Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer.

BACKGROUND: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations. METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment. RESULT: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment. CONCLUSION: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.

Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia.

Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.

Point-of-care lung ultrasound predicts hyperferritinemia and hospitalization, but not elevated troponin in SARS-CoV-2 viral pneumonitis in children.

SARS-CoV-2 often causes viral pneumonitis, hyperferritinemia, elevations in D-dimer, lactate dehydrogenase (LDH), transaminases, troponin, CRP, and other inflammatory markers. Lung ultrasound is increasingly used to diagnose and stratify viral pneumonitis severity. We retrospectively reviewed 427 visits in patients aged 14 days to 21 years who had had a point-of-care lung ultrasound in our pediatric emergency department from 30/November/2019 to 14/August/2021. Lung ultrasounds were categorized using a 6-point ordinal scale. Lung ultrasound abnormalities predicted increased hospitalization with a threshold effect. Increasingly abnormal laboratory values were associated with decreased discharge from the ED and increased admission to the ward and ICU. Among patients SARS-CoV-2 positive patients ferritin, LDH, and transaminases, but not CRP or troponin were significantly associated with abnormalities on lung ultrasound and also with threshold effects. This effect was not demonstrated in SARS-CoV-2 negative patients. D-Dimer, CRP, and troponin were sometimes elevated even when the lung ultrasound was normal.

Analysis of viral pneumonia and risk factors associated with severity of influenza virus infection in hospitalized patients from 2012 to 2016.

BACKGROUND: Influenza viruses cause pneumonia in approximately one-third of cases, and pneumonia is an important cause of death. The aim was to identify risk factors associated with severity and those that could predict the development of pneumonia. METHODS: This retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during four influenza seasons in Spain (October to May) from to 2012-2016. RESULTS: Overall, 666 patients with laboratory-confirmed influenza were included, 93 (14%) of which were severe; 73 (10.9%) were admitted to Intensive Care Unit (ICU), 39 (5.8%) died, and 185 (27.7%) developed pneumonia. Compared to less severe cases, patients with severe disease: were less vaccinated (40% vs. 28%, p = 0.021); presented with more confusion (26.9% vs. 6.8%), were more hypoxemic (Horowitz index (PaO2/FiO2) 261 vs. 280), had higher C-reactive protein (CRP) (12.3 vs. 4.0), had more coinfections (26.8% vs. 6.3%) and had more pleural effusion (14% vs. 2.6%) (last six all p < 0.001). Risk factors significantly associated with severity were pneumonia [OR (95% CI) = 4.14 (2.4-7.16)], history of heart disease (1.84, 1.03-3.28), and confusion at admission (4.99, 2.55-9.74). Influenza vaccination was protective (0.53, 0.28-0.98). Compared to those without pneumonia, the pneumonia group had higher CRP (11.3 vs. 4.0, p < 0.001), lower oxygen saturation (92% vs. 94%, p < 0.001), were more hypoxic (PaO2/FiO2 266 vs. 281, p < 0.001), and incurred more mechanical ventilation, septic shock, admission to the ICU, and deaths (all four p < 0.001). Higher CRP and lower oxygen saturation were independent variables for predicting the development of pneumonia. CONCLUSIONS: Pneumonia, history of heart disease, confusion and no influenza vaccination were independent variables to present complications in patients admitted with influenza infection.

Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review.

OBJECTIVE: To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. METHODS: This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. RESULTS: The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. CONCLUSION: This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

The effect of malnutrition on adult Covid-19 patient's ICU admission and mortality in Covid-19 isolation and treatment centers in Ethiopia: A prospective cohort study.

