The COVID-19 disease has spread rapidly across the world within just six months, affecting 169 million people and causing 3.5 million deaths globally (2021). The most affected countries include the USA, Brazil, India, and several European countries such as the UK and Russia. Healthcare professionals face new challenges in finding better ways to manage patients and save lives. In this regard, more comprehensive research is needed, including genomic and proteomic studies, personalized medicines and the design of suitable treatments. However, finding novel molecular entities (NME) using a standard or de novo strategy to drug development is a time-consuming and costly process. Another alternate strategy is discovering new therapeutic uses for old/existing/available medications, known as drug repurposing. There are a variety of computational repurposing methodologies, and some of them have been used to counter the coronavirus disease pandemic of 2019 (COVID-19). This review article compiles recently published data on the origin, transmission, pathogenesis, diagnosis, and management of the coronavirus by drug repurposing and vaccine development approach. We have attempted to screen probable drugs in clinical trials by using literature survey. This systematic review aims to create priorities for future research of drugs repurposed and vaccine development for COVID-19.

The spike protein (SP) is an outward-projecting transmembrane glycoprotein on viral surfaces. SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), responsible for COVID-19 (Coronavirus Disease 2019), uses SP to infect cells that express angiotensin converting enzyme 2 (ACE2) on their membrane. Remarkably, SP has the ability to cross the blood-brain barrier (BBB) into the brain and cause cerebral damage through various pathomechanisms. To combat the COVID-19 pandemic, novel gene-based products have been used worldwide to induce human body cells to produce SP to stimulate the immune system. This artificial SP also has a harmful effect on the human nervous system.

Narrative review.

This narrative review presents the crucial role of SP in neurological complaints after SARS-CoV-2 infection, but also of SP derived from novel gene-based anti-SARS-CoV-2 products (ASP).

Literature searches using broad terms such as "SARS-CoV-2", "spike protein", "COVID-19", "COVID-19 pandemic", "vaccines", "COVID-19 vaccines", "post-vaccination syndrome", "post-COVID-19 vaccination syndrome" and "proteinopathy" were performed using PubMed. Google Scholar was used to search for topic-specific full-text keywords.

The toxic properties of SP presented in this review provide a good explanation for many of the neurological symptoms following SARS-CoV-2 infection and after injection of SP-producing ASP. Both SP entities (from infection and injection) interfere, among others, with ACE2 and act on different cells, tissues and organs. Both SPs are able to cross the BBB and can trigger acute and chronic neurological complaints. Such SP-associated pathologies (spikeopathies) are further neurological proteinopathies with thrombogenic, neurotoxic, neuroinflammatory and neurodegenerative potential for the human nervous system, particularly the central nervous system. The potential neurotoxicity of SP from ASP needs to be critically examined, as ASPs have been administered to millions of people worldwide.

SARS-CoV-2 poses significant challenges to people living with diabetes (PLWD). This systematic review aimed to explore the impact of COVID-19 on mortality, complications associated with diabetes and haematological parameters among PLWD.

Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials and LILACS were searched between 1 December 2019 and 14 January 2025.

Eligible studies included case-control and cohort studies involving PLWD categorised into two groups: those with confirmed SARS-CoV-2 infection and those without.

Meta-analyses estimated the odds ratios (ORs) and mean differences (MDs) of outcomes including mortality, intensive care unit (ICU) admission, diabetic ketoacidosis (DKA), acute kidney injury, hospitalisation length and haematological parameters. We pooled results using random-effects models and assessed study quality with the Newcastle-Ottawa Scale. A funnel plot was used to detect potential publication bias. The overall certainty of evidence was assessed using GRADE.

25 of 7266 unique studies were eligible, including 1 154674 PLWD (561 558 with COVID-19 and 593 116 without COVID-19). SARS-CoV-2 infection in PLWD was associated with significantly increased mortality (OR 2.52, 95% CI 1.45 to 4.36, I2=99%), acute kidney injury (3.69, 95% CI 2.75 to 4.94, I2=0%), random plasma glucose in subjects with type 1 diabetes (MD 20.38 mg/dL, 95% CI 7.39 to 33.36, I2=0%), haemoglobin A1C in subjects with type 2 diabetes (0.21%, 95% CI 0.05 to 0.38, I2=13%), creatinine (0.12 mg/dL, 95% CI 0.04 to 0.19, I2=0%), C reactive protein (38.30 mg/L, 95% CI 4.79 to 71.82, I2=82%) and D-dimer (1.52 µg/mL, 95% CI 0.73 to 2.31, I2=0%). No significant differences were observed in the incidence of ICU admission and DKA, hospitalisation length, haemoglobin, leucocyte, lymphocyte, neutrophil to lymphocyte ratio, platelet, blood urea nitrogen, estimated glomerular filtration rate, procalcitonin, albumin, ferritin and bilirubin among PLWD with and without SARS-CoV-2 infection.

SARS-CoV-2 infection is associated with elevated risks of mortality and acute kidney injury and poor glycaemic control in PLWD, alongside increased levels of inflammatory and coagulation biomarkers. These findings underscore the urgent need for tailored clinical management strategies for PLWD with COVID-19.

CRD42023418039.

The COVID-19 pandemic has significantly impacted global healthcare systems, revealed vulnerabilities and prompted a re-evaluation of medical practices. Acute complications from the virus, including cardiovascular and neurological issues, have underscored the necessity for timely medical interventions. Advances in diagnostic methods and personalized therapies have been pivotal in mitigating severe outcomes. Additionally, Long COVID has emerged as a complex challenge, affecting various body systems and leading to respiratory, cardiovascular, neurological, psychological, and musculoskeletal problems. This broad spectrum of complications highlights the importance of multidisciplinary management approaches that prioritize therapy, rehabilitation, and patient-centered care. Vulnerable populations such as paediatric patients, pregnant women, and immunocompromised individuals face unique risks and complications, necessitating continuous monitoring and tailored management strategies to reduce morbidity and mortality associated with COVID-19.

Although Coronavirus disease 2019 (COVID-19) is primarily a respiratory infectious disease, it has also been associated with a wide range of other clinical manifestations. It is widely accepted in the scientific community that many patients after recovery continue to experience COVID-19-related symptoms, including cognitive impairment. The aim of this systematic review was to investigate the cognitive profile of patients with long-COVID syndrome.

A systematic search of empirical studies was conducted through the PubMed/Medline and Scopus electronic databases. Cross-sectional and longitudinal studies published between 2020 and 2023 were included.

Of the 516 studies assessed for eligibility, 36 studies met the inclusion criteria. All included studies support the presence of persistent cognitive changes after COVID-19 disease. Executive function, memory, attention, and processing speed appear to be the cognitive domains that are predominantly associated with long-COVID syndrome, whereas language is an area that has not been sufficiently investigated.

