Neurodegenerative diseases are chronic progressive disorders that impair memory, cognition, and motor functions, leading to conditions such as dementia, muscle weakness, and speech difficulties. Aging disrupts the stringent balance between pro- and anti-inflammatory cytokines, increasing neuroinflammation, which contributes to neurodegenerative diseases. The aging brain is particularly vulnerable to infections due to a weakened and compromised immune response and impaired integrity of the blood-brain barrier, allowing pathogens like viruses to trigger neurodegeneration. Coronaviruses have been linked to both acute and long-term neurological complications, including cognitive impairments, psychiatric disorders, and neuroinflammation. The virus can induce a cytokine storm, damaging the central nervous system (CNS) and worsening existing neurological conditions. Though its exact mechanism of neuroinvasion remains elusive, evidence suggests it disrupts the blood-brain barrier and triggers immune dysregulation, leading to persistent neurological sequelae in elderly individuals. This review aims to understand the interaction between the peripheral immune system and CNS glial cells in aged individuals, which is imperative in addressing coronavirus-induced neuroinflammation and concomitant neurodegeneration.

Long COVID has emerged as a significant challenge since the COVID-19 pandemic, which was declared as an outbreak in March 2020, marked by diverse symptoms and prolonged duration of disease. Defined by the WHO as symptoms persisting or emerging for at least two months post-SARS-CoV-2 infection without an alternative cause, its prevalence varies globally, with estimates of 10-20% in Europe, 7.3% in the USA, and 3.0% in the UK. The condition's etiology remains unclear, involving factors, such as renin-angiotensin system overactivation, persistent viral reservoirs, immune dysregulation, and autoantibodies. Reactivated viruses, like EBV and HSV-6, alongside epigenetic alterations, exacerbate mitochondrial dysfunction and energy imbalance. Emerging evidence links SARS-CoV-2 to chromatin and gut microbiome changes, further influencing long-term health impacts. Diagnosis of long COVID requires detailed systemic evaluation through medical history and physical examination. Management is highly individualized, focusing mainly on the patient's symptoms and affected systems. A multidisciplinary approach is essential, integrating diverse perspectives to address systemic manifestations, underlying mechanisms, and therapeutic strategies. Enhanced understanding of long COVID's pathophysiology and clinical features is critical to improving patient outcomes and quality of life. With a growing number of cases expected globally, advancing research and disseminating knowledge on long COVID remain vital for developing effective diagnostic and management frameworks, ultimately supporting better care for affected individuals.

Comorbidities, including obesity and type 2 diabetes mellitus (T2DM), are associated with increased disease severity and mortality following SARS-CoV-2 infection. Here, we investigated virus-host interactions under the effects of these comorbidities in diet-induced obesity (DIO) and leptin receptor-deficient (T2DM) mice following infection with SARS-CoV-2. DIO mice, as well as their lean counterparts, showed limited susceptibility to SARS-CoV-2 infection. In contrast, T2DM mice showed exacerbated pulmonary SARS-CoV-2 replication and delayed viral clearance associated with down-regulation of innate and adaptative immune gene signatures, ineffective type I interferon response, and delayed SARS-CoV-2-specific cell-mediated immune responses. While T2DM mice showed higher and prolonged SARS-CoV-2-specific immunoglobulin isotype responses compared to their lean counterparts, neutralizing antibody levels were equivalent. By silencing the leptin receptor in vitro using a human alveolar epithelial cell line, we observed an increase in SARS-CoV-2 replication and type I interferons. Altogether, our data provides for the first time evidence that disruption of leptin receptor signaling leading to obesity and T2DM induces altered type I interferon and cell-mediated responses against SARS-CoV-2, mediating increased viral replication and delayed clearance. These data shed light on the alteration of the innate immune pathway in the lung using in-depth transcriptomic analysis and on adaptive immune responses to SARS-CoV-2 under T2DM conditions. Finally, this study provides further insight into this risk factor aggravating SARS-CoV-2 infection and understanding the underlying cellular mechanisms that could help identify potential intervention points for this at-risk population.

Emerging evidence suggests coronavirus disease 2019 (COVID-19) infection may increase the risk of developing dementia, although studies have reported conflicting findings. This meta-analysis aimed to synthesise the literature on the association between COVID-19 and the risk of new-onset dementia.

PubMed, Embase and Web of Science were searched for cohort studies or case-control studies that investigated new-onset dementia development among adult COVID-19 survivors compared to individuals without COVID-19 infection from inception to 9 November 2023. Studies that exclusively involved populations younger than 18 years, with known dementia or lacked adequate data about the risk of dementia were excluded. Two authors independently conducted the screening of eligible studies, data extraction and risk of bias assessment. The primary outcome was new-onset dementia following COVID-19 infection. Data were pooled using random-effects models, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated.

A total of 15 retrospective cohort studies encompassing 26 408 378 participants were included. Pooled analysis indicated COVID-19 was associated with an increased risk of new-onset dementia (HR = 1.49, 95% CI: 1.33-1.68). This risk remained elevated when compared with non-COVID cohorts (HR = 1.65, 95% CI: 1.39-1.95), and respiratory tract infection cohorts (HR = 1.29, 95% CI: 1.12-1.49), but not influenza or sepsis cohorts. Increased dementia risk was observed in both males and females, as well as in individuals older than 65 years (HR = 1.68, 95% CI: 1.48-1.90), with the risk remaining elevated for up to 24 months.

This meta-analysis demonstrates a significant association between COVID-19 infection and increased risk of developing new-onset dementia, which underscores the need for cognitive monitoring and early intervention for COVID-19 survivors to address potential long-term neurological impacts.