BACKGROUND: A new coronavirus was first identified in Wuhan, China in December 2019. Since the times of the 1918 influenza pandemic, malnutrition has been known as a risk factor for severity and mortality from viral pneumonia. Similarly, the recently identified SARS-Cov2 infection (COVID-19) and related pneumonia may be closely linked to malnutrition. Therefore, this study will contribute to new knowledge and awareness of the recording and evaluation of each COVID-19 patient's nutritional status by assessing the effect of malnutrition on ICU admission and death of COVID-19 patients in developing countries. METHOD: We conducted a prospective cohort study in adult COVID-19 patients admitted to selected COVID-19 Isolation and Treatment Centers, Addis Ababa, Ethiopia. Baseline data of the patients were collected using interviewer-administered structured questionnaire and data on the adverse outcomes of follow up were extracted from follow up chart. The main clinical outcomes (ICU admission and death) were captured every week of follow up. We ran a multivariate Cox's regression analysis to determine the relationship between malnutrition at admission and its effect on ICU admission and death. RESULTS: A total of 581 COVID-19 patients were enrolled. From the total of recruited patients, 346 (59.6%) were males and 235 (40.4%) were females. The mean age of the respondents was 55 years (16.45) years. The Cox proportional hazard model controlled for sex, age group, number of co-morbidities, and number of medications found that malnutrition at admission was associated with ICU admission and death. When compared to well-nourished patients, the rate of ICU admission was significantly associated and found to be higher among underweight [(adjusted hazard ratio (AHR) = 10.02, 95% CI: (8.64-12.10)] and overweight [(AHR = 7.7, 95% CI: (6.41-9.62)] patients. The rate of survival probability was significantly associated and was found to be better among well-nourished patients (AHR = 0.06, 95% CI : (0.01-0.44) when compared with malnourished COVID-19 patients. CONCLUSION: Malnutrition at the time of admission was shown to increase the risk of ICU admission and mortality among COVID-19 patients. Therefore, it is vital to evaluate patients' nutritional condition early in their admission and provide timely intervention to minimize the effects on patients and the healthcare system.

Enhancing pediatric pneumonia diagnosis through masked autoencoders.

Pneumonia, an inflammatory lung condition primarily triggered by bacteria, viruses, or fungi, presents distinctive challenges in pediatric cases due to the unique characteristics of the respiratory system and the potential for rapid deterioration. Timely diagnosis is crucial, particularly in children under 5, who have immature immune systems, making them more susceptible to pneumonia. While chest X-rays are indispensable for diagnosis, challenges arise from subtle radiographic findings, varied clinical presentations, and the subjectivity of interpretations, especially in pediatric cases. Deep learning, particularly transfer learning, has shown promise in improving pneumonia diagnosis by leveraging large labeled datasets. However, the scarcity of labeled data for pediatric chest X-rays presents a hurdle in effective model training. To address this challenge, we explore the potential of self-supervised learning, focusing on the Masked Autoencoder (MAE). By pretraining the MAE model on adult chest X-ray images and fine-tuning the pretrained model on a pediatric pneumonia chest X-ray dataset, we aim to overcome data scarcity issues and enhance diagnostic accuracy for pediatric pneumonia. The proposed approach demonstrated competitive performance an AUC of 0.996 and an accuracy of 95.89% in distinguishing between normal and pneumonia. Additionally, the approach exhibited high AUC values (normal: 0.997, bacterial pneumonia: 0.983, viral pneumonia: 0.956) and an accuracy of 93.86% in classifying normal, bacterial pneumonia, and viral pneumonia. This study also investigated the impact of different masking ratios during pretraining and explored the labeled data efficiency of the MAE model, presenting enhanced diagnostic capabilities for pediatric pneumonia.

Adenovirus pneumonia mimicking osimertinib-induced pneumonitis in a patient with advanced NSCLC with EGFR mutation: A case report.

Drug-related pneumonitis (DRP) caused by epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a fatal adverse event in patients with EGFR-mutant non-small cell lung cancer (NSCLC). The diagnosis of DRP is based on radiological findings, the temporal association of presentation with the initiation of a systemic therapeutic agent, and the exclusion of other likely causes. Here we report a case in which severe adenoviral pneumonia mimicking DRP occurred during treatment with osimertinib, and osimertinib was successfully resumed after recovery from adenoviral pneumonia.

Radiographic findings of adenoviral pneumonia in children.