In this review, the high frequency of cognitive impairment after COVID-19 is evident. If we consider that cognitive functioning affects our ability to live independently and is a key determinant of our quality of life, it is imperative to precisely define those factors that may induce cognitive impairment in COVID-19 survivors, with the ultimate goal of early diagnosis of cognitive changes and, consequently, the development of targeted rehabilitation interventions to address them.

The Coronavirus Disease 2019 (COVID-19) pandemic, driven by the novel coronavirus and its variants, has caused over 518 million infections and 6.25 million deaths globally, leading to a significant health crisis. Beyond its primary respiratory impact, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been implicated in various extra-pulmonary complications. Research studies reveal that the virus affects multiple organs, including the kidneys, liver, pancreas, and central nervous system (CNS), largely due to the widespread expression of Angiotensin Converting Enzyme-2 (ACE-2) receptors. Clinical evidence shows that the virus can induce diabetes by disrupting pancreatic and liver functions as well as cause acute kidney injury. Additionally, neurological complications, including cognitive impairments and neuroinflammation, have been observed in a significant number of COVID-19 patients. This review discusses the mechanisms linking SARS-CoV-2 to acute kidney injury, Type 1 and Type 2 Diabetes Mellitus (T1DM and T2DM), emphasizing its effects on pancreatic beta cells, insulin resistance, and the regulation of gluconeogenesis. We also explore how SARS-CoV-2 induces neurological complications, detailing the intricate pathways of neuro-invasion and the potential to trigger conditions such as Alzheimer's disease (AD). By elucidating the metabolic and neurological manifestations of COVID-19 and the underlying pathogenic mechanisms, this review underscores the imperative for continued research and the development of effective therapeutic interventions to mitigate the long-term and short-term impacts of SARS-CoV-2 infection.

Even though respiratory dysfunctions are the primary symptom associated with SARS-CoV-2 infection, cerebrovascular events, and neurological symptoms are described in many patients. However, the connection between the neuroimmune profile and the lung's inflammatory condition during COVID-19 and its association with the neurological symptoms reported by COVID-19 patients still needs further exploration. The present study characterizes the SARS-CoV-2 infectivity profile in postmortem nervous and lung tissue samples of patients who died due to severe COVID-19, and the pro-inflammatory factors present in both nervous and lung tissue samples, via a proteomic profiling array. Additionally, Brain-Derived Neurotrophic Factor (BDNF) levels and intracellular pathways related to neuroplasticity/neuroprotection were assessed in the samples. Out of the 16 samples analyzed, all samples but 1 were positive for the viral genome (genes E or N2, but only 3.9% presented E and N2) in the olfactory brain pathway. The E or N2 gene were also detected in all lung samples, with 43.7% of the samples being positive for the E and N2 genes. In the E/N2 positive brain samples, the Spike protein of SARS-CoV-2 co-localized with TUJ-1+ (neuron-specific class III beta-tubulin) and GFAP+ (glial fibrillary acidic protein) astrocytes. IL-6, but not IL-10, expression was markedly higher in most nervous tissue samples compared to the lung specimens. While intracellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF), and plasminogen activator inhibitor 1 (PAI-1) were increased in lung samples from SARS-Cov-2 patients, only MIF and IL-18 were detected in nervous tissue samples. Correlation analysis suggested that high levels of IL-6 are followed by increased levels of IL-10 in the brain, but not in lung samples. Our analysis also demonstrated that the presence of comorbidities, such as cardiovascular disease, hypertension, and hypothyroidism, is associated with neuroinflammation, while chronic kidney conditions predict the presence of neurological symptoms, which correlate with lower levels of BDNF in the brain samples. Our results corroborate the hypothesis that a pro-inflammatory state might further impair neural homeostasis and induce brain abnormalities found in COVID-19 patients.

The association of anosmia/ageusia with a positive severe respiratory syndrome coronavirus 2 (SARS-CoV-2) test is well-established, suggesting these symptoms are reliable indicators of coronavirus disease 2019 (COVID-19) infection. This study investigates the clinical characteristics and systemic inflammatory markers in hospitalized COVID-19 patients in Taiwan, focusing on those with anosmia/ageusia. We conducted a retrospective observational study on 231 hospitalized COVID-19 patients (alpha variant) from April to July 2021. Clinical symptoms, dyspnea grading, and laboratory investigations, including neutrophil-lymphocyte ratios (NLRs), platelet-lymphocyte ratios (PLRs), and ANDC scores (an early warning score), were analyzed. Cough (64.1%), fever (58.9%), and dyspnea (56.3%) were the most common symptoms, while anosmia/ageusia affected 9% of patients. Those with anosmia/ageusia were younger, had lower BMI, lower systemic inflammatory markers, and better ANDC scores than those without these symptoms. Female patients exhibited lower NLR values and ANDC scores compared to male patients (all p < 0.05). Multivariable regression analysis demonstrated significant associations between NLR and CRP and ferritin levels (all p < 0.01), and between PLR and ESR and ferritin levels (p < 0.01). Categorized ANDC scores significantly correlated with the total hospital length of stay (all p < 0.05). Despite ethnic differences in the prevalence of anosmia/ageusia, our study highlights similar clinical presentations and inflammatory profiles to those observed in Western countries. The ANDC score effectively predicted hospital stay duration. These findings suggest that anosmia/ageusia may be associated with less severe disease and a lower inflammatory response, particularly in younger and female patients. The ANDC score can serve as a valuable prognostic tool in assessing the severity and expected hospital stay of COVID-19 patients.

Introduction Preclinically, fluvoxamine and other antidepressants (AD) exerted antiviral and anti-inflammatory properties also against SARS-COV-2. Therfore, It makes sense to test the clinical effect of AD against COVID-19 and Long COVID.

On May 20, 2024, this systematic scoping review in PUBMED identified 1016 articles related to AD and COVID-19, Long COVID and SARS-COV-2. These included 10 retrospective "large scale" studies (> 20000 chart reviews), 8 prospective clinical trials (plus 4 regarding Long COVID), 11 placebo-controlled randomized (RCT) (plus 2 regarding Long COVID) and 15 meta-analyses.

