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18 pages, 1216 KB  
Article
Post-Pandemic Resurgence and Seasonal Patterns of Influenza Viruses and Respiratory Syncytial Virus in Arequipa, Peru (2021–2023)
by Claudia Chipana-Ramos, Ynes Monroy Talavera, Luis Zamudio-Rodriguez, Lucia Villanueva-Sardon, Alexis Germán Murillo Carrasco, Ruy D. Chacón and Yuma Ita-Balta
Epidemiologia 2026, 7(2), 57; https://doi.org/10.3390/epidemiologia7020057 (registering DOI) - 21 Apr 2026
Abstract
Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic profoundly disrupted global respiratory virus circulation, with sharp declines during 2020–2021, followed by a resurgence after the relaxation of public health measures. In South America, post-pandemic respiratory virus dynamics remain insufficiently characterized, particularly in ecologically diverse [...] Read more.
Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic profoundly disrupted global respiratory virus circulation, with sharp declines during 2020–2021, followed by a resurgence after the relaxation of public health measures. In South America, post-pandemic respiratory virus dynamics remain insufficiently characterized, particularly in ecologically diverse regions. Arequipa, a high-altitude city in southern Peru, has unique environmental conditions, including marked seasonal temperature variability, that may influence viral transmission. Methods: We performed a cross-sectional analysis of 21,784 nasopharyngeal swabs collected from symptomatic patients at four major hospitals between June 2021 and September 2023. All samples were tested for SARS-CoV-2 by RT-qPCR. Because routine screening for other respiratory viruses was implemented only in SARS-CoV-2-negative cases during the study period, a subset of SARS-CoV-2-negative samples was subsequently analyzed for influenza A virus (IAV), influenza B virus (IBV), and respiratory syncytial virus (RSV) using VIASURE assays. Viral circulation patterns were evaluated by year, month, and epidemiological week. Meteorological data were obtained from the SENAMHI–La Pampilla station. Logistic regression models were used to assess epidemiological and climatic predictors of viral detection. Results: SARS-CoV-2 positivity declined from 20.0% in 2021 to 8.8% in 2023. Conversely, detection of other respiratory viruses among SARS-CoV-2-negative samples increased from 0.8% in 2021 to 29.0% in 2023 (p < 0.01). Temporal increases in detection were observed during 2022–2023, particularly for IAV and RSV. In exploratory analyses, calendar year and relative humidity were associated with IAV and RSV detection, while age and temperature variables were associated with IBV. Conclusions: Climatic and demographic variables were associated with changes in viral detection for IAV, IBV, and RSV during the post-pandemic transition period in Arequipa. These findings describe patterns of viral detection within SARS-CoV-2-negative symptomatic patients and should be interpreted as surveillance-based observations rather than population-level estimates. Strengthened integrated epidemiological and genomic surveillance will be essential for vaccine planning and outbreak preparedness in the post-pandemic era. Full article
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10 pages, 540 KB  
Article
Association Between Time to First Mobilization and Recovery of Oral Intake Function in Patients with Pneumonia: A Two-Center Retrospective Cohort Study
by Shinichi Watanabe, Takaaki Sakurai, Takahiro Kanaya, Takumi Iwasaki, Hyosuke Oshima, Tetsuya Furukawa, Tomohiro Yoshikawa, Seichi Nakahashi and Yasunari Morita
Life 2026, 16(4), 691; https://doi.org/10.3390/life16040691 - 20 Apr 2026
Abstract
Delayed recovery of oral intake is common in hospitalized patients with pneumonia, particularly among older adults with reduced physical activity. Despite the recent emphasis on early mobilization, the relationship between the timing of first mobilization and recovery of oral intake function remains unclear. [...] Read more.
Delayed recovery of oral intake is common in hospitalized patients with pneumonia, particularly among older adults with reduced physical activity. Despite the recent emphasis on early mobilization, the relationship between the timing of first mobilization and recovery of oral intake function remains unclear. Thus, this retrospective cohort study investigated the association between time to first mobilization and recovery of oral intake in patients hospitalized with pneumonia. We analyzed 431 admitted patients with pneumonia, including aspiration pneumonia and coronavirus disease 2019 pneumonia, at two institutions. The Functional Oral Intake Scale ≥ 4 (partial oral intake recovery) was designated as the primary outcome. The main exposure was the number of days from admission to first mobilization. Multivariable Cox proportional hazards models were used after appropriate adjustments. The median time to first mobilization was 4 days (IQR: 2–14 days). Longer time to first mobilization was significantly associated with delayed recovery of oral intake (HR: 0.96, 95% CI: 0.94–0.98, p < 0.001). Thus, early mobilization may promote the recovery of oral intake in patients with pneumonia. These findings suggest that avoiding excessive delays in mobilization may support the recovery of oral intake and swallowing function in hospitalized patients with pneumonia. Full article
(This article belongs to the Special Issue Intensive Care Medicine: Current Concepts and Future Perspectives)
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27 pages, 2044 KB  
Article
Open-Data Nowcasting of Ecuador’s International Tourist Arrivals: Regularized Dynamic Regression with Wikipedia Attention and Copernicus Land Reanalysis Climate Signals
by Julio Guerra, Sheyla Fernández, Danny Benavides, Víctor Caranquí and Mónica Meneses
Tour. Hosp. 2026, 7(4), 113; https://doi.org/10.3390/tourhosp7040113 - 20 Apr 2026
Abstract
Timely monitoring of tourism demand is essential for destination management, yet official monthly arrival statistics are often released with delays and can be difficult to use for near-real-time decision-making, particularly under structural shocks such as coronavirus disease 2019 (COVID-19). This study develops a [...] Read more.
