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Keywords = acute respiratory illness

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8 pages, 9195 KiB  
Case Report
Fatal Case of Viral Pneumonia Associated with Metapneumovirus Infection in a Patient with a Burdened Medical History
by Parandzem Khachatryan, Naira Karalyan, Hasmik Petunts, Sona Hakobyan, Hranush Avagyan, Zarine Ter-Pogossyan and Zaven Karalyan
Microorganisms 2025, 13(8), 1790; https://doi.org/10.3390/microorganisms13081790 - 31 Jul 2025
Viewed by 220
Abstract
Background: Human metapneumovirus (hMPV) is a respiratory pathogen that causes illness ranging from mild upper respiratory tract infections to severe pneumonia, particularly in individuals with comorbidities. Fatal cases of hMPV-induced hemorrhagic pneumonia are rare and likely under-reported. Diagnosis is often delayed due to [...] Read more.
Background: Human metapneumovirus (hMPV) is a respiratory pathogen that causes illness ranging from mild upper respiratory tract infections to severe pneumonia, particularly in individuals with comorbidities. Fatal cases of hMPV-induced hemorrhagic pneumonia are rare and likely under-reported. Diagnosis is often delayed due to overlapping symptoms with other respiratory viruses and the rapid progression of the disease. Case presentation: We report the case of a 55-year-old man with a complex medical history, including liver cirrhosis and diabetes mellitus, who developed acute viral pneumonia. Initial symptoms appeared three days before a sudden clinical deterioration marked by shortness of breath, hemoptysis, and respiratory failure. A nasopharyngeal swab taken on the third day of illness tested positive for hMPV by qRT-PCR. The patient died the following day. Postmortem molecular testing confirmed hMPV in lung tissue and alveolar contents. Autopsy revealed bilateral hemorrhagic pneumonia with regional lymphadenopathy. Histopathological examination showed alveolar hemorrhage, multinucleated cells, neutrophilic infiltration, activated autophagy in macrophages, and numerous cytoplasmic eosinophilic viral inclusions. Conclusions: This is the first documented case of fatal hMPV pneumonia in Armenia. It highlights the potential severity of hMPV in adults with chronic health conditions and emphasizes the need for timely molecular diagnostics. Postmortem identification of characteristic viral inclusions may serve as a cost-effective histopathological marker of hMPV-associated lung pathology. Full article
(This article belongs to the Section Virology)
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21 pages, 604 KiB  
Review
Autoantibodies in COVID-19: Pathogenic Mechanisms and Implications for Severe Illness and Post-Acute Sequelae
by Lais Alves do-Nascimento, Nicolle Rakanidis Machado, Isabella Siuffi Bergamasco, João Vitor da Silva Borges, Fabio da Ressureição Sgnotto and Jefferson Russo Victor
COVID 2025, 5(8), 121; https://doi.org/10.3390/covid5080121 - 30 Jul 2025
Viewed by 351
Abstract
The COVID-19 pandemic, caused by SARS-CoV-2, has led to a wide range of acute and chronic disease manifestations. While most infections are mild, a significant number of patients develop severe illness marked by respiratory failure, thromboinflammation, and multi-organ dysfunction. In addition, post-acute sequelae—commonly [...] Read more.
The COVID-19 pandemic, caused by SARS-CoV-2, has led to a wide range of acute and chronic disease manifestations. While most infections are mild, a significant number of patients develop severe illness marked by respiratory failure, thromboinflammation, and multi-organ dysfunction. In addition, post-acute sequelae—commonly known as long-COVID—can persist for months. Recent studies have identified the emergence of diverse autoantibodies in COVID-19, including those targeting nuclear antigens, phospholipids, type I interferons, cytokines, endothelial components, and G-protein-coupled receptors. These autoantibodies are more frequently detected in patients with moderate to severe disease and have been implicated in immune dysregulation, vascular injury, and persistent symptoms. This review examines the underlying immunological mechanisms driving autoantibody production during SARS-CoV-2 infection—including molecular mimicry, epitope spreading, and bystander activation—and discusses their functional roles in acute and post-acute disease. We further explore the relevance of autoantibodies in maternal–fetal immunity and comorbid conditions such as autoimmunity and cancer, and we summarize current and emerging therapeutic strategies. A comprehensive understanding of SARS-CoV-2-induced autoantibodies may improve risk stratification, inform clinical management, and guide the development of targeted immunomodulatory therapies. Full article
(This article belongs to the Section Host Genetics and Susceptibility/Resistance)
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17 pages, 627 KiB  
Review
Non-Invasive Positive Pressure Ventilation for Pre-Oxygenation of Critically Ill Patients Before Intubation
by Luigi La Via, Giuseppe Cuttone, Tarek Senussi Testa, Gilberto Duarte-Medrano, Natalia Nuno-Lambarri, Cristian Deana, Antonino Maniaci, Daniele Salvatore Paternò, Ivana Zdravkovic and Massimiliano Sorbello
J. Clin. Med. 2025, 14(15), 5356; https://doi.org/10.3390/jcm14155356 - 29 Jul 2025
Viewed by 503
Abstract
Pre-oxygenation is the key step prior to endotracheal intubation, particularly in a critically ill patient, to prevent life-threatening peri-procedural hypoxemia. This narrative review explores the emerging interest of Non-Invasive Positive Pressure Ventilation (NIPPV) as a pre-oxygenation modality in the intensive care unit (ICU) [...] Read more.