Although COVID-19 has been linked to worse outcomes in patients with neurological disorders, its impact on those with essential tremor (ET) remains unclear. To investigate clinical outcomes of ET patients with and without COVID-19 three and a half years post-pandemic.

1074 ET patients were evaluated in this retrospective study in the Montefiore Health System from January 2016 to July 2023. Comparisons between ET patients with and without a positive SARS-CoV-2 polymerase chain reaction test were made. Outcomes included post-index date major adverse cardiovascular events (MACEs), new-onset sleep disturbances, fatigue, dyspnea, first-time fall, new-onset anxiety, new-onset depression, headache, new-onset imbalance, new-onset mild cognitive impairment, and all-cause mortality, adjusted hazard ratios (aHR) adjusting for covariates were calculated.

ET patients with COVID-19 had higher prevalence of pre-existing type-2 diabetes, depression, and anxiety compared to ET patients without COVID-19. COVID-19 was significantly associated with higher risk of MACEs, (aHR = 2.39 [1.49, 3.82]), new-onset sleep disturbance, (aHR = 2.12 [1.44, 3.13]), fatigue, (aHR = 1.83 [1.27, 2.65]), dyspnea, (aHR = 1.98 [1.40, 2.80]), first-time fall, (aHR = 4.76 [2.24, 10.14]), new-onset anxiety, (aHR = 3.66 [2.02, 6.64]), and new-onset depression, (aHR = 2.38 [1.20, 4.70]). COVID-19 was not associated with all-cause mortality.

In patients with ET, COVID-19 significantly increases the risk of several long-term adverse health outcomes, but not mortality.

In 2019, coronavirus disease 2019 (COVID-19) started a global health crisis and was associated with high rates of depression and anxiety. Both mental disorders and COVID-19 exhibit similarities in pathophysiology, characterized by immune system overactivation, involvement of the purinergic system, and oxidative stress, besides additional factors and systems likely contributing to the complexities of these conditions. The purinergic system contributes to the disease-influenced immune response, an essential strategy for controlling pathophysiological effects. In this context, the hormone melatonin emerges as a substance that can modulate the purinergic system and contribute positively to the pathophysiology of SARS-CoV-2 infection and associated mental disorders. Melatonin is a hormone that regulates the body's circadian rhythms, plays an essential role in regulating sleep and mood, and modulates the purinergic system. Recent studies suggest melatonin's anti-inflammatory and antioxidant properties may benefit COVID-19. This review explores melatonin's impact on inflammatory cytokine storm in COVID-19 through purinergic system modulation.

COVID-19 vaccines reduced mortality, hospitalizations and ICUs admissions. Conversely, the impact of vaccination on Long COVID-19 syndrome is still unclear. This study compared the prevalence of post-acute sequelae at short and long-term follow-up among hospitalized unvaccinated and vaccinated COVID-19 survivors through a multidisciplinary approach.

After 2 months from discharge, unvaccinated and vaccinated COVID-19 survivors underwent a follow-up visit at a dedicated "post-COVID-19 Outpatient Clinic". The follow-up visit included a cardiovascular evaluation, blood tests, chest computed tomography, 6-min walking test (6MWT), spirometry. A one-year telephone follow-up was performed to assess re-hospitalizations, death and long-lasting symptoms. An additional 1:1 case-control matching analysis adjusted for baseline characteristics was performed.

Between June 2020 and June 2022, a total of 458 unvaccinated and vaccinated patients (229 per group) underwent the follow-up visit. Vaccinated patients had lower rates of ICU admissions (1.7 % vs 9.6 %, p= <0.001) and severe respiratory complications requiring intubation (1.3 % vs 7 %, p = 0.002) or non-invasive ventilation such as high-flow nasal oxygen therapy (1.7 % vs 7.9 %, p = 0.02), CPAP (1.3 % vs 20.1 %, p= < 0.001), and low-flow oxygen therapy (3.5 % vs 63.3 %, p= <0.001) compared to unvaccinated ones. At 2-month follow-up, vaccinated patients had fewer persistent ground-glass opacities (2.6 % vs 52.8 %, p= <0.001) or consolidations (0.9 % vs 8.3 %, p= <0.001). Additionally, unvaccinated patients experienced more frequent myocarditis (4.8 % vs 0.9 %, p = 0.013) and pulmonary embolism (1.8 % vs 0 %, p = 0.042) and exhibited more significant respiratory impairment as evidenced by desaturation during the 6MWT(10.2 % vs 3.5 %, p = 0.005) and altered spirometry (14 % vs 8.7 %, p = 0.043) compared to vaccinated ones. At one-year, unvaccinated patients reported more symptoms such as dyspnea (20.5 % vs 10 %, p = 0.002), psychological symptoms (10 % vs 3.5 %, p = 0.005) and chronic rhinosinusitis/cough (6,6 % vs 2,6 %, p = 0.04) as compared to vaccinated ones. The 1:1 case-control matching analysis also confirmed these results.

COVID-19 vaccines improve short-term outcomes and may reduce Long COVID-19 prevalence.