Timely monitoring of tourism demand is essential for destination management, yet official monthly arrival statistics are often released with delays and can be difficult to use for near-real-time decision-making, particularly under structural shocks such as coronavirus disease 2019 (COVID-19). This study develops a fully reproducible, open-data nowcasting pipeline for Ecuador’s international tourist arrivals using a Python workflow. The framework integrates (i) the official monthly arrivals series published by Ecuador’s Ministry of Tourism (MINTUR), (ii) open online attention proxies from Wikipedia pageviews retrieved via the Wikimedia REST application programming interface (API), and (iii) open climate covariates derived from the ERA5-Land land reanalysis. Multiple forecasting models are evaluated under a rolling-origin, one-step-ahead backtest, with a mandatory seasonal naïve benchmark and a regime-aware assessment that separates a stress-test window (2019–2021) from an operational post-COVID window (2022–2025). Forecast accuracy is summarized using root mean squared error (RMSE), mean absolute error (MAE), and symmetric mean absolute percentage error (sMAPE), and statistical significance of performance differences is assessed using the Diebold–Mariano (DM) test. Results show that a ridge-regularized autoregressive model (ridge_ar) achieves the best overall accuracy, reducing RMSE by approximately 79% relative to the seasonal naïve baseline over the full evaluation window. Windowed results confirm robust performance during the shock period and sustained improvements in the post-2022 operational regime, while the incremental benefit of broader exogenous signals is heterogeneous across windows, underscoring the importance of regularization and regime-aware reporting. The proposed approach provides a transparent, low-cost blueprint for reproducible tourism monitoring that is transferable to other destinations using open data and standard computational tools. Full article
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18 pages, 641 KB  
Article
Pulmonary Embolism in Hospitalized COVID-19 Patients: Incidence, Clinical Predictors, and Short-Term Outcomes
by Cristiana Adina Avram, Maria-Laura Craciun, Ana-Maria Pah, Stela Iurciuc, Simina Crisan, Cristina Vacarescu, Ioana Cotet, Claudia Raluca Balasa Virzob, Dan Alexandru Surducan and Claudiu Avram
J. Clin. Med. 2026, 15(8), 3117; https://doi.org/10.3390/jcm15083117 - 19 Apr 2026
Viewed by 53
Abstract
Background/Objectives: Pulmonary embolism (PE) represents a major thrombotic complication in hospitalized patients with coronavirus disease 2019 (COVID-19), yet data on its incidence, clinical predictors, and short-term outcomes in actual cohorts remain heterogeneous. Methods: We conducted a retrospective observational cohort study including [...] Read more.