Pre-oxygenation is the key step prior to endotracheal intubation, particularly in a critically ill patient, to prevent life-threatening peri-procedural hypoxemia. This narrative review explores the emerging interest of Non-Invasive Positive Pressure Ventilation (NIPPV) as a pre-oxygenation modality in the intensive care unit (ICU) context. We reviewed data from randomized controlled trials (RCTs) and observational studies published from 2000 to 2024 that compare NIPPV to conventional oxygen therapy and High Flow Nasal Cannula Oxygen (HFNCO). The pathophysiological mechanisms for the successful use of NIPPV, including alveolar recruitment, the decrease of shunting, and the maintenance of functional residual capacity, were reviewed in depth. Existing studies show that NIPPV significantly prolongs the apnea time, reduces the rate of peri-intubation severe hypoxaemia in selected patients and is especially effective for patients with acute hypoxaemic respiratory failure. Nevertheless, appropriate patient selection is still crucial because some diseases can contraindicate or even be harmful with NIPPV. We further discussed the practical aspects of how to use this ventilatory support (the best ventilator settings, which interface, and when to apply it). We lastly discuss unanswered questions and offer suggestions and opportunities for future exploration in guiding the role of NIPPV use in the pre-oxygenation of the critically ill patient requiring emergent airway management. Full article
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19 pages, 508 KiB  
Article
Improved Survival in Malnourished COVID-19 Inpatients with Oral Nutrition Supplementation
by Tyrus Vong, Lisa R. Yanek, Laura E. Matarese, Berkeley N. Limketkai and Gerard E. Mullin
Nutrients 2025, 17(15), 2401; https://doi.org/10.3390/nu17152401 - 23 Jul 2025
Viewed by 282
Abstract
Background: Malnutrition is associated with adverse clinical and economic outcomes. We recently reported that the hospital mortality rate in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected inpatients was higher in malnourished patients than in those without malnutrition. The present study aimed to determine [...] Read more.
Background: Malnutrition is associated with adverse clinical and economic outcomes. We recently reported that the hospital mortality rate in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected inpatients was higher in malnourished patients than in those without malnutrition. The present study aimed to determine if SARS-CoV-2-infected inpatients who received oral nutrition supplementation (ONS) had improved survival. We performed a retrospective cohort study including 37,215 adults (aged 18 and older) admitted with COVID-19 to five Johns Hopkins–affiliated hospitals between 1 March 2020, and 31 March 2023. Malnutrition risk was initially screened using the Malnutrition Universal Screening Tool (MUST), with cases subsequently confirmed by registered dietitians via a standardized, validated assessment protocol. Logistic regression analysis predicting hospital mortality examined the association of ONS with hospital survival in SARS-CoV-2-infected inpatients, incorporating covariates and weights for ONS receipt. Results: Malnutrition was an independent predictor of higher hospital mortality from COVID-19 illness. The prevalence of malnutrition among adult inpatients with SARS-CoV-2 infection in our cohort was 15.22%. Inpatient adults with moderate or severe malnutrition in the context of acute illness or injury who were given ONS had lower odds of inpatient mortality (moderate OR = 0.72, 95% CI 0.62–0.85; severe OR = 0.76, 95% CI 0.67–0.87; both p < 0.001). Overweight and obese patients who received ONS had higher odds of inpatient mortality (overweight OR = 1.15, 95% CI 1.08–1.22, p < 0.0001; obese OR = 1.08, 95% CI 1.01–1.14, p = 0.02, respectively). For inpatients who were underweight, receiving ONS was protective against inpatient mortality (OR = 0.78, 95% CI 0.68–0.88, p = 0.0001). Thus, among adult inpatients with SARS-CoV-2 infection, malnourished and underweight individuals appeared to experience improved survival when provided with oral nutritional supplements (ONS), whereas overweight or obese patients remain at an elevated risk of mortality. The timing of ONS receipt in hospitalized patients with SARS-CoV-2 influenced mortality. Patients who had earlier time to ONS had 13% lower odds of inpatient mortality (OR = 0.87, 95% CI 0.79–0.97, p = 0.0105). Conclusions: In a cohort of SARS-CoV-2 adult inpatients, those with confirmed malnutrition receiving oral nutrition supplements had a higher likelihood of hospital survival. This is the first study demonstrating an association of oral nutrition intervention with reduced hospital mortality in malnourished SARS-CoV-2-infected adults. Full article
(This article belongs to the Section Clinical Nutrition)
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22 pages, 680 KiB  
Review
Adaptation of the Vaccine Prophylaxis Strategy to Variants of the SARS-CoV-2 Virus
by Sofia M. Gulova, Uliana S. Veselkina and Irina V. Astrakhantseva
Vaccines 2025, 13(7), 761; https://doi.org/10.3390/vaccines13070761 - 17 Jul 2025
Viewed by 622
Abstract
The emergence of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus closely related to SARS-CoV and officially known as Betacoronavirus pandemicum precipitated a substantial surge in vaccine development that culminated during the global COVID-19 pandemic. At present, there are dozens of [...] Read more.