COVID-19: Retrospective studies with cohorts taking AD primarily for psychiatric comorbidities or chronic pain conditions directly prior to SARS-COV-2 infection described that this substance class (most studied: Selective Serotonin Re-Uptake Inhibitors (SSRI) and Selective Serotonin Noradrenaline Re-Uptake Inhibitors (SSNRI)) were associated with (i) significantly fewer SARS-COV-2 infections and (ii) a milder course of COVID-19 ("COVID-19 protection"). Ten of the 11 RCTs found regarding COVID-19 tested fluvoxamine, as this old AD appeared suitable as a prophylactic agent against severe COVID-19, taking into account its in vitro potency against the progression of intracellular sepsis cascades. Therefore, most (12 out of 15) meta-analyses also referred to fluvoxamine. They found (iii) a significant (40-70% reduction) in mortality, intubation and hospitalization rates when fluvoxamine was used as an add-on to standard therapy for mild to moderate COVID-19. When this AD was used in the early stages of the disease, it was more successful than when it was given later in advanced, severe COVID-19 (e.g. severe pneumonia, final sepsis stages). A dose dependency was observed: 2x50 mg fluvoxamine over 15 days was less effective than 2x100 or even 3x100 mg with an adverse event profile still at the placebo level. Direct comparisons with drugs approved for COVID-19 do not yet exist. A first indirect meta-analytical comparison showed an advantage of paxlovid or molnupiravir versus fluvoxamine against the development of severe COVID-19: risk reduction of 95% (I2 = N/A, but only one study) or 78% (I2=0) versus 5+-5% (I2=48). However, an add-on of fluvoxamine was still significantly more efficacious than symptom-oriented standard therapy alone. Long COVID: A common Long COVID phenotype with dominant anxiety and depression symptoms, which responds to AD, relaxation therapy and/or psychotherapy, has now been identified. Casuistics report positive effects of AD on fatigue, cognitive and autonomic dysfunctions. A first large prospective open-label RCT has just shown significantly more favourable courses, less viral load and less pro-inflammatory cytokines in the treatment of mild to moderate COVID-19 with fluvoxamine versus standard treatment, also with regard to the subsequent development of neuropsychiatric and pulmonary Long COVID or fatigue.

Overall, there is promising evidence of a preventive effect of AD (especially fluvoxamine) against progression to severe COVID-19 and against the development of Long COVID. It is likely, that the entire AD substance class could be effective here. This assumption is based on the results of retrospective large scale studies, but awaits verification by better controlled studies. The potential effectiveness/efficacy (currently low and moderate confidence of the evidence for the entire substance class and specifically fluvoxamine, respectively) of fluvoxamine as an add-on against COVID-19 and possibly also directly against Long COVID could stimulate similar projects in other infectious diseases that also have the potential to pose a lasting threat to the health of those affected. We consider the evidence to date to be sufficient to be able to emphasize a possible positive effect of these substances in the psychoeducation of patients with COVID-19 or Long COVID who are already receiving AD for other conditions - especially also against the symptoms associated with the viral disease or its consequences. In regions where neither vaccines nor antiviral agents currently approved for the prevention or treatment of COVID-19 are available, AD and in particular fluvoxamine would be a cost-effective alternative to protect against a severe course, even if this AD appears to have a smaller effect against COVID-19 than the currently approved antiviral agents, but with presumably better tolerability. A direct comparative clinical trial with approved antiviral agents is still pending and should be positive to further open the door for a guideline-based recommendation of fluvoxamine (or perhaps even AD) for COVID-19 or its aftermath.

COVID-19 can lead to encephalopathy and loss of consciousness. This double-blinded randomized clinical trial conducted in Tehran, Iran, aimed to assess the potential effectiveness of modafinil in patients with COVID-19-related encephalopathy.

Nineteen non-intubated COVID-19 patients with encephalopathy were randomized into two groups: a treatment group receiving crushed modafinil tablets and a placebo group receiving starch powder. Modafinil was administered at a dose of 100 mg every 2 h, reaching a peak dosage of 400 mg. The level of consciousness was assessed using the Glasgow Coma Score (GCS) at multiple time points on the day of medication administration. The trial was registered under IRCT20170903036041N3 on 23/5/2021.

The average age in the modafinil and placebo groups was 75.33 and 70 years, respectively. No significant differences were observed between the two groups in terms of chronic conditions, clinical symptoms, or laboratory data. GCS scores were similar between the groups at baseline (p-value = 0.699). After four doses of modafinil, GCS scores were slightly higher in the treatment group, but this difference was not statistically significant (p-value = 0.581). GCS scores after each round of drug administration didn't significantly differ between the treatment and placebo groups (p-value = 0.908).

Modafinil exhibited a slight improvement in the level of consciousness among COVID-19 patients with encephalopathy, although this improvement did not reach statistical significance when compared to the control group. Further research with larger sample sizes and longer treatment durations is recommended to explore modafinil's potential benefits in managing altered consciousness in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) infection has been associated with severe neurological consequences, including stroke or seizures, and less severe neurological sequelae, including headaches, dizziness, and anosmia. Earlier COVID-19 variants were associated with high morbidity and mortality; however, knowledge of the impact of neurological conditions in the setting of COVID-19 on healthcare outcomes is limited. We sought to determine the impact of acute neurological conditions and acute COVID-19 infection on inpatient hospitalization outcomes.

This was a retrospective, observational study of adult patients who were admitted to a large academic medical center in the Southeastern US between April 2020 and December 2021 with acute COVID-19 infection and a neurological diagnosis. Patient demographics, medical history, neurological diagnoses, and hospitalization outcomes were obtained from the medical record. Descriptive statistics and unadjusted and adjusted logistic regression analyses were performed.

Of the 1,387 patients included in this study, 27% died and 23% were kept under ventilation during hospitalization. The mean +/- standard deviation (SD) age was 64.6+/-16.9 years, with 52.8% women and 30.1% identifying as Black/African American. The most common neurological conditions included ischemic stroke (35.0%), movement disorder (12.0%), and hemorrhagic stroke (10.7%). In-hospital death was most common among those with epilepsy (p = 0.024), headache (p = 0.026), and dementia (p < 0.0001) compared to individuals without those conditions. Ventilation support was given more commonly to dementia patients (p = 0.020). Age was a significant risk factor for death (p < 0.001) and hospital length of stay (LOS) for ventilation (p < 0.001), but no neurological condition was a significant factor in adjusted logistic regression analyses.

Mortality was high in this study, with more than one-quarter of patients dying in the hospital. Death was the most common among those with epilepsy, headache, or dementia, but no neurological condition increased the risk of in-hospital mortality or ventilation. Future studies would determine the long-term neurological sequelae of those discharged from the hospital with COVID-19 and a neurological condition.

The COVID-19 pandemic, with over 83 million confirmed cases and 1.8 million deaths, has raised concerns about long-term cognitive issues, especially in populations facing disparities. Despite a few years since Peru's first COVID-19 wave, the cognitive effects on adults remain unclear. This study is the first in Peru to explore COVID-19's impact on general cognition and executive function.