Background/Objectives: Pulmonary embolism (PE) represents a major thrombotic complication in hospitalized patients with coronavirus disease 2019 (COVID-19), yet data on its incidence, clinical predictors, and short-term outcomes in actual cohorts remain heterogeneous. Methods: We conducted a retrospective observational cohort study including 395 consecutive adults hospitalized with RT-PCR-confirmed COVID-19 at a tertiary infectious diseases center between March 2020 and December 2024. Clinical, laboratory, imaging, and treatment data were extracted from electronic records, and PE was defined by computed tomography pulmonary angiography. Univariable and multivariable logistic regression analyses were used to identify independent predictors of PE in the subset of patients who underwent CTPA (n = 120), in whom PE status was definitively ascertained (47 with PE and 73 without PE). Results: Pulmonary embolism was diagnosed in 47 patients (11.9%). Patients with PE more frequently had prior venous thromboembolism (19.1% vs. 8.3%) and prolonged immobilization (61.7% vs. 23.0%), and were more often admitted to the intensive care unit (12.8% vs. 4.3%) than those without PE. Peak D-dimer levels were almost ten-fold higher in the PE group (median 5322 vs. 529.5 µg/L). In multivariable logistic regression, peak D-dimer was independently associated with PE (per log-unit increase, adjusted OR 3.9, 95% CI 2.1–7.1), and prolonged immobilization conferred a substantially higher risk of PE (adjusted OR 5.1, 95% CI 2.4–10.9). Patients with PE experienced more complex hospital courses and more frequent need for advanced therapies, although in-hospital mortality did not differ significantly between groups. Conclusions: In hospitalized COVID-19 patients, PE is frequent and closely linked to marked D-dimer elevation and acquired in-hospital risk factors, particularly prolonged immobilization. This evidence supports the use of dynamic D-dimer assessment and careful evaluation of immobilization status to improve risk stratification, guide decisions on diagnostic imaging and anticoagulation intensity, and identify patients who may benefit from closer post-discharge cardiovascular follow-up (this hypothesis requires confirmation in future prospective studies). Full article
(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)
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10 pages, 232 KB  
Article
Understanding Student Experience of Using Work-Integrated Learning to Develop Healthcare Redesign Capacity in a Hospital Setting: A Descriptive Qualitative Study
by Suzanne Louise Waddingham, Sarah J. Prior, Phoebe Griffin, Jennifer Barr, Mitchell Dwyer, Lauri O’Brien and Karrie Long
Trends High. Educ. 2026, 5(2), 35; https://doi.org/10.3390/higheredu5020035 - 17 Apr 2026
Viewed by 97
Abstract
Background: In 2021, an Australian Hospital Nursing Research Hub sponsored 13 healthcare staff to complete the Graduate Certificate (Clinical Redesign), to build capability in health service improvement though work-integrated learning (WIL). Healthcare professionals undertaking workplace-based WIL likely experience significant challenges including balancing professional [...] Read more.
Background: In 2021, an Australian Hospital Nursing Research Hub sponsored 13 healthcare staff to complete the Graduate Certificate (Clinical Redesign), to build capability in health service improvement though work-integrated learning (WIL). Healthcare professionals undertaking workplace-based WIL likely experience significant challenges including balancing professional and student roles and aligning work with academic requirement. These pressures were likely intensified during the Coronavirus disease 2019 (COVID-19) pandemic. This study aimed to explore and understand the experiences of hospital healthcare staff completing WIL redesign projects, including the impacts of COVID-19. Methods: A qualitative descriptive inquiry approach was used to explore individual student experiences. Thirteen staff, mostly nurses, who enrolled in the 2021 course were invited to participate. Online semi-structured interviews were conducted. Data were analyzed using a general inductive thematic analysis approach. Results: Four participants (36%) took part; all were female and working full-time. Five main themes were identified that centered around: COVID-19, Support, Motivation, Alignment and Relevance, and Success. Conclusions: Novel insights include the need to reconceptualize “success” to improve student experience, the critical role of organizational–university–student alignment in enabling WIL studies, and the unique pressures of completing WIL during crisis conditions that direct impact the health sector, such as COVID-19. Although not generalizable, these findings are likely to be important considerations more broadly to strengthen WIL design, support and student experiences, ultimately enhancing health service staff capability to lead quality improvement in the workplace. Full article
(This article belongs to the Special Issue The Graduate School Experience: Influential Factors for Success)
28 pages, 3252 KB  
Article
Psychiatric and Neurological Involvement in COVID-19 Hospitalized Patients Through the Global Pandemic in Central Romania
by Claudia Daniela Lupu, Vlad-Dan Cotuțiu and Victoria Birlutiu
J. Clin. Med. 2026, 15(8), 3030; https://doi.org/10.3390/jcm15083030 - 16 Apr 2026
Viewed by 213
Abstract
Background: Neuropsychiatric manifestations are a recognized complication of COVID-19, yet their temporal evolution across pandemic waves remains poorly characterized in hospitalized cohorts. This study examined whether their prevalence and composition changed across five successive waves. Methods: We conducted a retrospective observational study of [...] Read more.
