. Maximal inspiratory pressure was decreased by 14% and MEP by 8% from baseline in infected athletes with EIB during follow-up. Likewise, FEV 1 and FVC decreased by 4%. Maximal inspiratory pressure, MEP, FEV 1 , and FVC remained abnormal after 90 days of SARS-CoV-2 infection in EIB athletes but normalized rapidly in non-EIB athletes. Peak expiratory flow seemed unaffected during follow-up. Exercise-induced bronchoconstriction severity was moderately correlated with the maximum fall in MEP during follow-up.

Severe acute respiratory syndrome coronavirus-2 infection notably decreases respiratory muscle strength and pulmonary function in judokas, especially those with pre-existing EIB, thereby prolonging spontaneous recovery time.

Coronavirus disease 2019 (COVID-19) remains a health problem worldwide. The present study aimed to investigate the effect of blood pressure (BP) on the circadian pattern and prevalence of new-onset non-dipper hypertension in the post-COVID period in patients with known hypertension. This prospective single-center study included 722 patients hospitalized for COVID-19 infection. Ambulatory BP (ABP) data were collected during their initial hospitalization. The ABP data were reassessed 1 month after the patients were discharged. The results were compared with a healthy control group with known hypertension but without COVID-19 infection. After exclusion criteria were applied, the study included 187 patients with COVID-19 and 136 healthy hypertensive controls. Post-COVID ABP showed that patients with COVID-19 had significantly higher mean 24-h systolic and diastolic BP, mean nighttime systolic and diastolic BP, and mean daytime diastolic BP than the control group. In addition, new-onset non-dipper hypertension was significantly higher in patients with COVID-19. This study demonstrated for the first time that the circadian pattern is disturbed and a non-dipper pattern develops in individuals with known hypertension during the post-COVID period.

Background/Objectives: The oral cavity has garnered increasing attention as a site for viral infection and related pathological manifestations in coronavirus disease-19. This article aims to provide a comprehensive overview of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-related oral manifestations, including taste disturbances, oral lesions and osteonecrosis. Methods: A search was conducted up to September 2024 according to PRISMA (Preferred Reporting Items for Systematic Reviews) guidelines using the databases PubMed and Scopus. All the observational, case-series, case-report and cross-sectional studies written in English on oral manifestations related to COVID-19 disease and long-COVID disease were included. All other types of studies and studies based on oral manifestation after COVID-19 vaccination and oral impairment due to lockdown were excluded. The risk of bias of included studies was assessed using the Joanna Briggs Appraisal checklist. Results: A total of 104 articles including 23 case-report, 15 case-series, 8 case-control, 18 cohort and 40 cross-sectional studies were selected. The results showed that patients with COVID-19 were found to have a significantly higher prevalence of xerostomia (45-74%) and dysgeusia (32-59%) compared to non-infected individuals. Regarding oral mucosal lesions, ulcers, candidiasis and herpes simplex infections were frequently observed. As for osteonecrosis, a significant number of patients with COVID-19-associated rhinomaxillary mucormycosis presented with maxillary osteonecrosis due to fungal infection, primarily mucormycosis. The methodological quality of most of the studies was moderate/high. Conclusions: COVID-19 has been associated with a range of oral manifestations. The complex interplay of viral infection, immune response, medication use and stress likely contributes to these oral complications. Early recognition and management of these oral manifestations are crucial for improving patient outcomes and developing targeted preventive and therapeutic strategies for COVID-19-related oral health issues.