A retrospective cross-sectional study compared individuals with COVID-19 history to controls, assessing general cognition, verbal fluency, attention, and executive function. Among 240 assessed, 154 met the study inclusion criteria, with about 60% female and an average age of 38.89 ± 16.001 years. Groups included controls (n = 42), acute phase (AP, n = 74) (1-14 days of symptoms), and hyperinflammatory phase (HP, n = 38) (>14 days of symptoms).

Significant cognitive differences were observed. The HP group exhibited lower general cognitive performance (p = 0.02), working memory (p = 0.01), and executive function (planning; p < 0.001; flexibility; p = 0.03) than controls. Those with <14 days of illness (AP vs. HP) had deficits in general cognitive performance (p = 0.02), working memory (p = 0.02), and planning (p < 0.001), mainly during the hyperinflammatory phase, showing differences in working memory (p = 0.003) and planning (p = 0.01). Gender differences emerged, with males in the HP phase having poorer working memory (p = 0.003) and planning (p = 0.01).

This study underscores COVID-19's negative impact on cognitive function, even in mild cases, with potential heightened effects in men during acute or hyperinflammatory phases. The findings provide Peru's first evidence, highlighting the vulnerability of populations facing socioeconomic disparities.

Autopsy followed by histopathological examination is foundational in clinical and forensic medicine for discovering and understanding pathological changes in disease, their underlying processes, and cause of death. Imaging technology has become increasingly important for advancing clinical research and practice, given its noninvasive, in vivo and ex vivo applicability. Medical and forensic autopsy can benefit greatly from advances in imaging technology that lead toward minimally invasive, whole-brain virtual autopsy. Brain autopsy followed by histopathological examination is still the hallmark for understanding disease and a fundamental modus operandi in forensic pathology and forensic medicine, despite the fact that its practice has become progressively less frequent in medical settings. This situation is especially relevant with respect to new diseases such as COVID-19 caused by the SARS-CoV-2 virus, for which our neuroanatomical knowledge is sparse. In this narrative review, we show that ad hoc clinical autopsies and histopathological analyses combined with neuroimaging of the principal circumventricular organs are critical to gaining insight into the reconstruction of the pathophysiological mechanisms and the explanation of cause of death (ie, atrium mortis) related to the cardiovascular effects of SARS-CoV-2 infection in forensic and clinical medicine.

The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.

Respiratory viruses have a significant impact on health, as highlighted by the COVID-19 pandemic. Exposure to air pollution can contribute to viral susceptibility and be associated with severe outcomes, as suggested by recent epidemiological studies. Furthermore, exposure to particulate matter (PM), an important constituent of air pollution, is linked to adverse effects on the brain, including cognitive decline and Alzheimer's disease (AD). The olfactory mucosa (OM), a tissue located at the rooftop of the nasal cavity, is directly exposed to inhaled air and in direct contact with the brain. Increasing evidence of OM dysfunction related to neuropathogenesis and viral infection demonstrates the importance of elucidating the interplay between viruses and air pollutants at the OM. This study examined the effects of subacute exposure to urban PM 0.2 and PM 10-2.5 on SARS-CoV-2 infection using primary human OM cells obtained from cognitively healthy individuals and individuals diagnosed with AD. OM cells were exposed to PM and subsequently infected with the SARS-CoV-2 virus in the presence of pollutants. SARS-CoV-2 entry receptors and replication, toxicological endpoints, cytokine release, oxidative stress markers, and amyloid beta levels were measured. Exposure to PM did not enhance the expression of viral entry receptors or cellular viral load in human OM cells. However, PM-exposed and SARS-CoV-2-infected cells showed alterations in cellular and immune responses when compared to cells infected only with the virus or pollutants. These changes are highly pronounced in AD OM cells. These results suggest that exposure of human OM cells to PM does not increase susceptibility to SARS-CoV-2 infection in vitro, but it can alter cellular immune responses to the virus, particularly in AD. Understanding the interplay of air pollutants and COVID-19 can provide important insight for the development of public health policies and interventions to reduce the negative influences of air pollution exposure.

Many virological tests have been implemented during the Coronavirus Disease 2019 (COVID-19) pandemic for diagnostic purposes, but they appear unsuitable for screening purposes. Furthermore, current screening strategies are not accurate enough to effectively curb the spread of the disease. Therefore, the present study was conducted within a controlled clinical environment to determine eventual detectable variations in the voice of COVID-19 patients, recovered and healthy subjects, and also to determine whether machine learning-based voice assessment (MLVA) can accurately discriminate between them, thus potentially serving as a more effective mass-screening tool. Three different subpopulations were consecutively recruited: positive COVID-19 patients, recovered COVID-19 patients and healthy individuals as controls. Positive patients were recruited within 10 days from nasal swab positivity. Recovery from COVID-19 was established clinically, virologically and radiologically. Healthy individuals reported no COVID-19 symptoms and yielded negative results at serological testing. All study participants provided three trials for multiple vocal tasks (sustained vowel phonation, speech, cough). All recordings were initially divided into three different binary classifications with a feature selection, ranking and cross-validated RBF-SVM pipeline. This brough a mean accuracy of 90.24%, a mean sensitivity of 91.15%, a mean specificity of 89.13% and a mean AUC of 0.94 across all tasks and all comparisons, and outlined the sustained vowel as the most effective vocal task for COVID discrimination. Moreover, a three-way classification was carried out on an external test set comprised of 30 subjects, 10 per class, with a mean accuracy of 80% and an accuracy of 100% for the detection of positive subjects. Within this assessment, recovered individuals proved to be the most difficult class to identify, and all the misclassified subjects were declared positive; this might be related to mid and short-term vocal traces of COVID-19, even after the clinical resolution of the infection. In conclusion, MLVA may accurately discriminate between positive COVID-19 patients, recovered COVID-19 patients and healthy individuals. Further studies should test MLVA among larger populations and asymptomatic positive COVID-19 patients to validate this novel screening technology and test its potential application as a potentially more effective surveillance strategy for COVID-19.

The effects of Covid-19 vaccines on vascular function are still controversial. We evaluated the effects of BNT162b2 vaccine (BioNTech and Pfizer) on endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID). This study was a prospective observational study. A total of 23 medical staff at Hiroshima University Hospital were enrolled in this study. FMD and NID were measured before vaccination and two weeks and six months after the 2nd dose of vaccination. FMD was significantly smaller two weeks after the 2nd dose of vaccination than before vaccination (6.5±2.4% and 8.2±2.6%, p = 0.03). FMD was significantly larger at six months than at two weeks after the 2nd dose of vaccination (8.2±3.0% and 6.5±2.4%, p = 0.03). There was no significant difference between FMD before vaccination and that at six months after the 2nd dose of vaccination (8.2±2.6% to 8.2±3.0%, p = 0.96). NID values were similar before vaccination and at two weeks, and six months after vaccination (p = 0.89). The BNT162b2 Covid-19 vaccine temporally impaired endothelial function but not vascular smooth muscle function, and the impaired endothelial function returned to the baseline level within six months after vaccination.

