Pneumonia Lung Research Articles

Leukocyte kinetics and bacterial clearance during S. pneumoniae pneumonia and contributions of ICAM-1.

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that is highly expressed on the pulmonary capillary endothelium, alveolar epithelium and other cell types within the lung. ICAM-1 plays important roles in leukocyte adhesion, migration, and motility. To determine the contributions of ICAM-1 to bacterial clearance and leukocyte kinetics during pneumonia, mice were inoculated with S. pneumoniae and evaluated 1, 4 and 7 days later. Our results show that Icam1-/-mice have a greater number of viable bacteria within the lung at each time point. The impaired clearance observed in Icam1-/- mice was not due to an impediment in leukocyte recruitment. In fact, Icam1-/- mice had a greater number of neutrophils and recruited inflammatory macrophages in the lung tissue and the alveoli/airways on day 7. In contrast, fewer alveolar macrophages were present in the BAL of Icam1-/-mice. The loss of body weight and the concentrations of inflammatory mediators in the BAL were also significantly greater in Icam1-/- mice. Mechanistic studies to understand the defect in clearance show that neutrophils and macrophage subpopulations had no defect in phagocytosis or acidification of phagosomes. RNA sequencing reveals many differences in gene expression, but no suggestion of a defect in phagocytosis or killing. Thus, that ICAM-1 is necessary for the clearance of S. pneumoniae and for the resolution of pneumonia, but is not required for the recruitment of neutrophils or inflammatory macrophages into the pneumonic lung parenchyma or the alveoli/airways during S. pneumoniae-induced pneumonia.

Prognostic Impact of Pulmonary Diseases in 952 Patients with Thoracic and/or Abdominal Aortic Aneurysm

Background/Objectives: Pulmonary diseases are common in patients with thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). Although high prevalences of chronic obstructive pulmonary disease and lung cancer (LC) are known, the prevalence of these and other pulmonary diseases regarding their relation to the outcome of TAA and/or AAA are not determined. Methods: Pulmonary diseases present at aortic aneurysm (AA) diagnosis and follow-up periods and cause of death of 952 patients with TAA, AAA, or TAA + AAA (including thoracoabdominal AA) treated at our institution in Japan were retrospectively analyzed. Cox regression analysis was used to investigate potential risk factors of mortality. Results: The mean patient age was 72.4 years, and the median follow-up was 4.92 years. At diagnosis, 528 (55.5%) patients had pulmonary diseases, including emphysema without interstitial lung disease (ILD) or LC, LC, idiopathic pulmonary fibrosis (IPF) without LC, non-IPF ILD without LC, and interstitial lung abnormalities (ILAs) without LC in 250, 85, 65, 15, and 58 patients, respectively. During follow-up, LC and acute exacerbation (AE) of IPF developed in 50 and 12 patients, respectively. In 213 patients who died, there were 45 (21.1%) aortic disease-related deaths. Other causes of death included LC (27.7%), cardiovascular events (9.4%), pneumonia (5.6%), and interstitial lung disease (4.7%). In a multivariate Cox regression hazard model, age; larger maximum aneurysm diameter; and coexisting LC, IPF, or concomitant cancer were associated with poor prognosis. Conclusions: In patients with AA, not only age and aneurysm diameter but also coexisting LC and IPF were prognostic factors for mortality.

Complete hybrid genome assembly of Mannheimia haemolytica serotype A2 strain D95 isolated from ovine lung.

Mannheimia haemolytica is a major bacterial pathogen associated with broncho- and fibrinous pneumonia in ruminants. Here, we report the complete genome sequence of an isolate of serotype A2 M. haemolytica (D95) recovered from a pneumonic ovine lung. The D95 genome has a size of 2.7 Mb and contains 2,720 genes.

