Uncontrolled immune responses resulting from overactivated cellular signaling pathways, leading to inflammation and tissue injury, are a major cause of death in pathogen-infected individuals. This phenomenon has been well studied in mammals but is less explored in invertebrates. Bacteria of the genus Vibrio are among the most harmful pathogens to humans and aquatic animals. In shrimp, Vibrio infection is generally characterized by the sudden onset of disease, with pathological signs of opaque and whitish muscle tissue. The current study shows that shrimp acutely infected with high dose of Vibrio parahaemolyticus develop inflammation-like pathological changes, leading to rapid death. Excessive activation of JAK-STAT signaling, rather than the Dorsal and Relish pathways, results in overactivation of shrimp immunity and is a major cause of inflammation induced by acute Vibrio infection. Weakening JAK-STAT signaling attenuates the inflammatory response and reduces mortality caused by acute Vibrio infection in shrimp, whereas enhancing JAK-STAT signaling can convert a normal infection into an acute one, accelerating shrimp death. Therefore, this study indicates that, similar to that in mammals, the pathogenesis of infectious diseases in invertebrates is complicated by inflammatory responses triggered by dysregulated immune signaling.

The novel coronavirus, COVID-19, which was first identified in December 2019 rapidly spread worldwide and was declared a global pandemic. Beyond respiratory symptoms, COVID-19 often results in coagulation and vascular endothelium disorders, causing increased clotting and bleeding, which are closely linked to the acute phase of the infection. Factor VIII is a crucial protein in the blood coagulation cascade, and elevated FVIII levels have been linked to thrombotic events in COVID-19, highlighting the need to understand its behavior during treatment. Remdesivir is an antiviral drug that has shown promise in reducing recovery time and mortality rates in COVID-19 patients. This study aims to examine the changes in blood factors and the expression of the factor VIII gene in patients treated with Remdesivir. Blood samples were collected from 30 COVID-19 patients before and after Remdesivir treatment and from 20 healthy individuals. Patients with underlying diseases were excluded from the study. RNA was extracted from these samples, followed by cDNA synthesis. The expression of the factor VIII gene was analyzed using Real-Time PCR. The results indicated that blood factors such as Urea, ALK, AST, WBC, and CRP were elevated in the patient group compared to the control group. At the same time, FBS, Urea, ALK, AST, WBC, RDW, INR, and K levels increased in the Remdesivir treatment group (P < 0.001). Conversely, MCHC, RBC, and Ca levels decreased in both patient and treatment groups compared to the control group (P < 0.001). The expression of the FVIII gene was upregulated approaching 2 times in COVID-19 patients and 1.5-fold in the treatment group compared to the control group (P < 0.001). However, no significant changes were observed in FVIII expression before and after Remdesivir treatment. However, a positive correlation between RBC, FBS, and Urea in the patient group and a negative correlation between RDW and FVIII expression levels was observed. In the treatment group, FVIII expression level correlated negatively with Urea, P, and RDW. These findings suggest that elevated FVIII levels are associated with disease severity and excessive coagulation in COVID-19 patients. Additionally, Remdesivir does not appear to exacerbate the coagulation process.

Neuropsychiatric symptoms emerged early in the COVID-19 pandemic as a key feature of the virus, with research confirming a range of neuropsychiatric manifestations linked to acute SARS-CoV-2 infection. However, the persistence of neurological symptoms in the post-acute and chronic phases remains unclear. This meta-analysis assesses the long-term neurological effects of COVID-19 in recovered patients, providing insights for mental health service planning.

A comprehensive literature search was conducted across five electronic databases: PubMed, Scopus, Web of Science, EBSCO, and CENTRAL, up to March 22, 2024. Studies evaluating the prevalence of long-term neurological symptoms in COVID-19 survivors with at least six months of follow-up were included. Pooled prevalence estimates, subgroup analyses, and meta-regression were performed, and publication bias was assessed.

The prevalence rates for the different symptoms were as follows: fatigue 43.3% (95% CI [36.1-50.9%]), memory disorders 27.8% (95% CI [20.1-37.1%]), cognitive impairment 27.1% (95% CI [20.4-34.9%]), sleep disorders 24.4% (95% CI [18.1-32.1%]), concentration impairment 23.8% (95% CI [17.2-31.9%]), headache 20.3% (95% CI [15-26.9%]), dizziness 16% (95% CI [9.5-25.7%]), stress 15.9% (95% CI [10.2-24%]), depression 14.0% (95% CI [10.1-19.2%]), anxiety 13.2% (95% CI [9.6-17.9%]), and migraine 13% (95% CI [2.2-49.8%]). Significant heterogeneity was observed across all symptoms. Meta-regression analysis showed higher stress, fatigue, and headache in females, and increased stress and concentration impairment with higher BMI.

Neurological symptoms are common and persistent in COVID-19 survivors. This meta-analysis highlights the significant burden these symptoms place on individuals, emphasizing the need for well-resourced multidisciplinary healthcare services to support post-COVID recovery.

This meta-analysis was registered in PROSPERO with registration number CRD42024576237.

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

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

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

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

Probiotics and prebiotics have been suggested as natural agents against viral infections and dysbiosis and may encourage clinical applications. This review aims to analyze the main and recent advances related to viral infections such as Covid-19 and its gastrointestinal complications, antiviral immunity generated and possible preventive role that probiotics and/or prebiotics can play in controlling and promoting antiviral immunity. The literature search was performed through a critical analysis of relevant publications reported in PubMed and Scopus databases on clinical trials and assays conducted in vitro on colon cells and in vivo on mice. Some studies using probiotics and prebiotics for the prevention of viral infection in different age groups are discussed. Covid-19 patients have been shown to suffer from gastrointestinal complications in addition to respiratory symptoms due to interactions between the respiratory system and the gastrointestinal tract infected with SARS-CoV-2. Unfortunately, therapies used to prevent (or treat) symptoms of Covid-19 have proven to be of limited effectiveness. In addition, the lack of access to coronavirus vaccines around the world and vaccine hesitancy continue to hamper control of Covid-19. It is therefore crucial to find alternative methods that can prevent disease symptoms. Evidence-based efficacy of certain probiotics (Lactobacillus and Bifidobacterium) that may be useful in viral infections was shown with immunomodulatory properties (pro-inflammatory mediators reduction), promoting antiviral immunity (antibodies production, virus titers) and controlling inflammation (anti-inflammatory effect), as well as viral clearance and antimicrobial potential against opportunistic bacteria (anti-dysbiosis effect). But, available data about clinical application of probiotics in Covid-19 context remain limited and relevant scientific investigation is still in its early stages. Also, evidence for prebiotics potential in this field is limited, since the exact mechanism involved in systemic immune modulation by these compounds is till now unknown. Thus, further research is necessary to explore in the viral infection context the mechanism by which gut and lung interact in the presence of probiotics and prebiotics through more animal and clinical experiments.

