Viral Pneumonia Research Articles

Case report of a cardiac Harlequin syndrome – electrical storm during venoarterial extracorporeal membrane oxygenation

Abstract Background In sepsis-induced cardiogenic shock, venoarterial extracorporeal membrane oxygenation (VA-ECMO) can improve survival. Simultaneous acute respiratory distress syndrome (ARDS) increases the risk of differential hypoxia (Harlequin-syndrome). Due to desaturated blood ejected by the heart, the head becomes blue, whereas the lower body remains oxygenated by VA-ECMO. We report on an unusual cardiac manifestation, leading to electrical storm. Case summary We present the clinical case of a 55-year old man. During a minor viral pneumonia, superinfection led to severe ARDS and sepsis-induced refractory cardiogenic shock. VA-ECMO-support was initiated. In progressive respiratory failure, ECG revealed the onset of ST-segment elevations mirroring hypoxic coronary perfusion. As the mixing zone of blood from the heart and the VA-ECMO was in the ascending aorta, hypoxia was limited to the heart. Ventricular arrhythmias recurred, until ventricular fibrillation remained refractory to defibrillation. A second return cannula was inserted into the jugular vein and V-AV-ECMO was established. After the venous return was added to the circuit, ventricular fibrillation was defibrillated and sinus rhythm remained stable. Within an hour, ST-elevations receded. Systolic function recovered to normal within 26 days. Discussion In severe sepsis-related cardiogenic shock, cardiac output is likely to recover. VA-ECMO is a potential bridge to recovery. Apart from textbook knowledge, Harlequin syndrome can exclusively cause coronary ischemia, leading to ST-segment elevations and electrical storm. ECGs reveal ST-elevations for early detection. Isolated cardiac Harlequin syndrome can be overlooked or misinterpreted as result of coronary artery disease, but needs immediate therapy to save the patient’s life (e.g. V-AV-ECMO).

Cardiac events and procedures following COVID-19 compared with other pneumonias: a national register study

BackgroundStudies have shown an increased risk of cardiac disease following COVID-19, but how it compares to pneumonia of other etiologies is unclear.AimsTo determine the incidence and HRs of cardiac disease...

A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia.

Pneumonia stands as the primary cause of death among children under five, yet current diagnosis methods often result in inadequate or unnecessary treatments. Our research seeks to address this gap by identifying host transcriptomic biomarkers in the blood of children with definitive viral and bacterial pneumonia. We performed RNA sequencing on 192 prospectively collected whole blood samples, including 38 controls and 154 pneumonia cases, uncovering a 5-transcript signature (genes FAM20A, BAG3, TDRD9, MXRA7, and KLF14) that effectively distinguishes bacterial from viral pneumonia (area under the curve (AUC): 0.95 [0.88-1.00]). Initial validation using combined definitive and probable cases yielded an AUC of 0.87 [0.77-0.97], while full validation in a new prospective cohort of 32 patients achieved an AUC of 0.92 [0.83-1.00]. This robust signature holds significant potential to enhance diagnostics accuracy for pediatric pneumonia, reducing diagnostic delays and unnecessary treatments and potentially transforming clinical practice.

Patchouli alcohol from Pogostemon cablin Benth inhibits H1N1 infection by repressing inflammasome and proptosis by targeting ubiquitin specific peptidase USP18.

Influenza virus infection can cause lung inflammation and viral pneumonia in patients. Patchouli alcohol (PA), a tricyclic sesquiterpene derived from Pogostemonis Herba, has been shown to alleviate inflammation in various diseases. However, the molecular mechanism by which patchouli exerts its anti-inflammatory effects, particularly its role in mitigating influenza virus induced inflammation and pneumonia during H1N1 viral infection, remains largely unclear. Herein, we found that PA considerably reduced body weight loss, lung pathological index and attenuated lung histological damage in H1N1-infected mice. Mechanistically, PA reduced the production and secretion of inflammatory cytokines via inhibition of the NF-κB-signaling pathway and blocking inflammasome-mediated proptosis. Additionally, proteomic analysis identified several potential targets of PA, with ubiquitin-specific peptidase 18 (USP18) emerging as a key candidate. Further investigation revealed that PA binds to USP18, enhancing its stability and increasing its transcriptional and translational expression. Overall, our results emphasize the anti-inflammatory effects of PA during influenza virus infection. PA may alleviate lung inflammation and damage by targeting USP18, offering a potential therapeutic strategy for treating influenza-induced lung complications.

