The Coronavirus disease (COVID-19) has impacted pregnant women significantly, with increased mortality and morbidity. The implications of this virus are linked to extracellular vesicles (EVs) and maternal inflammation due to the cytokine storm. Hence, this study aims to investigate the impact of COVID-19 on the pro-inflammatory cytokine profile in both plasma and EVs of South African pregnant women.

Plasma samples were obtained from pregnant women in the third trimester, from which EVs were extracted using the Invitrogen Total Exosome Isolation Kit. These plasma-derived EVs were characterised using transmission electron microscopy and nanoparticle tracking analysis (NTA).

COVID-19 infection in pregnancy did not significantly affect the average particle size and concentration of isolated EVs. The levels of IFN gamma, IL-6, MIP-1 alpha and TNF alpha were analysed in the plasma and circulating EVs through a multiplex assay. Compared to the control group, a significant increase in IL-6, IFN-γ, TNF-α and MIP-1α levels were observed in both plasma and EVs content of COVID-19 pregnancies.

These findings suggest that COVID-19 infection impacts the pro-inflammatory cytokine profile in the plasma and EVs of South African pregnant women.

In recent years, the incidence of acute respiratory distress syndrome (ARDS) has been gradually increasing. Despite advances in supportive care, ARDS remains a significant cause of morbidity and mortality in critically ill patients. ARDS is characterized by acute hypoxaemic respiratory failure with diffuse pulmonary inflammation and bilateral edema due to excessive alveolocapillary permeability in patients with non-cardiogenic pulmonary diseases. Over the past seven decades, our understanding of the pathology and clinical characteristics of ARDS has evolved significantly, yet it remains an area of active research and discovery. ARDS is highly heterogeneous, including diverse pathological causes, clinical presentations, and treatment responses, presenting a significant challenge for clinicians and researchers. In this review, we comprehensively discuss the latest advancements in ARDS research, focusing on its heterogeneity, pathophysiological mechanisms, and emerging therapeutic approaches, such as cellular therapy, immunotherapy, and targeted therapy. Moreover, we also examine the pathological characteristics of COVID-19-related ARDS and discuss the corresponding therapeutic approaches. In the face of challenges posed by ARDS heterogeneity, recent advancements offer hope for improved patient outcomes. Further research is essential to translate these findings into effective clinical interventions and personalized treatment approaches for ARDS, ultimately leading to better outcomes for patients suffering from ARDS.

COVID-19 was the leading cause of death in Mexico between 2020 and 2021. SARS-CoV-2 infection varies widely among individuals and populations. Since variations in genes related to the immune response may play a role in the susceptibility to and outcome of COVID-19, the associations of gene polymorphisms (SNPs) of IL-6 (- 573G > C, rs1800796), TNF-α (- 308G > A, rs1800629), and IFN-γ (- 1615 C > T, rs2069705) with the expression levels of these proteins in the nasopharynx and serum were evaluated in a Mexican population with mild, severe, or critical COVID-19.

A total of 560 COVID-19 patients (309 mild, 163 severe, and 88 critical cases) and 560 age- and sex-matched COVID-19-negative controls were recruited for this case‒control study. The selected SNPs were genotyped via allelic discrimination. Logistic regression analysis was conducted considering four models of inheritance, and ORs were determined for each genotypic variant, adjusting for associated comorbidities in the multivariate model. The nasopharyngeal mRNA expression levels of IL-6, IFN-γ and TNF-α were determined. The levels of IL-6, IFN-γ, IFN-α2, and TNF-α in the serum were quantified. Significant differences were assessed via the Wilcoxon Mann‒Whitney U test.

The C allele of the IL-6 - 573 SNP was associated with a greater risk of mild and severe COVID-19 (OR: 2.3, CI: 1.897-2.838, p = 0.0001; and OR: 1.5, CI: 1.167-1.949, p = 0.002, respectively), whereas the A allele of the TNF-α - 308 SNP and the T allele of the IFN-γ - 1615 SNP were shown protective roles against severe COVID-19 (OR: 0.3, CI: 0.189-0.537, p = 0.0001; and OR: 0.7, CI: 0.563-1.006, p = 0.05) and against critical COVID-19 (OR: 0.3, CI: 0.158-0.640, p = 0.001; and OR: 0.4, CI: 0.290-0.678, p = 0.0001), adjusting for diabetes and hypertension. Nasopharyngeal IL-6 expression levels were lower in mild COVID-19 patients (p = 0.001) than in critical patients (p = 0.005). Serum IL-6 levels were significantly elevated in the critical cases (p = 0.01).

Our results revealed that the IL-6 - 573 G > C SNP and increased IL-6 nasopharyngeal and serum levels are associated with the risk of severe COVID-19 in a Mexican population.

To determine the risk of optic neuritis (ON) during nonpharmaceutical interventions (NPI), vaccination, and infection phases of the coronavirus disease 2019 (COVID-19) pandemic in comparison with levels before the outbreak in pediatric and adult populations in South Korea.

A nationwide, population-based retrospective study.

South Korean individuals with a primary diagnosis of ON received between January 2017 and December 2022.

The Korean Health Insurance Review and Assessment database was queried for new diagnoses of ON between January 2017 and December 2022. Data were divided into 4 periods: before COVID-19 (2017-2019), NPI (2020), nationwide vaccination (2021), and nationwide infection (2022). The risk of ON development for each period was calculated and compared with levels before COVID-19, with 95% confidence intervals (CIs) reported.

Incidence rate ratio (IRR) of ON for each period.