Abnormalities in liver biochemistry are common in COVID-19 patients. Hepatic vein Doppler waveform, typically triphasic, may become biphasic or monophasic in cirrhosis, correlating with liver dysfunction, fibrosis, inflammation, and portal hypertension. This study investigates liver ultrasound (US) features in COVID-19 patients, correlating hepatic vein Doppler waveform and portal vein velocity (PVV) with inflammatory indexes and clinical outcomes.

Fifty-seven patients with SARS-CoV-2 infection participated in a crosssectional study. Bedside upper abdomen US evaluations, including B-mode and Doppler, were conducted using a convex probe. Hepatic vein Doppler waveforms were classified as triphasic, biphasic, or monophasic, and the hepatic vein waveform index (HVWI) was calculated. PVV was measured over three cardiac cycles. Tracings were blindly analyzed by three operators to ensure consistency.

Low HVWI and high PVV correlated with elevated LDH, ALT, D-dimer, and ferritin (p < 0.05). HVWI showed significant negative correlations with ferritin, D-dimer, and ALT (p < 0.05). D-Dimer and ferritin were higher in patients with biphasic/monophasic waveforms (p < 0.05). High PVV and larger spleen diameters predicted worse respiratory outcomes, including CPAP and tracheal intubation (p < 0.05). Optimal cut-off values for PVV (21.7 cm/s) and spleen diameter (9.84 cm) maximized sensitivity and specificity for predicting these outcomes. FIB-4 scores did not correlate with respiratory outcomes or hepatic hemodynamics (p > 0.05). Hemodynamic alterations were not significantly influenced by the presence of SLD (Steatotic Liver Disease).

COVID-19 patients exhibit altered intrahepatic hemodynamics, with hepatic vein waveform abnormalities potentially reflecting liver inflammation and fibrosis. PVV and spleen diameter may serve as non-invasive predictors of respiratory outcomes.

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

Cytokine receptors play a pivotal role in mediating the immune response and are critical in cytokine storms, which underlie the pathogenesis of conditions such as acute respiratory distress syndrome (ARDS) and autoimmune disorders. Identifying cytokine receptors is essential for understanding their biological functions, exploring therapeutic targets, and guiding clinical interventions. Traditional biochemical methods to identify cytokine receptors are labor-intensive, costly, and time-consuming, prompting the need for more efficient alternatives. Recent advances in computational biology have enabled the use of machine learning to classify cytokine receptor proteins. Most existing approaches focused on homologous features and protein composition to classify cytokine families, but no dedicated studies have been conducted on cytokine receptor proteins. This gap presents an opportunity to develop a method specifically for classifying cytokine receptors among other membrane proteins. In this study, we present a novel classification framework combining pre-trained language models (PLMs) with a multi-window convolutional neural network (mCNN) architecture for the fast and accurate identification of cytokine receptor proteins. PLMs, such as ProtTrans and ESM variants, capture biochemical context directly from raw protein sequences, while mCNN efficiently extracts local and global sequence patterns using convolutional layers with varying window sizes. Our model achieved an AUC of 0.96 in the training as well as 0.97 and 0.93 in two independent tests, demonstrating its effectiveness in distinguishing cytokine receptors from non-cytokine receptor proteins. By eliminating the need for manual feature extraction, this approach offers a robust and scalable solution for protein classification, paving the way for its application in drug discovery and understanding cytokine-mediated diseases.

The JAK family, particularly JAK3, plays a crucial role in immune signaling and inflammatory responses. Dysregulated JAK3 activation in SARS-CoV-2 infections has been associated with severe inflammation and respiratory complications, making JAK inhibitors a viable therapeutic option. However, their use raises concerns regarding immunosuppression, which could increase susceptibility to secondary infections. While long-term adverse effects are less of a concern in acute COVID-19 treatment, patient selection and monitoring remain critical. Furthermore, adverse effects associated with oral JAK3 inhibitors necessitate the exploration of alternative strategies to optimize therapeutic efficacy while minimizing risks. This review highlights the role of JAK3 in immune and epithelial cells, examines the adverse effects of oral JAK3 inhibitors in COVID-19 and other treatments, and discusses alternative therapeutic strategies for improving patient outcomes.

Immunotherapy in the presence of COVID-19 infections raises concerns because of potential overlapping clinical complications and immune system enhancement. Further investigation is warranted to establish its safety and to improve clinical decisions.

We conducted a retrospective cohort study using linked health administrative data from Ontario, Canada to assess 30-day mortality in patients with solid tumors who were treated with immunotherapy within 120 days before testing positive for COVID-19. A stepwise multivariable logistic regression model was used to identify clinical factors associated with 30-day mortality.

Between January 2020 and April 2023, 281 patients tested positive for COVID-19 and were included in our study. The mean age was 68 (Standard Deviation: 10.3), 45% (127/281) were females and 58% (163/281) had lung cancer. 59% of patients (167/281) were treated with single agent immunotherapy, and almost 80% received at least one dose of COVID-19 vaccine. The 30-day mortality was 22% (63/281) and < 5% of patients were admitted to ICU or required ventilation. Factors associated with higher mortality were older age (Odds Ratio (OR) 1.60, 95% confidence interval (CI) 1.07-2.39), prior radiation therapy (OR 2.38, 95%CI 1.08-5.28), lower hemoglobin (< 10 g/dl) (OR 4.08, 95%CI 1.89-8.82) and higher leucocytes count (> 11,000/mm3) (OR 3.63, 95%CI 1.55-8.52).