OBJECTIVE: Adenovirus pneumonia is a common cause of community-acquired pneumonia in children and can mimic bacterial pneumonia, but there are few publications on its radiographic features. This study has evaluated the chest radiography findings of community-acquired adenovirus pneumonia in children. The frequency of radiological findings mimicking bacterial pneumonia was investigated. The clinical features of patients with adenovirus pneumonia possessing radiological findings mimicking bacterial pneumonia were also evaluated. MATERIALS AND METHODS: The chest radiographs of patients diagnosed with adenovirus pneumonia were retrospectively reviewed. The chest radiographs were interpreted independently by a pediatric infectious disease specialist and a pediatric radiologist. Chest radiography findings mimicking bacterial pneumonia (bacterial-like) were specified as consolidation +/- pleural effusion. Other findings on chest radiography or a completely normal chest X-ray were specified as findings that were compatible with "typical viral pneumonia". RESULTS: A total of 1407 patients were positive for adenovirus with respiratory multiplex PCR. The 219 patients who met the study criteria were included in the study. Chest radiographs were normal in 58 (26.5 %) patients. The chest radiograph findings mimicked bacterial pneumonia in 41 (18.7 %) patients. CONCLUSION: Adenovirus pneumonia occurs predominantly in children aged five years and younger, as with other viral pneumonias. The radiographic findings in adenovirus pneumonia are predominantly those seen in viral pneumonia. Increasing age and positivity for only adenovirus without other viruses on respiratory multiplex PCR were associated with the chest radiograph being more likely to be "bacterial-like". Adenovirus may lead to lobar/segmental consolidation at a rate that is not very rare.

Prolonged viral pneumonia and high mortality in COVID-19 patients on anti-CD20 monoclonal antibody therapy.

PURPOSE: In clinical practice, we observed an apparent overrepresentation of COVID-19 patients on anti-CD20 monoclonal antibody therapy. The aim of this study was to characterize the clinical picture of COVID-19 in these patients. METHODS: All adult patients from Turku University Hospital, Turku, Finland, with COVID-19 diagnosis and/or positive SARS-CoV-2 PCR test result up to March 2023, and with anti-CD20 therapy within 12 months before COVID-19 were included. Data was retrospectively obtained from electronic patient records. RESULTS: Ninety-eight patients were identified. 44/93 patients (47.3%) were hospitalized due to COVID-19. Patients with demyelinating disorder (n = 20) were youngest (median age 36.5 years, interquartile range 33-45 years), had less comorbidities, and were least likely to be hospitalized (2/20; 10.0%) or die (n = 0). COVID-19 mortality was 13.3% in the whole group, with age and male sex as independent risk factors. Persistent symptoms were documented in 33/94 patients (35.1%) alive by day 30, in 21/89 patients (23.6%) after 60 days, and in 15/85 after 90 days (17.6%), mostly in patients with haematological malignancy or connective tissue disease. Prolonged symptoms after 60 days predisposed to persistent radiological findings (odds ratio 64.0; 95% confidence interval 6.3-711; p < 0.0001) and persistently positive PCR (odds ratio 45.5, 95% confidence interval 4.0-535; p < 0.0001). Several patients displayed rapid response to late antiviral therapy. CONCLUSION: Anti-CD20 monoclonal antibody therapy is associated with high COVID-19 mortality and with a phenotype consistent with prolonged viral pneumonia. Our study provides rationale for retesting of immunocompromised patients with prolonged COVID-19 symptoms and considering antiviral therapy.

[Clinical and laboratory parameters and pathomorphological features of the lungs in patients who have had COVID-19 viral pneumonia]. / Kliniko-laboratornye pokazateli i patomorfologicheskie osobennosti legkikh u patsientov, perenesshikh virusnuyu pnevmoniyu COVID-19.

Post-Covid syndrome is characterized by general somatic manifestations, changes in the psycho-emotional sphere, cognitive disorders, disorders of the cardiovascular, respiratory systems and excretory function. However, there is little information in the literature about the mechanisms of thanatogenesis in patients who have had COVID-19. An analysis of clinical and laboratory parameters and pathomorphological changes was carried out in 9 autopsy cases of patients who had previously suffered a new coronavirus infection (COVID-19). The age of the deceased ranged from 80 to 96 years. At the time of hospitalization, the concentration of IgG varied from 32.61 to 1013.5 RLU, IgM - from 0.29 to 16.98 U/ml. The period from clinical diagnosis to death ranged from 12 to 46 days, and the time from clinical recovery (negative polymerase chain reaction) to death ranged from 2 to 30 days. In all cases, unresolved viral pneumonia and diffuse alveolar damage (exudative-proliferative phase) were diagnosed.