A total of 7216 patients (52.7% female patients) were included in the study, with patients receiving a diagnosis of ON as follows: 3770 patients before COVID-19 (2017-2019), 1193 patients during NPI, 1135 patients during vaccination, and 1118 patients during the infection phases. The annual incidence of ON during NPI (IRR, 0.92; 95% CI, 0.85-1.00; P = 0.043), vaccination (IRR, 0.88; 95% CI, 0.81-0.95; P = 0.001), and infection (IRR, 0.86; 95% CI, 0.80-0.93; P < 0.001) phases significantly decreased compared with levels before COVID-19 when adjusted for age and sex. The proportions of diagnosis with multiple sclerosis (MS), neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM) among patients in whom ON developed increased significantly in 2021 in comparison with levels before COVID-19 (10.93% vs. 6.43%; P = 0.0002).

The risks of ON development during the NPI, vaccination, and infection phases of COVID-19 did not increase in comparison with levels before the outbreak in the general population. However, COVID-19 vaccination may be associated with increased risks of ON associated with diseases such as ADEM, MS, and NMO.

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Acute respiratory distress syndrome (ARDS) is the leading cause of mortality in pathogen-mediated lung inflammation. Viral-induced cytokine release syndrome (CRS) has emerged as a global pandemic, characterized by a hyperactive immune response and excessive cytokine production causing irreversible lung injury. This study aimed to evaluate FDA-approved drugs for their potential to target hyperactive immune response and SARS-CoV-2 viral replication simultaneously. Six potential 3-CLpro inhibitors were identified by molecular docking using MOE software, including ebastine (1), orlistat (2), atracurium besylate (3), piperaquine phosphate (4), valsartan (5), and acarbose (6), among which 1-3 binds strongly to the target protein with binding affinity of - 8.22, - 9.12, and - 7.81, kcal/mol, respectively. Additionally, all identified inhibitors except 4 revealed significant anti-viral potential, with a 50-100% reduction in SARS-CoV-2 plaques. Significant attenuation of phagocyte oxidative burst and inflammatory cytokines (IFN-γ, GM-CSF, IL-6, IL-2, IL-1β, TNF-α) demonstrated the immunomodulatory potential of these drugs. This study demonstrates the potential of pre-existing drugs to ameliorate the cytokine storm and oxidative damage with simultaneous anti-viral effects. The data provide pre-clinical support to develop these drugs as potential therapeutic agent against ARDS.

Cardiovascular disease (CVD) is the leading cause of morbidity globally, with chronic inflammation as a key modifiable risk factor. Toll-like receptors (TLRs), pivotal components of the innate immune system, including TLR-3, -7, -8, and -9 within endosomes, trigger intracellular cascades, leading to inflammatory cytokine production by various cell types, contributing to systemic inflammation and atherosclerosis. Recent research highlights the role of endosomal TLRs in recognizing self-derived nucleic acids during sterile inflammation, implicated in autoimmune conditions like myocarditis.

This review explores the impact of endosomal TLRs on viral infections, autoimmunity, and inflammatory responses, shedding light on their intricate involvement in cardiovascular health and disease by examining literature on TLR-mediated mechanisms and their roles in CVD pathophysiology.

Removal of endosomal TLRs mitigates myocardial damage and immune reactions, applicable in myocardial injury. Targeting TLRs with agonists enhances innate immunity against fatal viruses, lowering viral loads and mortality. Prophylactic TLR agonist administration upregulates TLRs, protecting against fatal viruses and improving survival. TLRs play a complex role in CVDs like atherosclerosis and myocarditis, with therapeutic potential in modulating TLR reactions for cardiovascular health.

This study identifies the secondary metabolites from Alternaria alternate and evaluates their ACE-2: Spike RBD (SARS-CoV-2) inhibitory activity confirmed via immunoblotting in human lung microvascular endothelial cells. In addition, their in vitro anti-inflammatory potential was assessed using a cell-based assay in LPS-treated RAW 264.7 macrophage cells. Two novel compounds, altenuline (1), phthalic acid bis (7'/7'' pentyloxy) isohexyl ester (2), along with 1-deoxyrubralactone (3) alternariol-5-O-methyl ether (4) and alternariol (5) were identified. Molecular docking and in vitro studies showed that compounds 2 and 4 were promising to counteract SARS-CoV-2 attachment to human ACE-2. Thus, they are considered promising natural anti-viral agents. SwissADME in silico analysis was conducted to predict the drug-like potential. Immunoblotting analysis confirmed that the tested compounds (1-4) demonstrated downregulation of ACE-2 expression in the endothelial cells from the lungs with variable degrees. Furthermore, the tested compounds (1-4) showed promising anti-inflammatory activities through TNF-α: TNFR2 inhibitory activity and their inhibitory effect on the proinflammatory cytokines (TNF-α and IL-6) in LPS-stimulated monocytes. In conclusion, our study, for the first time, provides beneficial experimental confirmation for the efficiency of the A. alternate secondary metabolites for the treatment of COVID-19 as they hinder SARS-CoV-2 infection and lower inflammatory responses initiated by SARS-CoV-2. A. alternate and its metabolites are considered in developing preventative and therapeutic tactics for COVID-19.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms. Significant correlations were identified between specific AABs and symptoms such as fever, muscle aches, anosmia, and dysgeusia. Notably, anti-AGTR1 antibodies, which contribute to endothelial glycocalyx (eGC) degradation, a process reversed by losartan, have emerged as strong predictors of core symptoms. AAB levels increased with symptom accumulation, peaking in patients exhibiting all four key symptoms. These findings highlight the role of AABs, particularly anti-AGTR1 antibodies, in determining symptom severity and suggest their involvement in the pathophysiology of COVID-19, including vascular complications.