The emergence of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus closely related to SARS-CoV and officially known as Betacoronavirus pandemicum precipitated a substantial surge in vaccine development that culminated during the global COVID-19 pandemic. At present, there are dozens of vaccines for the prevention of SARS-CoV-2 being utilized across the globe. However, only 10 of these vaccines have been authorized by the World Health Organization (WHO). These include mRNA-based, viral vector, subunit and whole-virion inactivated vaccines. At the current end of the pandemic, there has been a decline in the global vaccination rate, both for the general population and for those most at risk of severe illness from the virus. This suggests that the effectiveness of the vaccines may be waning. The decline occurs alongside a decrease in testing and sequencing for SARS-CoV-2. Furthermore, the process of tracking viruses becomes increasingly complex, thereby providing a selective advantage for SARS-CoV-2 and allowing it to evolve stealthily. In this review, we provide a comprehensive overview of viral evolution and vaccine development. We also discuss ways to overcome viral variability and test universal vaccines for all SARS-CoV-2 variants. Full article
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18 pages, 309 KiB  
Review
Prevalence of Healthcare-Associated Infections in Patients with Cardiovascular Diseases: A Literature Review
by Daniela-Mirela Vîrtosu, Angela Munteanu Dragomir, Simina Crișan, Silvia Luca, Oana Pătru, Ruxandra-Maria Băghină, Mihai-Andrei Lazăr, Alina-Ramona Cozlac, Stela Iurciuc and Constantin-Tudor Luca
J. Clin. Med. 2025, 14(14), 4941; https://doi.org/10.3390/jcm14144941 - 12 Jul 2025
Viewed by 428
Abstract
This review aims to summarize the global prevalence of healthcare-associated infections in patients with acute heart failure who have been admitted to coronary care units, highlighting the underrepresented burden of infection in this high-risk population. Coronary care units (CCUs) play a pivotal role [...] Read more.
This review aims to summarize the global prevalence of healthcare-associated infections in patients with acute heart failure who have been admitted to coronary care units, highlighting the underrepresented burden of infection in this high-risk population. Coronary care units (CCUs) play a pivotal role in the care of patients experiencing acute or decompensated heart failure, offering a highly monitored environment with immediate access to advanced cardiac interventions. The management of heart failure in CCUs involves a multidisciplinary approach that includes hemodynamic monitoring, pharmacologic therapy, respiratory support, and, in selected cases, mechanical circulatory assistance. The early identification of deterioration, rapid therapeutic escalation, and close monitoring of cardiac function are hallmarks of CCU care. However, the complexity and severity of illness in this population are compounded by a high risk of infections, including hospital-acquired pneumonia, bloodstream infections, and device-related infections. These infections not only increase morbidity and prolong hospitalization but also significantly impact mortality and healthcare costs. The immunocompromised state of many heart failure patients—due to poor perfusion, malnutrition, and the use of invasive devices—further elevates their vulnerability. Effective infection prevention, early diagnosis, and targeted antimicrobial therapy are, therefore, critical components of heart failure management within CCUs. This intersection of advanced cardiac care and infection control highlights the need for integrated, multidisciplinary strategies to improve outcomes in this high-risk population. Full article
(This article belongs to the Special Issue Clinical Management of Patients with Heart Failure—2nd Edition)
25 pages, 559 KiB  
Systematic Review
Were Our Grandmothers Right? Soup as Medicine—A Systematic Review of Preliminary Evidence for Managing Acute Respiratory Tract Infections
by Sandra Lucas, Matthew J. Leach, Rachel Kimble and Joshua Cheyne
Nutrients 2025, 17(13), 2247; https://doi.org/10.3390/nu17132247 - 7 Jul 2025
Viewed by 4755
Abstract
Background/Objectives: Acute respiratory tract infections (ARTIs) are a significant global health burden, contributing to increased healthcare use, absenteeism, and economic strain. While clinical treatments exist, many individuals use traditional dietary remedies such as soup to relieve symptoms. Soup is thought to support recovery [...] Read more.
