The extracellular cyclophilin A-integrin ß2 complex as a therapeutic target of viral pneumonia.

The acute respiratory virus infection can induce uncontrolled inflammatory responses, such as cytokine storm and viral pneumonia, which are the major causes of death in clinical cases. Cyclophilin A (CypA) is mainly distributed in the cytoplasm of resting cells and released into the extracellular space in response to inflammatory stimuli. Extracellular CypA (eCypA) is upregulated and promotes inflammatory response in severe COVID-19 patients. However, how eCypA promotes virus-induced inflammatory response remains elusive. Here, we observe that eCypA is induced by influenza A and B viruses and SARS-CoV-2 in cells, mice, or patients. Anti-CypA mAb reduces pro-inflammatory cytokines production, leukocytes infiltration, and lung injury in virus-infected mice. Mechanistically, eCypA binding to integrin ß2 triggers integrin activation, thereby facilitating leukocyte trafficking and cytokines production via the focal adhesion kinase (FAK)/GTPase and FAK/ERK/P65 pathways, respectively. These functions are suppressed by the anti-CypA mAb that specifically blocks eCypA-integrin ß2 interaction. Overall, our findings reveal that eCypA-integrin ß2 signaling mediates virus-induced inflammatory response, indicating that eCypA is a potential target for antibody therapy against viral pneumonia.

Targeting ectromelia virus and TNF/NF-κB or STAT3 signaling for effective treatment of viral pneumonia.

Viral causes of pneumonia pose constant threats to global public health, but there are no specific treatments currently available for the condition. Antivirals are ineffective when administered late after the onset of symptoms. Pneumonia is caused by an exaggerated inflammatory cytokine response to infection, but tissue necrosis and damage caused by virus also contribute to lung pathology. We hypothesized that viral pneumonia can be treated effectively if both virus and inflammation are simultaneously targeted. Combined treatment with the antiviral drug cidofovir and etanercept, which targets tumor necrosis factor (TNF), down-regulated nuclear factor kappa B-signaling and effectively reduced morbidity and mortality during respiratory ectromelia virus (ECTV) infection in mice even when treatment was initiated after onset of clinical signs. Treatment with cidofovir alone reduced viral load, but animals died from severe lung pathology. Treatment with etanercept had no effect on viral load but diminished levels of inflammatory cytokines and chemokines including TNF, IL-6, IL-1ß, IL-12p40, TGF-ß, and CCL5 and dampened activation of the STAT3 cytokine-signaling pathway, which transduces signals from multiple cytokines implicated in lung pathology. Consequently, combined treatment with a STAT3 inhibitor and cidofovir was effective in improving clinical disease and lung pathology in ECTV-infected mice. Thus, the simultaneous targeting of virus and a specific inflammatory cytokine or cytokine-signaling pathway is effective in the treatment of pneumonia. This approach might be applicable to pneumonia caused by emerging and re-emerging viruses, like seasonal and pandemic influenza A virus strains and severe acute respiratory syndrome coronavirus 2.

Validation of Lung Ultrasound for COVID-19 Prognostication in an International Multicenter Cohort Study.

BACKGROUND: Despite many studies evaluating lung ultrasound (LUS) for COVID-19 prognostication, the generalizability and utility across clinical settings is uncertain. METHODS: Adults (≥18 years of age) with COVID-19 were enrolled at two military hospitals, an emergency department, home visits, and a homeless shelter in the United States, and in a referral hospital in Uganda. Participants had a 12-zone LUS scan performed at time of enrollment and clips were read off-site. The primary outcome was progression to higher level of care after the ultrasound scan. We calculated the cross-validated area under the curve for the validation cohort for individual LUS features. RESULTS: We enrolled 191 participants with COVID-19 were enrolled (57.9% female, median age 45.0 years, interquartile range [IQR]: 31.5, 58.0). Nine participants clinically deteriorated. The top predictors of worsening disease in the validation cohort measured by cross-validated area under the curve (cvAUC) were B-lines (0.88, 95% confidence interval [CI]: 0.87, 0.90), discrete B-lines (0.87, 95% CI: 0.85, 0.88), oxygen saturation (0.82, 95%: CI:0.81, 0.84), and A-lines (0.80, 95% CI: 0.78, 0.81). CONCLUSIONS: In an international multisite POCUS cohort, LUS parameters had high discriminative accuracy. Ultrasound can be applied towards triage across a wide breadth of care settings during a pandemic.