Pinelliae Rhizoma (PR), known as Banxia in Chinese, Hange in Japanese, and Banha in Korean, is a renowned herbal medicine in East Asia derived from the dry tuber of Pinellia ternata (Thunb.) Breit. (PT). It is extensively utilized in dispensing granules, classical prescriptions, and herbal formulas to treat various conditions, including cough, infection, phlegm, nausea, asthma, and inflammation. Despite numerous studies on PR and its classical prescriptions over recent decades, a comprehensive synthesis of available evidence regarding its multifunctional roles and therapeutic potential is lacking. This review aims to address this gap by examining emerging evidence from metabonomics, preclinical studies, and clinical trials, while exploring potential trends and prospects for future research. A systematic literature search was conducted across six electronic databases, including PubMed, Web of Science, Scopus, ScienceDirect, Wanfang, and China National Knowledge Infrastructure, to identify relevant articles on PR published until March 2023. PR contains 107 compounds with diverse pharmacological activities, including anti-inflammatory, immune regulatory, anti-viral, anti-cancer, anti-asthma, antitussive and expectorant, antioxidant, anti-obesity, anti-atherosclerosis, anti-microbial, emetic and anti-emetic, anti-convulsant and anti-epileptic, sedative and hypnotic, learning and memory enhancement, and anti-depressant effects. Metabonomic studies suggest that raw PR may exhibit cardiotoxicity and pregnancy toxicity while showing no apparent hepatorenal toxicity. However, limited pharmacokinetic investigations on PR constrain its clinical translation. Furthermore, clinical safety data on PR is scarce, with only four clinical trials assessing its positive effects in pediatric epilepsy, nausea and vomiting, soft tissue injury, and chronic sinus tract. This review aims to enhance understanding of PR and provide valuable information and recommendations for further research and development of herbal medicine.

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to a global health crisis with a spectrum of clinical manifestations. A potentially vulnerable category for SARS-CoV-2 infection was identified in patients with other medical conditions. Intriguingly, parallels exist between COVID-19 and cancer at the pathophysiological level, suggesting a possible connection between them. This review discusses all possible associations between COVID-19 and cancer. Expression of receptors like angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) increases COVID-19 susceptibility. SARS-CoV-2 infection might increase cancer susceptibility and accelerate cancer progression through mechanisms involving cytokine storm, tissue hypoxia, impaired T-cell responses, autophagy, neutrophil activation, and oxidative stress. These mechanisms collectively contribute to immune suppression, hindered apoptosis, and altered cellular signaling in the tumor microenvironment, creating conditions favorable for tumor growth, metastasis, and recurrence. Approved vaccines and their impact on cancer patients along-with new clinical trials are also described.

In 2020, the coronavirus disease 2019 (COVID-19) pandemic began worldwide. We examined the association between dental visit status and the incidence of COVID-19 and hospitalisation for it among older people based on medical claims data to help reduce COVID-19 severity. The study included 170,232 people who were 75-85 years old in fiscal 2019, with fiscal 2020 and 2021 serving as the follow-up period to ascertain the status of COVID-19. Using medical claims data, we investigated four types of dental visit (no visit, only periodontal treatment, periodontal and other treatment, and only other treatment) during fiscal 2019 and the incidence of COVID-19 and hospitalisation for COVID-19 during the follow-up period. Logistic regression analyses were performed with the incidence of COVID-19 and hospitalisation for COVID-19 as the dependent variables. Of the participants, 3206 (1.9%) developed COVID-19, of whom, 559 (17.4%) were hospitalised. There was not a significant association between the incidence of COVID-19 and type of dental visit. Participants with dental visits for periodontal treatment during the baseline year had a significantly lower odds ratio (OR) for hospitalisation due to COVID-19 compared to those without dental visits (OR: 0.71, 95% confidence interval: 0.58-0.78). The results suggest that dental visits for periodontal treatment including maintenance are important not only for maintaining oral health but also for preventing severe COVID-19.

SUMMARYSARS-CoV-2 can not only cause respiratory symptoms but also lead to neurological complications. Research has shown that more than 30% of SARS-CoV-2 patients present neurologic symptoms during COVID-19 (A. Pezzini and A. Padovani, Nat Rev Neurol 16:636-644, 2020, https://doi.org/10.1038/s41582-020-0398-3). Increasing evidence suggests that SARS-CoV-2 can invade both the central nervous system (CNS) (M.S. Xydakis, M.W. Albers, E.H. Holbrook, et al. Lancet Neurol 20: 753-761, 2021 https://doi.org/10.1016/S1474-4422(21)00182-4 ) and the peripheral nervous system (PNS) (M.N. Soares, M. Eggelbusch, E. Naddaf, et al. J Cachexia Sarcopenia Muscle 13:11-22, 2022, https://doi.org/10.1002/jcsm.12896), resulting in a variety of neurological disorders. This review summarized the CNS complications caused by SARS-CoV-2 infection, including encephalopathy, neurodegenerative diseases, and delirium. Additionally, some PNS disorders such as skeletal muscle damage and inflammation, anosmia, smell or taste impairment, myasthenia gravis, Guillain-Barré syndrome, ICU-acquired weakness, and post-acute sequelae of COVID-19 were described. Furthermore, the mechanisms underlying SARS-CoV-2-induced neurological disorders were also discussed, including entering the brain through retrograde neuronal or hematogenous routes, disrupting the normal function of the CNS through cytokine storms, inducing cerebral ischemia or hypoxia, thus leading to neurological complications. Moreover, an overview of long-COVID-19 symptoms is provided, along with some recommendations for care and therapeutic approaches of COVID-19 patients experiencing neurological complications.