Background/Objectives: Acute respiratory tract infections (ARTIs) are a significant global health burden, contributing to increased healthcare use, absenteeism, and economic strain. While clinical treatments exist, many individuals use traditional dietary remedies such as soup to relieve symptoms. Soup is thought to support recovery through hydration, warmth, nutritional content, and possible anti-inflammatory effects. This systematic review aimed to evaluate the therapeutic effects of soup consumption on adults with ARTIs, focusing on symptom severity, illness duration, absenteeism, immune response, inflammatory biomarkers, and overall well-being. Methods: A systematic literature search was conducted in February 2024 across MEDLINE, Scopus, CINAHL, the Cochrane Library, clinical trial registries, and supplementary sources. Eligible studies included randomized controlled trials, non-randomized trials, and controlled before-after studies evaluating soup as an intervention for ARTIs. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. A narrative synthesis was undertaken due to heterogeneity in study design and outcome measures. The protocol was registered with PROSPERO (CRD42023481236). Results: Four studies (n = 342) met inclusion criteria. Interventions commonly included chicken-based soups with vegetables and herbs. Comparators varied (e.g., no treatment, water, or alternative soup). Findings showed modest reductions in symptom severity and illness duration (by 1–2.5 days). Two studies reported reductions in inflammatory biomarkers (IL-6, TNF-α, CRP). No studies reported on absenteeism or well-being. Conclusions: Soup may offer modest benefits for ARTIs, particularly for symptom relief and inflammation. Further well-designed studies are needed to evaluate its broader clinical and functional impacts. Full article
(This article belongs to the Section Clinical Nutrition)
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15 pages, 940 KiB  
Article
Spatial Distribution and Post-COVID-19 Health Complications in Older People: A Brazilian Cohort Study
by Franciele Aline Machado de Brito, Carlos Laranjeira, Stéfane Lele Rossoni, Amira Mohammed Ali, Maria Aparecida Salci and Lígia Carreira
J. Clin. Med. 2025, 14(13), 4775; https://doi.org/10.3390/jcm14134775 - 6 Jul 2025
Viewed by 546
Abstract
Background/Objectives: In the aftermath of the COVID-19 pandemic, individuals infected with SARS-CoV-2 have progressively displayed a range of symptoms linked to protracted COVID during the post-acute phase of illness. Concurrently, in several nations globally, the phenomenon of population aging has been intensifying. In [...] Read more.
Background/Objectives: In the aftermath of the COVID-19 pandemic, individuals infected with SARS-CoV-2 have progressively displayed a range of symptoms linked to protracted COVID during the post-acute phase of illness. Concurrently, in several nations globally, the phenomenon of population aging has been intensifying. In this scenario, the aged population has become both vulnerable and high-risk during the acute phase of COVID-19, and faces significant dangers associated with long-COVID. This study seeks to analyze the incidence and spatial distribution of health complications in older people affected by COVID-19, in the first year of the pandemic (2020), in the State of Paraná, as well as to identify the factors associated with the development of cardiovascular, neurological, respiratory, and metabolic diseases. Method: An observational and retrospective study was carried out in the Brazilian state of Paraná. Participants were randomly selected from two databases. A total of 893 older people (≥60 years) participated in the study 12 months after acute COVID-19 infection. Telephone questionnaires were applied between March and December 2021. The Moran index test, logistic regression, and Poisson models were used to analyze the data. Results: In terms of age, most participants (66%) were between 60 and 69 years old, 25.8% were between 70 and 79 years old, and 8.2% were 80 years old or older. Most participants were female (51.2%), white (98.1%), had a partner (69.8%), and had been hospitalized due to COVID-19 (59.3%). Cardiovascular diseases were the most frequent in the population (39.5%), followed by metabolic diseases (27.3%). The long-term use of medication was associated with the development of metabolic diseases (aOR = 9.8), cardiovascular diseases (aOR = 6.6), and diseases in multiple organic systems (aOR = 3.2); living alone was associated with neurological diseases (aOR = 2.5), and the age group of 80 years or older (aOR = 2.4) was associated with cardiovascular events. The spatial distribution showed that complications in body groups are distributed randomly among the health regions of the state, with no influence from neighboring locations. Conclusions: Post-COVID-19 health complications are more frequent in older adults who have comorbidities and long-term medication use. Therefore, long-term monitoring of these individuals and investment in public policies for rehabilitation and prevention of complications are necessary. Full article
(This article belongs to the Section Geriatric Medicine)
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14 pages, 488 KiB  
Article
Is Altered Surfactant Protein Gene Expression in Peripheral Blood Associated with COVID-19 Disease Severity?
by Suna Koc, Kamil Cankut Senturk, Sefa Cetinkaya, Guven Yenmis, Hulya Arkan, Mahmut Demirbilek, Pinar Acar, Erhan Arikan and Mehmet Dokur
Diagnostics 2025, 15(13), 1690; https://doi.org/10.3390/diagnostics15131690 - 2 Jul 2025
Viewed by 745
Abstract
Background/Objectives: Severe COVID-19 pneumonia damages alveolar type II cells and disrupts surfactant homeostasis, contributing to acute respiratory distress syndrome (ARDS). Surfactant proteins (SP-A, SP-B, SP-C, SP-D) are critical for reducing alveolar surface tension and for innate immune defense. We aimed to evaluate whether [...] Read more.