Immunotherapy does not seem to increase the risk of 30-day mortality in patients with COVID-19 infections compared to published outcomes of patients with cancer and COVID-19. Mortality was associated with certain clinical characteristics that need to be carefully examined when prescribing immunotherapy during future comparable pandemics.

The integration of 2D-materials and optoelectronic devices has attracted great attention for advanced applications. We propose the first perovskite/graphene heterostructure-based FET biosensor with uniquely biotunable ternary logic gating functionality. The biosensor integrates a lateral perovskite-on-graphene heterostructure phototransistor with a vertical bio-nano-photonic filter, with a decoupled construction inset. In the phototransistor, photoactive perovskite quantum dots (PQDs) serve as sensitizers to absorb light while a high mobility single-layer graphene (SLG) acts as an expressway for carrier transport. In the bio-nano-photonic filter, a localized surface plasmon resonance (LSPR) is induced by gold nanoparticles (AuNPs) in conjunction with antigen-antibody binding, tuning the delivery of light passing through the filter and facilitating biotunable functionality with ternary modes. The biosensor is set up to detect human interleukin-6 (IL6) in order to determine and achieve ultrahigh sensitivity with a limit of detection (LOD) of 0.9 fg mL-1 (43 aM), which is 4 orders of magnitude greater than graphene-FET biosensors. This ultrahigh sensitivity is achieved due to the synergistic effect of PQDs/SLG heterostructure, exhibiting superior electrical, optical, and physicochemical properties, consequently providing significantly high performance of the biosensor in terms of label-free, ultrahigh sensitivity (attomolar level), rapid responsivity (5 min), excellent stability, and selectivity. This heterostructure-based biotunable configuration could open a new avenue for 2D materials in the realm of next-generation bio-nano-photonic platforms for applications in healthcare, early diagnosis, and rapid detection.

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.

The global prevalence of inflammatory bowel disease (IBD) has significantly increased in recent decades. IBD is a long-term, recurring, gastrointestinal inflammatory condition that mainly comprises two primary clinical types: ulcerative colitis and Crohn's disease. The current treatment paradigm for IBD primarily focuses on symptom management. However, this approach does not support mucosal epithelial repair, maintenance of barrier homeostasis, or regulation of biological functions in the gut. Conventional therapies rely on the frequent use of high-dose medications, including antibiotics, nonsteroidal anti-inflammatory drugs, biological agents, and immunomodulators. Recently, mesenchymal stem/stromal cells (MSCs) have gained interest in tissue regeneration owing to their unique ability to differentiate and secrete regulatory factors, including extracellular vesicles (EVs), which play crucial roles in abnormal organization. Various routes of administration have been explored in preclinical and clinical studies to deliver MSCs from diverse tissue sources. The routes include intraperitoneal, intravenous, and local (intracolonic or rectal) delivery. The MSCs employed were obtained from various tissues, including bone marrow, umbilical cord, and adipose tissue. This article reviews the research framework for the application of MSCs and EVs secretion in the treatment of IBD, emphasizing key immunological effects, such as immune microenvironment regulation, intestinal barrier stabilization, and therapeutic approaches targeting intestinal barrier disorders. The discussion primarily focuses on the advantages of MSCs over other biologics, impairment of gut mucosal tissue-resident mesenchymal stem cells in IBD development, immune targets (at the cellular and molecular levels) within the framework of IBD, and the reparative effects of MSCs in the microenvironment of IBD. We aimed to present an overview of the current trends in MSC research and therapy, as well as to identify the challenges and future directions that must be addressed to advance research on MSC-mediated therapeutic strategies for IBD.

COVID-19 can affect multiple organ systems beyond the respiratory tract, including the gastrointestinal tract, where gastrointestinal symptoms include nausea, vomiting, diarrhea, abdominal pain, and even serious manifestations such as ulcers, perforation, or gastrointestinal bleeding.

We report a case of a 45-year-old male patient with small bowel ulcers caused by chronic COVID-19 infection. Initially presenting with fever and transient unconsciousness, he developed ischemic necrosis and required a mid-thigh amputation. Despite treatment with anti-infection therapy, extracorporeal membrane oxygenation, and continuous renal replacement therapy, he experienced persistent abdominal pain and gastrointestinal bleeding. Imaging and colonoscopy confirmed partial small bowel obstruction and inflammation. After treatment with methylprednisolone and enteral nutrition, his symptoms improved. However, he suffered a gastrointestinal perforation requiring emergency surgery and later underwent a successful stoma reversal. The patient was subsequently discharged with improvement and was discharged with a primary diagnosis of "enterostomal status, perforation of small intestinal ulcer, viral myocarditis, COVID-19 infection, and post right lower extremity amputation". During the past year of follow-up, the patient has not experienced any recurrence of abdominal pain or rectal bleeding.

Although coronavirus pneumonia combined with small bowel ulcers is rare, it requires emergency treatment and has a high mortality rate. This case highlighted the severe gastrointestinal complications induced by COVID-19 infection and the effectiveness of comprehensive management strategies.

Predicting which patients will develop severe COVID-19 complications could improve clinical care. Peripheral blood cytokine profiles may predict the severity of SARS-CoV-2 infection, but none have been identified in US Veterans.

We analyzed peripheral blood cytokine profiles from 202 participants in the EPIC3 study, a prospective observational cohort of US Veterans tested for SARS-CoV-2 across 15 VA medical centers. Illness severity was assessed based on the highest level documented during the first 60 days after recruitment. We correlated cytokine levels with illness severity using LASSO logistic regression, random forest, and XGBoost models on a 70% training set and calculated the AUC on a 30% test set.