Background: Neuropsychiatric manifestations are a recognized complication of COVID-19, yet their temporal evolution across pandemic waves remains poorly characterized in hospitalized cohorts. This study examined whether their prevalence and composition changed across five successive waves. Methods: We conducted a retrospective observational study of 1471 hospitalized adults with confirmed Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at Sibiu County Emergency Clinical Hospital, Romania (March 2020–January 2025), spanning ancestral through Omicron variants. A custom natural language processing pipeline extracted symptoms, medications, and International Classification of Diseases, 10th Revision (ICD-10) codes from electronic medical records. Nine hierarchical clinical clusters were defined; temporal trends were assessed using multivariable logistic regression with age-stratified replication. Results: Severe neurological presentations (stroke, seizures, hemiparesis) increased six-fold from 3.5% in Wave 1 to 20.1% in Wave 5, while psychiatric symptoms (anxiety, insomnia) declined from 13.3% to 4.3%. Overall, neuropsychiatric burden remained stable (~40–45%), revealing a compositional shift. This neurological trend persisted after multivariable adjustment (adjusted odds ratio 4.34, for Wave 5 vs. Wave 1) and within age-stratified subgroups, was inversely associated with respiratory severity and could not be attributed to vaccination status. The composite neurological severity index independently predicted mortality and intensive care unit admission. Conclusions: Neuropsychiatric manifestations in hospitalized Coronavirus disease of 2019 (COVID-19) patients underwent a compositional shift from psychiatric dominance in early waves to severe neurological dominance in later waves, consistent with a transition from reactive psychiatric presentations toward progressive neurological injury. This pattern, largely independent of measured confounders, underscores the need for sustained neurological surveillance beyond the acute respiratory phase. Full article
(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)
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17 pages, 1462 KB  
Article
C-Reactive Protein Trajectories by Summary Metric Across the Coronavirus-2019 Period: A 16-Year Interrupted Time-Series Analysis (2008–2023)
by Jeong Su Han, Bo Kyeung Jung, Jae-Sik Jeon and Jae Kyung Kim
Diagnostics 2026, 16(7), 1081; https://doi.org/10.3390/diagnostics16071081 - 3 Apr 2026
Viewed by 321
Abstract
Background/Objectives: The clinical utility of summarizing long-term C-reactive protein (CRP) trends with a single mean remains unclear. We systematically characterized annual changes in CRP test volume and CRP level distributions using large-scale laboratory data collected at Dankook University Hospital (2008–2023) across the [...] Read more.
Background/Objectives: The clinical utility of summarizing long-term C-reactive protein (CRP) trends with a single mean remains unclear. We systematically characterized annual changes in CRP test volume and CRP level distributions using large-scale laboratory data collected at Dankook University Hospital (2008–2023) across the coronavirus 2019 pandemic period. Methods: Overall, 1,845,258 CRP values were analyzed; annual arithmetic, harmonic, and geometric means were calculated; long-term trends were assessed using weighted least squares (WLS) regression weighted by annual test volume; and temporal changes around the pandemic period were examined using a WLS-based interrupted time-series (ITS) segmented model with a prespecified 2020 break. Results: The annual test volume rose from 2008 to 2013 and 2019, dropped in 2020, increased in 2022, and declined in 2023. The arithmetic mean showed no long-term trend, whereas the harmonic and geometric means declined. ITS models exhibited no statistically significant immediate level-change term in 2020; however, post-2020 slope changes indicated a decline in the arithmetic mean and attenuation of the prior decline in the harmonic mean. As only four annual observations were available after 2020, these post-2020 trend estimates should be interpreted cautiously. Conclusions: Within this single-center tertiary-care dataset, different CRP summary measures showed different long-term patterns and post-2020 trend changes, without evidence of an abrupt shift in 2020, suggesting stratum-specific shifts that may be invisible to arithmetic mean-based surveillance. These findings are best interpreted as institution-specific and hypothesis-generating, and broader interpretive or operational implications require validation in multicenter settings with differing case-mix and care structures. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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24 pages, 1812 KB  
Article
SARS-CoV-2 Seroprevalence of Surinamese Children and Determinants of Seropositivity in the CCREOH/MeKiTamara Cohort
by Delmaliz Barreto-Vázquez, Jeanine M. Buchanich, Ernesto T. A. Marques, Hannah H. Covert, Firoz Abdoel Wahid, Ashna D. Hindori-Mohangoo, Wilco C. W. R. Zijlmans, Arti Shankar and Maureen Y. Lichtveld
Children 2026, 13(4), 493; https://doi.org/10.3390/children13040493 - 31 Mar 2026
Viewed by 321
Abstract
Background/Objectives: The main goal of this study is to identify predictors associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) seropositivity in children, including demographics, history of coronavirus disease 2019 (COVID-19) infection of the child and the household members, prevention practices, and maternal [...] Read more.