Targeting SIRT1 by Scopoletin to Inhibit XBB.1.5 COVID-19 Life Cycle.

Natural products have historically driven pharmaceutical discovery, but their reliance has diminished with synthetic drugs. Approximately 35% of medicines originate from natural products. Scopoletin, a natural coumarin compound found in herbs, exhibits antioxidant, hepatoprotective, antiviral, and antimicrobial properties through diverse intracellular signaling mechanisms. Furthermore, it also enhances the activity of antioxidants. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes viral pneumonia through cytokine storms and systemic inflammation. Cellular autophagy pathways play a role in coronavirus replication and inflammation. The Silent Information Regulator 1 (SIRT1) pathway, linked to autophagy, protects cells via FOXO3, inhibits apoptosis, and modulates SIRT1 in type-II epithelial cells. SIRT1 activation by adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) enhances the autophagy cascade. This pathway holds therapeutic potential for alveolar and pulmonary diseases and is crucial in lung inflammation. Angiotensin-converting enzyme 2 (ACE-2) activation, inhibited by reduced expression, prevents COVID-19 virus entry into type-II epithelial cells. The coronavirus disease 2019 (COVID-19) virus binds ACE-2 to enter into the host cells, and XBB.1.5 COVID-19 displays high ACE-2-binding affinity. ACE-2 expression in pneumocytes is regulated by signal transducers and activators of transcription-3 (STAT3), which can increase COVID-19 virus replication. SIRT1 regulates STAT3, and the SIRT1/STAT3 pathway is involved in lung diseases. Therapeutic regulation of SIRT1 protects the lungs from inflammation caused by viral-mediated oxidative stress. Scopoletin, as a modulator of the SIRT1 cascade, can regulate autophagy and inhibit the entry and life cycle of XBB.1.5 COVID-19 in host cells.

P-723. Incidence, Etiology, and Outcomes of Viral Pneumonia in Adults with Cancer at a Tertiary Care Centre in Eastern India: A One Year Prospective Cohort Study

Abstract Background We identified pneumonia in adult cancer patients admitted to the ICU over one year, delineated viral pneumonia, assessed etiology, and studied clinical outcomes.Figure 1:Etiology of pneumonia cases where viruses were detected (n=90) Methods Pneumonia cases were clinically and radiologically identified from October 2022-September 2023. Pneumonia was categorized as community-acquired or healthcare-associated. Viral detection was done using Qiagen’s QIAstat-Dx Respiratory SARS-CoV-2 Panel and bioMeriéux’s BioFire® FilmArray® Pneumonia Panel. Bacterial, fungal, and mycobacterial detection involved microscopy, culture, ELISA, PCR, and CBNAATs. All cases where bacteria, mycobacteria, and fungi were detected along with viruses were assigned “co-infection/ superadded infections". Frequency of pathogens were compared using a modified Z-test. Seasonality was assessed using the chi-square test for homogeneity. Lengths of hospital and ICU stay were compared using linear regression and mortality was compared using logistic regression and Kaplan-Meier survival analysis.Figure 2:Kaplan-Meier survival analysis for pneumonia cases where viruses were detected stratified by etiology Results 355 cases of pneumonia were identified. Viruses were detected in 90 (25.4%). Of these 40 were viral pneumonia [incidence: 1.8% (95% CI: 1.3-2.4%)] among 2279 in-patients, and 50 were viral co-infections/ superadded infections (figure 1). Rhinovirus/ enterovirus (27) was the commonest followed by SARS-CoV2 (15), influenza A (12), and RSV A/B (10). RSV A/B was more common in CAP cases (p=0.005). CMV was more common in HAP (p=0.042). Seasonal variation was seen in influenza A/B only with the highest frequency during monsoon (p=0.000). Aspergillus (23) was most frequently detected alongside viruses, followed by Klebsiella pneumoniae (17), Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter (10 each). The overall length of hospital stay in this cohort was 16.3 days, length of ICU stay was 9.6 days, and 90-day mortality was 54.4%. Length of ICU stay was higher in viral co-infections/ superadded infections (table 2, figure 2). Conclusion Majority of pneumonia cases with viral detection are co-infections/ superadded infections associated with prolonged ICU stay. There is a need for diagnostic stewardship to ensure rapid diagnosis, and appropriate antimicrobial prophylaxis for antibacterial and antifungal cover. Disclosures All Authors: No reported disclosures