Background/Objectives: Premature ovarian insufficiency (POI) is a disorder that affects women under the age of 40. It is characterized by decreased ovarian function, elevated gonadotropin levels, and decreased estradiol. SARS-CoV-2 disrupts ovarian function largely through oxidative stress, inflammation, and immunological dysregulation, which are enhanced by its entrance into ovarian tissues via ACE2 receptors. The purpose of this comprehensive review was to investigate the molecular pathways that link SARS-CoV-2 infection to POI and analyze their consequences for ovarian reserve and fertility. Methods: We searched databases such as PubMed, Scopus, EMBASE, and Google Scholar for papers published between 2020 and 2024. Eligible studies investigated the effects of SARS-CoV-2 on ovarian function, including the hormonal indicators anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH), oocyte quality, and ovarian reserve. The data were compiled into a complete examination of molecules and clinical findings. Increased inflammatory indicators, such as interleukin-6 and NLRP3 inflammasome activation, impaired ovarian homeostasis. Anti-SARS-CoV-2 antibodies in follicular fluid could have impaired oocyte quality. Observational studies showed transitory decreases in AMH and changed FSH levels following infection, with variable effects on antral follicle count and IVF results. Changes in lipid profiles and VEGF expression emphasized the virus's influence on ovarian angiogenesis and the ovarian microenvironment. Conclusions: SARS-CoV-2 infection impairs ovarian function by causing oxidative stress, inflammation, and hormonal disruption, thereby increasing the incidence of POI. While most alterations are temporary, the long-term reproductive consequences remain unknown. Continuous monitoring and specific treatments are required to reduce the reproductive risks associated with COVID-19.

To extract sinapine from rapeseed meal and investigate its antihypertensive function and mechanism. Blood pressure was measured before and after sinapine administration to evaluate sinapine's immediate antihypertensive function. Twokidney, oneclip (2K1C) hypertensive rats were given sinapine for four weeks, with weekly blood pressure monitoring. The renin angiotensin aldosterone system (RAAS), including the levels of renin, angiotensin I (Ang I), angiotensin II (Ang II), aldosterone (ALD), angiotensin-converting enzyme (ACE) and other molecules related to blood pressure, such as NO, prostacyclin (PGI2), endothelin-1 (ET1), and thromboxane A2 (TXA2), were measured in rat blood. The impact of sinapine on vascular endothelial cell (A10) calcium and potassium channels was assessed using the patch-clamp technique. One-time or long-term administration of sinapine significantly reduced the rats' systolic blood pressure (SBP), diastolic pressure (DBP), and mean blood pressure (MBP). Sinapine also decreased the levels of Ang II and ALD. Furthermore, sinapine effectively inhibited ACE activation, increased NO levels, and blocked L-type calcium channels. Sinapine has an antihypertensive function and achieves this process through multiple targets.

The rapid global spread of Coronavirus Disease 2019 (COVID-19) has resulted in millions of infections and deaths, particularly impacting older adults. This study systematically analyzes risk factors reported in different geographical regions such as Asia and Europe that are associated with adverse outcomes in older adults with COVID-19. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched five databases up to December 2023 and conducted meta-analyses of odds ratios for 27 risk factors reported in at least two studies using R software (version 4.3.2). Our meta-analysis identified 19 risk factors linked to adverse outcomes, with many of them common across regions, particularly in Asia and Europe. Key factors include old age (above 65 years), male gender, symptoms such as fever and dyspnea, and comorbidities like dementia, chronic obstructive pulmonary disease (COPD), chronic heart disease, hypertension, chronic kidney disease, and malnutrition. Laboratory biomarkers such as low oxygen saturation, thrombocytopenia, and elevated D-dimer were also associated with adverse outcomes. COVID-19 patients in Asia and Europe who are older adults, male, or have specific symptoms combined with underlying health conditions are at an increased risk of progressing to severe illness or mortality.

COVID-19 was a nightmare in humankind's history that challenged our advanced medical technology. All credit goes to the researchers who played a crucial role in curbing COVID-19 and proved our medical technology supremacy. However, COVID-19 has left some mysterious scars on human well-being. It is believed that COVID-19 has a significant negative impact on various cardiovascular (CVS) and central nervous system (CNS) diseases, especially in the case of CNS diseases like Alzheimer's. Surprisingly, COVID-19 affects the respiratory system, whereas Alzheimer's disease (AD) alters brain function. To explain this phenomenon, several hypotheses were proposed, but the mechanism needs to be clearly understood. Another critical thing to be concerned about is that COVID-19 will worsen pre-existing conditions and lead to the onset of AD. In the race to curb COVID-19, the invention of vaccines was speeded up, and it is necessary to fight against COVID-19. However, postvaccination follow-up is mandatory when an individual is a victim of AD. In this review article, we compiled the various dreadful effects of the COVID-19 virus on AD, the Post effects of the virus on AD, and the effect of the COVID-19 vaccination on AD. This article provides a new direction for research concerning COVID-19 and AD.