Background/Objectives: Severe COVID-19 pneumonia damages alveolar type II cells and disrupts surfactant homeostasis, contributing to acute respiratory distress syndrome (ARDS). Surfactant proteins (SP-A, SP-B, SP-C, SP-D) are critical for reducing alveolar surface tension and for innate immune defense. We aimed to evaluate whether surfactant protein gene expression varies with the severity of COVID-19. Methods: Peripheral blood was collected from 122 adults with confirmed COVID-19, categorized as asymptomatic (no symptoms), mild (requiring hospitalization), or severe (requiring ICU admission). We quantified mRNA expression of surfactant protein genes (SFTPA1, SFTPA2, SFTPB, SFTPC, SFTPD) in blood cells using RT-qPCR. Relative expression was normalized to GAPDH and compared among the groups using the 2−ΔΔCt method. Outliers (Ct values > 3 SD from the mean) were excluded before analysis. Results: Distinct surfactant gene expression patterns were markedly associated with disease severity. Transcripts of SFTPB and SFTPC decreased with increasing severity of the disease. Notably, SFTPC expression was ~49-fold higher in mild cases compared to asymptomatic COVID-19-positive patients (p < 0.0001), but then decreased by ~54-fold in severe cases relative to mild (p < 0.0001), returning to near-baseline levels. In contrast, SFTPA2 and SFTPD were dramatically upregulated in severe cases. SFTPA2 was ~50-fold higher in severe versus mild cases (p < 0.0001), and SFTPD was ~4346-fold higher in severe versus asymptomatic cases (p < 0.0001; ~9.6-fold higher than in mild). SFTPA1 showed only a modest ~1.4-fold decrease in severe cases (vs. mild). All noted differences remained statistically significant after outlier exclusion. Conclusions: COVID-19 severity is correlated with profound changes in surfactant gene expression in blood. Critically ill patients exhibit loss of key surfactant components (SP-B and SP-C transcripts) alongside an excessive SP-D response. These preliminary findings suggest an imbalance that may contribute to lung injury in severe disease. However, further validation is needed to establish surfactant proteins, such as SP-D, as biomarkers of COVID-19 severity. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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18 pages, 1104 KiB  
Systematic Review
Current Trends of Human Adenovirus Types Among Hospitalized Children—A Systematic Review
by Janina Soler Wenglein, Luca Scarsella, Christine Kotlewski, Albert Heim and Malik Aydin
Viruses 2025, 17(7), 914; https://doi.org/10.3390/v17070914 - 27 Jun 2025
Viewed by 570
Abstract
Human adenoviruses (HAdVs) are pathogens causing different illnesses, particularly in pediatric and immunocompromised patients in developed countries. The clinical spectrum of HAdV-infections ranges from mild to severe, and the clinical presentation varies widely. Certain HAdVs types, including types B3, E4, B7, B14, B21, [...] Read more.
Human adenoviruses (HAdVs) are pathogens causing different illnesses, particularly in pediatric and immunocompromised patients in developed countries. The clinical spectrum of HAdV-infections ranges from mild to severe, and the clinical presentation varies widely. Certain HAdVs types, including types B3, E4, B7, B14, B21, G55, and B66, may be associated with lower respiratory tract infections and thus lead to higher hospitalization, increased morbidity, as well as lethality rates. The aim of this article is to synthesize and analyze the prevalence of specific HAdV types in pediatric patients worldwide. A systematic literature search was performed using MEDLINE, Scopus, and Web of Science. In total, n = 1167 titles and abstracts were screened, and 105 full-text articles were assessed for eligibility. Screening, data extraction, and appraisal were analyzed by reviewers, in accordance with PRISMA guidelines and JBI recommendations. We included studies reporting on currently circulating HAdV types (n = 16). Based on a systematic and narrative approach, relevant types of HAdV biology and infections in children are presented. In detail, HAdV-B3 and HAdV-B7 were commonly associated with severe respiratory tract infections, while HAdV-F40 and HAdV-F41 caused acute gastroenteritis. Moreover, detailed research revealed the critical role of HAdV-C2 and the necessity for particular attention to HAdVs in acute neurological infections. This comprehensive analysis highlights the significant global distribution and diverse clinical implications of different HAdV types in children, pointing out the need for continued surveillance to better understand HAdVs epidemiology and its implications for public health, and future preventive measures, in particular among vulnerable patients. Full article
(This article belongs to the Special Issue Research and Clinical Application of Adenovirus (AdV), 3rd Edition)
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12 pages, 3830 KiB  
Article
Nasal Emulgel’s Role in Preventing Coronavirus Infection
by Francesca Accioni, Giovanna Rassu, Antonio Brunetti, Erika Plicanti, Giulia Freer, Antonio Carta, Paolo Giunchedi and Elisabetta Gavini
Pharmaceutics 2025, 17(6), 795; https://doi.org/10.3390/pharmaceutics17060795 - 19 Jun 2025
Viewed by 501
Abstract
Background/Objectives: Coronaviruses (CoVs) are a large family of respiratory viruses that cause respiratory illnesses ranging from mild colds to severe diseases such as severe acute respiratory syndrome and pandemics. The nasal cavity is a primary site for CoV entry and transmission. The study [...] Read more.