Pulmonary Aspects of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory virus that gains entry via angiotensin-converting enzyme 2 (ACE2) within airway epithelium. Patients exhibit a spectrum of respiratory symptoms from asymptomatic to respiratory failure. Patient factors including obesity, tobacco use, and black race are all associated with increased ACE2 expression and may contribute to increased complications. Consolidation and ground-glass opacities on chest imaging are typical but not specific for coronavirus disease 2019 (COVID-19). Venous thromboembolism occurs infrequently when prophylactic anticoagulation is provided. However, capillary microthrombosis is nearly ubiquitous, suggesting that it contributes to hypoxemia. Remdesivir and glucocorticoids may benefit some hospitalized patients. Many of those afflicted remain symptomatic two weeks following diagnosis and continue to require health care. Total lung capacity, diffusion capacity, and maximal oxygen consumption may be reduced for months in some survivors. Lung transplant offers chronically critically ill patients new hope, and this option may have increasing potential for outpatients with COVID-19-associated fibrosis.

Value of a secretomic approach for distinguishing patients with COVID-19 viral pneumonia among patients with respiratory distress admitted to intensive care unit.

In intensive care units, COVID-19 viral pneumonia patients (VPP) present symptoms similar to those of other patients with Nonviral infection (NV-ICU). To better manage VPP, it is therefore interesting to better understand the molecular pathophysiology of viral pneumonia and to search for biomarkers that may clarify the diagnosis. The secretome being a set of proteins secreted by cells in response to stimuli represents an opportunity to discover new biomarkers. The objective of this study is to identify the secretomic signatures of VPP with those of NV-ICU. Plasma samples and clinical data from NV-ICU (n = 104), VPP (n = 30) or healthy donors (HD, n = 20) were collected at Nantes Hospital (France) upon admission. Samples were enriched for the low-abundant proteins and analyzed using nontarget mass spectrometry. Specifically deregulated proteins (DEP) in VPP versus NV-ICU were selected. Combinations of 2 to 4 DEPs were established. The differences in secretome profiles of the VPP and NV-ICU groups were highlighted. Forty-one DEPs were specifically identified in VPP compared to NV-ICU. We describe five of the best combinations of 3 proteins (complement component C9, Ficolin-3, Galectin-3-binding protein, Fibrinogen alpha, gamma and beta chain, Proteoglycan 4, Coagulation factor IX and Cdc42 effector protein 4) that show a characteristic receptor function curve with an area under the curve of 95.0%. This study identifies five combinations of candidate biomarkers in VPP compared to NV-ICU that may help distinguish the underlying causal molecular alterations.

Broad-spectrum antiviral effect of MoringaA-loaded exosomes against IAV by mediating the GCN5-TFEB-autolysosome pathway.

Influenza virus-induced viral pneumonia is a major threat to human health, and specific therapeutic agents for viral pneumonia are still lacking. MoringaA (MA) is an anti-influenza virus active compound isolated from Moringa seeds, which can inhibit influenza virus by activating the TFEB-autophagic lysosomal pathway in host cells. In this study, we obtained exosomes from M2-type macrophages and encapsulated and delivered MA (MA-Exos), and we investigated the efficacy of MA-Exos in antiviral and viral pneumonia in vivo and in vitro, respectively. In addition, we provided insights into the mechanism by which MA-Exos regulates TFEB-lysosomal autophagy by RNA sequencing. The MA-Exos showed broad-spectrum inhibition of IAV, and significant promotion of the autophagic lysosomal pathway. Meanwhile, we found that GCN5 gene and protein were significantly down-regulated in IAV-infected cells after MA-Exos intervention, indicating its blocking the acetylation of TFEB by GCN5. In addition, MA-Exos also significantly promoted autophagy in lung tissue cells of mice with viral pneumonia. MA-Exos can inhibit and clear influenza virus by mediating the TFEB-autophagy lysosomal pathway by a mechanism related to the down-regulation of histone acetyltransferase GCN5. Our study provides a strategy for targeting MA-Exos for the treatment of viral pneumonia from both antiviral and virus-induced inflammation inhibition pathways.

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.

Differential associations of fine and coarse particulate air pollution with cause-specific pneumonia mortality: A nationwide, individual-level, case-crossover study.