Electronic cigarettes (EC) have emerged as a popular alternative to traditional tobacco products, but their impact on immune function has raised significant health concerns. This review explores the immunological effects of EC exposure, focusing on innate and adaptive immune responses. Electronic cigarette aerosol (ECA) induces widespread inflammation. These changes compromise immune cell function, impairing neutrophil chemotaxis, phagocytosis, and oxidative burst while increasing macrophage and dendritic cell recruitment and activation. ECA also disrupts epithelial barriers, increasing susceptibility to bacterial and viral infections. Studies show enhanced biofilm formation in bacteria such as Staphylococcus aureus and Streptococcus pneumoniae and impaired antiviral responses against pathogens like influenza A and SARS-CoV-2. Additionally, EC exposure modulates adaptive immunity, affecting T and B cell function and increasing systemic inflammatory markers. The long-term consequences of these immunological disruptions include heightened risks for chronic inflammatory diseases, respiratory infections, and potentially autoimmune conditions. The widespread adoption of EC, particularly among younger users, poses a growing public health challenge. As the popularity of vaping continues to rise, these immunological disruptions could result in increased healthcare burdens in the future, with higher rates of infections, chronic inflammatory diseases, and immune system-related disorders among those who begin using e-cigarettes at a young age. Understanding the full scope of EC-related health risks is essential for informing public health policies and protecting future generations from the potential long-term effects of vaping.

Postacute sequelae of SARS-CoV-2 infection (PASC) are extensive. Also known as long COVID, primary outcomes reported are neurologic, cardiac and respiratory in nature. However, several studies have also reported an increase in gastrointestinal (GI) symptoms and syndromes following COVID-19. This study of PASC will include extensive analyses of GI symptoms, determine if people with pre-existing irritable bowel syndrome (IBS) are at higher risk of developing PASC generally or PASC-GI, and which biomarkers are impacted and to what degree. This R01 study is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK135483-01) from 2023 to 2028.

This study combines a longitudinal epidemiologic cohort study and in-depth, novel biologic analyses. In collaboration with a pre-existing study, the Arizona CoVID-19 Cohort (CoVHORT)-GI will recruit participants based on the history of COVID infection(s), new or ongoing GI symptoms 3-6 months postinfection, and pre-existing or incident IBS diagnosis to represent five study groups for comparison and analyses. A subset (n=1000) of those recruited will submit both stool and blood samples. Both samples will undergo a novel method to quantitate humoral and mucosal immune responses to host-derived faecal communities in conjunction with magnetic bead-based separation and high-depth shotgun microbial sequencing. Stool samples will also undergo traditional microbiome analyses (diversity and abundance) and faecal calprotectin assays. Additional serum analyses will aim to determine if a proteomics-based signature exists that differentiates a unique biomarker compositional signature discriminating PASC-GI versus no PASC. All laboratory data will be linked with in-depth epidemiologic data on demographics, symptoms and chronic conditions.

This study involves human participants and was approved by the University of Arizona Institutional Review Board (IRB (#00002332) and has been deemed minimal risk. Participants gave informed consent to participate in the study before taking part. All publications from the study will be shared back to participants along with alternative lay summaries and webinars to communicate key findings. The data management plan has been published and is publicly available online, including protocols for data requests.

COVID-19 disease, triggered by SARS-CoV-2 virus infection, has led to more than 7.0 million deaths worldwide, with a significant fraction of recovered infected people reporting postviral symptoms. Smart surfaces functionalized with nanoparticles are a powerful tool to inactivate the virus and prevent the further spreading of the disease. Literature reports usually focus on the role of nanomaterial composition and size dispersion in evaluating their efficacy against SARS-CoV-2. Here, the anti-SARS-CoV-2 activity of oleylamine (OAm) used as a capping agent of silver nanoparticles is quantified for the first time. Spherical hydrophobic nanoparticles with 8 ± 2 nm diameter were prepared and characterized by Fourier transform infrared, dynamic light scattering, and transmission electron microscopy techniques. Biological assays showed that microgram amounts of nanoparticles, deposited on nonwoven textile obtained from surgical masks, efficiently inactivated up to 99.6(2)% of the virus with just 2 min of exposure. The virucidal activity of the corresponding amount of free OAm has been determined as well, reaching up to 67(1)% of activity for an exposure time of 10 min. Inductively coupled plasma optical emission spectrometry results pointed out a low leaching out of the nanoparticles in contact with water or culture medium. All in all, these results propose the capping molecules as an important chemical variable to be taken into account in the design of fast, efficient, and long-lasting anti-SARS-CoV-2 coatings.