Use of a Handheld Ultrasonographic Device to Identify Heart Failure and Pulmonary Disease in Rural Africa.

Importance: Agreement in lung ultrasonography findings between clinicians using a handheld ultrasonographic device and expert sonographers using a high-end ultrasonographic machine has not been studied in sub-Saharan Africa. Objective: To determine the agreement in ultrasonographic findings and diagnoses between primary care clinicians trained in lung ultrasonography, board-certified expert sonographers, and senior physicians. Design, Setting, and Participants: This cross-sectional single-center study was conducted from February 1, 2022, to April 30, 2023 at a referral center in rural Tanzania. Individuals 5 years or older with respiratory symptoms and at least 2 distinct respiratory signs or symptoms were eligible. A total of 459 individuals were screened. Exposures: Participants provided their medical history and underwent a clinical examination and lung ultrasonography performed by a clinician, followed by a lung ultrasonography performed by an expert sonographer, and finally chest radiography and a final evaluation performed by a senior physician. Other tests, such as echocardiography and Mycobacterium tuberculosis testing, were conducted on the decision of the physician. Clinicians received 2 hours of instruction and three 2-hour sessions of clinical training in the use of a handheld lung ultrasonographic device; expert sonographers were board-certified. Main Outcomes and Measures: Percentage agreement and Cohen κ coefficient for sonographic findings and diagnoses compared between clinicians and expert sonographers, and between clinicians and senior physicians. Results: The median (IQR) age of 438 included participants was 54 (38-66) years, and 225 (51%) were male. The median (range) percentage agreement of ultrasonographic findings between clinicians and expert sonographers was 93% (71%-99%), with κ ranging from -0.003 to 0.83. Median (range) agreement of diagnoses between clinicians and expert sonographers was 90% (50%-99%), with κ ranging from -0.002 to 0.76. Between clinicians and senior physicians, median (range) agreement of diagnoses was 89% (55%-90%), with κ ranging from -0.008 to 0.76. Between clinicians and senior physicians, diagnosis agreements were 85% (κ, 0.69) for heart failure, 78% (κ, 0.57) for definite or probable tuberculosis, 50% (κ, 0.002) for viral pneumonia, and 56% (κ, 0.06) for bacterial pneumonia. Conclusions and Relevance: In this cross-sectional study, the agreement of ultrasonographic findings between clinicians and sonographers was mostly substantial. Between clinicians and senior physicians, agreement was substantial in the diagnosis of heart failure, moderate in the diagnosis of tuberculosis, but slight in the diagnosis of pneumonia. These findings suggest that handheld ultrasonographic devices used in addition to clinical examination may support clinicians in diagnosing cardiac and pulmonary diseases in rural sub-Saharan Africa.

PulmoNet: a novel deep learning based pulmonary diseases detection model.

Pulmonary diseases are various pathological conditions that affect respiratory tissues and organs, making the exchange of gas challenging for animals inhaling and exhaling. It varies from gentle and self-limiting such as the common cold and catarrh, to life-threatening ones, such as viral pneumonia (VP), bacterial pneumonia (BP), and tuberculosis, as well as a severe acute respiratory syndrome, such as the coronavirus 2019 (COVID-19). The cost of diagnosis and treatment of pulmonary infections is on the high side, most especially in developing countries, and since radiography images (X-ray and computed tomography (CT) scan images) have proven beneficial in detecting various pulmonary infections, many machine learning (ML) models and image processing procedures have been utilized to identify these infections. The need for timely and accurate detection can be lifesaving, especially during a pandemic. This paper, therefore, suggested a deep convolutional neural network (DCNN) founded image detection model, optimized with image augmentation technique, to detect three (3) different pulmonary diseases (COVID-19, bacterial pneumonia, and viral pneumonia). The dataset containing four (4) different classes (healthy (10,325), COVID-19 (3,749), BP (883), and VP (1,478)) was utilized as training/testing data for the suggested model. The model's performance indicates high potential in detecting the three (3) classes of pulmonary diseases. The model recorded average detection accuracy of 94%, 95.4%, 99.4%, and 98.30%, and training/detection time of about 60/50 s. This result indicates the proficiency of the suggested approach when likened to the traditional texture descriptors technique of pulmonary disease recognition utilizing X-ray and CT scan images. This study introduces an innovative deep convolutional neural network model to enhance the detection of pulmonary diseases like COVID-19 and pneumonia using radiography. This model, notable for its accuracy and efficiency, promises significant advancements in medical diagnostics, particularly beneficial in developing countries due to its potential to surpass traditional diagnostic methods.