Background/Objectives: Coronaviruses (CoVs) are a large family of respiratory viruses that cause respiratory illnesses ranging from mild colds to severe diseases such as severe acute respiratory syndrome and pandemics. The nasal cavity is a primary site for CoV entry and transmission. The study aimed to prepare a novel mucoadhesive emulgel specifically formulated with simple, safe, and cost-effective excipients to create a barrier on the nasal mucosa that impedes CoV infection. This formulation strategy was specifically designed to enable rapid and straightforward in vivo translation, addressing a critical gap in preventive measures against respiratory viruses. Methods: Three emulgels, containing macadamia oil, Carbopol and different percentages of hydroxypropyl methylcellulose (1, 1.2 and 1.5% (w/v), HPMC), were properly prepared and characterized for mucoadhesion, viscosity, and spreadability. The biological activity against SARS-CoV-2 was evaluated in vitro on infected epithelial cells. Results: The emulgel with 1.2% HPMC demonstrated optimal physicochemical properties (mucoadhesion: 342 ± 9 mN/cm2; viscosity: 1080 ± 83 cp; spreadability: 7.27 ± 0.06 cm) suitable for nasal application. Importantly, in vitro biological assays demonstrated that this emulgel significantly inhibits SARS-CoV-2 infection in epithelial cells, indicating an effective barrier to viral diffusion. Conclusions: By employing readily available, safe, and inexpensive excipients, this novel mucoadhesive emulgel offers a practical, scalable, and rapidly translatable nasal prophylactic approach to prevent early SARS-CoV-2 infection, addressing a critical unmet need in pandemic preparedness. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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18 pages, 797 KiB  
Article
Risk of Incidence and Lethality by Etiology of Severe Acute Respiratory Syndrome in Hospitalized Children Under 1 Year of Age in Brazil in 2024: A Cross-Sectional Study
by Tamires de Nazaré Soares, Natasha Cristina Oliveira Andrade, Suziane do Socorro dos Santos, Marcela Raíssa Asevedo Dergan, Karina Faine Freitas Takeda, Jully Greyce Freitas de Paula Ramalho, Luany Rafaele da Conceição Cruz, Perla Katheleen Valente Corrêa, Marli de Oliveira Almeida, Joyce dos Santos Freitas, Wilker Alves Silva, Marcos Jessé Abrahão Silva, Daniele Melo Sardinha and Luana Nepomuceno Gondim Costa Lima
Trop. Med. Infect. Dis. 2025, 10(6), 168; https://doi.org/10.3390/tropicalmed10060168 - 14 Jun 2025
Viewed by 671
Abstract
Severe Acute Respiratory Syndrome (SARS) represents a significant cause of morbidity and mortality in children under one year of age, a particularly vulnerable population due to immunological and respiratory immaturity. The diverse etiology includes multiple respiratory viruses such as Respiratory Syncytial Virus (RSV), [...] Read more.