Some of the millions of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have developed new sequelae after recovering from the initial disease, termed post-acute sequelae of coronavirus disease 2019 (PASC). One symptom is anxiety, which is likely due to three etiologies: brain structural changes, neuroendocrine disruption, and neurotransmitter alterations. This review provides an overview of the current literature on the pathophysiological pathways linking coronavirus disease 2019 to anxiety, as well as the possible mechanisms of action in which an increasingly scrutinized treatment method, enhanced external counter-pulsation (EECP), is able to alleviate anxiety. SARS-CoV-2 triggers increased inflammatory cytokine production, as well as oxidative stress; these processes contribute to the aforementioned three etiologies. The potential treatment approach of EECP, involving sequenced inflation and deflation of specifically-placed airbags, has become of increasing interest, as it has been found to alleviate PASC-associated anxiety by improving patient cardiovascular function. These functional improvements were achieved by EECP stimulating anti-inflammatory and pro-angiogenic processes, as well as improving endothelial cell function and coronary blood flow, partially via counteracting against the negative effects of SARS-CoV-2 infection on the renin-angiotensin-aldosterone system. Therefore, EECP could promote both psychosomatic and cardiac rehabilitation. Further research, though, is still needed to fully determine its benefits and mechanism of action.

GenBank® (https://www.ncbi.nlm.nih.gov/genbank/) is a comprehensive, public data repository that contains 34 trillion base pairs from over 4.7 billion nucleotide sequences for 581 000 formally described species. Daily data exchange with the European Nucleotide Archive and the DNA Data Bank of Japan ensures worldwide coverage. We summarize the content of the database in 2025 and recent updates such as accelerated processing of influenza sequences and the ability to upload feature tables to Submission Portal for messenger RNA sequences. We provide an overview of the web, application programming and command-line interfaces that allow users to access GenBank data. We also discuss the importance of creating BioProject and BioSample records during submissions, particularly for viruses and metagenomes. Finally, we summarize educational materials and recent community outreach efforts.

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is closely related to SARS-CoV and uses angiotensin-converting enzyme 2 as its cellular receptor. In early 2020, reports emerged linking CoV disease 2019 (COVID-19) to olfactory and gustatory disturbances. These disturbances could be attributed to virus-induced damage to olfactory neurons or immune responses, thereby affecting sensory functions. This randomized controlled trial aimed to evaluate the effectiveness of a structured orofacial rehabilitation program in improving smell (olfaction) and taste (gustation) sensations in children post-COVID-19. Methods: Forty children recovering from COVID-19 in government hospitals in Saudi Arabia were included and randomly assigned to the control group or the experimental group. The orofacial program included (a) facilitation of olfactory function using the 40-item modified Arabic version of the University of Pennsylvania Smell Identification Test (UPSIT); (b) assessment of gustatory function using taste strips with four varying concentrations; and (c) orofacial myofunctional therapy. The intervention was applied three times a week and lasted for 3 months. Results: The experimental group showed a significantly greater improvement in UPSIT scores (median change of 24.1%) than the control group (14.7%; p = 0.010). However, no significant difference was found in the taste strip test scores among the groups or between male and female participants. Conclusions: This study suggests that a structured orofacial rehabilitation program could enhance olfactory and gustatory functions in children recovering from COVID-19.