Precision treatment of viral pneumonia through macrophage-targeted lipid nanoparticle delivery.

Macrophages are integral components of the innate immune system, playing a dual role in host defense during infection and pathophysiological states. Macrophages contribute to immune responses and aid in combatting various infections, yet their production of abundant proinflammatory cytokines can lead to uncontrolled inflammation and worsened tissue damage. Therefore, reducing macrophage-derived proinflammatory cytokine release represents a promising approach for treating various acute and chronic inflammatory disorders. However, limited macrophage-specific delivery vehicles have hindered the development of macrophage-targeted therapies. In this study, we screened a pool of 112 lipid nanoparticles (LNPs) to identify an optimal LNP formulation for efficient siRNA delivery. Subsequently, by conjugating the macrophage-specific antibody F4/80 to the LNP surface, we constructed MacLNP, an enhanced LNP formulation designed for targeted macrophage delivery. In both in vitro and in vivo experiments, MacLNP demonstrated a significant enhancement in targeting macrophages. Specifically, delivery of siRNA targeting TAK1, a critical kinase upstream of multiple inflammatory pathways, effectively suppressed the phosphorylation/activation of NF-kB. LNP-mediated inhibition of NF-kB, a key upstream regulator in the classic inflammatory signaling pathway, in the murine macrophage cell line RAW264.7 significantly reduced the release of proinflammatory cytokines after stimulation with the viral RNA mimic Poly(I:C). Finally, intranasal administration of MacLNP-encapsulated TAK1 siRNA markedly ameliorated lung injury induced by influenza infection. In conclusion, our findings validate the potential of targeted macrophage interventions in attenuating inflammatory responses, reinforcing the potential of LNP-mediated macrophage targeting to treat pulmonary inflammatory disorders.

Functional decline at 1 year in hospitalized elderly pneumonia with SARS-CoV-2 Omicron variant: Comparison with the ancestral strain and Alpha variant.

In the SARS-CoV-2 Omicron period, the pattern of pneumonia changed from primarily viral pneumonia to pneumonia mixed with bacteria in the elderly. We investigated functional outcomes at 1 year after hospital discharge in patients with primary Omicron pneumonia and pneumonia mixed with bacteria, mainly aspiration pneumonia. Functional decline rates calculated using the Barthel Index at 1 year after hospital discharge were significantly higher in the pneumonia mixed with bacteria group than the primary viral pneumonia group (42.6% vs. 20.5%, p < 0.0001). It is necessary to consider early rehabilitation and treatment in elderly patients even when the predominant strain is the Omicron variant.

Prevalence and progression of pneumonia in immunocompetent adults with varicella.

Pneumonia is the most common complication of varicella infections. Although previous studies have tended to focus mainly on immunocompromised patients, varicella pneumonia can also occur in healthy adults. Therefore, in this study, we aimed to assess the progression of varicella pneumonia in immunocompetent hosts. This retrospective study involved immunocompetent adult outpatients with varicella who attended the adult Fever Emergency facility of Peking University Third Hospital from April 1, 2020, to October 31, 2022. Varicella pneumonia was defined as a classic chickenpox-type rash in patients with infiltrates on chest computed tomography. The study included 186 patients, 57 of whom had a contact history of chickenpox exposure. Antiviral pneumonia therapy was administered to 175 patients by treating physicians. Computed tomography identified pneumonia in 132 patients, although no deaths from respiratory failure occurred. Seventy of the discharged patients were subsequently contacted, all of whom reported being well. Follow-up information, including computed tomography findings, was available for 37 patients with pneumonia, among whom 24 reported complete resolution whereas the remaining 13 developed persistent calcifications. Notably, we established that the true incidence of varicella pneumonia is higher than that previously reported, although the prognosis for immunocompetent hosts is generally good.