Background/Objectives: The main goal of this study is to identify predictors associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) seropositivity in children, including demographics, history of coronavirus disease 2019 (COVID-19) infection of the child and the household members, prevention practices, and maternal vaccination. Methods: This retrospective cross-sectional study within the Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH)/MeKiTamara cohort included 300 mother-child dyads recruited in Paramaribo and Nickerie, Suriname (February–April 2023). The total immunoglobulin G (IgG) anti-spike domain 1 (S1) and anti-nucleoprotein (NP) were quantified in dried blood spot (DBS) eluates from children using indirect enzyme-linked immunosorbent assays (ELISAs). Demographic information, COVID-19 prevention measures, history of viral infection of the child and the household members, and COVID-19 vaccination questionnaire data were recorded. Predictors of SARS-CoV-2 seroprevalence were determined using binary logistic regression. Results: Among 278 seropositive children in 2023, 73.4% were in the 5–6-year-old age group, 54.7% were female, 36.3% were of Asian descent, and 69.8% were recruited in Paramaribo. Seroprevalence increased from 33.8% in 2021–2022 to 93.3% in 2023, with a mean follow-up of 21.5 months. Of the 100 children previously tested by Polymerase Chain Reaction (PCR) or antigen test, 25 had confirmed COVID-19, as reported by mothers. Children from unvaccinated mothers were 6.11 times more likely to be seropositive (p = 0.022). Conclusions: This study shows a significant increase in SARS-CoV-2 seropositivity in Surinamese children aged 3–6 years between collection periods, indicating multiple exposures. Future public health interventions and policies should account for maternal vaccination status to reduce children’s exposure to COVID-19 during future outbreaks. Full article
(This article belongs to the Section Pediatric Infectious Diseases)
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10 pages, 1162 KB  
Article
A Post-Pandemic Surge: Sustained High Prevalence and Epidemiological Shift in Pediatric Epstein–Barr Virus Infection
by Huamei Li, Ran Tao, Wei Li and Shiqiang Shang
Pathogens 2026, 15(4), 361; https://doi.org/10.3390/pathogens15040361 - 29 Mar 2026
Viewed by 415
Abstract
The coronavirus disease 2019 (COVID-19) pandemic altered the infection patterns of various pathogens; however, its impact on pediatric active Epstein–Barr virus (EBV) infection has not been sufficiently investigated in large-scale studies, and its long-term effects remain unexplored. We analyzed 57,403 pediatric patients from [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic altered the infection patterns of various pathogens; however, its impact on pediatric active Epstein–Barr virus (EBV) infection has not been sufficiently investigated in large-scale studies, and its long-term effects remain unexplored. We analyzed 57,403 pediatric patients from January 2018 to December 2024. Positivity rates of active EBV infection remained consistently elevated throughout the two-year period following the onset of the COVID-19 pandemic, significantly exceeding both pre-pandemic and during-pandemic levels (5329 [22.83%] vs. 1866 [13.55%] vs. 2188 [14.40%], p < 0.001), with concomitantly higher viral loads (median: 8.00 × 103 vs. 1.78 × 103 vs. 1.88 × 103 copies/mL, p < 0.001). Post-pandemic, patients with EBV more frequently presented with pneumonia and allergic dermatitis, and the 6–11-year-old group accounted for a higher proportion of cases. This study reveals a prolonged surge of pediatric active EBV infection after the pandemic, characterized by sustained high prevalence, an age shift toward school children, and evolving clinical features. In the post-pandemic era, heightened and sustained attention should be paid to EBV infection in children, particularly among school-aged children. The sustained high prevalence of pediatric active EBV infection in the post-pandemic period warrants further investigation into its underlying causes. Full article
(This article belongs to the Section Epidemiology of Infectious Diseases)
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27 pages, 666 KB  
Systematic Review
Efficacy and Safety of Vagus Nerve Stimulation for Hospitalized COVID-19 Patients: A Systematic Review and Methodological Evaluation of Randomized Controlled Trials
by Adrian Balan, Giles Graham, Herban Sorin, Marius Marcu, Nini Gheorghe, Mara Gabriela, Andreea-Roxana Florescu, Alina-Mirela Popa, Ana Lascu, Cristian Ion Mot, Stefan Mihaicuta and Stefan Marian Frent
Medicina 2026, 62(4), 649; https://doi.org/10.3390/medicina62040649 - 28 Mar 2026
Viewed by 477
Abstract
Background and Objectives: Coronavirus disease 2019 (COVID-19) is characterized by excessive inflammatory responses, including the so-called cytokine storm, which contributes substantially to morbidity and mortality in hospitalized patients. The vagus nerve, through the cholinergic anti-inflammatory pathway, represents a theoretically attractive therapeutic target [...] Read more.