Phytochemicals as Adjuvant Therapies in RND Efflux-mediated Multidrug Resistant Pseudomonas aeruginosa Infections and Evaluation Techniques of Efflux Inhibitory Activities in Bacteria

: One of the top-listed opportunistic pathogens that are frequently found in medical devices such as ventilation systems is Pseudomonas aeruginosa. These bacteria often cause infections in the lungs (pneumonia), blood after surgery, and other parts of the body. Extreme susceptibility to P. aeruginosa infection primarily exists in immunosuppressed individuals, and long-term evolution has led to the development of genetic resistance mechanisms that have high genetic flexibility against damaging antibiotics. Several lines of research evidence point to efflux as the primary reason for the organism's effectiveness against antibiotic treat-ment in infections caused by this bacterium. Drug Efflux pumps play a crucial role in medicine because they expulse a variety of unique and unrelated chemical structures with either antibi-otics or antimicrobials before they reach the concentration necessary to kill bacteria, confer-ring multiple resistance to more than one class of antibiotics. Targeting this mechanism for example by blocking the most active efflux pump MexAB-orpM would probably lead to the discovery of new ways to circumvent the bacterial system of antibiotic resistance and boost treatment effectiveness.

Evaluation of Bacterial Pneumonia and Pathological Changes in Lungs of Cattle Slaughtered in Maiduguri Central Abattoir, Borno State Nigeria

The study was designed to determine level of lungs inflammation and associated bacterial flora that influenced gross and histopathological lesions related to bovine pneumonic lungs amongst cattle slaughter in Maiduguri central abattoir. The study was conducted in Maiduguri, North-Eastern Nigeria. A total of 100 pneumonic lungs sampled from cattle slaughtered at Maiduguri central abattoir, 63 (63 %) were positive isolate and 37 were negative isolate (37 %). The results indicate isolates recovered were gram-positive and gram-negative bacteria with five bacterial genera isolated consist of 3 Gram-positive and 2 Gram-negative bacteria. The isolates were subjected to sensitivity test of various antibiotics like Ciprofloxacin, Pefloxacin, and Oflaxacinm and they were sensitive, while Chloramphenicol, Ciprofloxacin, Gentamicin, Streptomycin and Oflaxacin were Intermediate and Amoxicillin, Erythromycin, Cotrimoxazole, Gentamycin, and Ceftriaxone were resistance to the antimicrobial sensitivity tests. Pneumonic bacteria isolates based on sex and age of the cattle slaughtered at Maiduguri abattoir were recorded. Bull has the highest 58 (92.0%) compare to the cow 5 (8.0%). While age-wise, Isolates were recorded with highest 97.0 % among adult cattle when compare to the young cattle (3.0%). Three types of pneumonia were identified based on the Pathological examinations of 25 pneumonic lungs randomly selected from the 100 lungs samples which were recorded.

Correlation of the severity of the clinical presentation of SARS-CoV-2 pneumonia with respiratory function parameters in the post-COVID period.

Since COVID-19 first surfaced in 2019, it has seriously threatened public health. The most prevalent symptoms are respiratory ones. This study aimed to present the correlation between the severity of the clinical presentation of the disease and the results of respiratory function tests conducted within 6 months after hospital discharge. This retrospective study included 99 patients with confirmed SARS-CoV-2 virus infection. Of all patients 24.2% had accentuated bronchovascular pattern, 9.1% had unilateral, and 29.3% had bilateral pneumonia. In comparison, 35.4% patients had diffuse changes, which were described as acute respiratory distress syndrome (ARDS) on computed tomography (CT). Patients with unilateral, bilateral pneumonia or diffuse lung damage had significantly lower forced vital capacity (FVC) values. They were treated with non-invasive mechanical ventilation (NIV) or invasive mechanical ventilation (MV) and had lower FVC values (0.039). A negative, weak correlation existed between CT findings during the infection and Diffusing capacity for carbon monoxide (DLCO) measured after the infection (0.003). A negative, weak correlation was found between oxygen therapy, the use of NIV, and MV findings during the infection with DLCO. A negative correlation was noted between leukocyte values during the infection and forced expiratory volume in the first second (FEV1) and FVC after the infection. Patients with COVID-19 infection who need oxygen support and MV continue to suffer from loss of respiratory function after the resolution of COVID-19 infection. These findings highlight the negative predictive value of pulmonary tests in the long-term follow-up for the development of PC-ILD as well as decreased pulmonary capacity.

The Effects of the Pneumonia Lung Microenvironment on MSC Function.