Measures reflecting cardiac sympathovagal activity, particularly those associated with heart rate variability (HRV), are widely recognized and utilized in both scientific and clinical contexts. This study aimed to assess the inter- and intra-examiner reliability of short-term HRV parameters in patients hospitalized with coronavirus disease 2019 (COVID-19). A total of 103 patients (both sexes) diagnosed with COVID-19 were included in the study. HRV was analyzed using both linear and nonlinear methods. Reliability was evaluated through intraclass correlation coefficient (ICC2.1), minimum detectable change (MDC), standard error of measurement (SEM), and coefficient of variation (CV). According to Fleiss' criteria, excellent reliability was demonstrated, with ICC values ranging from 0.970 to 0.999 for Examiner 1, and from 0.956 to 0.999, for Examiner 2. In the inter-examiner analysis, the ICCs of HRV parameters ranged from 0.972 to 0.999. SEM values for intra-examiner reliability for Examiner 1 ranged from 0.02 to 5.64, with MDC values from 0.05 to 15.64, and CV (%) from 0.28 to 8.04. For Examiner 2, SEM values ranged from 0.02 to 8.18, MDC values from 0.05 to 22.68, and CV (%) from 0.24 to 8.14. For inter-examiner reliability, SEM values ranged from 0.02 to 6.17, MDC from 0.06 to 17.11, and CV (%) from 0.34 to 9.81. Across all analyses, CVs for HRV parameters remained below 10%. Considering different time points and different examiners, short-term resting HRV measurements in patients hospitalized with COVID-19, as evaluated using a portable heart rate device, exhibit high reliability.

Long coronavirus disease (COVID), also known as the post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC), is a significant concern since the end of the COVID-19 pandemic, as it still manifests in individuals with persistent symptoms and complications beyond the acute phase of infection. Defining this disease is challenging, as it manifests as a spectrum of symptoms varying in severity among individuals who have previously tested positive for COVID-19. Long COVID is more prevalent in hospitalized COVID-19 patients and presents in various ways, ranging from pulmonary to extrapulmonary symptoms. This literature review examines the current body of research on long COVID with a focus on its effects on the cardiovascular, hematological, respiratory, renal, and neurological systems with systematically analyzed, peer-reviewed articles retrieved from the PubMed database. There have been several proposed pathophysiological mechanisms by which severe acute respiratory syndrome coronavirus 2 affects the aforementioned organ systems; however, research on the definite mechanisms is lacking, especially when considering the management of long COVID in the perioperative setting. The impact of post-COVID sequelae necessitates individualized management strategies tailored to each symptomatic profile, particularly in patients with comorbidities. The COVID-19 pandemic affected millions of people and had a profound impact on those who developed PASC, lowering their quality of life and increasing potential surgical risks. However, there is still uncertainty regarding the specific risk factors for long COVID and who is most susceptible to it. Further research is required to fill these gaps and explore potential avenues for preventing PASC.

Neurotropic pathogens, notably, herpesviruses, have been associated with significant neuropsychiatric effects. As a group, these pathogens can exploit molecular mimicry mechanisms to manipulate the host central nervous system to their advantage. Here, we present a systematic computational approach that may ultimately be used to unravel protein-protein interactions and molecular mimicry processes that have not yet been solved experimentally. Toward this end, we validate this approach by replicating a set of pre-existing experimental findings that document the structural and functional similarities shared by the human cytomegalovirus-encoded UL144 glycoprotein and human tumor necrosis factor receptor superfamily member 14 (TNFRSF14). We began with a thorough exploration of the Homo sapiens protein database using the Basic Local Alignment Search Tool (BLASTx) to identify proteins sharing sequence homology with UL144. Subsequently, we used AlphaFold2 to predict the independent three-dimensional structures of UL144 and TNFRSF14. This was followed by a comprehensive structural comparison facilitated by Distance-Matrix Alignment and Foldseek. Finally, we used AlphaFold-multimer and PPIscreenML to elucidate potential protein complexes and confirm the predicted binding activities of both UL144 and TNFRSF14. We then used our in silico approach to replicate the experimental finding that revealed TNFRSF14 binding to both B- and T-lymphocyte attenuator (BTLA) and glycoprotein domain and UL144 binding to BTLA alone. This computational framework offers promise in identifying structural similarities and interactions between pathogen-encoded proteins and their host counterparts. This information will provide valuable insights into the cognitive mechanisms underlying the neuropsychiatric effects of viral infections.

Once the nature and number of patients with Long COVID was more fully understood, UK secondary care developed services to investigate, treat and support these patients. We aimed to identify evidence for demographic health inequalities based on general practitioner (GP) Long COVID referrals to available secondary care services. Despite Long COVID demographics broadly reflecting the multiethnic and socially disadvantaged profile of the study population, we found that secondary care referral was mainly focussed on older age patients and those born in the UK with co-morbid anxiety; although co-morbid diabetes was associated with reduced referrals.

Studies integrating an exhaustive longitudinal long-term follow-up of postintensive care syndrome (PICS) in critically ill COVID-19 survivors are scarce. We aimed to 1) describe PICS-related sequelae over a 12-month period after intensive care unit (ICU) discharge, 2) identify relevant demographic and clinical factors related to PICS, and 3) explore how PICS-related sequelae may influence health-related quality of life (HRQoL) in critically ill COVID-19 survivors.

We conducted a prospective cohort study in adult critically ill survivors of SARS-CoV-2 infection that did or did not need invasive mechanical ventilation (IMV) during the COVID-19 pandemic in Spain (March 2020 to January 2021). We performed a telemedicine follow-up of PICS-related sequelae (physical/functional, cognitive, and mental health) and HRQoL with five data collection points. We retrospectively collected demographic and clinical data. We used multivariable mixed-effects models for data analysis.