Background and Objectives: Coronavirus disease 2019 (COVID-19) is characterized by excessive inflammatory responses, including the so-called cytokine storm, which contributes substantially to morbidity and mortality in hospitalized patients. The vagus nerve, through the cholinergic anti-inflammatory pathway, represents a theoretically attractive therapeutic target for modulating systemic inflammation. Vagus nerve stimulation (VNS) has emerged as a potential adjunctive treatment for COVID-19, with several randomized controlled trials (RCTs) investigating its efficacy on inflammatory biomarkers and clinical outcomes. The quality of this evidence base has not been rigorously evaluated. This systematic review critically appraises all available RCT evidence for VNS in hospitalized COVID-19 patients. Materials and Methods: We systematically searched PubMed, Scopus, Cochrane (CENTRAL), and Web of Science from database inception to January 2026, for RCTs evaluating any form of VNS (invasive, non-invasive, cervical, or auricular) in hospitalized patients with confirmed acute COVID-19. Two reviewers independently screened titles, abstracts, and full texts according to pre-specified eligibility criteria. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, with assessments initially performed using multiple artificial intelligence tools and subsequently validated by the authors in accordance with PRISMA 2020 guidelines. Given substantial heterogeneity and high risk of bias, narrative synthesis was performed rather than meta-analysis. Also, GRADE assessment was performed. Results: From 437 records identified, six RCTs comprising 221 patients met the inclusion criteria. Five trials (83%) were rated as high risk of bias, primarily due to inadequate blinding, substantial baseline imbalances, significant missing data and extensive multiple testing without statistical correction. The single double-blind trial with a credible sham control (Rangon et al.) found null results across all outcomes, including clinical progression, ICU transfer, and mortality, while the five “high” risk-of-bias trials generally reported positive findings on various inflammatory markers and clinical outcomes. One trial (Corrêa et al.) measured heart rate variability as a direct indicator of vagal activation and found no change despite claiming anti-inflammatory effects, contradicting the proposed mechanism of action. Significant cognitive findings from an interim analysis (Uehara et al., n = 21) disappeared in the larger completed trial (Corrêa et al., n = 52), providing empirical demonstration of false positive findings in small, underpowered studies. Conclusions: Currently available evidence supporting the use of VNS for acute COVID-19 remains scarce; however, the physiological rationale remains sound, although the absence of reliable target engagement markers in the included studies limits confidence in this treatment method. Large-scale, double-blind, sham-controlled trials are required before VNS can be firmly recommended for COVID-19 management. Full article
(This article belongs to the Section Epidemiology & Public Health)
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18 pages, 3468 KB  
Article
Identifying ICAM-1 as a Therapeutic Target for Cytokine Storm in Human Macrophages Through Integrative Bioinformatics Approaches
by Shaojun Chen, Dapeng Wu, Zhe Zheng, Yiyuan Luo and Lihua Zhang
Molecules 2026, 31(7), 1111; https://doi.org/10.3390/molecules31071111 - 27 Mar 2026
Viewed by 462
Abstract
Excessive macrophage activation is thought to be the primary cause of the cytokine storm that results in severe coronavirus disease 2019 (COVID-19) complications. The underlying mechanisms remain elusive, and more research is needed to find disease-critical genes and develop effective therapies. In this [...] Read more.
Excessive macrophage activation is thought to be the primary cause of the cytokine storm that results in severe coronavirus disease 2019 (COVID-19) complications. The underlying mechanisms remain elusive, and more research is needed to find disease-critical genes and develop effective therapies. In this study, we used publicly accessible microarray datasets of cytokine storm in cultured human monocyte-derived macrophages challenged with cytokines, and employed bioinformatics, such as weighted gene co-expression network analysis (WGCNA) and differential expression analysis, to dissect gene expression profiles and identify putative disease-related molecules. Initially, three co-expression modules and related key genes were discovered, which highly correlated to macrophages challenged with cytokines. Then, a preliminary gene expression signature consisting of 203 upregulated and 24 downregulated genes was identified. Next, protein–protein interaction analysis and hub gene identification were used to identify 11 crucial hub genes, namely tripartite motif-containing 21 (TRIM21), interferon regulatory factor 1 (IRF1), guanylate binding protein 1 (GBP1), transporter associated with antigen processing 1 (TAP1), nuclear myosin I (NMI), interleukin 15 receptor subunit alpha (IL15RA), apolipoprotein L1 (APOL1), intercellular adhesion molecule 1 (ICAM-1), protein tyrosine phosphatase non-receptor type 1 (PTPN1), E74-like ETS transcription factor 4 (ELF4) and guanylate binding protein 2 (GBP2). Then, the LINCS L1000 characteristic direction signatures search engine (L1000CDS2) was employed for drug repurposing studies. Dasatinib was predicted to be the leading therapeutic compound to perturb the gene signature of cytokine storm in human macrophages. Connectivity Map results suggested that dasatinib may normalize ICAM-1 expression. In addition, the results of molecular docking studies and molecular dynamics simulation revealed that dasatinib may spontaneously interact with ICAM-1 via several key residues and form a relatively stable protein–ligand complex. Overall, this work, based on an analysis of co-expression correlation networks, gene expression signatures and pivotal genes in human macrophages challenged with cytokines, combined with drug repurposing studies, demonstrated that dasatinib may interact with ICAM-1 and could be a potential candidate for cytokine storm. However, due to the limitations of computational approaches, further experimental validation is necessary. Full article
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21 pages, 8614 KB  
Article
Eupatorium lindleyanum DC. Suppresses Cytokine Storm by Inhibiting NF-κB and PI3K–Akt Signaling in Sepsis-Associated and Virus-Related Acute Lung Injury
by Chen Luo, Peilin He, Yan Yang, Lian Xia, Wenjie Xu, Daike Zou, Yiduo Feng, Lian Duan, Junjie Deng, Yong Jing and Xianqin Luo
Curr. Issues Mol. Biol. 2026, 48(3), 333; https://doi.org/10.3390/cimb48030333 - 21 Mar 2026
Viewed by 489
Abstract
Cytokine storm is a central pathogenic mechanism underlying sepsis-induced acute lung injury (SALI) and severe coronavirus disease 2019 (COVID-19), yet effective therapeutic strategies remain limited. Eupatorium lindleyanum DC. (EL), a traditional Chinese medicinal herb, has been reported to possess anti-inflammatory, antioxidant, and antiviral-related [...] Read more.