Mast cells (MC) are ubiquitous in the body, and they are critical for not only in allergic diseases but also in immunity and inflammation, including having potential involvement in the pathophysiology of dysautonomias and neuroinflammatory disorders. MC are located perivascularly close to nerve endings and sites such as the carotid bodies, heart, hypothalamus, the pineal gland, and the adrenal gland that would allow them not only to regulate but also to be affected by the autonomic nervous system (ANS). MC are stimulated not only by allergens but also many other triggers including some from the ANS that can affect MC release of neurosensitizing, proinflammatory, and vasoactive mediators. Hence, MC may be able to regulate homeostatic functions that seem to be dysfunctional in many conditions, such as postural orthostatic tachycardia syndrome, autism spectrum disorder, myalgic encephalomyelitis/chronic fatigue syndrome, and Long-COVID syndrome. The evidence indicates that there is a possible association between these conditions and diseases associated with MC activation. There is no effective treatment for any form of these conditions other than minimizing symptoms. Given the many ways MC could be activated and the numerous mediators released, it would be important to develop ways to inhibit stimulation of MC and the release of ANS-relevant mediators.

Current views on immunity support the idea that immunity extends beyond defense functions and is tightly intertwined with several other fields of biology such as virology, microbiology, physiology and ecology. It is also critical for our understanding of autoimmunity and cancer, two topics of great biological relevance and for critical public health considerations such as disease prevention and treatment. Central to this review, the immune system is known to interact intimately with the nervous system and has been recently hypothesized to be involved not only in autonomic and limbic bio-behaviors but also in cognitive function. Herein we review the structural architecture of the brain network involved in immune response. Furthermore, we elaborate upon the implications of inflammatory processes affecting brain-immune interactions as reported recently in pathological conditions due to SARS-Cov-2 virus infection, namely in acute and post-acute COVID-19. Moreover, we discuss how current neuroimaging techniques combined with ad hoc clinical autopsies and histopathological analyses could critically affect the validity of clinical translation in studies of human brain-immune interactions using neuroimaging. Advances in our understanding of brain-immune interactions are expected to translate into novel therapeutic avenues in a vast array of domains including cancer, autoimmune diseases or viral infections such as in acute and post-acute or Long COVID-19.

An infection with SARS-CoV‑2 can affect the central nervous system, leading to neurological as well as psychiatric symptoms. In this respect, mechanisms of inflammation seem to be of much greater importance than the virus itself. This paper deals with the possible contributions of organic changes to psychiatric symptomatology and deals especially with delirium, cognitive symptoms, depression, anxiety, posttraumatic stress disorder and psychosis. Processes of neuroinflammation with infection of capillary endothelial cells and activation of microglia and astrocytes releasing high amounts of cytokines seem to be of key importance in all kinds of disturbances. They can lead to damage in grey and white matter, impairment of cerebral metabolism and loss of connectivity. Such neuroimmunological processes have been described as a organic basis for many psychiatric disorders, as affective disorders, psychoses and dementia. As the activation of the glia cells can persist for a long time after the offending agent has been cleared, this can contribute to long term sequalae of the infection.

Sleep disturbances are highly prevalent during the COVID-19 pandemic, especially among older adults. We aimed to evaluate sleep heath during COVID-19 pandemic and assess the differences among geographical regions and pandemic periods. We searched three databases (PubMed, Embase, Web of Science) to find articles up to March 12, 2023. We included observational studies that reported the prevalence of sleep disturbances among adults aged 60 years or older in any setting. Two researchers independently reviewed the literature and retrieved the data. We used Der Simonian-Laird random effects meta-analyses to pool the data, followed by subgroup analysis, sensitivity analysis, and meta-regression. A total of 64 studies with 181,224 older adults during the pandemic were included. The prevalence of poor sleep quality, short sleep duration, long sleep duration, and insomnia symptoms were 47.12% (95% CI: 25.97%, 68.27%), 40.81% (95% CI: 18.49%, 63.12%), 31.61% (95% CI: 24.83%, 38.38%), and 21.15% (95% CI: 15.30%, 27.00%), respectively. The prevalence of sleep problems reported by self-constructed items was 26.97% (95% CI: 20.73%, 33.22%). When compared to America (64.13%), Europe (20.23%) and the Western Pacific (21.31%) showed a lower prevalence of sleep problems (all P < 0.0001). The prevalence of worsened sleep problems was 27.88% (95% CI: 11.94%, 43.82%). Compared to 2020 (15.14%), it increased to 47.42% in 2021 (P < 0.05). Eight studies on sleep disturbances among 672 older COVID-19 patients were included. The prevalence of sleep problems and insomnia symptoms among older COVID-19 patients were 41.58% (95% CI: 21.97%, 61.20%) and 41.56% (95% CI: 28.11%, 58.02%), respectively. A significant burden related to poor sleep has been observed among older adults worldwide over the past three years, with variations across different regions and time periods. It is important to make more efforts in prevention and intervention to identify the risk factors, treatment, and rehabilitation of sleep disturbances for healthy aging.

The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). A total of 211 COVID-19 patients were included in the study: of which 59 were vaccinated with mRNA vaccines against SARS-CoV-2 while 152 were unvaccinated. Patients were enrolled in three waves: from September 2020 to October 2022, corresponding to the emergence of the pre-Delta, Delta, and Omicron variants of the SARS-CoV-2 virus. The three criteria for enrolling patients were: oropharyngeal swab positivity or fecal findings; moderate symptoms with antibiotic intake; and measurement of blood oxygen saturation during the period of illness. The use of antibiotic combinations, such as amoxicillin with clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 mg tablets every 12 h), as first choice, as suggested from the previous data, or azithromycin (500 mg tablets every 24 h), plus rifaximin as above, allows healthcare professionals to focus on the gut microbiome and its implications in COVID-19 disease during patient care. The primary outcome measured in this study was the estimated average treatment effect, which quantified the difference in mean recovery between patients receiving antibiotics and those not receiving antibiotics at 3 and 9 days after the start of treatment. In the analysis, both vaccinated and unvaccinated groups had a median illness duration of 7 days (interquartile range [IQR] 6-9 days for each; recovery crude hazard ratio [HR] = 0.94, p = 0.700). The median illness duration for the pre-Delta and Delta waves was 8 days (IQR 7-10 days), while it was shorter, 6.5 days, for Omicron (IQR 6-8 days; recovery crude HR = 1.71, p < 0.001). These results were confirmed by multivariate analysis. Patients with comorbidities had a significantly longer disease duration: median 8 days (IQR 7-10 days) compared to 7 days (IQR 6-8 days) for those without comorbidities (crude HR = 0.75, p = 0.038), but this result was not confirmed in multivariate analysis as statistical significance was lost. Early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude HR = 4.74, p < 0.001). Concomitant use of NSAIDs did not reduce disease duration and in multivariate analysis prolonged the disease (p = 0.041). A subgroup of 42 patients receiving corticosteroids for a median of 3 days (IQR 3-6 days) had a longer recovery time (median 9 days, IQR 8-10 days) compared to others (median 7 days, IQR 6-8 days; crude HR = 0.542, p < 0.001), as confirmed also by the adjusted HR. In this study, a statistically significant reduction in recovery time was observed among patients who received early antibiotic treatment. Early initiation of antibiotics played a crucial role in maintaining higher levels of blood oxygen saturation. In addition, it is worth noting that a significant number of patients who received antibiotics in the first 3 days and for a duration of 7 days, during the acute phase did not develop LC.