LASSO regression identified 6 cytokines as predictors of SARS-CoV-2 severity with 77.3% AUC in the test set. Random forest and XGBoost models achieved an AUC of 80.4% and 80.7% in the test set, respectively. All models assigned a feature importance to each cytokine, with IP-10, MCP-1, and HGF consistently identified as key markers.

Cytokine profiles are predictive of SARS-CoV-2 severity in US Veterans and may guide tailored interventions for improved patient management.

Severe COVID-19 is characterized by complex immunopathology that involves inflammation, endothelial dysfunction, and immunothrombosis. Neutrophil extracellular traps (NETs) have been recognized as key factors in the severity of the disease, with their emergence correlating to viral load, immmunothrombosis, and organ damage. In this study, we investigated the role of NETosis and macrophage activation in the course of severe COVID-19. We analyzed 23 autopsy samples from patients who died from COVID-19 and performed immunohistochemical staining and stereological point counting to quantify leukocyte infiltration and NET formation among other histopathological parameters. Our results showcase 2 evident immunophenotypes: lowNET and highNET. The lowNET group displayed lower NET formation, higher viral loads, and an increased incidence of secondary infections, as well as shorter survival times. In contrast, the highNET group exhibited increased neutrophil activation, pronounced endothelial damage and thrombotic complications, as well as prolonged survival times. Our data suggest a dual role of NETosis in COVID-19: initially protective, limiting viral replication, but later likely detrimental through immunothrombosis and tissue damage. These findings underline the need for tailored therapeutic actions, with early antiviral and immune-modulating interventions for lowNET patients and strategies aiming to limit excessive NETosis and coagulopathy in highNET patients. Further research is needed to define the timing of interventions based on the dynamics of NETosis.

The expansion of social media has fundamentally transformed biomedical research dissemination and collaboration, particularly within the interferon and cytokine research community. This paper explores recent trends (2024-2025) that have amplified the role of platforms such as Twitter (now "X"), LinkedIn, Mastodon, Threads, and Bluesky. These tools have facilitated rapid knowledge exchange, democratized access to scientific discourse, enabled diverse voices to participate meaningfully, and fostered cross-disciplinary and global collaborations. Additionally, the integration of preprint repositories like bioRxiv and medRxiv, along with the evolution of open access publishing, further accelerates the accessibility and immediacy of scientific communication. Despite evident benefits, the rapid dissemination facilitated by social media also poses ethical challenges, including concerns about misinformation, premature dissemination of preliminary data, and privacy considerations. Practical strategies for researchers and institutions to effectively navigate these platforms responsibly are presented, aiming to optimize the impact of social media on scientific discovery and public engagement.

Despite the growing clinical need, the therapeutic efficacy of drugs for acute lung injury (ALI) remains inadequate. Traditional Chinese Medicine (TCM) holds potential in managing ALI due to its unique therapeutic properties. However, the intricate nature of TCM formulations hinders global adoption. Component-based Chinese medicine (CCM) offers a promising pathway for TCM's internationalization. Phillyrin-Emodin-Baicalin-Liquiritin (PEBL), a CCM with significant anti-inflammatory activity, is derived from the well-established TCM formula Liang-Ge-San. Whether PEBL effectively addresses viral ALI, however, remains unclear.

This study aims to investigate the therapeutic effects and underlying mechanisms of PEBL on viral ALI.

The efficacy of PEBL against Poly(I:C)-induced ALI was assessed by analyzing cytokine production, macrophage infiltration, pulmonary damage, and mortality. Bioinformatics and network pharmacology were employed to identify key targets and signaling pathways. The molecular mechanisms were further validated using Poly(I:C)-treated RAW264.7 cells, Tg(coro1α: GFP) zebrafish, BALB/c mice, and models of Influenza A/Puerto Rico/8/1934 (H1N1) virus strain (PR8)-induced ALI in BALB/c mice and SARS-CoV-2 Omicron XBB.1.16 subvariant (XBB)-induced ALI in hACE2-transgenic C57BL/6 mice.

PEBL mitigated Poly(I:C)-induced ALI, as evidenced by reduced cytokine levels, diminished macrophage infiltration, alleviated lung damage, and decreased mortality. Virtual screening identified the farnesyl X receptor (FXR) and angiotensin-converting enzyme 2 (ACE2) as key therapeutic targets for viral pneumonia. Mechanistically, PEBL downregulated FXR expression, inhibiting FXR binding to ACE2 promoters, which subsequently suppressed NF-κB-p65 nuclear translocation and cytokine production. In vivo, PEBL attenuated cytokine production by inhibiting ACE2 transcription through FXR downregulation, leading to alleviation of Poly(I:C)-induced ALI in both zebrafish and mice. Additionally, PEBL significantly improved symptoms of ALI caused by PR8 and XBB infections, by disrupting the FXR/ACE2 signaling axis, resulting in reduced weight loss, lower lung indices, diminished viral load and titer, fewer pulmonary lesions, and suppressed NF-κB-p65 nuclear translocation, along with decreased cytokine storm.

This study provides the first evidence that PEBL offers protective effects against ALI induced by acute respiratory viruses. PEBL prevents FXR from binding to ACE2 by inhibiting FXR transcription, which reduces macrophage infiltration, cytokine storm formation, and inflammatory injury, thereby ameliorating viral ALI. These findings underscore the potential of PEBL as a candidate for further exploration in the treatment of viral ALI.

Pneumonia caused by SARS-CoV-2 is a public health problem. Older adults are vulnerable and the atypical presentation delays diagnosis and increases mortality. In this group the atypical clinical manifestations are more frequent.

To identify the clinical manifestations and mortality of COVID-19 pneumonia in hospitalized older adults.

A comparative cross-sectional observational study was carried out, from July 1, 2020, to December 31, 2021, in a general hospital of Mexico City. Patients aged 60 years or more who were hospitalized with a diagnosis of COVID-19 were included.

267 older adults participated; 53.9% were men, with a median age of 74 years. The most frequent comorbidities in this population were type 2 diabetes mellitus (T2DM), hypertension and chronic obstructive pulmonary disease (COPD). 41.2% showed atypical presentation of the disease; mortality in the studied population was 53.5%.