We included 142 study participants in the final analysis, with a median [interquartile range] age of 61 [53-68] yr; 35% were female and 59% needed IMV. Fatigue/dyspnea, pain, impaired muscle function, psychiatric symptomatology and reduced physical HRQoL were prominent sequelae early after ICU discharge. Over the 12-month follow-up, functionality and fatigue/dyspnea improved progressively, while pain remained stable. We observed slight fluctuations in anxiety symptoms and perception of cognitive deficit, whereas posttraumatic stress disorder (PTSD) and depressive symptoms improved, with a mild rebound at the end of the follow-up. Female sex, younger age, and the need for IMV were risk factors for PICS, while having higher cognitive reserve was a potential protective factor. Physical HRQoL scores showed a general improvement over time, whereas mental HRQoL remained stable. Shorter ICU stay, better functionality, and lower scores for fatigue/dyspnea and pain were associated with better physical HRQoL, while lower scores for anxiety, depression, and PTSD were associated with better mental HRQoL.

Postintensive care syndrome was common in COVID-19 critical illness survivors and persisted in a significant proportion of patients one year after ICU discharge, impacting HRQoL. The presence of risk factors for PICS may identify patients who are more likely to develop the condition and who would benefit from more specific and closer follow-up after ICU admission.

ClinicalTrials.gov ( NCT04422444 ); first submitted 9 June 2020.

Reticulation, ground glass opacities and post-infection bronchiectasis are present three months following hospitalisation in patients recovering from SARS-CoV-2 infection and are associated with the severity of acute infection. However, scarce data exist on small airways impairment and lung hyperinflation in patients with long COVID-19.

To evaluate small airways function and lung hyperinflation in previously hospitalised patients with long COVID-19 and their association with post-COVID-19 breathlessness.

In total, 33 patients (mean ± SD, 53 ± 11 years) with long COVID-19 were recruited 149 ± 90 days following hospital discharge. Pulmonary function tests were performed and lung hyperinflation was defined as RV/TLC ≥ 40%. Small airways function was evaluated by measuring the closing volume (CV) and closing capacity (CC) using the single-breath nitrogen washout technique (SBN2W).

CC was 115 ± 28% pred. and open capacity (OC) was 90 ± 19. CC was abnormal in 13 patients (39%), CV in 2 patients (6.1%) and OC in 9 patients (27%). Lung hyperinflation was present in 15 patients, whilst the mean mMRC score was 2.2 ± 1.0. Lung hyperinflation was associated with CC (r = 0.772, p = 0.001), OC (r = 0.895, p = 0.001) and mMRC (r = 0.444, p = 0.010).

Long COVID-19 patients present with small airways dysfunction and lung hyperinflation, which is associated with persistent dyspnoea, following hospitalisation.

COVID-19 has rapidly proliferated around 180 countries, and new cases are reported frequently. No peptide medication has been developed that can reliably block SARS-CoV-2 infection. The investigation focuses on the crucial host receptors angiotensin-converting enzyme 2 (ACE2) , which can bind receptor-binding domain (RBD) on the SARS-CoV-2 spike protein (S). To investigate the inhibitory effects of human Eosinophil Cationic Protein (hECP) and Latarcin-1 (L1)on SARS-CoV-2 infection, we have selected them as research subjects. Further, we ran extensive molecular dynamics simulations to bring the docked peptide-ACE2 complex into its equilibrium state. The outcomes were then evaluated with g_MMPBSA and interaction analysis. We have also considered the Delta and Omicron variants to examine these peptides' inhibitory effects. The experimental findings revealed an enhanced capability of L1 and hECP as SARS-CoV-2 inhibitors, occupying hot spots and numerous key residues in ACE2. These include ASP30, ASP38, GLU35 and GLU75, which significantly inhibit the binding of RBD and ACE2 and are effective against two common variants in a similar manner. In addition, this study can serve as a springboard for future research on SARS-CoV-2 inhibitors.Communicated by Ramaswamy H. Sarma.

There is concern that people who had COVID-19 will develop pulmonary fibrosis. Using mouse models, we compared pulmonary inflammation following injection of the spike protein of SARS-CoV-2 (COVID-19) to radiation-induced inflammation to demonstrate similarities between the two models. SARS-CoV-2 (COVID-19) induces inflammatory cytokines and stress responses, which are also common to ionizing irradiation-induced acute pulmonary damage. Cellular senescence, which is a late effect following exposure to SARS-CoV-2 as well as radiation, was investigated.

We evaluated the effect of SARS-CoV-2 spike protein compared to ionizing irradiation in K18-hACE2 mouse lung, human lung cell lines, and in freshly explanted human lung. We measured reactive oxygen species, DNA double-strand breaks, stimulation of transforming growth factor-beta pathways, and cellular senescence following exposure to SARS-CoV-2 spike protein, irradiation or SARS-COV-2 and irradiation. We also measured the effects of the antioxidant radiation mitigator MMS350 following irradiation or exposure to SARS-CoV-2.

SARS-CoV-2 spike protein induced reactive oxygen species, DNA double-strand breaks, transforming growth factor-β signaling pathways, and senescence, which were exacerbated by prior or subsequent ionizing irradiation. The water-soluble radiation countermeasure, MMS350, reduced spike protein-induced changes.

In both the SARS-Co-2 and the irradiation mouse models, similar responses were seen indicating that irradiation or exposure to SARS-CoV-2 virus may lead to similar lung diseases such as pulmonary fibrosis. Combination of irradiation and SARS-CoV-2 may result in a more severe case of pulmonary fibrosis. Cellular senescence may explain some of the late effects of exposure to SARS-CoV-2 spike protein and to ionizing irradiation.

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.

This study analyzed the influence of 23 comorbidities on COVID-associated acute distress respiratory syndrome (CARDS) mortality in people with a history of diabetes mellitus.

An observational, analytical, cross sectional study was utilized to investigate data from 6723 health services in Brazil, comprising 5433 people with diabetes. Adjusted logistic regression models for demographic factors such as age, sex, and race were used to analyze the association between CARDS mortality and comorbidities.