Adult patients with chronic respiratory diseases (CRDs) are considered high risk group who are more likely to experience worse clinical outcomes if they acquire viral or bacterial infections. Vaccination is the best preventive tool to reduce the risk of infection and disease occurrence and to reduce the level of severity of complications associated with the various vaccine-preventable infections. These guidelines were developed by the Saudi Thoracic Society task force to emphasize the critical importance of improving the vaccine coverage rates in adult patients with CRD. They are intended to serve as a reference for healthcare practitioners managing CRD patients. The guidelines aimed to review the current knowledge related to vaccination efficacy in adult patients with CRD, based on the recent evidence and recommendations. Integrating the administration of the recommended vaccines in routine healthcare, such as during outpatient visits or before hospital discharge, is crucial for improving the vaccination rates in high-risk patients. The key strategies to address this public health priority include simplifying vaccination guidelines to enhance their accessibility and implementation by healthcare providers, increasing awareness in both the patients and healthcare providers that vaccines are not only intended for children. Additional strategies include maintaining continuous surveillance and advance research to discover novel vaccines. This approach aims to expand the range of preventable diseases and improve overall health and well-being. Vaccine hesitancy remains a significant challenge that necessitates a clear understanding of the community concerns. Providing appropriate education and communication, as well as addressing these concerns, are the crucial steps toward improving vaccine acceptance and uptake. By implementing these guidelines and multifaceted strategies, healthcare systems can optimize vaccine coverage and protection for patients with CRD, reduce the burden of vaccine-preventable complications, and improve the clinical outcomes in this vulnerable population.

COVID-19 infection can cause bowel ischemia, with an incidence ranging from 0.22% to 10.5. The COVID-19 vaccine reduces respiratory symptoms and the need for cardiopulmonary support. However, its effects on other manifestations, such as bowel ischemia, have not been extensively studied. Despite having mild respiratory symptoms and receiving three doses of the COVID-19 vaccine, our patient developed ischemic colitis after her first infection and small bowel ischemia following her second infection.

An 86-year-old woman presented to the emergency department (ED) with abdominal pain after a mild COVID-19 infection. She was admitted with ischemic colitis, but conservative treatment failed. In the operating room, her entire colon was found to be ischemic, necessitating a total colectomy with end ileostomy. Nine months later, she returned to the ED with mild respiratory symptoms and severe right upper quadrant pain. Imaging revealed pneumoperitoneum and a mid-abdominal abscess. An emergency laparotomy revealed small bowel perforation, with final histology confirming ischemia. The patient had received three doses of the COVID-19 vaccine and was on therapeutic anticoagulation for a history of pulmonary embolism.

COVID-19 may increase the risk of bowel and colon ischemia even after vaccination. Patients presenting to the ED with severe abdominal pain and a recent COVID-19 infection should be carefully evaluated for ischemic events.

In this review, our objective was to analyze the association between serum magnesium (Mg) levels, Mg supplementation, and coronavirus disease 2019 (COVID-19) outcomes. This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching major databases until February 2023. Twenty-six studies (11,363 patients) were included: 22 examining serum Mg levels (8474 patients) and four investigating Mg supplementations (2889 patients). Most studies indicated an association between lower serum Mg levels and increased COVID-19 severity, including higher mortality rates and prolonged recovery periods. Critical patients demonstrated significantly lower Mg levels compared to moderate/severe cases. However, some studies reported conflicting findings, with hypermagnesemia also associated with poor outcomes in specific patient populations. Regarding supplementation, higher dietary Mg intake correlated with shorter hospitalization duration and faster recovery. Mg supplementation exceeding 450 mg showed potential benefits, including increased antibody titers in pregnant women and reduced oxygen support requirements in elderly patients when combined with vitamins D and B12. While evidence suggests a potential relationship between Mg status and COVID-19 outcomes, findings are heterogeneous. Further investigation through well-designed clinical trials is required to gain deeper insights into the role of Mg in COVID-19 pathophysiology and the therapeutic potential of Mg supplementation.