To investigate the serum IL-6 levels and their rate of change in predicting the mortality of critically ill patients with COVID-19 in Vietnam.

A single-centre, cross-sectional study.

An Intensive Care Centre for the Treatment of Critically Ill Patients with COVID-19 in Ho Chi Minh City, Vietnam.

We included patients aged 18 years or older who were critically ill with COVID-19 and presented to the study centre from 30 July 2021 to 15 October 2021. We excluded patients who did not have serum IL-6 measurements between admission and the end of the first day.

The primary outcome was hospital all-cause mortality.

Of 90 patients, 41.1% were men, the median age was 60.5 years (Q1-Q3: 52.0-71.0), and 76.7% of patients died in the hospital. Elevated IL-6 levels were observed on admission (41.79 pg/mL; Q1-Q3: 20.68-106.27) and on the third day after admission (72.00 pg/mL; Q1-Q3: 26.98-186.50), along with a significant rate of change in IL-6 during that period (839.5%; SD: 2753.2). While admission IL-6 level (areas under the receiver operator characteristic curve (AUROC): 0.610 (95% CI: 0.459 to 0.761); cut-off value ≥15.8 pg/mL) and rate of change in IL-6 on the third day of admission (AUROC: 0.586 (95% CI: 0.420 to 0.751); cut-off value ≥-58.7%) demonstrated poor discriminatory ability in predicting hospital mortality, the third day IL-6 rate of change from admission ≥-58.7% (adjusted OR: 12.812; 95% CI: 2.104 to 78.005) emerged as an independent predictor of hospital mortality.

This study focused on a highly selected cohort of critically ill COVID-19 patients with a high IL-6 level and mortality rate. Despite the poor discriminatory value of admission IL-6 levels, the rate of change in IL-6 proved valuable in predicting mortality. To identify critically ill COVID-19 patients with the highest risk for mortality, monitoring the serial serum IL-6 measurements and observing the rate of change in serum IL-6 levels over time are needed.

Background/Objective: The aim of our study is to comprehensively assess the diagnostic usefulness of serum hyaluronic acid (HA) determination in COVID-19 patients. Methods: The study group included 87 patients with COVID-19 disease and 45 healthy subjects. The HA concentration was measured using the immunochemical method. Results: The serum HA concentration was significantly higher in the COVID-19 patients before admission to hospital than that in the controls (p < 0.001). Differences were found in HA levels between the groups categorized according to disease severity (p = 002), being significantly higher in patients with critical as compared to moderate disease severity (p < 0.001). The HA concentration varied depending on the type of oxygen therapy (p = 0.004). It was significantly higher in patients on a ventilator than in those without oxygen therapy (p = 0.002). In patients who qualified for the steroid treatment and immunotherapy, the HA levels were significantly higher compared to those who did not qualify for such therapies (p = 0.043, p = 0.049, respectively). The HA levels were significantly higher in patients with cytokine storm compared to those without it (p < 0.001) and were significantly more elevated in non-survivors than in survivors (p < 0.001). HA had an excellent diagnostic power (AUC = 0.994) with sensitivity (83.3%) and specificity (97.8%) in identifying patients with critical disease severity and an excellent diagnostic power (AUC = 0.932) with sensitivity (88.2%) and specificity (95.6%) in identifying non-surviving patients. Conclusions: In summary, the results of our study indicate that HA is closely associated with severe SARS-CoV-2 infection and could be used as a novel serum biomarker to predict the risk of disease progression and as a predictor of COVID-19 mortality.

Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) against both the ancestral SARS-CoV-2 strain and different variants of concern (VoCs). Additionally, this protocol induced robust and polyfunctional RBD-specific CD4 and CD8 T cell responses, particularly in animals primed with mLNP-RBD. In K18-hACE2 transgenic mice, the LNP-RBD/MVA combination provided complete protection from morbidity and mortality following a live SARS-CoV-2 challenge compared with the partial protection observed with mNE-RBD/MVA or MVA/MVA regimens. Although the mNE-RBD/MVA regimen only protects half of the animals, it was able to induce antibodies with Fc-mediated effector functions besides NAbs. Moreover, viral replication and viral load in the respiratory tract were markedly reduced and decreased pro-inflammatory cytokine levels were observed. These results support the efficacy of heterologous mRNA/MVA vaccine combinations over homologous MVA/MVA regimen, using alternative nanocarriers that circumvent intellectual property restrictions of current mRNA vaccine formulations.

The angiotensin converting enzyme 2 (ACE2) plays a regulatory role in the cardiovascular system and serves SARS-CoV-2 as an entry receptor. The aim of this study was to synthesize and evaluate radiofluorinated derivatives of the ACE2 inhibitor MLN-4760. [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were demonstrated to be suitable for non-invasive imaging of ACE2, potentially enabling a better understanding of its expression dynamics.

Computational molecular modeling, based on the structures of human ACE2 (hACE2) and mouse ACE2 (mACE2), revealed that the ACE2-binding modes of F-MLN-4760 and F-Aza-MLN-4760 were similar to that of MLN-4760. Co-crystallization of the hACE2/F-MLN-4760 protein complex was performed for confirmation. Displacement experiments using [3H]MLN-4760 enabled the determination of the binding affinities of the synthesized F-MLN-4760 and F-Aza-MLN-4760 to hACE2 expressed in HEK-ACE2 cells. Aryl trimethylstannane-based and pyridine-based radiofluorination precursors were synthesized and used for the preparation of the respective radiotracers. [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were evaluated with regard to the uptake in HEK-ACE2 and HEK-ACE cells and in vitro binding to tissue sections of HEK-ACE2 xenografts and normal organs of mice. Biodistribution and PET/CT imaging studies of [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were performed using HEK-ACE2 and HEK-ACE xenografted nude mice.