P-1815. Estimation of the cases with suspected community-acquired pneumonia where antibiotic intervention could occur after 48 hours: Application of an electronic algorithm for real-time screening

Abstract Background Timely identification of unnecessary antibiotics (abx) started for suspected community-acquired pneumonia (CAP) is vital for antibiotic stewardship programs (ASPs). We estimated potential opportunities for ASP intervention among patients flagged as potentially having CAP by an electronic algorithm using electronic health record data that allows for real-time case detection. Methods We screened all adult patients admitted to Johns Hopkins Hospital (1,150 beds) between 12/2023-2/2024 using the algorithm which is based on the following variables: i) abx targeting CAP ≥48h, ii) respiration rate ≥24/min, iii) white blood cell (WBC) >12,000/mm3, and iv) natural language processing (NLP)-derived radiology results compatible with pneumonia. Patients admitted to oncology or with sickle cell disease were excluded. Manual chart review was performed to adjudicate true CAP, defined as the presence of signs/symptoms of pneumonia with corresponding radiographic findings, while excluding alternative diagnoses, based on the clinical course observed within 48 h. We characterized factors associated with patients without CAP, particularly radiological interpretation, and the proportion eligible for ASP intervention at 48 h of admission. Results 122 of the 152 cases (80.3%) identified by the electronic algorithm were adjudicated as non-CAP based on clinical criteria. Compared to CAP cases, non-CAP cases were less likely to have fever (40.0% vs. 9.8%, P < 0.001) and cough/sputum (76.7% vs. 42.6%, P = 0.001). Common diagnoses for non-CAP cases were volume overload (19.7%), other pulmonary disorders (18.9%), chronic lung disease exacerbation (14.8%), and viral pneumonia (12.3%). Most unnecessary abx were initiated in the emergency room (85.2%, 104/122); 60.6% (63/104) were continued for >24 hours after admission, and 48.4% (59/122) could have been intervened upon at 48 hours of admission. 63.1% of non-CAP cases had radiographic interpretations suggesting CAP, with poor correlation between radiological interpretation and clinical diagnosis of true CAP (kappa 0.221). Conclusion ASP interventions to stop abx within 48 h of admission were indicated in ∼50% of non-CAP cases identified by the electronic algorithm. Disclosures All Authors: No reported disclosures

P-688. Pediatric Pneumonia trapped in ‘NET’ (Neutrophil Extracellular Traps)

Abstract Background Neutrophil extracellular traps (NETs) were initially recognized for their role in the immune system, primarily immobilizing and sometimes killing microorganisms. However, further research has revealed their involvement in various diseases due to the harmful effects of their components on surrounding tissues. The innate immune system's role in pneumonia pathogenesis has been emphasized in several studies. Investigating the involvement of NETs in pulmonary infections and their potential as biomarkers for community-acquired pneumonia (CAP) outcomes has been explored in adult patients. Current data suggests that controlled NET release and clearance are beneficial in pneumonia, but any imbalance in this process could lead to harmful inflammation or increased risk of infection dissemination and sepsis. However, there is a gap in understanding NET activity in pediatric lung infections. Therefore, this study aimed to assess NET activity in pediatric pneumonia patients and correlate it with blood culture results and viral panels for respiratory infections. Methods It was a Cross sectional Observational study at a tertiary care hospital and all children diagnosed to be suffering from pnuemonia. 30 Pediatric pneumonia patients were assessed at the time of presentation and evaluated clinically, radiologically and severity was scored based on Modified respiratory distress assessment instrument score (mRDAI). NET values were checked at the time of presentation and at the time of recovery. These values of NET were correlated with blood culture results, Respiratory viral panel and mRDAI score. Results Higher levels of Neutrophil extracellular traps (NETs) correlated with increased disease severity (mRDAI score) and with a poor prognosis and higher hospital stay and increased mortality. There was no statistical significance in the NET score of bacterial and viral pneumonia. Conclusion An increase in Neutrophil extracellular traps (NETs) levels is a common occurrence during severe respiratory infections. It is plausible to hypothesize that their migration to the lungs and subsequent activation could worsen tissue damage and contribute to the progression of the disease. NET has been identified as one of the markers linked with poor prognosis and severe pediatric respiratory symptoms. Disclosures All Authors: No reported disclosures