Biomarkers: Are They Useful in Severe Community-Acquired Pneumonia?

Community acquired pneumonia (CAP) is a prevalent infectious disease often requiring hospitalization, although its diagnosis remains challenging as there is no gold standard test. In severe CAP, clinical and radiologic criteria have poor sensitivity and specificity, and microbiologic documentation is usually delayed and obtained in less than half of sCAP patients. Biomarkers could be an alternative for diagnosis, treatment monitoring and establish resolution. Beyond the existing evidence about biomarkers as an adjunct diagnostic tool, most evidence comes from studies including CAP patients in primary care or emergency departments, and not only sCAP patients. Ideally, biomarkers used in combination with signs, symptoms, and radiological findings can improve clinical judgment to confirm or rule out CAP diagnosis, and may be valuable adjunctive tools for risk stratification, differentiate viral pneumonia and monitoring the course of CAP. While no single biomarker has emerged as an ideal one, CRP and PCT have gathered the most evidence. Overall, biomarkers offer valuable information and can enhance clinical decision-making in the management of CAP, but further research and validation are needed to establish their optimal use and clinical utility.

Integrated serum pharmacochemistry and investigation of the anti-influenza A virus pneumonia effect of Qingjin Huatan decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingjin Huatan Decoction (QJHTT) consists of 11 herbal medicines: Scutellaria baicalensis Georgi, Gardenia jasminoides J. Ellis, Platycodon grandiflorus (Jacq.) A. DC., Ophiopogon japonicus (Thunb.) Ker Gawl., Morus alba L., Fritillaria thunbergii Miq., Anemarrhena asphodeloides Bunge, Trichosanthes kirilowii Maxim., Citrus reticulata Blanco, Poria cocos (Schw.) Wolf, and Glycyrrhiza uralensis Fisch. As a traditional Chinese medicinal formula, QJHTT has been used for more than 400 years in China. It has shown promising results in treating influenza A virus (IAV) pneumonia. AIM OF THE STUDY: To elusive the specific pharmacological constituents and mechanisms underlying its anti-IAV pneumonia effects. MATERIALS AND METHODS: The components in QJHTT were analyzed through the use of a serum pharmacology-based ultra high-performance liquid chromatography Q- Exactive Orbitrap mass spectrometry (UHPLC-Q Exactive Orbitrap-MS) method. Simultaneously, the dynamic changes in IAV-infected mouse lung viral load, lung index, and expression of lung inflammation factors were monitored by qRT-PCR. RESULTS: We successfully identified 152 chemical components within QJHTT, along with 59 absorbed chemical prototype constituents found in the serum of mice treated with QJHTT. 43.45% of these chemical components and 43.10% of the prototype constituents were derived from the monarch drugs, namely Huangqin and Zhizi, aligning perfectly with traditional Chinese medicine theory. Notably, our analysis led to the discovery of 14 compounds within QJHTT for the first time, three of which were absorbed into the bloodstream. Simultaneously, we observed that QJHTT not only reduced the viral load but also modulated the expression of inflammation factors in the lung tissue including TNF-α, IL-1ß, IL-4, IL-6, IFN-γ, and IL17A. A time-effect analysis further revealed that QJHTT intervention effectively suppressed the peak of inflammatory responses, demonstrating a robust anti-IAV pneumonia effect. CONCLUSIONS: We comprehensively analyzed the pharmacological material basis of QJHTT by a highly sensitive and high-resolution UHPLC-Q Exactive Orbitrap-MS method, and demonstrated its efficacy in combating IAV pneumonia by reducing lung viral load and inflammatory factors. This study has significant importance for elucidating the pharmacological basis and pharmacological mechanism of QJHTT in combating IAV pneumonia.