Crystallography data revealed an equal hACE2-binding mode for F-MLN-4760 as previously found for MLN-4760. Moreover, computer-based modeling indicated that similar binding to hACE2 and mACE2 holds true for both, F-MLN-4760 and F-Aza-MLN-4760, as is the case for MLN-4760. The IC50 values were three-fold and seven-fold higher for F-MLN-4760 and F-Aza-MLN-4760, respectively, than for MLN-4760. [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were obtained in 1.4 ± 0.3 GBq and 0.5 ± 0.1 GBq activity with > 99% radiochemical purity in a 5.3% and 1.2% radiochemical yield, respectively. Uptake in HEK-ACE2 cells was higher for [18F]F-MLN-4760 (67 ± 9%) than for [18F]F-Aza-MLN-4760 (37 ± 8%) after 3-h incubation while negligible uptake was seen in HEK-ACE cells (< 0.3%). [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 accumulated specifically in HEK-ACE2 xenografts of mice (13 ± 2% IA/g and 15 ± 2% IA/g at 1 h p.i.) with almost no uptake observed in HEK-ACE xenografts (< 0.3% IA/g). This was confirmed by PET/CT imaging, which also visualized unspecific accumulation in the gall bladder and intestinal tract.

Both radiotracers showed specific and selective binding to ACE2 in vitro and in vivo. [18F]F-MLN-4760 was, however, obtained in higher yields and the ACE2-binding affinity was superior over that of [18F]F-Aza-MLN-4760. [18F]F-MLN-4760 would, thus, be the candidate of choice for further development in view of its use for PET imaging of ACE2.

Patients infected with SARS-CoV-2 and vaccinated against COVID-19 could develop aplastic anemia (AA). Comprehensive review and analysis were conducted through a selective literature search in PubMed, Scopus, EMBASE, and Web of Science. For this analysis, 26 studies were included, comprising 16 case reports, 7 case series, and 3 observational studies, totaling 53 patients. The causes of acquired or idiopathic AA are diverse; this review presents recent findings, including possible new etiologies such as SARS-CoV-2 infection and COVID-19 vaccines. This possible association is explored, addressing the existing gap, and aiming to improve daily medical practice. This article reviews the relationship between AA and SARS-CoV-2 infection, as well as COVID-19 vaccines, analyzing cases of de novo occurrence and relapses of AA. Although a definitive mechanistic link has not yet been established, possible underlying pathophysiological mechanisms are explored.

Since the coronavirus disease 2019 (COVID-19) outbreak, although have controlled, severe acute respiratory syndrome coronavirus 2 is constantly mutating and affects people's health. FDA has approved Paxlovid and Molnupiravir for COVID-19 treatment, however, they have not been approved for children under 12 years old. Therefore, it is urgent to explore new drugs for treating COVID-19 in children. As a traditional Chinese medicine, Qing Yan He Ji (QYHJ) has been widely used as an antiviral in our hospital. Therefore, we presumed that it may be ideal for treating COVID-19 and explored its therapeutic effect in patients with COVID-19. The targets and underlying mechanisms of QYHJ against COVID-19 in children were investigated using bioinformatics. QYHJ target sets, and related target genes of COVID-19 were retrieved from public databases. Subsequently, gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to investigate the potential mechanism of QYHJ against COVID-19. Finally, molecular docking was carried out to analyze the affinity between the effective molecule and the target protein. A total of 15 bioactive ingredients of QYHJ and 111 predicted potential targets of QYHJ against COVID-19 were screened. A protein-protein interaction network and subnetworks identified 21 core target genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that QYHJ functions against COVID-19 primarily through antiviral and anti-inflammatory effects. Molecular docking of interleukin-6 (IL-6) revealed that 5 active compounds had relatively stable binding activities with IL-6. Molecular dynamics simulation was performed for molecular docking results, showing IL-6-(4aS,6aR,6aS,6bR,8aR,10R,12aR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid (4aS) complex, IL-6-stigmasterol complex, IL-6-poriferasterol complex, IL-6-sitosterol complex, and IL-6-beta-sitosterol complex had relatively good binding stability. In conclusion, the multi-component and multi-target intervention of QYHJ against COVID-19 is closely related to antiviral and anti-inflammatory activities, which provides a theoretical basis for clinical application.

Advanced age is a primary risk factor for adverse COVID-19 outcomes, potentially attributed to immunosenescence and dysregulated inflammatory responses. In the post-pandemic era, with containment measures lifted, the elderly remain particularly susceptible, highlighting the need for intensified focus on immune health management.

A total of 281 elderly patients were enrolled in this study and categorized based on their clinical status at the time of admission into three groups: non-severe (n = 212), severe survivors (n = 49), and severe non-survivors (n = 20). Binary logistic regression analysis was employed to identify independent risk factors associated with disease severity and in-hospital outcomes. The diagnostic performance of risk factors was assessed using the receiver operating characteristic (ROC) curves. Kaplan-Meier survival analysis and log-rank test were utilized to compare the 30-day survival rates. Furthermore, the transcriptomic data of CD4+ T cells were extracted from Gene Expression Omnibus (GEO) database. Gene Set Enrichment Analysis (GSEA) was applied to reveal biological processes and pathways involved.