P-684. Wheezing, Fever, Snot, Oh My! Comparing Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV) in Adults: Implications for Vaccine Development

Abstract Background RSV and HMPV cause acute respiratory infections (ARI) in children and adults. Two RSV vaccines for older adults are now licensed, and HMPV vaccines are in development. Limited data exist comparing clinical disease and impact of HMPV to RSV in older adults.Table 1.Demographic and Baseline Characteristics Methods We analyzed data from two studies of prospectively enrolled hospitalized adults with ARI from 2008-2012 and 2018-2023 and compared demographics, clinical characteristics and outcomes of HMPV and RSV. Similar inclusion/exclusion criteria and RT-PCR diagnosis were used for both studies, with addition of serology only in the first. All cases were adjudicated for bacterial coinfection and radiographic pneumonia by 1 pulmonary and 3 ID physicians. Comparisons used t-test or χ2.Table 2.Signs and Symptoms at Admission, Clinical Characteristics, and Outcomes Results Of 2,012 patients enrolled, 127 (6.3%) and 90 (4.5%) had RSV or HMPV, respectively: 5 patients with RSV/HMPV co-infection were excluded from analysis. Mean age (67 years), sex, race and ethnicity were similar (Table 1). HMPV patients were less likely to reside in congregate settings (7.8 v 14.9%, p=0.14) or have COPD (31.5 v 40.9%, p=0.16), CHF (17.8 v 26.0%, p=0.15), or active tobacco use (17.8 v 30.7%, p=0.03). Clinical presentation also differed with HMPV more associated with sore throat (50.0 v 33.9%, p=0.02), feverishness (64.4 v 48.0%, p=0.02), temperature >38oC (33.3 v 21.3%, p=0.05), and constitutional symptoms (75.6 v 66.1%, p=0.14). (Table 2) HMPV patients required less ICU care (5.6 v 12.6%, p=0.08) and mechanical ventilation (1.1 v 5.5%, p=0.09). Bacterial coinfection occurred equally, but HMPV patients judged as viral infection alone were more often adjudicated as pneumonia (35.6 v 22.8%, p=0.006). (Fig. 1).Figure 1.Adjudicated Radiographic Pneumonia with Microbiologic Diagnosis Conclusion Although RSV and HMPV are closely related viruses, we found differences in the clinical features of adults hospitalized with ARI. While HMPV accounted for about 3/4 the number of cases compared to RSV, HPMV patients were generally healthier and community-dwelling with fewer high-risk cardiopulmonary conditions. Notably, HMPV patients presented with more flu-like symptoms and were judged more often to have viral pneumonia. These results support development of an adult HMPV vaccine. Ongoing gene expression analyses may elucidate mechanisms underlying these differences. Disclosures Ann R. Falsey, MD, ADMA: Board Member|BioFire Diagnostics: Grant/Research Support|CyanVac: Grant/Research Support|GSK: Advisor/Consultant|GSK: Travel support|Janssen: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Travel support|VaxCo: Grant/Research Support Angela R. Branche, MD, Cyanvac: Grant/Research Support|GSK: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Grant/Research Support|Moderna: Honoraria|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi: Honoraria|VaxCo: Grant/Research Support Edward E. Walsh, MD, Enanta: Advisor/Consultant|Enanta: Honoraria|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support

P-1865. Immunotherapy with Nebulized Toll-Like Receptor Agonists Restores Severe Immune Paralysis and Improves Outcomes in Mice with Influenza-Associated Pulmonary Aspergillosis