Persons with two (p < 0.001), three (p < 0.001), four (p < 0.001), and five (p < 0.001) simultaneous comorbidities had a higher chance of dying. We identified that diabetes patients who had concomitant metabolic diseases (p = 0.019), neurological disorders (p < 0.001), or were smokers (p < 0.001) had a higher predicted mortality risk based on CADRS.

The number of comorbidities plays a determining role in CARDS mortality in people with diabetes, especially those who suffer from smoking and neurological diseases simultaneously.

SARS-CoV-2 is the causative virus of the devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts and therapeutic interventions, the fight against COVID-19 continues as the rapid emergence of different SARS-CoV-2 variants of concern and the increasing challenge of long COVID-19, raising a vast demand to understand the pathomechanisms of COVID-19 and its long-term sequelae and develop therapeutic strategies beyond the virus per se. Notably, in addition to the virus itself, the replication cycle of SARS-CoV-2 and clinical severity of COVID-19 is also governed by host factors. In this review, we therefore comprehensively overview the replication cycle and pathogenesis of SARS-CoV-2 from the perspective of host factors and host-virus interactions. We sequentially outline the pathological implications of molecular interactions between host factors and SARS-CoV-2 in multi-organ and multi-system long COVID-19, and summarize current therapeutic strategies and agents targeting host factors for treating these diseases. This knowledge would be key for the identification of new pathophysiological aspects and mechanisms, and the development of actionable therapeutic targets and strategies for tackling COVID-19 and its sequelae.

Thesium chinense Turcz. (Named as Bai Rui Cao in Chinese) and its preparations (e.g., Bairui Granules) have been used to treat inflammatory diseases, such as acute mastitis, lobar pneumonia, tonsillitis, coronavirus disease 2019 (COVID-19), and upper respiratory tract infection. However, the material basis, pharmacological efficiency, and safety have not been illustrated.

Anti-inflammatory activity-guided isolation of constituents has been performed using multiple column chromatography, and their structures were elucidated by NMR spectroscopy and ECD calculations. The inhibitory effects on lung inflammation and safety of the crude ethanol extract (CE), Bairui Granules (BG), and the purified active constituents were evaluated using lipopolysaccharide (LPS)-stimulated acute lung inflammation (ALI) mice model or normal mice.

Seven new compounds (1-7) and fifty-six known compounds (8-63) were isolated from T. chinense, and fifty-four were reported from this plant for the first time. The new flavonoid glycosides 1-2, new fatty acids 4-5, new alkaloid 7 as well as the known constituents including flavonoid aglycones 8-11, lignans 46-54, alkaloids 34 and 45, coumarins 57, phenylpropionic acids 27, and simple aromatic compounds 39, 44 and 58 exhibited anti-inflammatory activity. Network pharmacology analysis indicated that anti-inflammation of T. chinense was attributed to flavonoids and alkaloids by regulating inflammation-related proteins (e.g., TNF, NF-κB, TGF-β). Furthermore, constituents of T. chinense including kaempferol-3-O-glucorhamnoside (KN, also named as Bairuisu I, 19), astragalin (AG, Bairuisu II, 12), and kaempferol (KF, Bairuisu III, 8), as well as CE and BG could alleviate lung inflammation caused by LPS in mice by preventing neutrophils infiltration and the expression of the genes for pro-inflammatory cytokines NLRP3, caspase-1, IL-1β, and COX-2. After a 28-day subacute toxicity test, BG at doses of 4.875 g/kg and 9.750 g/kg (equivalent to onefold and twofold the clinically recommended dose) and CE at a dose of 11.138 g/kg (equivalent to fourfold the clinical dose of BG) were found to be safe and non-toxic.

The discovery of sixty-three constituents comprehensively illustrated the material basis of T. chinense. T. chinense and Bairui Granules could alleviate lung inflammation by regulating inflammation-related proteins and no toxicity was observed under the twofold of clinically used doses.

This study investigated long COVID of patients in the Montefiore Health System COVID-19 (CORE) Clinics in the Bronx with an emphasis on identifying health related social needs (HRSNs). We analyzed a cohort of 643 CORE patients (6/26/2020-2/24/2023) and 52,089 non-CORE COVID-19 patients. Outcomes included symptoms, physical, emotional, and cognitive function test scores obtained at least three months post-infection. Socioeconomic variables included median incomes, insurance status, and HRSNs. The CORE cohort was older age (53.38 ± 14.50 vs. 45.91 ± 23.79 years old, p < 0.001), more female (72.47% vs. 56.86%, p < 0.001), had higher prevalence of hypertension (45.88% vs. 23.28%, p < 0.001), diabetes (22.86% vs. 13.83%, p < 0.001), COPD (7.15% vs. 2.28%, p < 0.001), asthma (25.51% vs. 12.66%, p < 0.001), lower incomes (53.81% vs. 43.67%, 1st quintile, p < 0.001), and more unmet social needs (29.81% vs. 18.49%, p < 0.001) compared to non-CORE COVID-19 survivors. CORE patients reported a wide range of severe long-COVID symptoms. CORE patients with unmet HRSNs experienced more severe symptoms, worse ESAS-r scores (tiredness, wellbeing, shortness of breath, and pain), PHQ-9 scores (12.5 (6, 17.75) vs. 7 (2, 12), p < 0.001), and GAD-7 scores (8.5 (3, 15) vs. 4 (0, 9), p < 0.001) compared to CORE patients without. Patients with unmet HRSNs experienced worse long-COVID outcomes compared to those without.