Stroke is one of the neurological manifestations of COVID-19, leading to a significant risk of morbidity and mortality. Clinical manifestations and laboratory parameters were investigated to determine mortality predictors in this case.

The case control study was conducted at Dr. Sardjito General Hospital,Yogyakarta, Indonesia, with data collected between July 2020 and August 2021. All recorded clinical and laboratory data from acute stroke patients with confirmed COVID-19 were collected. Baseline characteristics, bivariate, and multivariate analyses were assessed to determine significant predictors for mortality.

This study involved 72 subjects with COVID-19 and stroke. The majority experienced ischemic stroke, with hypertension as the most prevalent comorbidity. Notably, 45.8% of subjects (p < 0.05) loss of consciousness and 72.2% of exhibited motor deficits (p < 0.05). Severe degree of COVID-19 was observed in 52.8% of patients, with respiratory distress and death rates of 56.9% and 58.3%. Comparison of surviving and deceased groups highlighted significant differences in various clinical and laboratory characteristics differences. Hazard ratio (HR) analysis identified loss of consciousness (HR = 2.68; p = 0.01), motor deficit (HR = 2.34; p = 0.03), respiratory distress (HR = 81.51; p < 0.001), and monocyte count (HR:1.002; p = 0.04) as significant predictors of mortality.

Mortality in COVID-19 patients with stroke was significantly associated with loss of consciousness, motor deficit, respiratory distress, and raised monocyte count. The risk of mortality is heightened when multiple factors coexist.

Currently, there exists a limited comprehension regarding the correlation between COVID-19 and Alzheimer's disease (AD). To elucidate the interrelationship and its impact on outcomes, a comprehensive investigation was carried out utilising time-unrestricted searches of reputable databases such as Scopus, PubMed, Web of Science, and Google Scholar. Our objective was to evaluate the impact of various medical conditions on severe COVID-19-related events. We focused on identifying and analysing articles that discussed the clinical characteristics of COVID-19 patients, particularly those pertaining to severe events such as ICU admission, mechanical ventilation, pneumonia, mortality and acute respiratory distress syndrome (ARDS) a serious lung condition that causes low blood oxygen. Through careful data analysis and information gathering, we tried to figure out how likely it was that people with conditions, like AD, would have serious events. Our research investigated potential mechanisms that link AD and COVID-19. The ability of the virus to directly invade the central nervous system and the role of ACE-2 receptors were investigated. Furthermore, the OAS1 gene served as the genetic link between AD and COVID-19. In the context of COVID-19, our findings suggest that individuals with AD may be more susceptible to experiencing severe outcomes. Consequently, it is crucial to provide personalised care and management for this demographic. Further investigation is required to attain a comprehensive comprehension of the intricate correlation between Alzheimer's disease and COVID-19, as well as its ramifications for patient outcomes.

Alzheimer's disease (AD) is a recognized complex and severe neurodegenerative disorder, presenting a significant challenge to global health. Its hallmark pathological features include the deposition of β-amyloid plaques and the formation of neurofibrillary tangles. Given this context, it becomes imperative to develop an early and accurate biomarker model for AD diagnosis, employing machine learning and bioinformatics analysis.

In this study, single-cell data analysis was employed to identify cellular subtypes that exhibited significant differences between the diseased and control groups. Following the identification of NK cells, hdWGCNA analysis and cellular communication analysis were conducted to pinpoint NK cell subset with the most robust communication effects. Subsequently, three machine learning algorithms-LASSO, Random Forest, and SVM-RFE-were employed to jointly screen for NK cell subset modular genes highly associated with AD. A logistic regression diagnostic model was then designed based on these characterized genes. Additionally, a protein-protein interaction (PPI) networks of model genes was established. Furthermore, unsupervised cluster analysis was conducted to classify AD subtypes based on the model genes, followed by the analysis of immune infiltration in the different subtypes. Finally, Spearman correlation coefficient analysis was utilized to explore the correlation between model genes and immune cells, as well as inflammatory factors.

We have successfully identified three genes (RPLP2, RPSA, and RPL18A) that exhibit a high association with AD. The nomogram based on these genes provides practical assistance in diagnosing and predicting patients' outcomes. The interconnected genes screened through PPI are intricately linked to ribosome metabolism and the COVID-19 pathway. Utilizing the expression of modular genes, unsupervised cluster analysis unveiled three distinct AD subtypes. Particularly noteworthy is subtype C3, characterized by high expression, which correlates with immune cell infiltration and elevated levels of inflammatory factors. Hence, it can be inferred that the establishment of an immune environment in AD patients is closely intertwined with the heightened expression of model genes.

This study has not only established a valuable diagnostic model for AD patients but has also delved deeply into the pivotal role of model genes in shaping the immune environment of individuals with AD. These findings offer crucial insights into early AD diagnosis and patient management strategies.

Imaging has been demonstrated to play a crucial role in both the diagnosis and management of COVID-19. Depending on resources, pre-test probability, and risk factors for severe disease progression, real-time polymerase chain reaction (RT-PCR) testing may be followed by chest radiography (CXR) or chest computed tomography (CT) to further aid in diagnosis or excluding COVID-19 disease. SARS-CoV-2 has been shown not only to pathologically impact the pulmonary system, but also the cardiovascular, gastrointestinal, and neurological systems to name a few. Imaging has again proven useful in further investigating and managing extrapulmonary disease, with the use of echocardiogram, CT angiography of the cardiovascular and cerebrovascular structures, MRI of the brain, as well as ultrasound of the abdomen and CT of the abdomen and pelvis proving particularly useful. Research in artificial intelligence and its application in the diagnosis of COVID-19 and disease severity prediction is underway, and point-of-care ultrasound is an emerging bedside technique that may allow for more efficient and timely diagnosis of COVID-19.