Abstract Background Given the poor outcomes of influenza-associated pulmonary aspergillosis (IAPA), there is a major unmet need for innovative therapeutic strategies. Impairment of pathogen recognition receptor (PRR) signaling is a known pathomechanism and prognostic factor in IAPA patients. Therefore, we performed immunotherapy with nebulized PRR agonists in a murine IAPA model and studied its impact on infection outcomes and pulmonary immunopathology. Timeline of experimental interventions. Abbreviations: AF = Aspergillus fumigatus, CA = cortisone acetate (10 mg intraperitoneally), IAV = nebulization with influenza A virus (7.5% of the 90% lethal dose), PBS = phosphate-buffered saline (mock therapy), P/O = Pam2/ODN, VPS = viral pneumonia score (0 = healthy – 12 = moribund). Methods 8-week-old BALB/c mice were infected with influenza A virus (IAV, H3N2), immunosuppressed with cortisone acetate (CA) on days (d) 5 and 8 after IAV infection, and infected intranasally with 50,000 Aspergillus fumigatus (AF) conidia on d9 (Fig. 1). Mice received nebulized Pam2+ODN (P/O, 4 µM/1 µM) or phosphate-buffered saline (mock therapy) before and after AF super-infection (d8/d12). Therapeutic outcomes were assessed using a combined morbidity (viral pneumonia score ≥ 7/12) and mortality endpoint. On d14, nCounter-based transcriptomics with Ingenuity pathway enrichment analysis was performed on lung tissue, along with histopathology and flow cytometry. Event-free survival (A; Mantel-Cox log-rank test) and median viral pneumonia scores of survivors (B) depending on the treatment arm. Results All mock-treated mice with IAPA reached the morbidity/mortality endpoint by d13 (Fig. 2). Compared to CA-immunosuppressed mice with IAV infection only (100% survival), nCounter analysis revealed minimal incremental inflammatory response and suppression of several PRR pathways, interferon signaling, and neutrophil activation in the IAPA group. P/O therapy led to 80% event-free survival until d21 (p < 0.001 vs. mock therapy) and full recovery of all survivors (Fig. 2). Histopathology revealed significantly reduced fungal burden and hemorrhagic lesions in P/O-treated animals. nCounter analysis showed induction of PRR signaling, several key effector cytokine pathways, and epithelial signaling after P/O therapy. Moreover, nCounter and flow cytometry revealed enhanced recruitment of macrophages, natural killer cells, and T cells in P/O-treated mice (Fig. 3). Summary of nCounter and flow cytometry results. Conclusion Consistent with previous studies in human IAPA patients, our data revealed severe immune paralysis in mice with IAPA. Immunotherapy with nebulized P/O strongly improved infection outcomes, enhanced mobilization of key immune effector cells, and re-invigorated PRR and cytokine signaling. Disclosures Sebastian Wurster, MD, MSc, Astellas Pharma: Grant/Research Support|Gilead Sciences: Grant/Research Support Dimitrios P. Kontoyiannis, MD, AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Knight: Advisor/Consultant|Merck: Advisor/Consultant|Scynexis: Advisor/Consultant

Pneumonia and pregnancy

Acute community-acquired pneumonia (CAP) during pregnancy is a frequently encountered and potentially severe condition. CAP incidence and ecology are unchanged during pregnancy as compared with the overall young adult population. Risk factors specifically identified in pregnant women include advanced gestational age, asthma, anemia and repeated courses of corticosteroid therapy for fetal lung maturation. The clinical presentation of CAP is not altered during pregnancy. Key points in the pregnant host encompass: (i) reduced maternal tolerance to hypoxia, due to physiological adaptations during pregnancy; (ii) heightened severity of some infections, notably viral pneumonias such as influenza, varicella or SARS-CoV-2 pneumonia; (iii) potentially deleterious fetal repercussions of infection and maternal hypoxia, with an increased risk of premature delivery and prematurity; (iv) the need for specific attention to the risk of fetal irradiation in the performance of possibly repeated radiological examinations and (v) therapeutic specificities arising from the possible embryo-fetal toxicity of certain anti-infectious agents. CAP prevention is premised on compliance with universal hygiene measures and on vaccination, which guarantees protection against severe forms of pneumonia not only in the mother (Streptococcus pneumoniae, seasonal flu, chickenpox, COVID-19), but also in the child during the first few months of life (whooping cough, RSV).