The atypical presentation of COVID-19 pneumonia is common in adults over 60 years of age and it increases significantly as they become older. The absence of typical symptoms of pneumonia and the ignorance of the most common signs could delay diagnosis and timely care in this age group, which may increase complications and mortality.

To assess COVID-19-related morphological brain changes in individuals who recovered from mild-to-moderate COVID-19.

This prospective cohort study enrolled 112 consecutive individuals who recovered from mild-to-moderate COVID-19 and underwent an MRI of the brain between September 2020 and March 2022. MR exams were consistently obtained on a clinical 3T MR scanner in all study participants and 50 age-matched matched controls. The following clinical neuroradiological MR imaging findings were analyzed: post- and acute ischemic lesions, cortical signal alterations, microbleeds, perfusion abnormalities, cytotoxic lesions of the corpus callosum, and vascular abnormalities. Additionally, we manually quantified white matter lesion loads and the number of perivascular spaces and performed an automated brain volumetric analysis.

In 112 consecutive individuals the mean age was 45 years, female: male = 70:42, mean days at MRI after SARS CoV-2 infection: 228 (sd: 140), and hospitalized: non-hospitalized ratio = 30:82. Using general linear regression models, adjusting for age and gender, the frequency of white matter hyperintensities was not significantly different between subjects who recovered from COVID-19 and matched controls: 9.8 (sd: 17.3) vs. 7.6 (sd: 12.7), p = 0.590. Similarly, the number of enlarged perivascular spaces was not significantly different between the two groups: 62.7 (sd: 43.5) vs. 61.3 (sd: 47.2), p = 0.902. A subgroup analysis between those who were hospitalized in the course of the disease, in which no one required intensive care, and those who remained outpatients, also did not reveal any differences in MRI measures. We did not find evidence for perfusion-/diffusion abnormalities, (micro-)hemorrhages, or cortical abnormalities.

In the present cohort, there was currently no evidence of COVID-19-related morphological brain changes in individuals who recovered from mild-to-moderate COVID-19.

While previous studies have primarily focused on post-acute sequelae of COVID-19, the long-term effects of SARS-CoV-2 infection on alopecia areata (AA) among individuals with mental illness remain underexplored. Thus, this study aimed to address this gap by examining the association between post-acute sequelae of COVID-19 and AA, with a specific focus on individuals with mental illness. This study utilized bi-national, large-scale, and population-based cohorts of individuals with pre-existing mental illness: a Korean nationwide cohort (K-COV-N cohort; main cohort; total n = 3 248 448) and a Japanese claims-based cohort (JMDC cohort; replication cohort; total n = 696 332). The outcome focused on the new onset of AA following 30 days after SARS-CoV-2 infection, defined using ICD-10 codes L63. Using a propensity score-based overlap weighted algorithm, the adjusted hazard ratio (aHR) for AA following COVID-19 was calculated for individuals with mental illness. In the main cohort, the risk of AA as post-acute sequelae of COVID-19 was identified among individuals with mental illness (aHR, 1.32 [95% CI, 1.23-1.43]). The risk was significant for mild mental illness (aHR, 1.33 [95% CI, 1.24-1.44]) and within 6 months postinfection (aHR, 1.48 [95% CI, 1.35-1.63]). Similar findings were observed in the replication cohort. In conclusion, among individuals with mental illness, the risk of post-acute sequelae of COVID-19 on AA was elevated-particularly in those with mild mental illness-though this risk decreased over time. Our findings highlight the importance of early screening, integrated care, and equitable healthcare access for managing post-acute sequelae of COVID-19.

Traditional Chinese medicine has been recognized for its significant role in treating acute lung injury (ALI) due to its distinct therapeutic advantages. Liang-Ge-San (LGS), a formulation from the ancient "Taiping Huimin Hejiju Fang", is believed to possess beneficial effects for treating ALI. However, LGS's precise mechanisms and efficacy in addressing viral ALI remain inadequately explored.

To evaluate LGS's therapeutic effects and underlying mechanisms in treating viral-induced ALI.

The protective effects of LGS were examined in a Polyinosinic-polycytidylic acid [Poly(I:C)]-induced ALI model using real-time quantitative PCR, enzyme-linked immunosorbent assay, and histopathological analysis. A bioinformatics approach combined with network pharmacology was utilized to ascertain the key targets of LGS in viral pneumonia. The pharmacodynamic mechanisms of LGS in viral ALI were further validated through immunofluorescence, overexpression, short hairpin RNA, chromatin immunoprecipitation, and target agonist assays.

LGS administration resulted in a reduction of IL-1β, IL-6, and TNF-α levels, along with a decrease in macrophage infiltration, pulmonary damage, and pneumonedema following the Poly(I:C) challenge. Bioinformatics and network pharmacology analyses suggested that Farnesyl X receptor (FXR) and angiotensin converting enzyme 2 (ACE2) are potential therapeutic targets for LGS in viral pneumonia. Further experiments revealed that LGS suppressed the expression of FXR, ACE2, and NF-κB-p65 in Poly(I:C)-infected cells. Notably, overexpression of FXR counteracted the repressive effects of LGS, while ACE2 expression remained unchanged in FXR-knockdown RAW264.7 cells upon treatment with Poly(I:C) or LGS. Additionally, LGS inhibited the interaction between FXR and ACE2 transcriptional promoters. In vivo, LGS attenuated the Poly(I:C)-induced upregulation of FXR, ACE2, IL-1β, IL-6, and TNF-α in ALI zebrafish and mice models, effects that could be reversed by chenodeoxycholic acid (CDCA), an FXR agonist. Moreover, LGS markedly alleviated weight loss, improved survival rates, reduced lung index, diminished viral load, and inhibited lung pathological changes in H1N1-PR8-induced ALI mice. IL-1β, IL-6, TNF-α, INF-γ, FXR, ACE2, small heterodimer partner, and NF-κB-p65 levels were markedly reduced by LGS, with these effects being reversed by CDCA.