In the comparison between severe and non-severe COVID-19 cases, significant elevations were observed in the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and Serum Amyloid A (SAA) levels, concurrent with a notable reduction in CD8+ T cells, CD4+ T cells, natural killer (NK) cells, and monocytes (all p < 0.05). CD4+ T cells (OR: 0.997 [0.995-1.000], p<0.05) and NLR (OR: 1.03 [1.001-1.060], p<0.05) were independent risk factors affecting disease severity. The diagnostic accuracy for COVID-19 severity, as measured by the area under the curve (AUC) for CD4+ T cells and NLR, was 0.715 (95% CI: 0.645-0.784) and 0.741 (95% CI: 0.675-0.807), respectively. Moreover, patients with elevated NLR or IL-6 levels at admission exhibited significantly shorter survival times. Gene Set Enrichment Analysis (GSEA) revealed several biological pathways that are implicated in the regulation of immune responses and metabolic processes.

Lymphocytopenia and the cytokine storm onset are significant predictors of an unfavorable prognosis in elderly patients. The decrease in CD4+ T cells among elderly patients is detrimental to disease recovery, and the biological pathways regulated by these cells could potentially heighten vulnerability to SARS-CoV-2 infection, thereby exacerbating the development of associated complications.

Background: SARS-CoV-2 can trigger hyperinflammation, leading to severe COVID-19, presenting with pneumonia, acute respiratory distress syndrome (ARDS), and multiple organ failure. Specific biomarkers like leukocytes, CRP, NLR, AST, LDH, D-dimer, ferritin, and IL-6 are associated with disease severity. Anakinra, an IL-1 receptor antagonist, has been proposed to mitigate hyperinflammation, but its clinical efficacy remains uncertain. This study aimed to evaluate the effect of Anakinra on inflammatory biomarkers, oxygenation status, and survival outcomes in hospitalized patients with moderate to severe COVID-19 (according to the National Institute of Health severity scale), compared to standard treatment. Methods: A retrospective analysis included 65 patients (mean age 75.51 ± 9.54 years; 58.5% male, 41.5% female) hospitalized with moderate to severe COVID-19. Patients were divided into two groups: a control group receiving standard treatment (n = 24) and a target group treated with Anakinra (n = 41). Biomarkers and oxygenation status were assessed on Days 0, 3, and 7. Statistical analyses compared the groups for changes in leukocytes, NLR, CRP, AST, LDH, D-dimer, ferritin, and IL-6. Results: Anakinra treatment was associated with significant reductions in leukocytes, NLR, D-dimer, ferritin, IL-6, and CRP by Days 3 and 7. Improvements in oxygenation status were observed, although no survival benefits were noted. The control group showed no significant biomarker changes except for AST and LDH on Day 7. Conclusions: Anakinra demonstrated favorable effects on biomarkers and oxygenation in moderate to severe COVID-19 but did not improve survival. Further studies are needed to validate these findings.

The COVID-19 pandemic has led to the emergence of acute and chronic post-COVID syndromes, which present diverse clinical manifestations. The underlying pathophysiology of these conditions is not yet fully understood, but genetic instability has been proposed as a potential contributing factor. This study aimed to explore the differential impact of physical and psychological health factors on genetic instability in individuals with acute and chronic post-COVID syndromes. In this study, three groups of subjects were analyzed: a control group, an acute post-COVID group, and a chronic post-COVID group, with a total of 231 participants. The participants were assessed using a questionnaire for long-COVID-19COVID, and female participants reported more symptoms than male participants in areas related to fatigue, memory, mental health, and well-being during the chronic phase. Genetic instability was assessed using the comet assay, and participants' physical and psychological profiles were evaluated. The overall results showed no significant differences in DNA damage, as measured by the comet assay, among the three groups, suggesting that genetic instability, as assessed by this method, may not be a primary driver of the distinct clinical presentations observed in post-COVID syndromes. However, when gender was considered, male participants in the acute long COVID group exhibited higher levels of genetic instability compared to females. Multiple linear regression analysis revealed that gender, age, and waist circumference were significant predictors of DNA damage. Among females in the acute group, sexual health, and eye-related symptoms significantly influenced the increase in DNA damage. These findings indicate the need for further investigation on the gender-specific differences in genetic instability and their potential implications for the pathophysiology of post-COVID syndromes. Exploring alternative markers of genetic instability and the interplay between genetic, inflammatory, and cellular processes could provide valuable insights for the management of these debilitating post-viral sequelae.

MicroRNAs in exosomes play a role in biological processes such as inflammation and Epithelial-mesenchymal transition (EMT). In EMT, epithelial cells undergo phenotypic changes and become similar to mesenchymal cells. EMT increases the invasion and metastasis of cancer cells. We aimed to evaluate the expression levels of miRNA-21, miRNA-218, miRNA-155, and miRNA-10b, which are effective in the pathway of inflammation and EMT in serum-derived exosome of COVID-19 patients.

Blood samples were taken from 30 patients with COVID-19 and five healthy individuals as a control group. After separating the serum from the collected blood, the exosomes were purified from the serum. Relative expression of microRNAs was measured by real-time PCR method.

The relative expression of miRNA-21, miRNA-218, and miRNA-155 in serum-derived exosomes of patients with COVID-19 had a significant increase (p < 0.0001). Also, the relative expression of miRNA-10b was significantly increased in the patient group (p < 0.01), but the changes in the expression level of miRNA-10b were not as significant as the changes in the expression level of other microRNAs.

miRNA-21, miRNA-218, miRNA-155, and miRNA-10b are involved in the pathogenesis of COVID-19 disease, and their transmission by exosomes leads to pathogenic lesions and problems in other parts of the body.

The purpose of this study was to identify independent risk factors affecting patient survival and explore predictors of severe cases of coronavirus disease 2019 (COVID-19).