Anesthetics have been linked to cognitive alterations, particularly in the elderly. The current research delineates how Fibroblast Growth Factor 2 (Fgf2) modulates tau protein phosphorylation, contributing to cognitive impairments in aged rats upon sevoflurane administration.

Rats aged 3, 12, and 18 months were subjected to a 2.5% sevoflurane exposure to form a neurotoxicity model. Cognitive performance was gauged, and the GEO database was employed to identify differentially expressed genes (DEGs) in the 18-month-old cohort post sevoflurane exposure. Bioinformatics tools, inclusive of STRING and GeneCards, facilitated detailed analysis. Experimental validations, both in vivo and in vitro, examined Fgf2's effect on tau phosphorylation.

Sevoflurane notably altered cognitive behavior in older rats. Out of 128 DEGs discerned, Fgf2 stood out as instrumental in regulating tau protein phosphorylation. Sevoflurane exposure spiked Fgf2 expression in cortical neurons, intensifying tau phosphorylation via the PI3K/AKT/Gsk3b trajectory. Diminishing Fgf2 expression correspondingly curtailed tau phosphorylation, neurofibrillary tangles, and enhanced cognitive capacities in aged rats.

Sevoflurane elicits a surge in Fgf2 expression in aging rats, directing tau protein phosphorylation through the PI3K/AKT/Gsk3b route, instigating cognitive aberrations.

COVID-19, caused by the SARS-CoV-2 virus, can have neurological effects, including cognitive symptoms like brain fog and memory problems. Research on the neurological effects of COVID-19 is ongoing, and factors such as inflammation, disrupted blood flow, and damage to blood vessels may contribute to cognitive symptoms. Notably, some authors and existing evidence suggest that the SARS-CoV-2 virus can enter the central nervous system through different routes, including the olfactory nerve and the bloodstream. COVID-19 infection has been associated with neurological symptoms such as altered consciousness, headaches, dizziness, and mental disorders. The exact mechanisms and impact on memory formation and brain shrinkage are still being studied. This review will focus on pathways such as the olfactory nerve and blood-brain barrier disruption, and it will then highlight the interactions of the virus with different cell types in the brain, namely neurons, astrocytes, oligodendrocytes, and microglia.

Bronchial asthma, a common chronic respiratory disease, should be managed and controlled correctly to prevent symptoms and maintain a good quality of life. Viral upper respiratory infections, especially the widespread COVID-19 virus, can exacerbate asthma. This study investigated the impact of COVID-19 severity (mild, moderate, severe) on asthma control compared to a control group without COVID-19. Asthma control was assessed using Asthma Control Test (ACT) scores and spirometry before and after COVID-19 infection. Statistical analysis revealed a significant decline (P = 0.001) in asthma control following mild to moderate COVID-19 recovery, evidenced by increased asthma symptoms, lower ACT scores, difficulty managing asthma, and increased need for asthma medication.

The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social and economic burdens on nations. While most of the attention and therapeutic efforts have concentrated on the acute phase of the disease, a notable proportion of survivors experience persistent symptoms post-infection clearance. This diverse set of symptoms, loosely categorized as long COVID, presents a potential additional public health crisis. It is estimated that 1 in 5 COVID-19 survivors exhibit clinical manifestations consistent with long COVID. Despite this prevalence, the mechanisms and pathophysiology of long COVID remain poorly understood. Alarmingly, evidence suggests that a significant proportion of cases within this clinical condition develop debilitating or disabling symptoms. Hence, urgent priority should be given to further studies on this condition to equip global public health systems for its management. This review provides an overview of available information on this emerging clinical condition, focusing on the affected individuals' epidemiology, pathophysiological mechanisms, and immunological and inflammatory profiles.

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.

Anxiety and depression are prevalent mental disorders around the world. The etiology of both diseases is multifactorial, involving biological and psychological issues. The COVID-19 pandemic settled in 2020 and culminated in several changes in the routine of individuals around the world, affecting mental health. People infected with COVID-19 are at greater risk of developing anxiety and depression, and individuals previously affected by these disorders have worsened the condition. In addition, individuals diagnosed with anxiety or depression before being affected by COVID-19 developed the severe illness at higher rates than individuals without mental disorders. This harmful cycle involves several mechanisms, including systemic hyper-inflammation and neuroinflammation. Furthermore, the context of the pandemic and some previous psychosocial factors can aggravate or trigger anxiety and depression. Disorders are also risks for a more severe picture of COVID-19. This review discusses research on a scientific basis, which brings evidence on biopsychosocial factors from COVID-19 and the context of the pandemic involved in anxiety and depression disorders.

The vascular endothelium serves as a physical barrier between the circulating blood and surrounding tissue and acts as a critical regulator of various physiological processes. In vitro models involving vasculature rely on the maintenance of the endothelial barrier function. In this study, we fabricated 2D aligned nanofibrous membranes with distinct pore sizes via electrospinning and investigated the effect of membrane pore size on endothelial barrier function. Our results demonstrated that the use of the nanofibrous membranes promoted the formation of a tight vascular endothelium and sustained barrier function for over one month in comparison with conventional transwell setups. Moreover, the examination of the nucleocytoplasmic localization of yes-associated protein (YAP) in the endothelial cells indicated that nanofibrous membrane promoted YAP expression and its nuclear localization, critical to endothelial barrier function. Furthermore, the comparison of permeability between random and aligned nanofibrous membranes underscored the importance of pore size in preserving barrier function. Our findings offer a valuable strategy for creating more physiologically relevant in vitro vascular models and contribute to the understanding of endothelial barrier formation and maintenance mechanisms.