This investigation provides the first evidence that FXR/ACE2 signaling is pivotal in acute respiratory viral infections, while LGS demonstrates antiviral activity against viral-induced ALI. LGS inhibits ACE2 expression induced by viral infection via FXR inhibition and modulates the cytokine storm, thus alleviating viral ALI. These findings suggest that LGS may be a promising treatment strategy for treating viral ALI.

Introduction: SARS-CoV-2 in patients who need Intensive Care (ICU) is associated with a mortality rate ranging from 10 to 40%-45%, with an increase in morbidity and mortality in presence of sepsis. Methods: We assumed that immunoglobulin (Ig) M and IgA enriched IgG (IGAM) therapy may support SARS COV-2 sepsis-related phase improving patient outcome. We conducted a retrospective case-control study on all the patients admitted to our ICU during the three pandemic waves between February 2020 and April 2021. Upon ICU admission, patients received anticoagulants with the standard supportive treatment (ST) ± IGAM therapy. After matching for the baseline characteristics and treatments, the patients receiving IGAM therapy too (group A), were compared with those undergoing ST (group B) only. Results: 85 patients were enrolled in group A, whereas 111 in group B. The mortality resulted lower in group A [37.6% versus 55.8%, OR: 0.7 (02-08), P = .01)]. A logistic regression analysis identified IGAM treatment as a survival predictor [OR: 0.35 (95%CI, 0.2-0.8)], whereas experiencing a super-infection [OR: 1.88 (95%CI, 1.5-4.9)] and a septic shock [OR: 1.92 (95%CI, 1.4-4.3)] as predictors of death. On day 7, the probability of dying was 3 times higher in patients treated with ST only. Variable life adjustment display (VLAD) was equal to 2.4 in group A, while - 2.2 group B (in terms of lives saved in relation with those expected, in according with Simplified Acute Physiology Score II (SAPS II) score. Conclusion: The treatment based on IGAM infusion seems to give an advantage chance of survival in SARS-CoV-2 severe infection. Further prospective studies are warranted.

BACKGROUND Acute necrotizing encephalopathy (ANE) is a severe and rapidly progressive form of encephalopathy predominantly observed in children following various systemic infections. Although rare, cases of ANE have been increasingly associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This report details a fatal case of ANE in a 17-year-old girl diagnosed with coronavirus disease 2019 (COVID-19), emphasizing the critical need for early diagnosis and prompt intervention to improve clinical outcomes. CASE REPORT A previously healthy 17-year-old girl presented with a 3-day history of fever followed by onset of seizures and consciousness disorders after testing positive for SARS-CoV-2. Cranial magnetic resonance imaging (MRI) revealed bilateral symmetrical thalamus, which is a typical imaging presentation of ANE. Cerebrospinal fluid (CSF) examination revealed a normal cell count. Differential diagnoses such as acute disseminated encephalomyelitis (ADEM) and Leigh syndrome were excluded, leading to a diagnosis of ANE. Despite aggressive treatment, including respiratory support, intravenous immunoglobulin, and high-dose glucocorticoids, the patient's condition deteriorated rapidly, resulting in death the following day. CONCLUSIONS ANE is a rare but devastating condition in adolescents, particularly following viral infections such as COVID-19. It should be considered in patients presenting with seizures and progressive consciousness disorders after viral infection. Urgent neuroimaging and lumbar puncture are essential for diagnosis. Early recognition, immunotherapy, and aggressive management are crucial to mitigate the high mortality associated with this severe neurological disorder.

Inflammation is a pathogenic driver of many diseases, including atherosclerosis and rheumatoid arthritis. Hyperinflammation can be seen as any inflammatory response that is deleterious to the host, regardless of cause. In medicine, hyperinflammation is defined as severe, deleterious, and fluctuating systemic or local inflammation with presence of a cytokine storm. It has been associated with rare autoinflammatory disorders. However, advances in omics technologies, including genomics, proteomics, and metabolomics, have revealed it to be more common, occurring in sepsis and severe coronavirus disease 2019. With a focus on proteomics, this review highlights the key role of omics in this shift. Through an exploration of research, we present how omics technologies have contributed to improved diagnostics, prognostics, and targeted therapeutics in the field of hyperinflammation. We also discuss the integration of advanced technologies, multiomics approaches, and artificial intelligence in analyzing complex datasets to develop targeted therapies, and we address their potential for revolutionizing the clinical aspects of hyperinflammation. We emphasize personalized medicine approaches for effective treatments and outline challenges, including the need for standardized methodologies, robust bioinformatics tools, and ethical considerations regarding data privacy. This review aims to provide a comprehensive overview of the molecular mechanisms underpinning hyperinflammation and underscores the potential of omics technologies in enabling successful clinical management.

Trauma-Induced Coagulopathy is a severe condition that rapidly manifests following traumatic injury and is characterized by shock, hypoperfusion, and vascular damage. This study employed bioinformatics methods to identify crucial hub genes and pathways associated with TIC.

Microarray datasets (accession number GSE223245) were obtained from the Gene Expression Omnibus (GEO) database. The data were subjected analyses to identify the Differentially Expressed Genes (DEGs), which were further subjected to GO and KEGG pathway analyses. Subsequently, a Protein-Protein Interaction (PPI) network was constructed and hub DEGs closely linked to TIC were identified using CytoHubba, MCODE, and CTD scores. The diagnostic value of these hub genes was evaluated using Receiver Operating Characteristic (ROC) analysis.

Among the analyzed genes, 269 were identified as DEGs, comprising 103 upregulated and 739 downregulated genes. Notably, several significant hub genes were associated with the development of TIC, as revealed by bioinformatic analyses.

This study highlights the critical impact of newly discovered genes on the development and progression of TIC. Further validation through experimental research and clinical trials is required to confirm these findings.