We conducted a retrospective, observational, case-control study on adult patients with severe COVID-19 who were admitted to affiliated hospitals in Tianjin between December 18, 2022, and January 31, 2023. We used univariate and multifactorial logistic regression analyses to analyze demographic indicators, comorbidity profiles, and laboratory parameters in two groups of patients (deceased and surviving) to identify independent risk factors for death in patients with severe COVID-19.

Patients in the deceased group were older than those in the survival group (p = 0.018), and there were more cases of coexisting respiratory insufficiency in the deceased group (p = 0.002). Additionally, laboratory test results for white blood cell count (WBC) and creatine kinase (CK) showed significantly higher values in the deceased group (p = 0.047 and p = 0.029, respectively), while arterial oxygen partial pressure (PAO2) showed significantly lower values compared to the survival group (p = 0.021). Age, respiratory insufficiency, WBCH (highest WBC value), CKH (highest CK value), and PAO2F (first PAO2 value) had area under curve (AUC) values of 0.698, 0.838, 0.721, 0.744, and 0.633, respectively.

The main risk factors for mortality in patients with severe COVID-19 that we identified in this study were the advanced age of patients, coexisting respiratory insufficiency, elevated levels of WBC and CK, and decreased levels of PAO2. Elevated WBC and CK laboratory parameters, in particular, demonstrated good predictive value for in-hospital mortality risk.

COVID-19 is characterized by pronounced hypercytokinemia. The cytokine switch, marked by an imbalance between pro-inflammatory and anti-inflammatory cytokines, emerged as a focal point of investigation throughout the COVID-19 pandemic. However, the kinetics and temporal dynamics of cytokine release remain contradictory, making the development of new therapeutics difficult, especially in severe cases. This study collected serum samples from SARS-CoV-2 infected patients at 72 h intervals and monitored them for various cytokines at each timepoint until hospital discharge or death. Cytokine levels were analyzed based on time since symptom onset and patient outcomes. All cytokines studied prospectively were strong predictors of mortality, particularly IL-4 (AUC = 0.98) and IL-1β (AUC = 0.96). First-timepoint evaluations showed elevated cytokine levels in the mortality group (p < 0.001). Interestingly, IFN-γ levels decreased over time in the death group but increased in the survival group. Patients who died exhibited sustained levels of IL-1β and IL-4 and increased IL-6 levels over time. These findings suggest cytokine elevation is crucial in predicting COVID-19 mortality. The dynamic interplay between IFN-γ and IL-4 highlights the balance between Th1/Th2 immune responses and underscores IFN-γ as a powerful indicator of immune dysregulation throughout the infection.

The 2019 outbreak of SARS-CoV-2 has caused a major worldwide health crisis with high rates of morbidity and death. Interestingly, it has also been linked to cancer, which begs the issue of whether it plays a role in carcinogenesis. Recent studies have revealed various mechanisms by which SARS-CoV-2 can influence oncogenic pathways, potentially promoting cancer development. The virus encodes several proteins that alter key signaling pathways associated with cancer hallmarks. Unlike classical oncogenic viruses, which transform cells through viral oncogenes or by activating host oncogenes, SARS-CoV-2 appears to promote tumorigenesis by inhibiting tumor suppressor genes and pathways while activating survival, proliferation, and inflammation-associated signaling cascades. Bioinformatic analyses and experimental studies have identified numerous interactions between SARS-CoV-2 proteins and cellular components involved in cancer-related processes. This review explores the intricate relationship between SARS-CoV-2 infection and cancer, focusing on the regulation of key hallmarks driving initiation, promotion and progression of cancer by viral proteins. By elucidating the underlying mechanisms driving cellular transformation, the potential of SARS-CoV-2 as an oncovirus is highlighted. Comprehending these interplays is essential to enhance our understanding of COVID-19 and cancer biology and further formulating strategies to alleviate SARS-CoV-2 influence on cancer consequences.

Angiotensin-converting enzyme 2 (ACE2) has become a hot topic in neuroscience research in recent years, especially in the context of the global COVID-19 pandemic, where its role in neurological diseases has received widespread attention. ACE2, as a multifunctional metalloprotease, not only plays a critical role in the cardiovascular system but also plays an important role in the protection, development, and inflammation regulation of the nervous system. The COVID-19 pandemic further highlights the importance of ACE2 in the nervous system. SARS-CoV-2 enters host cells by binding to ACE2, which may directly or indirectly affect the nervous system, leading to a range of neurological symptoms. This review aims to explore the function of ACE2 in the nervous system as well as its potential impact and therapeutic potential in various neurological diseases, providing a new perspective for the treatment of neurological disorders.