Thrombocytopenia During Venovenous Extracorporeal Membrane Oxygenation in Adult Patients With Bacterial, Viral, and COVID-19 Pneumonia

Contact of blood with artificial surfaces triggers platelet activation. The aim was to compare platelet kinetics after venovenous extracorporeal membrane oxygenation (V-V ECMO) start and after system exchange in different etiologies of acute lung failure. Platelet counts and coagulation parameters were analyzed from adult patients with long and exchange-free (≥8 days) ECMO runs (n = 330) caused by bacterial (n = 142), viral (n = 76), or coronavirus disease 2019 (COVID-19) (n = 112) pneumonia. A subpopulation requiring a system exchange and with long, exchange-free runs of the second oxygenator (≥7 days) (n = 110) was analyzed analogously. Patients with COVID-19 showed the highest platelet levels before ECMO implantation. Independent of the underlying disease and ECMO type, platelet counts decreased significantly within 24 hours and reached a steady state after 5 days. In the subpopulation, at the day of a system exchange, platelet counts were lower compared with ECMO start, but without differences between underlying diseases. Subsequently, platelets remained unchanged in the bacterial pneumonia group, but increased in the COVID-19 and viral pneumonia groups within 2–4 days, whereas D-dimers decreased and fibrinogen levels increased. Thus, overall platelet counts on V-V ECMO show disease-specific initial dynamics followed by an ongoing consumption by the ECMO device, which is not boosted by new artificial surfaces after a system exchange.

Enhanced Multi-Model Deep Learning for Rapid and Precise Diagnosis of Pulmonary Diseases Using Chest X-Ray Imaging

Background: The global burden of respiratory diseases such as influenza, tuberculosis, and viral pneumonia necessitates rapid, accurate diagnostic tools to improve healthcare responses. Current methods, including RT-PCR and chest radiography, face limitations in accuracy, speed, accessibility, and cost-effectiveness, especially in resource-constrained settings, often delaying treatment and increasing transmission. Methods: This study introduces an Enhanced Multi-Model Deep Learning (EMDL) approach to address these challenges. EMDL integrates an ensemble of five pre-trained deep learning models (VGG-16, VGG-19, ResNet, AlexNet, and GoogleNet) with advanced image preprocessing (histogram equalization and contrast enhancement) and a novel multi-stage feature selection and optimization pipeline (PCA, SelectKBest, Binary Particle Swarm Optimization (BPSO), and Binary Grey Wolf Optimization (BGWO)). Results: Evaluated on two independent chest X-ray datasets, EMDL achieved high accuracy in the multiclass classification of influenza, pneumonia, and tuberculosis. The combined image enhancement and feature optimization strategies significantly improved diagnostic precision and model robustness. Conclusions: The EMDL framework provides a scalable and efficient solution for accurate and accessible pulmonary disease diagnosis, potentially improving treatment efficacy and patient outcomes, particularly in resource-limited settings.

Pneumocystis Pneumonia Severity Is Associated with Taxonomic Shifts in the Respiratory Microbiota.

Pneumonia caused by Pneumocystis jirovecii infection (PCP) is a potentially life-threatening illness, particularly affecting the immunocompromised. The past two decades have shown an increase in PCP incidence; however, the underlying factors that promote disease severity and fatality have yet to be fully elucidated. Recent evidence suggests that the microbiota of the respiratory tract may play a role in stimulating or repressing pulmonary inflammation, as well as the progression of both bacterial and viral pneumonia. Here, we employed 16S rRNA metataxonomic sequencing to profile the respiratory microbiota of patients with mild-moderate and severe PCP. Our results show that the upper and lower airways of PCP patients have bacterial profiles which have been associated with a pro-inflammatory response. Furthermore, we find that severe PCP is associated with lower bacterial diversity and an increase in Prevotella and a decrease in Neisseria. Functionally, severe PCP was associated with a decrease in metabolic pathways of molecules with anti-inflammatory and antimicrobial properties. To our knowledge, this is the first study showing an association of PCP severity with shifts in the respiratory microbiome and may provide some insight into which patients are more susceptible to the more severe manifestations of the disease.