The continuous emergence of SARS-CoV-2 variants underscores the need for novel antiviral candidates. Hypericin (HY), a compound derived from Hypericum perforatum, exhibited potent in vitro activity against SARS-CoV-2 in Vero E6 cells, with low cytotoxicity (CC50 > 200 nM). HY showed no significant activity against Influenza A (H1N1) or dengue virus serotype 2, supporting its selective action. Antiviral effects were most evident when HY was administered post-infection, in a concentration-dependent manner, while cellular pretreatment or viral pre-incubation produced limited effects. Notably, HY also displayed virucidal activity, significantly reducing viral titers at 4 °C, 22 °C, and 37 °C. Combination treatments with remdesivir or nirmatrelvir enhanced antiviral efficacy by 50-70% relative to monotherapy, depending on compound concentration. Molecular simulations revealed stable interactions with conserved residues in RdRp and 3CLpro, suggesting a low risk of resistance. Together, these findings highlight the potential of HY as a selective antiviral and virucidal agent against SARS-CoV-2, particularly in combination regimens.

Acute surgical abdomen is characterized by intense, sudden abdominal pain due to intra-abdominal conditions requiring prompt surgical intervention. The coronavirus disease 2019 (COVID-19) pandemic has led to various complications related to the disease's complex pathophysiological mechanisms, hence the hypothesis of COVID-19-induced acute abdominal surgical pathologies. The connection between acute surgical abdomen and COVID-19 involves two primary mechanisms. First, there is the presence of angiotensin-converting enzyme 2 (ACE2) receptors in multiple abdominal organs. This facilitates the cytokine storm through direct viral injury and inflammation. Second, the hypercoagulable state induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases the thrombotic risk within abdominal vessels, which can subsequently lead to ischemia. ACE2 receptors are notably expressed in the gastric, duodenal, and rectal epithelium, with SARS-CoV-2 viral RNA and nucleocapsid proteins detected in these tissues. The inflammatory response results in significant endothelial damage, activating coagulation pathways that cause monocellular infiltration, lymphocytic inflammation, and uncontrolled coagulation. These findings highlight the need for further research to clarify how COVID-19 leads to acute abdominal pathologies. Understanding these mechanisms is vital for improving clinical management and patient outcomes during future health crises and in the aftermath of the pandemic.

Acute macular neuroretinopathy (AMN) is a rare retinal condition that predominantly affects young females. The incidence of AMN increased significantly during the COVID-19 pandemic, thereby providing a unique opportunity to elucidate the etiology of this disease. In the present study, 24 articles reporting 59 patients were reviewed. The average age of the patients was 33.51 ± 14.02 years, ranging from 16 to 75 years, with females comprising 71.19% of the cases. The average duration of ocular symptoms post-infection was 8.22 ± 10.69 days, ranging from 4 to 150 days. This study investigated the potential pathogenesis of AMN, including the impact of COVID-19 on retinal neurovascular structure and function, immune-mediated inflammatory factor production, blood-retinal barrier disruption, and retinal microvascular damage, as well as potential clinical therapeutic interventions. This research provides a theoretical framework that can inform further investigations of AMN.

The COVID-19 pandemic, caused by SARS-CoV-2, has significantly affected global health, with severe inflammatory responses leading to tissue damage and persistent symptoms. Macrophage-derived extracellular vesicles (EVs) are involved in the modulation of immune responses, but their involvement in SARS-CoV-2-induced inflammation and senescence remains unclear. Triggering receptors expressed on myeloid cell-1 (TREM-1) are myeloid cell receptors that amplify inflammation, described as a biomarker of the severity and mortality of COVID-19. This study investigated the composition and effects of macrophage-derived EVs stimulated by SARS-CoV-2 (MφV-EVs) on the recipient cell response. Our results, for the first time, show that SARS-CoV-2 stimulation modifies the cargo profile of MφV-EVs, enriching them with TREM-1 and miRNA-155 association, along with MMP-9 and IL-8/CXCL8. These EVs carry senescence-associated secretory phenotype (SASP) components, promote cellular senescence, and compromise antibacterial defenses upon internalization. Our findings provide evidence that MφV-EVs are key drivers of inflammation and immune dysfunction, underscoring their potential as therapeutic targets in COVID-19.

The outcome of the immune response depends on the content and magnitude of inflammatory mediators, the right time to start, and the duration of inflammatory responses. Patients with coronavirus disease 2019 (COVID-19) represent diverse disease severity. Understanding differences in immune responses in individuals with different disease severity levels can help elucidate disease mechanisms. Here, we serially analyzed the cytokine profiles of 809 patients with mild to critical COVID-19. The cytokine profile revealed an overall increase in IL-1β, IL-1Ra, TNF-α, IL-6, IL-2, IL-8, and IL-18 and impaired production of IFN-α and -β. Only an early rise in IL-1Ra, IL-6, and IL-2 levels was linked to worse disease outcomes. On the other hand, long-term rises in IL-1β, IL-1Ra, TNF-α, IL-6, IL-2, IL-8, and IL-18 levels were linked to worse disease outcomes. Principal component analysis identified a component, including IL-1β, TNF-α, IFN-α, and IL-12, that was associated with disease severity. Spearman analysis revealed that the correlation of IL-1β and IFN-α was entirely different between mild and critical patients. Therefore, the ratio of IL-1β to IFN-α seemed to be a suitable criterion for distinguishing critical patients from mild ones. The higher levels of the IL-1β to IFN-α ratio correlated with improved outcomes. These data point to an imbalance of IL-1β/IFNα, contributing to hyperinflammation in COVID-19.

This study investigated the clinical and molecular characteristics of Staphylococcus aureus (S. aureus) isolates from patients with coronavirus disease 19 (COVID- 19) at West China Hospital between December 1, 2022 and January 31, 2023.

In total, 102 strains isolated from sputum, bronchoalveolar lavage fluid, endotracheal aspirates, and blood were collected from 102 patients and subjected to multilocus sequence typing and antimicrobial susceptibility testing. Eighteen virulence genes were also analyzed by polymerase chain reaction.