Polygonatum odoratum is appreciated for its edible and medicinal benefits especially for lung protection. However, the contained active components have been understudied, and further research is required to fully exploit its potential application. We aimed to probe into the beneficial effects of Polygonatum odoratum polysaccharide (POP) in lipopolysaccharide-induced lung inflammatory injury mice. POP treatment could ameliorate the survival rate, pulmonary function, lung pathological lesions, and immune inflammatory response. POP treatment could repair intestinal barrier, and modulate the composition of gut microbiota, especially reducing the abundance of Klebsiella, which were closely associated with the therapeutic effects of POP. Investigation of the underlying anti-inflammatory mechanism showed that POP suppressed the generation of pro-inflammatory molecules in lung by inhibiting iNOS+ M1 macrophages. Collectively, POP is a promising multi-target microecological regulator to prevent and treat the immuno-inflammation and lung injury by modulating gut microbiota.

Accurate and portable respiratory parameter measurements are critical for properly managing chronic obstructive pulmonary diseases (COPDs) such as asthma or sleep apnea, as well as controlling ventilation for patients in intensive care units, during surgical procedures, or when using a positive airway pressure device for sleep apnea.

The purpose of this research is to develop a new nonprescription portable measurement device that utilizes relative humidity sensors (RHS) to accurately measure key respiratory parameters at a cost that is approximately 10 times less than the industry standard.

We present the development, implementation, and assessment of a wearable respiratory measurement device using the commercial Bosch BME280 RHS. In the initial stage, the RHS was connected to the pneumotach (PNT) gold standard device via its external connector to gather breathing metrics. Data collection was facilitated using the Arduino platform with a Bluetooth Low Energy connection, and all measurements were taken in real time without any additional data processing. The device's efficacy was tested with 7 participants (5 men and 2 women), all in good health. In the subsequent phase, we specifically focused on comparing breathing cycle and respiratory rate measurements and determining the tidal volume by calculating the region between inhalation and exhalation peaks. Each participant's data were recorded over a span of 15 minutes. After the experiment, detailed statistical analysis was conducted using ANOVA and Bland-Altman to examine the accuracy and efficiency of our wearable device compared with the traditional methods.

The perfused air measured with the respiratory monitor enables clinicians to evaluate the absolute value of the tidal volume during ventilation of a patient. In contrast, directly connecting our RHS device to the surgical mask facilitates continuous lung volume monitoring. The results of the 1-way ANOVA showed high P values of .68 for respiratory volume and .89 for respiratory rate, which indicate that the group averages with the PNT standard are equivalent to those with our RHS platform, within the error margins of a typical instrument. Furthermore, analysis utilizing the Bland-Altman statistical method revealed a small bias of 0.03 with limits of agreement (LoAs) of -0.25 and 0.33. The RR bias was 0.018, and the LoAs were -1.89 and 1.89.

Based on the encouraging results, we conclude that our proposed design can be a viable, low-cost wearable medical device for pulmonary parametric measurement to prevent and predict the progression of pulmonary diseases. We believe that this will encourage the research community to investigate the application of RHS for monitoring the pulmonary health of individuals.

COVID-19 sequelae are varied, and whether they are temporary or permanent is still unknown. Identifying these sequelae may guide therapeutic strategies to improve these individuals' recovery. This prospective cohort aimed to assess body composition, cardiopulmonary fitness, and long-term symptoms of overweight individuals affected by COVID-19. Participants (n = 90) were divided into three groups according to the severity of acute COVID-19: mild (no hospitalization), moderate (hospitalization, without oxygen support), and severe/critical cases (hospitalized in Intensive Care Unit). We assessed body composition with a tetrapolar multifrequency bioimpedance, hemodynamic variables (heart rate, blood pressure, and peripheral oxygen saturation-SpO2) at rest, and the Bruce test with direct gas exchange. Two assessments with a one-year interval were performed. The most prevalent long-term symptoms were memory deficit (66.7%), lack of concentration (51.7%), fatigue (65.6%), and dyspnea (40%). Bruce test presented a time effect with an increase in the distance walked after 1 year just for severe/critical group (p < 0.05). SpO2 was significantly lower in the severe/critical group up to 5 min after the Bruce test when compared to the mild group, and diastolic blood pressure at the end of the Bruce test was significantly higher in the severe/critical group when compared to mild group (p < 0.05; for all comparisons). A time effect was observed for body composition, with increased lean mass, skeletal muscle mass, fat-free mass, and lean mass just for the severe/critical group after 1 year (p < 0.05). Cardiopulmonary fitness parameters did not differ among the groups, except for respiratory quotient with higher values for the severe/critical group when compared to itself after 1 year. All COVID-19 patients might present long-term sequelae, regardless of the acute disease severity. Reassessing and identifying the most prevalent long-term sequelae are essential to perform more precise health promotion interventions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with inflammatory and imaging alterations that vary depending on the disease severity.

Monitoring changes in inflammatory biomarkers may offer insights into the extent of pulmonary alterations observed in chest-CT. This study aimed to evaluate the profile of different inflammatory biomarkers, widely available and routinely measured in COVID-19 patients, and to determine whether alterations in their activity at admission and discharge correlate with lung involvement assessed through CT scans.

We conducted a retrospective observational study, wherein chest-CT scans were performed upon admission, and blood tests were conducted at admission and discharge. Treatment and monitoring adhered to national and international guidelines.

The profile of serum inflammatory markers (including values at admission and discharge, as well as their evolution during hospitalization) demonstrated a correlation with lung involvement as assessed by the total severity score. The high activity of serum inflammatory markers upon admission, accompanied by minimal changes during hospitalization, indicated a severe form of COVID-19 with notable lung involvement. While statistically significant differences were observed in C-reactive protein, fibrinogen, erythrocyte sedimentation rate, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio, C-reactive protein emerged as the most reliable marker for assessing pulmonary involvement.