Emerging and re-emerging viral pandemics have emerged as a major public health concern. Highly pathogenic coronaviruses, which cause severe respiratory disease, threaten human health and socioeconomic development. Great efforts are being devoted to the development of safe and efficacious therapeutic agents and preventive vaccines to combat them. Nevertheless, the highly mutated virus poses a challenge to drug development and vaccine efficacy, and the use of common immunomodulatory agents lacks specificity. Benefiting from the burgeoning intersection of biological engineering and biotechnology, membrane-derived vesicles have shown superior potential as therapeutics due to their biocompatibility, design flexibility, remarkable bionics, and inherent interaction with phagocytes. The interactions between membrane-derived vesicles, viruses, and the immune system have emerged as a new and promising topic. This review provides insight into considerations for developing innovative antiviral strategies and vaccines against SARS-CoV-2. First, membrane-derived vesicles may provide potential biomimetic decoys with a high affinity for viruses to block virus-receptor interactions for early interruption of infection. Second, membrane-derived vesicles could help achieve a balanced interplay between the virus and the host's innate immunity. Finally, membrane-derived vesicles have revealed numerous possibilities for their employment as vaccines.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has been studied predominantly in terms of its immediate respiratory and systemic effects. However, emerging evidence suggests possible long-term effects, including its role in carcinogenesis. This comprehensive review explores the complex relationship between COVID-19 and cancer development, focusing on immune dysregulation, chronic inflammation, genetic and epigenetic alterations, and the impact of therapeutic interventions. We also focused on the molecular mechanisms by which SARS-CoV-2 may facilitate cancer progression, including the roles of angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and FURIN. Additionally, we examined the possible carcinogenic effects of long-term COVID-19 treatments and the interaction between co-infections and cancer risk. Our findings highlight the need for increased cancer surveillance in COVID-19 survivors. In the post-COVID-19 period, it can be thought that inflammation associated with excessive cytokine release, especially interleukin-6, genetic and epigenetic changes, and co-infections with oncogenic viruses such as Epstein-Barr virus or human papillomavirus may be effective in the development and progression of cancer. Further research is needed to explain the mechanisms underlying this relationship.

This study aims to investigate the prognostic significance of inflammatory cytokines and lymphocyte levels in predicting disease progression among patients with COVID-19 infection.

Ninety-two hospitalized COVID-19 patients were retrospectively included as subjects for this study. General clinical information and various indicators, including lymphocyte count, interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor (TNF), were collected. All patients received treatment according to the ninth edition of the guidelines for COVID-19. Incidences of endotracheal intubation and mortality within 28 days were observed.

1.In the analysis of intubation impact, multivariate analysis identified age, immunoglobulins, lymphocytes, and IL-6 as independent risk factors. When analyzing the impact on patient mortality, multivariate analysis revealed age, prealbumin, and BNP as independent risk factors. 2. Lymphocyte count and inflammatory factors demonstrated predictive value for endotracheal intubation in COVID-19 patients. The critical lymphocyte count value was 0.91, with a sensitivity of 38.8%, specificity of 92.9%, and AUC of 0.687 (95% CI: 0.580-0.795). The critical IL-6 value was 38.21, with a sensitivity of 81%, specificity of 63.3%, and AUC of 0.771 (95% CI: 0.6670.872). The area under the ROC curve for IL-8, IL-10 and TNF is 0.665, 0.712 and 0.648, respectively. 3.Lymphocyte count and inflammatory factors also exhibited predictive value for death in COVID-19 patients. The critical lymphocyte count value was 0.56, with a sensitivity of 71.2%, specificity of 57.5%, and AUC of 0.641 (95% CI: 0.528-0.754). The critical IL-6 value was 53.05, with a sensitivity of 75%, specificity of 71.2%, and AUC of 0.770 (95% CI: 0.6690.870). The area under the ROC curve for IL-8, IL-10 and TNF is 0.687, 0.683 and 0.636, respectively.

Elevated inflammatory factors and decreased lymphocyte levels have prognostic value for predicting endotracheal intubation and mortality in COVID-19 patients, providing valuable insights for clinicians in anticipating disease progression.

In severe COVID-19 cases, an exacerbated inflammatory response triggers a cytokine storm that can worsen the prognosis. Compounds with both antiviral and anti-inflammatory activities show promise as candidates for COVID-19 therapy, as they potentially act against the SARS-CoV-2 infection regardless of the disease stage. One of the most attractive drug targets among coronaviruses is the main protease (MPro). This enzyme is crucial for cleaving polyproteins into non-structural proteins required for viral replication. The aim of this review was to identify SARS-CoV-2 MPro inhibitors with both antiviral and anti-inflammatory properties. The interactions of the compounds within the SARS-CoV-2 MPro binding site were analyzed through molecular docking when data from crystallographic structures were unavailable. 18 compounds were selected and classified into five different superclasses. Five of them exhibit high potency against MPro: GC-376, baicalein, naringenin, heparin, and carmofur, with IC50 values below 0.2 μM. The MPro inhibitors selected have the potential to alleviate lung edema and decrease cytokine release. These molecules mainly target three critical inflammatory pathways: NF-κB, JAK/STAT, and MAPK, all previously associated with COVID-19 pathogenesis. The structures of the compounds occupy the S1/S2 substrate binding subsite of the MPro. They interact with residues from the catalytic dyad (His41 and Cys145) and/or with the oxyanion hole (Gly143, Ser144, and Cys145), which are pivotal for substrate recognition. The MPro SARS-CoV-2 inhibitors with potential anti-inflammatory activities present here could be optimized for maximum efficacy and safety and be explored as potential treatment of both mild and severe COVID-19.

Extreme inflammation that continues even after infections can lead to a cytokine storm. In recent times, one of the most common causes of cytokine storm activation has been SARS-CoV-2 infection. A cytokine storm leads to dysregulation and excessive stimulation of the immune system, producing symptoms typical of post-COVID syndrome, including chronic fatigue, shortness of breath, joint pain, trouble concentrating (known as "brain fog"), and even direct organ damage in the heart, lungs, kidneys, and brain. This work summarizes the current knowledge regarding inflammation and the cytokine storm related to SARS-CoV-2 infection. Additionally, changes in lipid metabolism and microbiota composition under the influence of inflammation in COVID-19, along with the possible underlying mechanisms, are described. Finally, this text explores potential health implications related to changes in eating behaviors and nutritional status in COVID-19 patients. Although research on the cytokine storm is still ongoing, there is convincing evidence suggesting that severe immune and inflammatory responses during the acute phase of COVID-19 may lead to long-term health consequences. Understanding these links is key to developing treatment strategies and supporting patients after infection.