Despite promise in preclinical models of acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC) have failed to translate to therapeutic benefit in clinical trials. The MSC is a live cell medicine and interacts with the patient's disease state. Here, we explored this interaction, seeking to devise strategies to enhance MSC therapeutic function. Human bone-marrow-derived MSCs were exposed to lung homogenate from healthy and E. coli-induced ARDS rat models. Apoptosis and functional assays of the MSCs were performed. The ARDS model showed reduced arterial oxygenation, decreased lung compliance and an inflammatory microenvironment compared to controls. MSCs underwent more apoptosis after stimulation by lung homogenate from controls compared to E. coli, which may explain why MSCs persist longer in ARDS subjects after administration. Changes in expression of cell surface markers and cytokines were associated with lung homogenate from different groups. The anti-microbial effects of MSCs did not change with the stimulation. Moreover, the conditioned media from lung-homogenate-stimulated MSCs inhibited T-cell proliferation. These findings suggest that the ARDS microenvironment plays an important role in the MSC's therapeutic mechanism of action, and changes can inform strategies to modulate MSC-based cell therapy for ARDS.

Predictors for prescription of noninvasive ventilation in the postoperative period of cardiac surgery: a systematic review

Introduction The postoperative (PO) period after cardiac surgery is associated with the occurrence of respiratory complications. Noninvasive positive pressure ventilation (NIPPV) is largely used as a ventilatory support strategy after the interruption of invasive mechanical ventilation. However, the variables associated with NIPPV prescription are unclear. Objective To describe the literature on predictors of NIPPV prescription in patients during the PO period of cardiac surgery. Materials and methods This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) platform in December 2021 (CRD42021291973). Bibliographic searches were performed in February 2022 using the PubMed, Lilacs, Embase and PEDro databases, with no year or language restrictions. The Predictors for the prescription of NIPPV were considered among patients who achieved curative NIPPV. Results A total of 349 articles were identified, of which four were deemed eligible and were included in this review. Three studies were retrospective studies, and one was a prospective safety pilot study. The total sample size in each study ranged from 109 to 1657 subjects, with a total of 3456 participants, of whom 283 realized NIPPV. Curative NIPPV was the only form of NIPPV in 75% of the studies, which presented this form of prescription in 5–9% of the total sample size, with men around 65 years old being the majority of the participants receiving curative NIPPV. The main indication for curative NIPPV was acute respiratory failure. Only one study realized prophylactic NIPPV (28% of 32 participants). The main predictors for the prescription of curative NIPPV in the PO period of cardiac surgery observed in this study were elevated body mass index (BMI), hypercapnia, PO lung injury, cardiogenic oedema and pneumonia. Conclusions BMI and lung alterations related to gas exchange disturbances are major predictors for NIPPV prescription in patients during the PO period of cardiac surgery. The identification of these predictors can benefit clinical decision-making regarding the prescription of NIPPV and help conserve human and material resources, thereby preventing the indiscriminate use of NIPPV.

The Role of Artificial Intelligence in Supporting Radiologists in Detecting Lung Lesions Caused by COVID-19 - A Scoping Review

The COVID-19 pandemic has posed significant challenges to healthcare systems, particularly in the realm of medical imaging and the diagnosis of COVID-19 pneumonia lung lesions. Artificial intelligence (AI) has become essential in assisting radiologists by swiftly analyzing extensive volumes of computed tomography (CT) scan data to identify lung abnormalities. Radiologists, who typically conduct thorough examinations of CT scans, benefit from AI's capability to pre-screen images, flag potential issues, and prioritize urgent cases, thereby enhancing efficiency during times of high demand. AI, especially through deep learning, can recognize subtle patterns in lung images that may be overlooked by human eyes, offering valuable second opinions and improving diagnostic accuracy and consistency. The early detection of COVID-19 lung lesions by AI facilitates prompt treatment, helping to prevent disease progression and improve patient outcomes. This review article aims to consolidate current knowledge on the topic by examining existing literature and discussing the advantages and disadvantages of employing CT imaging and AI tools for diagnosing COVID-19.