Deep learning Models for Multi-class Pneumonia Detection with emphasis on Covid-19

Pneumonia is a dangerous condition that can lead to death. Bacteria, fungi, or viruses are common causes of this condition, which can affect one or both lungs. The x-ray scans can be used to identify this lung ailment. Pneumonia is a dangerous condition that can lead to death. Bacteria, fungi, or viruses are common causes of this condition, which can affect one or both lungs. The x-ray scans can be used to identify this lung ailment. This illness usually presents itself with a cloudy white structure on the chest x-rays. The Kaggle datasets used for chest X-rays contains a variety of images that are divided into 4 categories – “Normal”, “Viral Pneumonia”, “Bacterial Pneumoia”, “Covid-19”. A deep learning model will be developed that can truly tell us whether or not a person has pneumonia disease. The model will be able to accurately assess the illness severity by detecting the degree of this cloudiness with an automated pneumonia detection system. This project is based purely on ‘Deep Learning’ concepts and will be scalable in types of complications covered, model accuracy and utility convenience analysis/application. Statistical results obtained demonstrate that CNN models can be trained to analyze chest X-ray images, specifically to detect Pneumonia and even to differentiate between Covid-19 and Pneumonia. The attempt to differentiate between viral and bacterial pneumonia has been partially successful, and suggests that it is difficult to distinguish between them due to similar patterns on the X-rays. With the help of MobileNet Architecture is possible to scale this model, the results also suggest that it is also possible to differentiate between pneumonia and COVID-19, which present similarly on the x-rays, which most models fail to undertake. It is thus deduced that the lung damage is most similar in viral and bacterial pneumonia, but the pattern is different for lungs affected with Covid-19.

A diagnostic host-specific transcriptome response for Mycoplasma pneumoniae pneumonia to guide pediatric patient treatment

Mycoplasma pneumoniae causes atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to beta-lactams, which are the first-line treatment for typical pneumonia. Current diagnostic tests are time-consuming and have low specificity, leading clinicians to administer empirical antibiotics. Using a LASSO regression simulation approach and blood microarray data from 107 children with pneumonia (including 30 M. pneumoniae) we identify eight different transcriptomic signatures, ranging from 3-10 transcripts, that differentiate mycoplasma pneumonia from other bacterial/viral pneumonias with high accuracy (AUC: 0.84–0.95). Additionally, we demonstrate that existing signatures for broadly distinguishing viral/bacterial infections and viral/bacterial pneumonias are ineffective in distinguishing M. pneumoniae from viral pneumonia. The new signatures are successfully validated in an independent RNAseq cohort of children with pneumonia, demonstrating their robustness. The high sensibility of these signatures presents a valuable opportunity to guide the treatment and management of M. pneumoniae pneumonia patients.

Tissue-resident skeletal muscle macrophages promote recovery from viral pneumonia-induced sarcopenia in normal aging.

Sarcopenia, which diminishes lifespan and healthspan in the elderly, is commonly exacerbated by viral pneumonia, including influenza and COVID-19. In a study of influenza A pneumonia in mice, young mice fully recovered from sarcopenia, while older mice did not. We identified a population of tissue-resident skeletal muscle macrophages that form a spatial niche with satellite cells and myofibers in young mice but are lost with age. Mice with a gain-of-function mutation in the Mertk receptor maintained this macrophage-myofiber interaction during aging and fully recovered from influenza-induced sarcopenia. In contrast, deletion of Mertk in macrophages or loss of Cx3cr1 disrupted this niche, preventing muscle regeneration. Heterochronic parabiosis did not restore the niche in old mice. These findings suggest that age-related loss of Mertk in muscle tissue-resident macrophages disrupts the cellular signaling necessary for muscle regeneration after viral pneumonia, offering a potential target to mitigate sarcopenia in aging.

Proteomic, metabolomic and lipidomic profiles in community acquired pneumonia for differentiating viral and bacterial infections