Seventy-five patients were discharged and 27 died. The predominant comorbidities were hypertension, diabetes mellitus, and cardiac disease. Twenty-eight known sequence types (STs) and 10 novel ones (ST8773/CC398, ST9221/CC5, ST9222/CC59, ST9223/CC8, ST9224/CC22, ST9225/CC1, ST9226/CC5, ST9227/CC59, ST9228/CC59, ST9229/CC398) were identified. The dominant molecular types were ST15 (CC15), ST59 (CC59), and ST5 (CC5). Among the three most prevalent STs, ST5 was significantly more resistant to levofloxacin, moxifloxacin, ciprofloxacin, and sulfamethoxazole than were ST59 and ST15. ST59 and ST5 had higher rates of resistance to erythromycin and clindamycin than ST15. All isolates contained at least eight virulence genes. The hemolysin gene hlb was found to be more prevalent in ST59 (100%) and ST5 (84.6%) than in ST15 (0) (P < 0.001). The prevalence of the enterotoxin gene seb in ST59 (100%) was significantly higher than that in ST5 (23.1%) and ST15 (20%) (P < 0.001), while the carrying rate of the sec gene was significantly higher in ST5 (76.9%) than that in ST59 (0) and ST15 (0) (P < 0.001).

The S. aureus isolates from patients with COVID- 19 in Southwest China exhibited a high degree of genetic diversity. Different STs exhibited different antimicrobial resistance patterns and virulence gene carrying rates.

Contributions of leukocytes to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) defense have been reported extensively. However, it remains unclear whether there are different leukocyte responses to ancestral SARS-CoV-2 and its variants.

We analyzed peripheral blood leukocyte and subtype concentrations from 575 COVID-19 patients and 950 non-COVID-19 subjects registered at the University of Connecticut John Dempsey Hospital between 2020 and 2022, which covers the ancestral strain, Delta, and Omicron variants.

We found that neutrophils, immature granulocytes, and monocytes were elevated, and lymphocytes were reduced after infection. These hyperactive neutrophils/immature granulocytes and suppressed lymphocytes/monocytes were associated with poorer prognosis in ancestral strain infection. Different from the ancestral strain, hyperactive immature granulocytes were not shown in the decedents of Delta infection, and immature granulocyte concentration was not observed to be associated with mortality. In Omicron infection, suppressed lymphocytes and monocytes were not shown in the decedents, and lymphocyte/monocyte concentrations were not associated with mortality.

Our findings provided insights into different leukocyte immune responses to ancestral SARS-CoV-2, Delta, and Omicron variants.

The aim of this study is to assess the effectiveness of the Early Warning Score [ANDC (age (A), neutrophil-to-lymphocyte ratio (NLR (N)), D-dimer (D), and CRP (C)] in predicting the treatment response in patients receiving tocilizumab for Coronavirus Disease 2019 (COVID-19)-related cytokine storm.

A retrospective review of medical records was conducted for patients treated with tocili- zumab for a cytokine storm related to COVID-19 between April 1, 2020, and April 1, 2021. Patient demographics, clinical characteristics, and laboratory parameters within 24 hours before tocilizumab were recorded. 1.14 × (age - 20) (years) + 1.63 × NLR + 5.00 × D-dimer (mg/L) + 0.14 × C-reactive protein (CRP) (mg/L) was used as the formula for the ANDC score. The study population was divided into 2 groups: those who died within 28 days of receiving tocilizumab and those who recovered. A comparative analysis was conducted.

Within 28 days of tocilizumab treatment, 59 (35.32%) patients died. In comparison with living patients, deceased patients exhibited considerably higher levels of interleukin (IL)-6, lactate dehydro- genase (LDH), ANDC score, and CRP (P < .05). Lactate dehydrogenase was an independent predictor of response to tocilizumab treatment (P < .001) in a multivariate logistic regression analysis. In patients who did not receive steroid therapy before tocilizumab treatment, the ANDC score had the highest area under the curve (AUC). The optimal cut-off value was determined to be 92.56, with a sensitivity of 91.67% and a specificity of 60.61% (P < .001). In patients receiving steroids before tocilizumab, LDH had the highest AUC. The optimal cut-off value was 484.5 U/L (P < .001).

Lactate dehydrogenase was identified as an independent predictor of response to tocili- zumab treatment. The ANDC score showed the highest AUC value in steroid-naïve patients before tocilizumab, whereas LDH showed the highest AUC value in patients receiving steroids before tocili- zumab. Both the ANDC score and LDH levels show potential as valuable tools to guide treatment decisions.

This perspective examines the potential oncogenic mechanisms of SARS-CoV-2 through comparative analysis with established cancer-causing viruses, integrating classical virological approaches with artificial intelligence (AI)-driven analysis. The paper explores four key themes: shared oncogenic mechanisms between classical viruses and SARS-CoV-2 (including cell cycle dysregulation, inflammatory signaling, immune evasion, and metabolic reprogramming); the application of AI in understanding viral oncogenesis; the integration of neuroimaging evidence; and future research directions. The author presents novel hypotheses regarding SARS-CoV-2's potential oncogenic mechanisms, supported by recent PET/FDG imaging studies showing persistent metabolic alterations. The manuscript emphasizes the transformative potential of combining traditional virological methods with advanced AI technologies for better understanding and preventing virus-induced cancers, while highlighting the importance of long-term monitoring of COVID-19 survivors for potential oncogenic developments.

Cell-free DNA (cfDNA) holds significant promise for diagnostic and therapeutic advancements in medicine. This review delineates the utility of cfDNA in diagnostics and its therapeutic potential through clearance mechanisms for an array of diseases. Damage-associated molecular patterns (DAMPs) are endogenous molecules released by host cells during stress, or injury. As a trigger for inflammatory responses via damage-associated molecular patterns (DAMPs), cfDNA's removal via nanotechnological approaches can attenuate inflammation and promote tissue repair. While the application of cfDNA clearance is particularly auspicious in cancer, sepsis, and inflammatory conditions, it is confronted with challenges including toxicity, specificity, and the rigors of clinical trial validation. Collectively, this review delineates novel therapeutic targets to inform the development of innovative treatment strategies.