Detection of Aerobic Bacterial Species Causing Pneumonia in Sheep and Goats and their Susceptibility to Antibiotics in Sudan

Aims: This study was conducted in Khartoum and Gezira States slaughterhouses to investigate the bacterial spp. associated with pneumonia in condemned sheep and goat lungs. Study Design: A total of 2085 animals were examined grossly for respiratory lesions (sheep= 1601 and goats= 484). Place and Duration of Study: Khartoum and Gezira States slaughterhouses during different seasons, from 2018-2020 and conducted in Central Veterinary Research Laboratory, Sudan. Methodology: Bacterial spp. were isolated and identified using analytical profile index strips then more characterization done using Polymerase chain reaction for representative 20 selected isolates and finally antimicrobial susceptibility test was performed. Results: Out of 320 pneumonic lung samples, 116 samples showed pure colonies and 41 were mixed culture while 163 revealed no bacterial growth. The main bacteria isolated were Staphylococcus aureus, Escherichia coli, Pasteurella multocida, Mannheimia haemolytica, Streptococcus spp. Corynebacterium spp. Pseudomonas spp. Staph spp. and Bacillus spp. Twenty representative bacterial isolates examined by PCR technique 10 were Staph aureus and 10 were E. coli to confirm identification. Seven of each were found positive. The Gram-positive bacteria resulted in 41 resistant isolates, 21 intermediate and 141 sensitive to different antibiotics. Ten bacterial species were reported resistant for more than two Antibiotics from different classes mainly tetracycline, methicillin, penicillin and erythromycin. The Gram-negative bacteria resulted in 59 were resistant, 13 intermediate and 108 sensitive to antibiotics. Seventeen of them were multidrug resistance to tetracycline, gentamicin, Imipenem and ceftriaxone. Conclusion: It was concluded that bacteria could be the main cause responsible for pneumonia in sheep and goats, some of these bacterial isolates were resistance to several Antibiotic which have an impact on public health.

Increase of pyogenic bacterial infections after relaxation of social distancing measures linked to COVID-19 pandemic.

After the relaxation of COVID-19 mitigation measures, we observed a dramatic increase in pyogenic infections. Based on this observation, we retrospectively analysed all cases of invasive bacterial infections of brain, lung and complicated ear-nose-throat (ENT) infections, in the period from 1 August to 31 March from the years 2018-2019 to 2022-2023. The study was conducted in two Paediatric Emergency Departments, at IRCCS 'Burlo Garofolo' of Trieste and at Treviso Hospital. Electronic medical records were searched for all cases with a definitive diagnosis at discharge of mastoiditis, suppurative cervical lymphadenitis, retropharyngeal, parapharyngeal and peritonsillar abscess (ENT group), bacterial brain abscesses, epidural empyema, subdural empyema (central nervous system group), thoracic empyema and necrotising pneumonia (lung group). In 2022-2023, we observed an increase in infections compared to the previous years. Total number of cases were 22, 29, 8, 27 and 63 in 2018-2019, 2019-2020, 2020-2021, 2021-2022 and 2022-2023, respectively. The greater increase occurred in thoracic empyema, with a peak incidence of +120% in 2022-2023 in respect of 2021-2022. We reported an important increase in paediatric bacterial complicated infections in two North East Italian regions, possibly correlated with the relaxation of COVID-19 social distancing measures.

Prediction of early-phase cytomegalovirus pneumonia in post-stem cell transplantation using a deep learning model.

Diagnostic challenges exist for CMV pneumonia in post-hematopoietic stem cell transplantation (post-HSCT) patients, despite early-phase radiographic changes. The study aims to employ a deep learning model distinguishing CMV pneumonia from COVID-19 pneumonia, community-acquired pneumonia, and normal lungs post-HSCT. Initially, 6 neural network models were pre-trained with COVID-19 pneumonia, community-acquired pneumonia, and normal lung CT images from Kaggle's COVID multiclass dataset (Dataset A), then Dataset A was combined with the CMV pneumonia images from our center, forming Dataset B. We use a few-shot transfer learning strategy to fine-tune the pre-trained models and evaluate model performance in Dataset B. 34 cases of CMV pneumonia were found between January 2018 and December 2022 post-HSCT. Dataset A contained 1681 images of each subgroup from Kaggle. Combined with Dataset A, Dataset B was initially formed by 98 images of CMV pneumonia and normal lung. The optimal model (Xception) achieved an accuracy of 0.9034. Precision, recall, and F1-score all reached 0.9091, with an AUC of 0.9668 in the test set of Dataset B. This framework demonstrates the deep learning model's ability to distinguish rare pneumonia types utilizing a small volume of CT images, facilitating early detection of CMV pneumonia post-HSCT.