Community-acquired pneumonia (CAP) has a significant impact on public health, especially in light of the recent SARS-CoV-2 pandemic. To enhance disease characterization and improve understanding of the underlying mechanisms, a comprehensive analysis of the plasma lipidome, metabolome and proteome was conducted in patients with viral and bacterial CAP infections, including those induced by SARS-CoV-2. Lipidomic, metabolomic and proteomic profiling were conducted on plasma samples of 69 patients suffering either from viral or bacterial CAP. Lipid and metabolite analyses were LC-MS-based, while proteomic analyses were performed using multiple panels of the Olink platform. Statistical methods, machine learning and pathway analyses were conducted investigating differences between the infection types. Through comparison of the bacterial and viral pathogen groups, distinct signatures were observed in the plasma profiles. Notably, linoleic acid-derived inflammation signaling metabolites (EpOME and DiHOME) were increased in viral CAP compared to bacterial CAP. Similarly, proteins involved in cellular immune response and apoptosis (LAG-3 and TRAIL) showed elevated levels in viral CAP, while bacterial CAP exhibited notable elevation in pattern-recognizing receptors (CLEC4D and EN-RAGE). Additionally, within the lipidomic profile at baseline, several lipids displayed notable differences between viral and bacterial pneumonia, including bile acids (GCA, TCA, TCDCA), various tri- and diglycerides (TGs and DGs), and several phosphatidylcholines (PCs). These findings hold promise for facilitating the differential diagnosis of viral and bacterial pulmonary infections based on the systemic lipidome, metabolome and proteome, enabling timely treatment decisions. Additionally, they highlight potential targets for drug research, advancing therapeutic interventions in CAP. By providing valuable insights into the molecular characterization of CAP, this study contributes to the improvement of understanding the disease and, ultimately, the development of effective treatment strategies.

ZooCNN: A Zero-Order Optimized Convolutional Neural Network for Pneumonia Classification Using Chest Radiographs.

Pneumonia, a leading cause of mortality in children under five, is usually diagnosed through chest X-ray (CXR) images due to its efficiency and cost-effectiveness. However, the shortage of radiologists in the Least Developed Countries (LDCs) emphasizes the need for automated pneumonia diagnostic systems. This article presents a Deep Learning model, Zero-Order Optimized Convolutional Neural Network (ZooCNN), a Zero-Order Optimization (Zoo)-based CNN model for classifying CXR images into three classes, Normal Lungs (NL), Bacterial Pneumonia (BP), and Viral Pneumonia (VP); this model utilizes the Adaptive Synthetic Sampling (ADASYN) approach to ensure class balance in the Kaggle CXR Images (Pneumonia) dataset. Conventional CNN models, though promising, face challenges such as overfitting and have high computational costs. The use of ZooPlatform (ZooPT), a hyperparameter finetuning strategy, on a baseline CNN model finetunes the hyperparameters and provides a modified architecture, ZooCNN, with a 72% reduction in weights. The model was trained, tested, and validated on the Kaggle CXR Images (Pneumonia) dataset. The ZooCNN achieved an accuracy of 97.27%, a sensitivity of 97.00%, a specificity of 98.60%, and an F1 score of 97.03%. The results were compared with contemporary models to highlight the efficacy of the ZooCNN in pneumonia classification (PC), offering a potential tool to aid physicians in clinical settings.

Influenza and Aging: Clinical Manifestations, Complications, and Treatment Approaches in Older Adults.

Influenza, a highly contagious respiratory viral illness, poses significant global health risks, particularly affecting older and those with chronic health conditions. Influenza viruses, primarily types A and B, are responsible for seasonal human infections and exhibit a propensity for antigenic drift and shift, contributing to seasonal epidemics and pandemics. The severity of influenza varies, but severe cases often lead to pneumonia, acute respiratory distress syndrome, and multiorgan failure. Older adults, especially those over 65 years of age, face increased risks of immune senescence, chronic comorbidities, and decreased vaccine efficacy. Globally, influenza affects millions of people annually, with significant morbidity and mortality among older. Epidemiological patterns vary with climate, and risk factors include age, immunocompromised status, and preexisting chronic conditions. In older adults, influenza frequently results in hospitalization and death, which is exacerbated by immunosenescence and biological organ changes associated with aging. Clinical manifestations range from mild symptoms to severe complications such as viral pneumonia and multiorgan failure. Diagnosis often relies on antigen or molecular tests, with radiological examination aiding in severe cases. Treatment primarily involves antiviral agents, such as oseltamivir and peramivir, with the greatest benefit observed when initiated early. Management of severe cases may require hospitalization and supportive care, including addressing complications, such as secondary bacterial infections and cardiovascular events. This article highlights the need for improved vaccination strategies and novel treatments, including monoclonal antibodies and adoptive T cell therapies, to better manage severe influenza infections in vulnerable populations such as older.