Cytokine storm is a central pathogenic mechanism underlying sepsis-induced acute lung injury (SALI) and severe coronavirus disease 2019 (COVID-19), yet effective therapeutic strategies remain limited. Eupatorium lindleyanum DC. (EL), a traditional Chinese medicinal herb, has been reported to possess anti-inflammatory, antioxidant, and antiviral-related activities; however, its protective mechanisms in SALI and virus-associated inflammatory lung injury remain incompletely understood. In this study, an integrated strategy combining computational prediction and experimental validation was employed to investigate the therapeutic potential and underlying mechanisms of EL. The chemical constituents of EL were characterized by UPLC–Q–TOF/MS, followed by network pharmacology, molecular docking, and molecular dynamics analyses to predict key targets and signaling pathways. A cecal ligation and puncture (CLP)-induced SALI rat model was used to evaluate lung histopathology, pulmonary edema, cytokine production, and inflammatory signaling activation. In parallel, LPS-stimulated RAW264.7 macrophages were used to assess cytokine secretion and pathway regulation in vitro. In addition, a SARS-CoV-2 pseudovirus-induced mouse model was employed to further evaluate the in vivo relevance of the representative bioactive compound hyperoside in pseudovirus-associated lung injury. A total of 32 active compounds and 697 putative targets were identified, among which 116 were associated with sepsis and COVID-19. In vivo, EL markedly alleviated lung injury, reduced the lung coefficient and wet/dry ratio, and suppressed excessive production of proinflammatory cytokines and activation of key signaling proteins. In vitro, EL dose-dependently inhibited TNF-α and IL-6 secretion and regulated the PI3K–Akt and NF-κB signaling pathways. Notably, hyperoside showed favorable predicted interactions with PI3K–Akt pathway-related targets (EGFR, PI3K, and Akt), while molecular dynamics simulations supported stable interactions with several COVID-19-related targets, including ACE2, Mpro, and RdRp. Furthermore, hyperoside significantly alleviated SARS-CoV-2 pseudovirus-associated lung injury, reduced ACE2 protein expression, and downregulated EGFR, PI3K, and Akt mRNA levels in vivo. Collectively, these findings indicate that EL exerts protective effects through multi-component, multi-target, and multi-pathway mechanisms, and support its potential value for further investigation in SALI and virus-associated inflammatory lung injury. Full article
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10 pages, 1831 KB  
Case Report
Successful Treatment of Persistent and Relapsing COVID-19 with Ensitrelvir in a Patient with Obinutuzumab-Induced Long-Term B-Cell Depletion: A Case Report
by Yoshitaka Haino, Tsuneaki Kenzaka, Tomohiro Hayashi and Kimikazu Yakushijin
Reports 2026, 9(1), 89; https://doi.org/10.3390/reports9010089 - 18 Mar 2026
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Abstract
Background and Clinical Significance: Ensitrelvir is an oral inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (3CL pro). Compared with remdesivir and molnupiravir, ensitrelvir achieves higher rates of SARS-CoV-2 antigen clearance and a more favorable viral shedding profile. [...] Read more.