Toxicological evidence integration to confirm the biological plausibility of the association between humidifier disinfectant exposure and respiratory diseases using the AEP-AOP framework.

Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into 3 lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway-adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. The integration of each AEP-AOP component for PHMG and CMIT/MIT led to the development of an AEP-AOP model, wherein disinfectants released from humidifiers in aerosol or gaseous form reached target sites, causing respiratory damage through molecular initiating events and key events. The model demonstrated high reliability and relevance to the pathogenesis of respiratory diseases. The AEP-AOP model developed in this study provides strong evidence that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

Lung Ultrasound Evaluation of Pulmonary Abnormalities in Children with Congenital Heart Diseases

Abstract Background and Aims Congenital heart disease (CHD) can cause several abnormalities of the lungs, such as pulmonary overflow (PO), pulmonary hypertension and chest infection like pneumonia. We aimed to assess pulmonary abnormalities using lung ultrasound (LUS) in children with congenital heart diseases. Patients and Methods This is a cross-sectional study, which included (33) CHD patients aged between 0.5 to 3.5 years who were admitted to the Cardiology Unit,Ain Shams University, Children’s Hospital. The patients were subjected to detecting any consolidation and measuring B vertical lines in all lung zones. LUS score was recorded at baseline and after course of management. Results There was statistically reduction in the after management group compared to the before management group according to LUS score with p-value (p < 0.001). There was a difference between types of management according to LUS score and its severity in the before management group, with p-value (p < 0.001) whereas, surgical type of management had the highest mean value of the LUS score compared to other types of management among our studied patients before management with a highly statistically significant difference, with p-value (p < 0.001). Conclusion Lung ultrasound is an ideal tool for the diagnosis and follow-up of pulmonary complications such as lung congestion, pulmonary edema and pneumonia. Also, there was improvement in pulmonary congestion after management among CHD children.

In vitro comparison of viral replication and cytopathology induced by SARS-CoV-2 variants.

A myriad of coronaviruses cause diseases from a common cold to severe lung infections and pneumonia. SARS-CoV-2 was discovered to be the etiologic agent of the Coronavirus pandemic and many laboratory techniques were examined for virus culture and basic and applied research. Understanding the replication kinetics and characterizing the effect the virus has on different cell lines is crucial for developing in vitro studies. With the emergence of multiple variants of SARS-CoV-2, a comparison between their infectivity and replication in common cell lines will help give us a clear understanding of their characteristic differences in pathogenicity. In this study we compared the cytopathic effect and replication of Wild-Type (USA/WA1), Omicron (B.1.1.529), and Delta (B.1.617.2) variants on five different cell lines; VeroE6, VeroE6 cells expressing high endogenous ACE2, VeroE6 cells expressing human ACE2 and TMPRSS2, Calu3 cells highly expressing human ACE2 and A549 cells. This data will aid researchers with experimental planning and viral pathogenicity analysis and provide a baseline for testing any future variants.

Pneumonia Detection through Deep Learning: A Comparative Exploration of Classification and Segmentation Strategies

The Convolution Neural Network (CNN) algorithm is one of the most widely used methods for identifying and categorizing lung cancer. This paper covers the most suitable architecture and CNN algorithms for lung cancer and pneumonia deduction and classification. The main contributions to the diagnosis and classification of lung cancer with four steps are Nonlinear transfer learning framework (NLTF), Hierarchical Feature Mapping (HFM), Lifelong Partial Dissection (LPD), and Deep Lifelong Convolutional Neural Network (DLCNN). The application of non-local total fuzzy (NLTF) filtering removes various categories of noise after lung CT imageries and enhances cancer areas. The application of Hybrid Fuzzy Morphology (HFM) constructed segmentation to minimize the region of interest (ROI) for cancer using morphology opening and closing processes. Extraction of traits unique to each disease employing Lung Parenchyma Division (LPD) and extraction of deep seismic features using the Geometric Optimal Algorithm (GOA). Training and testing the proposed Deep Learning Convolutional Neural Network (DLCNN) model using the extracted features to classify benign, malignant lung cancers and Recent advancements in deep learning methods have shown accurate results in the investigation and diagnosis of medical image data, including the detection of pneumonia.