We examined the relationship between RAAS inhibitor use and Omicron infection in mildly symptomatic patients. This retrospective case-control observational study included 50,121 patients with mild Omicron infection from the largest "Fangcang" shelter hospital in Shanghai between April 9, 2022, and May 21, 2022. Using 1:1 propensity score matching (PSM), we classified 4394 COVID-19 patients into hypertension and non-hypertension groups, and 406 hypertensive patients into RAAS inhibitor and non-RAAS inhibitor groups. The risk of initial symptoms of infection, cumulative negative conversion rates, time to nucleic-acid negative conversion, and viral loads were compared. In the hypertension group, the median number of days for nucleic-acid negative conversion was 7.0 (IQR, 5.0-9.0), which was greater than non-hypertensive group (median (IQR) 6.0 (4.0-8.0), P < 0.001, Cohen's d = 0.29); the mean and minimum cycle threshold values (CT-values) were significantly lower (P < 0.001, Cohen's d = 0.23). In the RAAS inhibitors group, the median number of days for nucleic-acid negative conversion was 7.0 days (IQR, 5.0-9.0), which was shorter than the non-RAAS inhibitors group ([median (IQR)] 8.0 (6.0-10.0), P < 0.001, Cohen's d = 0.34), the cumulative negative conversion rates at 3-8 days being all higher than non-RAAS inhibitors groups (P < 0.05). The most significant difference in negative conversion rate between the RAAS inhibitor and non-RAAS inhibitor group was on the 4th day. No significant difference was observed in mean and minimum CT-values from RAAS inhibitor and non-RAAS inhibitor groups (P > 0.05). RAAS inhibitor use in patients with hypertension is associated with nucleic-acid negative conversion duration and negative conversion rate. RAAS inhibitors clearly do not aggravate or prolong COVID-19.

Understanding the fundamental biochemical and metabolic requirements for the replication of coronaviruses within infected cells is of notable interest for the development of broad-based therapeutic strategies, given the likelihood of the emergence of new pandemic-potential virus species, as well as future variants of SARS-CoV-2. Here we demonstrate members of the glutaminase family of enzymes (GLS and GLS2), which catalyze the hydrolysis of glutamine to glutamate (i.e., the first step in glutamine metabolism), play key roles in coronavirus replication in host cells. Using a range of human seasonal and zoonotic coronaviruses, we show three examples where GLS expression increases during coronavirus infection of host cells, and another where GLS2 is upregulated. The viruses hijack the metabolic machinery responsible for glutamine metabolism to generate the building blocks for biosynthetic processes and satisfy the bioenergetic requirements demanded by the "glutamine addiction" of virus-infected cells. We demonstrate that genetic silencing of glutaminase enzymes reduces coronavirus infection and that newer members of two classes of allosteric inhibitors targeting these enzymes, designated as SU1, a pan-GLS/GLS2 inhibitor, and UP4, a specific GLS inhibitor, block viral replication in epithelial cells. Moreover, treatment of SARS-CoV-2 infected K18-human ACE2 transgenic mice with SU1 resulted in their complete survival compared to untreated control animals, which succumbed within 10 days post-infection. Overall, these findings highlight the importance of glutamine metabolism for coronavirus replication in human cells and mice and show that glutaminase inhibitors can block coronavirus infection and thereby may represent a novel class of broad-based anti-viral drug candidates.

The SARS-CoV-2 infection manifests with diverse clinical manifestations, with severity potentially influenced by the viral variant. COVID-19 has also been shown to impact ocular microcirculation in some patients, but whether this effect varies by viral lineage remains unclear. This prospective study compared clinical features and ocular parameters assessed via optical coherence tomography angiography (OCTA) in patients recovering from SARS-CoV-2 infections during the dominance of two distinctive viral lineages, Alpha (B.1.1.7) and Delta (B.1.617.2), and compared them to a control group. The following parameters were measured: vessel density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CCP) using OCTA, with a manual assessment of the foveal avascular zones in the SCP (FAZs) and DCP (FAZd). A control group was also included. Among 63 patients in the Alpha group and 41 in the Delta group, no eye-related symptoms were reported during the examination. However, the Delta group showed significantly lower VD in the SCP and DCP across all quadrants (p < 0.001-0.039), while the Alpha group showed reduced VD in the foveal CCP (p = 0.005) and significantly wider FAZs and FAZd (p = 0.002 for both). In conclusion, ocular microcirculatory changes differed between the two variants, with Alpha associated with foveal choroidal VD reduction and larger FAZs and Delta linked to lower SCP and DCP VD across multiple regions. These findings highlight the potential for SARS-CoV-2 variants to differentially impact ocular vasculature, underscoring the need for variant-specific follow-up in COVID-19 patients.