The neurological effects of the coronavirus disease of 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk of Alzheimer's disease (AD). Neuroinflammation and other AD-associated pathologies are also suggested to increase the risk of serious SARS-CoV-2 infection. Anosmia is a common neurological symptom reported in COVID-19 and in early AD. The olfactory mucosa (OM) is important for the perception of smell and a proposed site of viral entry to the brain. However, little is known about SARS-CoV-2 infection at the OM of individuals with AD.

To address this gap, we established a 3D in vitro model of the OM from primary cells derived from cognitively healthy and AD individuals. We cultured the cells at the air-liquid interface (ALI) to study SARS-CoV-2 infection under controlled experimental conditions. Primary OM cells in ALI expressed angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and several other known SARS-CoV-2 receptor and were highly vulnerable to infection. Infection was determined by secreted viral RNA content and confirmed with SARS-CoV-2 nucleocapsid protein (NP) in the infected cells by immunocytochemistry. Differential responses of healthy and AD individuals-derived OM cells to SARS-CoV-2 were determined by RNA sequencing.

Results indicate that cells derived from cognitively healthy donors and individuals with AD do not differ in susceptibility to infection with the wild-type SARS-CoV-2 virus. However, transcriptomic signatures in cells from individuals with AD are highly distinct. Specifically, the cells from AD patients that were infected with the virus showed increased levels of oxidative stress, desensitized inflammation and immune responses, and alterations to genes associated with olfaction. These results imply that individuals with AD may be at a greater risk of experiencing severe outcomes from the infection, potentially driven by pre-existing neuroinflammation.

The study sheds light on the interplay between AD pathology and SARS-CoV-2 infection. Altered transcriptomic signatures in AD cells may contribute to unique symptoms and a more severe disease course, with a notable involvement of neuroinflammation. Furthermore, the research emphasizes the need for targeted interventions to enhance outcomes for AD patients with viral infection. The study is crucial to better comprehend the relationship between AD, COVID-19, and anosmia. It highlights the importance of ongoing research to develop more effective treatments for those at high risk of severe SARS-CoV-2 infection.

Maintaining and improving brain health, one of the most critical global challenges of this century, necessitates innovative, interdisciplinary, and collaborative strategies to address the growing challenges in Latin America and the Caribbean. This paper introduces Brain Health Diplomacy (BHD) as a pioneering approach to bridge disciplinary and geographic boundaries and mobilize resources to promote equitable brain health outcomes in the region. Our framework provides a toolkit for emerging brain health leaders, equipping them with essential concepts and practical resources to apply in their professional work and collaborations. By providing case studies, we highlight the importance of culturally sensitive, region-specific interventions to address unique needs of vulnerable populations. By encouraging dialogue, ideation, and cross-sector discussions, we aspire to develop new research, policy, and programmatic avenues. The novel BHD approach has the potential to revolutionize brain health across the region and beyond, ultimately contributing to a more equitable global cognitive health landscape.

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has brought a conglomerate of novel chronic disabling conditions described as 'Long COVID/Post-COVID-19 Syndrome'. Recent evidence suggests that the multifaceted nature of this syndrome results in both pulmonary and extrapulmonary sequelae,chronic dyspnoea, persistent fatigue, and cognitive dysfunction being the most common, debilitating symptoms. Several mechanisms engender or exacerbate cognitive impairment, including central nervous system and extra-central nervous system causes, although the exact mechanism remains unclear. Both hospitalized and non-hospitalized patients may suffer varying degrees of cognitive impairment, ranging from fatigue and brain fog to prolonged deficits in memory and attention, detrimental to the quality-of-life years post-recovery. The aim of this review is to understand the underlying mechanisms, associations, and attempts for prevention with early intervention of long-term cognitive impairment post-COVID-19.

A systematic search was conducted through multiple databases such as Medline, National Library of Medicine, Ovid, Scopus database to retrieve all the articles on the long-term sequalae of cognitive dysfunction after SARS-CoV-2 infection. The inclusion criteria included all articles pertinent to this specific topic and exclusion criteria subtracted studies pertaining to other aetiologies of cognitive dysfunction. This search was carefully screened for duplicates and the relevant information was extracted and analysed.

To date, the exact pathogenesis, and underlying mechanisms behind cognitive dysfunction in COVID-19, remain unclear, hindering the development of adequate management strategies. However, the proposed mechanisms suggested by various studies include direct damage to the blood-brain barrier, systemic inflammation, prolonged hypoxia, and extended intensive care admissions. However, no clear-cut guidelines for management are apparent.

This review of the COVID-19 pandemic has elucidated a new global challenge which is affecting individuals' quality of life by inducing long-term impaired cognitive function. The authors have found that comprehensive evaluations and interventions are crucial to address the cognitive sequelae in all COVID-19 patients, especially in patients with pre-existing cognitive impairment. Nevertheless, the authors recommend further research for the development of relevant, timely neurocognitive assessments and treatment plans.

SARS-CoV-2 infects cells via its spike (S) protein binding to its surface receptor angiotensin converting enzyme 2 (ACE2) on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that SARS-CoV-2 infection produces neuroinflammation associated with neurological, neuropsychiatric, and cognitive symptoms persists well past the resolution of the infection, known as post-COVID-19 sequalae or long-COVID. The neuroimmune mechanism(s) involved in long-COVID have not been adequately characterized. In this study, we show that recombinant SARS-CoV-2 full-length S protein stimulates release of pro-inflammatory IL-1b, CXCL8, IL-6, and MMP-9 from cultured human microglia via TLR4 receptor activation. Instead, recombinant receptor-binding domain (RBD) stimulates release of TNF-α, IL-18, and S100B via ACE2 signaling. These results provide evidence that SARS-CoV-2 spike protein contributes to neuroinflammation through different mechanisms that may be involved in CNS pathologies associated with long-COVID.

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate the potential of small molecules from natural products to offer neuroprotection in models of neurodegenerative diseases. Through our analysis, we discovered that flavonoids, alkaloids, terpenoids, and other natural compounds exhibit neuroprotective effects by modulating signaling pathways known to be impacted by COVID-19. Some of these compounds also directly target SARS-CoV-2 viral replication. Therefore, molecules of natural origin show promise as potential agents to prevent or mitigate nervous system damage in COVID-19 patients. Further research and the evaluation of different stages of the disease are warranted to explore their potential benefits.