Systemic lupus erythematous in men with interstitial lung pneumonia: a rare case report

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with unknown etiology and very diverse clinical manifestations, disease course, and prognosis. It is most common in African-American women, the prevalence being 4 per 1000 females. SLE predominantly affects young women, most presenting between 20 and 40 years of age. Male SLE is rare, with only one male patient reported per nine females. Pulmonary involvement in SLE is various. SLE-associated interstitial lung disease (ILD), while rare, is a predictor of poor prognosis. We report a 50-year-old male patient with complaints of shortness of breath, previously diagnosed with systemic lupus erythematous by examination of the antinuclear antibody (ANA) profile. The patient underwent a computed tomography (CT) scan of the thorax and the results showed interstitial lung pneumonia. The patient was given azathioprine and methylprednisolone therapy for Systemic lupus erythematous and ceftriaxone and acetylcysteine ​​for interstitial lung pneumonia.

Cytomegalovirus pneumonia with intermittent pulmonary hemorrhage leading to asphyxia death: a case report and literature review

Neonatal pulmonary hemorrhage is a late manifestation of various diseases. Premature delivery and low body weight are frequently observed as high-risk factors, characterized by acute onset, rapid progression, and high mortality rates. Pulmonary hemorrhage caused by cytomegalovirus infection in newborns with normal immune function is a rare occurrence. This case report focuses on a term neonate with normal birth weight who presented solely with nasal obstruction shortly after birth. However, 4 days after birth, the newborn experienced a sudden onset of blood gushing from both the mouth and nasal cavity. The patient was diagnosed with gastrointestinal bleeding, neonatal pneumonia and neonatal lung consolidation. And he was discharged after ten days of symptomatic treatment. However, upon returning home, the patient experienced a sudden onset of bleeding from the mouth and nose, leading to his untimely demise. Subsequent autopsy revealed the presence of pulmonary hemorrhage in newborn, which presented as interstitial pneumonia. The cause of pulmonary hemorrhage is cytomegalovirus infection. This case emphasizes the importance of pediatricians enhancing their skills in differentiating pulmonary hemorrhage, especially from cytomegalovirus pneumonia.

Research Progress on Chinese Medicine Regulation of Mitochondrial Damage for Intervention in Respiratory System Diseases

AbstractMitochondria are important organelles in cells for energy production, and mitochondrial damage caused by various reasons is an important factor promoting disease progression. Mitochondrial damage involves structural damage and mitochondrial DNA damage, which are closely related to the occurrence and development of respiratory system diseases. In recent years, a large number of studies have confirmed the significant role of mitochondrial damage in the progression of respiratory system diseases, which may be an important target for the treatment of respiratory system diseases with traditional Chinese medicine (TCM). This article reviews the role of TCM in regulating mitochondrial damage for intervention in respiratory system diseases such as chronic obstructive pulmonary disease, lung cancer, pulmonary fibrosis, acute lung injury, asthma, and pneumonia, aiming to provide a basis for the study of the pathogenesis and drug action targets of respiratory system diseases.

Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2

In the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads in tissues determined by RT-qPCR, histopathology in brain and lungs, immunohistochemical study in brain (IHC) as well as mortality rates, clinical signs and plasma inflammatory and coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 challenged mice presented higher viral loads in the brain and an increased frequency of neuroinvasion, with the greatest differences observed between groups at 3–4 days post-infection (dpi). Histopathological examination showed a higher severity of brain lesions in BCG-SARS-CoV-2 challenged mice, mainly consisting of neuroinflammation, increased glial cell population and neuronal degeneration, from 5 dpi onwards. This group also presented higher interstitial pneumonia and vascular thrombosis in lungs (3–4 dpi), BCG-SARS-CoV-2 mice showed higher values for TNF-α and D-dimer values, while iNOS values were higher in SARS-CoV-2 mice at 3–4 dpi. Results presented in this study indicate that BCG stimulation could have intensified the inflammatory and neurodegenerative lesions promoting virus neuroinvasion and dissemination in this experimental model. Although k18-hACE2 mice show higher hACE2 expression and neurodissemination, this study suggests that, although the benefits of BCG on enhancing heterologous protection against pathogens and tumour cells have been broadly demonstrated, potential adverse outcomes due to the non-specific effects of BCG should be considered.