Background and Clinical Significance: Ensitrelvir is an oral inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (3CL pro). Compared with remdesivir and molnupiravir, ensitrelvir achieves higher rates of SARS-CoV-2 antigen clearance and a more favorable viral shedding profile. Case Presentation: A 67-year-old Japanese man with follicular lymphoma had received obinutuzumab plus bendamustine, followed by obinutuzumab maintenance therapy. Hypogammaglobulinemia and profound B-cell depletion persisted for more than 1 year after the final maintenance dose. Three months prior to the current admission, the patient developed coronavirus disease 2019 (COVID-19) and was treated with a 10-day course of remdesivir and dexamethasone. The patient subsequently presented with recurrent COVID-19 pneumonia. Treatment with remdesivir and dexamethasone did not result in clinical improvement, and the SARS-CoV-2 antigen level increased despite adjunctive intravenous immunoglobulin. After ensitrelvir was added to remdesivir, the SARS-CoV-2 antigen levels declined rapidly, and clinical parameters, including fever, inflammatory markers (C-reactive protein), and oxygenation, improved promptly, allowing for discharge. Conclusions: Ensitrelvir may be an effective therapeutic option for the treatment of persistent or refractory COVID-19 in immunocompromised patients. Clinicians should recognize that patients treated with obinutuzumab may remain immunosuppressed for several years after therapy. Full article
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25 pages, 1110 KB  
Review
Unraveling the Link Between COVID-19 and Memory Deficits: The Role of Brain Microglia Activation
by Md. Aktaruzzaman, Md. Ahsan Abid, Md. Asaduzzaman Rakib, Md. Sazzadul Islam, Humayra Afroz Dona, Afrida Tabassum, Nazmul Hossain, Sabekun Nahar Sezin, Chowdhury Lutfun Nahar Metu and Md. Obayed Raihan
Neuroglia 2026, 7(1), 10; https://doi.org/10.3390/neuroglia7010010 - 16 Mar 2026
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Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been associated with a wide range of neurological complications, among which persistent cognitive impairment and memory deficits are increasingly recognized as key symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID). Although clinical [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has been associated with a wide range of neurological complications, among which persistent cognitive impairment and memory deficits are increasingly recognized as key symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID). Although clinical and epidemiological studies have documented these symptoms across diverse patient populations, the underlying neurobiological mechanisms remain incompletely understood. Growing evidence from human studies, neuropathological analyses, and experimental models indicates that neuroimmune and inflammatory processes plays a central role in COVID-19-associated cognitive dysfunction. As the brain’s resident immune cells, microglia are vital for synaptic health, neuroplasticity, and memory, yet these processes may be compromised after SARS-CoV-2 infection. Systemic inflammation, blood–brain barrier (BBB) disruption, endothelial injury, and cytokine signaling can induce sustained microglial activation and priming, leading to inflammasome activation, complement-mediated synaptic remodeling, oxidative stress, and impaired hippocampal neurogenesis. These processes collectively disrupt neural circuits involved in learning and memory and may underlie the persistent “brain fog” reported by COVID-19 survivors. This review synthesizes clinical, biomarker, neuroimaging, and mechanistic evidence linking SARS-CoV-2 infection to microglia-mediated neuroinflammation and memory impairment. In contrast to prior reviews that broadly describe neuroinflammation in COVID-19, we integrate multidimensional evidence into a microglia-centric immunovascular framework that highlights converging pathogenic pathways underlying cognitive symptoms. We further discuss emerging biomarkers of glial activation and evaluate current and prospective therapeutic strategies targeting microglial and neuroimmune pathways. Understanding the role of microglial dysregulation in post-COVID cognitive impairment may facilitate the development of targeted interventions to mitigate long-term neurological consequences of COVID-19. Full article
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23 pages, 2143 KB  
Article
Bibliometric and Descriptive Analysis of SARS-CoV-2 Immune Escape Using Bioinformatics Approaches (2020–2025)
by Maha Ouarab, Zineb Rhazzar, Nadia Touil and Elmostafa El Fahime
COVID 2026, 6(3), 50; https://doi.org/10.3390/covid6030050 - 16 Mar 2026
Viewed by 448
Abstract
Vaccines worldwide reduce severe coronavirus disease 2019 (COVID-19) consequences; however, viral evolution escapes immunity, raising global concerns about vaccine protection and requiring monitoring. Bioinformatics is crucial for studying vaccine escape, speeding up variant detection, mapping antibody evasion epitopes and ensuring updated vaccines and [...] Read more.
Vaccines worldwide reduce severe coronavirus disease 2019 (COVID-19) consequences; however, viral evolution escapes immunity, raising global concerns about vaccine protection and requiring monitoring. Bioinformatics is crucial for studying vaccine escape, speeding up variant detection, mapping antibody evasion epitopes and ensuring updated vaccines and public health responses. This study combines bibliometric analysis of the Scopus literature (n = 416) on SARS-CoV-2 immune evasion using bioinformatics tools with descriptive analysis of the top ten most highly cited original articles. Our results showed the United States (USA) as the dominant contributor, leading in publication output, citation impact and collaboration networks. The key themes identified were immune evasion, spike protein mutations, and viral evolution, highlighting the structural, functional and immune evasion mechanisms of spike mutations. Leading authors and journals reveal a globally connected research community that is making advances in our understanding of SARS-CoV-2 vaccine evasion, and supporting the development of future treatments and vaccines. The top ten articles showed molecular docking, dynamics simulations, and protein modeling as crucial to studying vaccine escape. In conclusion, global research led mainly by the USA and supported by active contributions has used bioinformatics to elucidate SARS-CoV-2 immune evasion, guiding variant future vaccine and treatment development, variant monitoring, and preparedness for emerging variants. Full article
(This article belongs to the Section Human or Animal Coronaviruses)
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