Seizures may be one of the neurological consequences of COVID-19. The present study aims to review the prevalence of seizures in COVID-19 patients considering sex and geographical origin. A review protocol was submitted to the PROSPERO database (CRD42021281467). PRISMA statement was used to report the meta-analysis. The authors selected studies for the meta-analysis by searching the principal databases. Studies were eligible if they reported seizures in COVID-19 patients, regardless of study design. Data were analyzed by proportion meta-analysis with a 95 % confidence interval (95 % CI). Cochran's Q and Higgins' I2 were used to measure heterogeneity. R software was used for meta-analysis. Subgroup analyses were carried out for sex, geographical origin of the subjects, and illness severity. A checklist for prevalence studies was used to assess the risk of bias in the included studies. A total of 32 studies (n = 251,997 analyzed patients) were included in this meta-analysis. A prevalence of 1.03 % (95 % CI 0.73 to 1.37, I2 = 93 %, p < 0.001) was found. No statistically significant differences were found in the analysis by geographical subgroups. Men were found to be less likely to had COVID-19 seizures (OR = 0.75, 95 % CI 0.21-2.74), while mildly ill patients were found to be more likely to had COVID-19-induced seizures (OR = 2.08, 95 % CI 0.86-5.06). Our results show a slight prevalence of seizures in COVID-19 patients. In addition, we found that the groups analyzed had differences in the odds of having COVID-19-induced seizures.

With the decline in the number of new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections, the World Health Organization announced the end of the SARS-CoV-2 pandemic. However, the repercussions of this viral pandemic may remain with us for a longer period of time, as it has remodeled the lives of humankind in many ways, including social and economic. Of course, its most important repercussions remain on the human health level. Long-coronavirus disease (COVID) or post-COVID is a state for which we do not have a concrete definition, a specific international classification of diseases Code, clear diagnostic tools, or well-known effective cures as of yet. In this second article from the Intrinsic Factors behind long-COVID Series, we try to link long-COVID symptoms with their causes, starting from the nervous system. Extracellular vesicles (ECVs) play very complex and ramified roles in the bodies of both healthy and not-healthy individuals. ECVs may facilitate the entry of many bioactive molecules and pathogens into the tissues and cells of the nervous system across the blood-brain barrier. Based on the size, quantity, and quality of their cargo, ECVs are directly proportional to the pathological condition and its severity through intertwined mechanisms that evoke inflammatory immune responses typically accompanied by pathological symptoms over variable time periods according to the type of these symptoms.

One of the negative effects of the COVID-19 illness, which has affected people all across the world, is Alzheimer's disease. Oblivion after COVID-19 has created a variety of issues for many people. Predicting this issue in COVID-19 patients can considerably lessen the severity of the problem.

Alzheimer's disease was predicted in Iranian persons with COVID-19 in using three algorithms: Nave Bayes, Random Forest, and KNN. Data collected by private questioner from hospitals of Tehran Province, Iran, during Oct 2020 to Sep 2021. For ML models, performance is quantified using measures such as Precision, Recall, Accuracy, and F1-score.

The Nave Bayes, Random Forest algorithm has a prediction accuracy of higher than 80%. The predicted accuracy of the random forest algorithm was higher than the other two algorithms.

The Random Forest algorithm outperformed the other two algorithms in predicting Alzheimer's disease in persons using COVID-19. The findings of this study could help persons with COVID-19 avoid Alzheimer's problems.

Bilateral vocal fold paresis (BVFP) is a rare complication in COVID-19 and should be considered as differential diagnosis in COVID-19-patients presenting with dyspnea and stridor. High-dose intravenous corticosteroids can be useful treating COVID-19-related laryngeal edema and vocal fold paresis. This case shows the complexity of laryngeal complications in COVID-19 requiring surgeries and functional therapies.

Although COVID-19 is known to affect peripheral as well as cranial nerves, there is a paucity of reports on vocal fold paresis in COVID-19, bilateral vocal fold paresis (BVFP) in particular. We describe a case of BVFP and glottal bridge synechia following COVID-19-pneumonia discussing pathomechanisms and treatment options.

The COVID-19 pandemic has significantly impacted public health, putting people with Alzheimer's disease at significant risk. This study used bibliometric analysis method to conduct in-depth research on the relationship between COVID-19 and Alzheimer's disease, as well as to predict its development trends.

The Web of Science Core Collection was searched for relevant literature on Alzheimer's and Coronavirus-19 during 2019-2023. We used a search query string in our advanced search. Using Microsoft Excel 2021 and VOSviewer software, a statistical analysis of primary high-yield authors, research institutions, countries, and journals was performed. Knowledge networks, collaboration maps, hotspots, and regional trends were analyzed using VOSviewer and CiteSpace.

During 2020-2023, 866 academic studies were published in international journals. United States, Italy, and the United Kingdom rank top three in the survey; in terms of productivity, the top three schools were Harvard Medical School, the University of Padua, and the University of Oxford; Bonanni, Laura, from Gabriele d'Annunzio University (Italy), Tedeschi, Gioacchino from the University of Campania Luigi Vanvitelli (Italy), Vanacore, Nicola from Natl Ctr Dis Prevent and Health Promot (Italy), Reddy, P. Hemachandra from Texas Tech University (USA), and El Haj, Mohamad from University of Nantes (France) were the authors who published the most articles; The Journal of Alzheimer's Disease is the journals with the most published articles; "COVID-19," "Alzheimer's disease," "neurodegenerative diseases," "cognitive impairment," "neuroinflammation," "quality of life," and "neurological complications" have been the focus of attention in the last 3 years.

The disease caused by the COVID-19 virus infection related to Alzheimer's disease has attracted significant attention worldwide. The major hot topics in 2020 were: "Alzheimer' disease," COVID-19," risk factors," care," and "Parkinson's disease." During the 2 years 2021 and 2022, researchers were also interested in "neurodegenerative diseases," "cognitive impairment," and "quality of life," which require further investigation.

Externalizing traits have been related with the outcomes of coronavirus disease 2019 (COVID-19) and Alzheimer's dementia (AD); however, whether these associations are causal remains unknown. We used the two-sample Mendelian randomization (MR) approach with more than 200 single-nucleotide polymorphisms (SNPs) for externalizing traits to explore the causal associations of externalizing traits with the risk of COVID-19 (infected COVID-19, hospitalized COVID-19, and severe COVID-19) or AD based on the summary data. The inverse variance-weighted method (IVW) was used to estimate the main effect, followed by several sensitivity analyses. IVW analysis showed significant associations of externalizing traits with COVID-19 infection (odds ratio [OR] = 1.456, 95% confidence interval [95% CI] = 1.224-1.731), hospitalized COVID-19 (OR = 1.970, 95% CI = 1.374-2.826), and AD (OR = 1.077, 95% CI = 1.037-1.119). The results were consistent using weighted median (WM), penalized weighted median (PWM), MR-robust adjusted profile score (MR-RAPS), and leave-one-out sensitivity analyses. Our findings assist in exploring the causal effect of externalizing traits on the pathophysiology of infection and severe infection of COVID-19 and AD. Furthermore, our study provides evidence that shared externalizing traits underpin the two diseases.