Severe Acute Respiratory Syndrome (SARS) represents a significant cause of morbidity and mortality in children under one year of age, a particularly vulnerable population due to immunological and respiratory immaturity. The diverse etiology includes multiple respiratory viruses such as Respiratory Syncytial Virus (RSV), influenza, rhinovirus, and SARS-CoV-2, each with distinct potential to cause severe illness and death. Understanding the specific incidence and lethality by etiological agents in the recent Brazilian context (2024), after the COVID-19 pandemic, is essential to guide surveillance and public health strategies. This study aimed to analyze the risk of incidence and lethality by specific etiology of SARS in children under one year of age hospitalized in Brazil during the year 2024. A descriptive cross-sectional study was performed using secondary data from the 2024 Influenza Epidemiological Surveillance Information System (SIVEP-Gripe), obtained via OpenDataSUS. Reported cases of SARS hospitalized in children <1 year of age in Brazil were included. Distribution by final classification and epidemiological week (EW) was analyzed; the incidence rate by Federative Unit (FU) (cases/100,000 < 1 year) with risk classification (Low/Moderate/High) was assessed; and, for cases with positive viral RT-PCR, the etiological frequency and virus-specific lethality rate (deaths/total cases of etiology ×100), also with risk classification, were extracted. A multivariate logistic regression model was performed for the risk factors of death. A total of 66,170 cases of SARS were reported in children under 1 year old (national incidence: 2663/100,000), with a seasonal peak between April and May. The majority of cases were classified as “SARS due to another respiratory virus” (49.06%) or “unspecified” (37.46%). Among 36,009 cases with positive RT-PCR, RSV (50.06%) and rhinovirus (26.97%) were the most frequent. The overall lethality in RT-PCR-positive cases was 1.28%. Viruses such as parainfluenza 4 (8.57%), influenza B (2.86%), parainfluenza 3 (2.49%), and SARS-CoV-2 (2.47%) had higher lethality. The multivariate model identified parainfluenza 4 (OR = 6.806), chronic kidney disease (OR = 3.820), immunodeficiency (OR = 3.680), Down Syndrome (OR = 3.590), heart disease (OR = 3.129), neurological disease (OR = 2.250), low O2 saturation (OR = 1.758), SARS-CoV-2 (OR = 1.569) and respiratory distress (OR = 1.390) as risk factors for death. Cough (OR = 0.477) and RSV (OR = 0.736) were associated with a lower chance of death. The model had good calibration (Hosmer–Lemeshow p = 0.693) and overall significance (p < 0.001). SARS represented a substantial burden of hospitalizations, with marked seasonal and geographic patterns. RSV and rhinovirus were the main agents responsible for the volume of confirmed cases but had a relatively low to moderate risk of lethality. In contrast, less frequent viruses such as parainfluenza 4, influenza B, parainfluenza 3, and SARS-CoV-2 were associated with a significantly higher risk of death. These findings highlight the importance of dissociating frequency from lethality and reinforce the need to strengthen etiological surveillance, improve diagnosis, and direct preventive strategies (such as immunizations) considering the specific risk of each pathogen for this vulnerable population. Full article
(This article belongs to the Special Issue Respiratory Infectious Disease Epidemiology and Control)
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14 pages, 1461 KiB  
Case Report
Fatal Influenza B–MRSA Coinfection in a Healthy Adolescent: Necrotizing Pneumonia, Cytokine Storm, and Multi-Organ Failure
by Irina Profir, Cristina-Mihaela Popescu and Aurel Nechita
Children 2025, 12(6), 766; https://doi.org/10.3390/children12060766 - 13 Jun 2025
Viewed by 958
Abstract
Background: Influenza B usually causes mild illness in children. Severe and fatal cases can occur when complicated by secondary Staphylococcus aureus (S. aureus) pneumonia, including community-acquired methicillin-resistant Staphylococcus aureus (MRSA). We present a rare, rapidly progressive fatal case in an adolescent with [...] Read more.
Background: Influenza B usually causes mild illness in children. Severe and fatal cases can occur when complicated by secondary Staphylococcus aureus (S. aureus) pneumonia, including community-acquired methicillin-resistant Staphylococcus aureus (MRSA). We present a rare, rapidly progressive fatal case in an adolescent with no known medical history to highlight diagnostic and therapeutic pitfalls. Case Presentation: A 16-year-old boy with no known underlying conditions (unvaccinated for influenza) presented critically ill at “Sf. Ioan” Clinical Emergency Pediatric Hospital in Galați after one week of high fever and cough. He was in respiratory failure with septic shock, requiring immediate intubation and vasopressors. Chest X-ray (CXR) showed diffuse bilateral infiltrates (acute respiratory distress syndrome, ARDS). Initial laboratory tests revealed leukopenia, severe thrombocytopenia, disseminated intravascular coagulation (DIC), rhabdomyolysis, and acute kidney injury (AKI). Reverse transcription polymerase chain reaction (RT-PCR) confirmed influenza B, and blood cultures grew MRSA. Despite maximal intensive care, including mechanical ventilation, antibiotics (escalated for MRSA), antiviral therapy, and cytokine hemoadsorption therapy, the patient developed refractory multi-organ failure and died on hospital day 6. Autopsy revealed bilateral necrotizing pneumonia (NP) without radiographic cavitation, underscoring the diagnostic challenge. Discussion: The initial chest radiography showed diffuse bilateral pulmonary infiltrates, predominantly in the lower zones, with an ill-defined, patchy, and confluent appearance. Such appearance, in our case, was more suggestive of rapid progressive NP caused by MRSA rather than the typical pneumococcal one. This is one of the few reported cases of influenza B–MRSA coinfection with fulminant rhabdomyolysis and autopsy-confirmed necrosis. Our fulminant case illustrates the synergistic virulence of influenza and MRSA. Toxin-producing MRSA strains can cause NP and a “cytokine storm,” causing capillary leak, ARDS, shock, and DIC. Once multi-organ failure ensues, the prognosis is grim despite aggressive care. The absence of early radiographic necrosis and delayed anti-MRSA therapy (initiated after culture results) likely contributed to the poor outcome. Conclusions: Influenza B–MRSA co-infection, though rare, demands urgent empiric anti-MRSA therapy in severe influenza cases with leukopenia or shock, even without radiographic necrosis. This fatal outcome underscores the dual imperative of influenza vaccination and early, aggressive dual-pathogen targeting in high-risk presentations. Full article
(This article belongs to the Section Pediatric Infectious Diseases)
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21 pages, 4768 KiB  
Article
Differential Expression of Host miRNAs During Ad14 and Ad14p1 Infection
by Eric R. McIndoo, Ethan Wood, Gina Kuffel, Michael J. Zilliox and Jay R. Radke
Viruses 2025, 17(6), 838; https://doi.org/10.3390/v17060838 - 11 Jun 2025
Viewed by 509
Abstract
Adenovirus is a frequent cause of mild, usually self-limited infections in infants and young children. Severe infections occur in immunocompromised patients but are rarely observed in healthy, immunocompetent adults. However, there have been outbreaks of infections with different adenoviral (Ad) types around the [...] Read more.