Background/Objectives: SARS-CoV-2 was responsible for the global pandemic. Approximately 10-15% of patients with COVID-19 developed respiratory failure with adult acute respiratory distress syndrome (ARDS), which required treatment in the Intensive Care Unit (ICU). The cytokine storm observed in severe COVID-19 was frequently handled with steroids. Synergically, tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, gained popularity as a cytokine storm-suppressing agent. However, immunosuppression was proven to increase the predisposition to infections with resistant bacteria. Our study aimed to assess the relationship between positive tests for secondary infections and the survival of patients with severe COVID-19-attributed ARDS treated with immunosuppressive agents. Methods: This study included 342 patients qualified for the ICU and mechanical ventilation (MV). The patients were divided based on the type of immunomodulating therapy and the culture tests results. Results: The results showed the highest survival rate among patients <61 years, favoring the combined treatment (tocilizumab + steroids). Atrial fibrillation (AF) and coronary heart disease (CHD) correlated with a lower survival rate than other comorbidities. Tocilizumab was associated with an increased risk of positive pathogen cultures, which could potentially cause secondary infections; however, the survival rate among these patients was higher. Conclusions: MV and ICU procedures as well as the application of tocilizumab significantly decreased the mortality rate in patients with severe COVID-19-related ARDS. The suppression of cytokine storms played a crucial role in survival. Tocilizumab was found to be both efficient and safe despite the 'side effect' of the increased risk of positive results for secondary infections.

Herein, we have selected eight Zn(II)-based complexes viz., [Zn(bpy)(acac)Cl] (1), [Zn(phen)(acac)Cl] (2), [Zn(dppz)(acac)Cl] (3), [Zn(dppn)(acac)Cl] (4), [Zn(bpy)(cur)Cl] (5), [Zn(phen)(cur)Cl] (6), [Zn(dppz)(cur)Cl] (7), [Zn(dppn)(cur)Cl] (8), where bpy=2,2'-bipyridine, phen=1,10-phenanthroline, dppz=benzo[i]dipyrido[3,2-a:2',3'-c]phenazine, dppn=naphtho[2,3-i]dipyrido[3,2-a:2',3'-c]phenazine, acac=acetylacetonate, cur=curcumin and performed in silico molecular docking studies with the viral proteins, i. e., spike protein (S), Angiotensin-converting enzyme II Receptor protein (ACE2), nucleocapsid protein (N), main protease protein (Mpro), and RNA-dependent RNA polymerase protein (RdRp) of SARS-CoV-2. The binding energy calculations, visualization of the docking orientation, and analysis of the interactions revealed that these complexes could be potential inhibitors of the viral proteins. Among complexes 1-8, complex 6 showed the strongest binding affinity with S and ACE2 proteins. 4 exerted better binding affinity in the case of the N protein, whereas 8 presented the highest binding affinities with Mpro and RdRp among all the complexes. Overall, the study indicated that Zn(II) complexes have the potential as alternative and viable therapeutic solutions for COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that caused the Coronavirus Disease 2019 (COVID-19) pandemic, has a spike glycoprotein that is involved in recognizing and fusing to host cell receptors, such as angiotensin-converting enzyme 2 (ACE2), neuropilin-1 (NRP1), and AXL tyrosine-protein kinase. Since the major spike protein receptor is ACE2, an enzyme that regulates angiotensin II (1-8), this study tested the hypothesis that angiotensin II (1-8) influences the binding of the spike protein to its receptors. While angiotensin II (1-8) did not influence spike-ACE2 binding, we found that it significantly enhances spike-AXL binding. Our experiments showed that longer lengths of angiotensin, such as angiotensin I (1-10), did not significantly affect spike-AXL binding. In contrast, shorter lengths of angiotensin peptides, in particular, angiotensin IV (3-8), strongly increased spike-AXL binding. Angiotensin IV (3-8) also enhanced spike protein binding to ACE2 and NRP1. The discovery of the enhancing effects of angiotensin peptides on spike-host cell receptor binding may suggest that these peptides could be pharmacological targets to treat COVID-19 and post-acute sequelae of SARS-CoV-2 (PASC), which is also known as long COVID.

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes. Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice. Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury. Vaccination reduced but did not eliminate spike protein accumulation after infection in mice. Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.