Changes in serum inflammatory markers during hospitalization exhibited a weak to moderate negative correlation with the severity of lung involvement. Orv Hetil. 2023; 164(41): 1607-1615.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), later renamed coronavirus disease 2019 (COVID-19), was first identified in Wuhan, China, in early December 2019. Initially, the China office of the World Health Organization was informed of numerous cases of pneumonia of unidentified etiology in Wuhan, Hubei Province at the end of 2019. This would subsequently result in a global pandemic with millions of confirmed cases of COVID-19 and millions of deaths reported to the WHO. We have analyzed most of the data published since the beginning of the pandemic to compile this comprehensive review of SARS-CoV-2. We looked at the core ideas, such as the etiology, epidemiology, pathogenesis, clinical symptoms, diagnostics, histopathologic findings, consequences, therapies, and vaccines. We have also included the long-term effects and myths associated with some therapeutics of COVID-19. This study presents a comprehensive assessment of the SARS-CoV-2 virology, vaccines, medicines, and significant variants identified during the course of the pandemic. Our review article is intended to provide medical practitioners with a better understanding of the fundamental sciences, clinical treatment, and prevention of COVID-19. As of May 2023, this paper contains the most recent data made accessible.

Introduction Neurological manifestations are frequent after acquiring COVID-19 and may persist long-term as part of post-COVID-19 syndrome. Cognitive impairment, chronic fatigue, sleep disturbances, and headache complaints are the most reported neurological features. During the COVID-19 pandemic, health care workers were particularly vulnerable due to the high workload and levels of stress associated with this period, but acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may also contribute. The authors aimed to evaluate the neurological involvement of acquiring SARS-CoV-2 in a population of hospital health care workers and its impact on their personal and professional lives. Methods A sample of health care workers who did and did not acquire SARS-CoV-2 matched by age and sociodemographic variables was studied. Through an online questionnaire, data were collected regarding the symptoms in the acute phase of the disease (for those who acquired it) and for all in the last 6 months of the study period. Proportion of neurological complaints were compared between groups, adjusting for age, sex, and professional class (using a rate ratio (RR)). Results This study included 326 participants (174 cases and 152 controls). The mean age (standard deviation) was 39.7 (10.2) years, and the female:male ratio was 3:1. Headache and cognitive complaints were the most prevalent neurological complaints in the last 6 months of the study period. The health care workers who acquired SARS-CoV-2 were more likely to report headache and cognitive complaints than the control group (RR = 1.51, 95% confidence interval = 1.17-1.9 and RR = 2.02, 95% confidence interval = 1.53-2.65, respectively). Conclusion In a population of health care workers, those who acquired SARS-CoV-2 were more likely to have long-term cognitive complaints and persistent headaches.

Prion' is a term used to describe a protein infectious particle responsible for several neurodegenerative diseases in mammals, e.g., Creutzfeldt-Jakob disease. The novelty is that it is protein based infectious agent not involving a nucleic acid genome as found in viruses and bacteria. Prion disorders exhibit, in part, incubation periods, neuronal loss, and induce abnormal folding of specific normal cellular proteins due to enhancing reactive oxygen species associated with mitochondria energy metabolism. These agents may also induce memory, personality and movement abnormalities as well as depression, confusion and disorientation. Interestingly, some of these behavioral changes also occur in COVID-19 and mechanistically include mitochondrial damage caused by SARS-CoV-2 and subsequenct production of reactive oxygen species. Taken together, we surmise, in part, long COVID may involve the induction of spontaneous prion emergence, especially in individuals susceptible to its origin may thus explain some of its manesfestions post-acute viral infection.

Global Coronavir us disease 2019 (COVID-19) vaccination efforts are being intensified to combat the pandemic. As the frequency of immunization against COVID-19 has increased, some adverse effects related to vaccination have emerged. Within this context, this article reviewed 62 Graves' disease (GD) cases following COVID-19 vaccination, to probe the potential association between the vaccination and the onset of GD. A comprehensive search of the PubMed, Web of Science, and Scopus databases was conducted to collect GD cases following COVID-19 vaccination up to June 7, 2023. Among the 62 GD cases included in this review, there were 33 (53.2%) new-onset GD and 10 (16.1%) relapsed GD patients following mRNA vaccination, 14 (22.6%) new-onset GD and 4 (6.5%) relapsed GD patients following viral vector vaccination, and 1 (1.6%) relapsed GD patients following inactivated vaccination. Median durations to symptoms onset for new-onset and relapsed GD were 12 (range: 1-60) and 21 (range: 5-30) days following mRNA vaccination, while 7 (range: 1-28) and 14 (range: 10-14) days following viral vector vaccination, respectively. While the definitive pathogenesis of GD following COVID-19 vaccination remains unclear, it might be associated with cross-immune responses triggered by molecular mimicry, and an adjuvant-induced autoimmune/inflammatory syndrome. However, due to the limited number of observed GD cases following COVID-19 vaccination and the lack of systematic experimental studies, a causal relationship between COVID-19 vaccination and the onset of GD has not been definitively confirmed. It should be highlighted that most of GD patients following COVID-19 vaccination experienced positive outcomes after treatment. In the broader context of ending the COVID-19 pandemic and reducing mortality rates, the benefits of COVID-19 vaccination significantly outweigh mild risks such as treatable GD. Adherence to the COVID-19 vaccination schedule is therefore imperative in effectively managing the pandemic.