Adenovirus is a frequent cause of mild, usually self-limited infections in infants and young children. Severe infections occur in immunocompromised patients but are rarely observed in healthy, immunocompetent adults. However, there have been outbreaks of infections with different adenoviral (Ad) types around the world that have resulted in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in some of those infected. Ad14p1 is the predominant circulating strain of Ad14 worldwide that has caused ARDS. An explanation for the severity of illness caused by Ad14p1 infection in immunocompetent patients is unknown. Previously, we have shown that A549 cells infected with Ad14 repress macrophage pro-inflammatory responses, whereas cells infected with Ad14p1 fail to repress macrophages and instead can increase pro-inflammatory responses. Adenoviral infection has been shown to modulate host miRNA expression, and we hypothesized that differences in miRNA expression between Ad14- and Ad14p1-infected cells might explain the differential responses of macrophages to Ad14- and Ad14p1-infected cells. Analysis of host miRNA showed that 98 miRNAs are differentially expressed when infection reaches full cytopathic effect (CPE), the same point at which Ad14 and Ad14p1 CPE corpses induce differential inflammatory responses in macrophages. Only 10 of the miRNAs that were enriched in Ad14 CPE corpses were expressed at levels that are potentially biologically relevant. Pathway enrichment analysis showed that the differentially expressed miRNAs might explain the increased pathogenesis of Ad14p1 through strain-related loss of modulation of cytokine expression when compared with prototype Ad14. Overall, the data suggest a role for viral regulation of host miRNA expression in pathogenesis by regulating host inflammatory responses through the delivery of de-regulated miRNAs by viral CPE corpses to macrophages. Full article
(This article belongs to the Special Issue Epidemiology, Pathogenesis and Immunity of Adenovirus)
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14 pages, 545 KiB  
Article
The Hungry Heart: Managing Cardiogenic Shock in Patients with Severe Anorexia Nervosa—A Case Report Series
by Manuela Thienel, Rainer Kaiser, Jonas Gmeiner, Martin Orban, Stefan Kääb, Tobias Petzold, Steffen Massberg and Clemens Scherer
J. Clin. Med. 2025, 14(11), 4011; https://doi.org/10.3390/jcm14114011 - 5 Jun 2025
Viewed by 763
Abstract
Background: Cardiogenic shock is a life-threatening condition characterized by the failure of the heart to maintain adequate circulation, leading to multi-organ dysfunction. While it is most commonly associated with acute myocardial infarction or cardiomyopathies, cardiogenic shock can also arise in unusual settings, such [...] Read more.
Background: Cardiogenic shock is a life-threatening condition characterized by the failure of the heart to maintain adequate circulation, leading to multi-organ dysfunction. While it is most commonly associated with acute myocardial infarction or cardiomyopathies, cardiogenic shock can also arise in unusual settings, such as severe malnutrition in patients with anorexia nervosa, a psychiatric disorder characterized by extreme restriction of food intake. Methods: Here, we describe the management of three patients with anorexia nervosa and severe cardiogenic shock, who were treated in our cardiological intensive care unit between December 2022 and January 2025. Two patients were successfully resuscitated after experiencing cardiac arrest, and two required mechanical circulatory support, including Venoarterial Extracorporeal Membrane Oxygenation and microaxial flow pump. The patients presented with a range of complications including multi-organ failure and respiratory distress. Due to the fragile balance between intensive cardiac and nutritional management, as well as the comorbidity of chronic malnutrition, therapeutic decisions were made carefully, including cautious electrolyte management, targeted nutritional therapy, and the use of advanced circulatory support. Conclusions: The treatment approach and beneficious outcomes underline the necessity of a multidisciplinary strategy in managing these critically ill patients with complex, interwoven pathologies. Our experience suggests that early recognition of cardiogenic shock and timely intervention with mechanical circulatory support may significantly improve patient survival in this high-risk cohort. Careful management of nutritional therapy and supplementation of trace elements and vitamins is crucial. Full article
(This article belongs to the Section Cardiology)
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