BACKGROUND: The connections between fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) and daily mortality of viral pneumonia and bacterial pneumonia were unclear. OBJECTIVES: To distinguish the connections between PM2.5 and PM2.5-10 and daily mortality due to viral pneumonia and bacterial pneumonia. METHODS: Using a comprehensive national death registry encompassing all areas of mainland China, we conducted a case-crossover investigation from 2013 to 2019 at an individual level. Residential daily particle concentrations were evaluated using satellite-based models with a spatial resolution of 1 km. To analyze the data, we employed the conditional logistic regression model in conjunction with polynomial distributed lag models. RESULTS: We included 221,507 pneumonia deaths in China. Every interquartile range (IQR) elevation in concentrations of PM2.5 (lag 0-2 d, 37.6 µg/m3) was associated with higher magnitude of mortality for viral pneumonia (3.03%) than bacterial pneumonia (2.14%), whereas the difference was not significant (p-value for difference = 0.38). An IQR increase in concentrations of PM2.5-10 (lag 0-2 d, 28.4 µg/m3) was also linked to higher magnitude of mortality from viral pneumonia (3.06%) compared to bacterial pneumonia (2.31%), whereas the difference was not significant (p-value for difference = 0.52). After controlling for gaseous pollutants, their effects were all stable; however, with mutual adjustment, the associations of PM2.5 remained, and those of PM2.5-10 were no longer statistically significant. Greater magnitude of associations was noted in individuals aged 75 years and above, as well as during the cold season. CONCLUSION: This nationwide study presents compelling evidence that both PM2.5 and PM2.5-10 exposures could increase pneumonia mortality of viral and bacterial causes, highlighting the more robust effects of PM2.5 and somewhat higher sensitivity of viral pneumonia.

A ternary correlation multi-symptom network strategy based on in vivo chemical profile identification and metabolomics to explore the molecular basis of Ephedra herb against viral pneumonia.

Ephedra herb (EH), an important medicine prescribed in herbal formulas by Traditional Chinese Medicine practitioners, has been widely used in the treatment of viral pneumonia in China. However, the molecular basis of EH in viral pneumonia remains unclear. In this study, a ternary correlation multi-symptom network strategy was established based on in vivo chemical profile identification and metabolomics to explore the molecular basis of EH against viral pneumonia. Results showed that 143 compounds of EH and 70 prototype components were identified in vivo. EH could reduce alveolar-capillary barrier disruption in rats with viral pneumonia and significantly downregulate the expression of inflammatory factors and bronchoalveolar lavage fluid. Plasma metabolomics revealed that EH may be involved in the regulation of arachidonic acid, tryptophan, tyrosine, nicotinate, and nicotinamide metabolism. The multi-symptom network showed that 12 compounds have an integral function in the treatment of viral pneumonia by intervening in many pathways related to viruses, immunity and inflammation, and lung injury. Further verification demonstrated that sinapic acid and frambinone can regulate the expression of related genes. It has been shown to be a promising representative of the pharmacological constituents of ephedra.

Predicting the potentially exacerbation of severe viral pneumonia in hospital by MuLBSTA score joint CD4 + and CD8 +T cell counts: construction and verification of risk warning model.

PURPOSE: This study mainly focuses on the immune function and introduces CD4+, CD8+ T cells and their ratios based on the MuLBSTA score, a previous viral pneumonia mortality risk warning model, to construct an early warning model of severe viral pneumonia risk. METHODS: A retrospective single-center observational study was operated from January 2021 to December 2022 at the People's Hospital of Liangjiang New Area, Chongqing, China. A total of 138 patients who met the criteria for viral pneumonia in hospital were selected and their data, including demographic data, comorbidities, laboratory results, CT scans, immunologic and pathogenic tests, treatment regimens, and clinical outcomes, were collected and statistically analyzed. RESULTS: Forty-one patients (29.7%) developed severe or critical illness. A viral pneumonia severe risk warning model was successfully constructed, including eight parameters: age, bacterial coinfection, CD4+, CD4+/CD8+, multiple lung lobe infiltrations, smoking, hypertension, and hospital admission days. The risk score for severe illness in patients was set at 600 points. The model had good predictive performance (AUROC = 0.94397), better than the original MuLBSTA score (AUROC = 0.8241). CONCLUSION: A warning system constructed based on immune function has a good warning effect on the risk of severe conversion in patients with viral pneumonia.

Inhibition Effects and Mechanisms of Marine Compound Mycophenolic Acid Methyl Ester against Influenza A Virus.

Influenza A virus (IAV) can cause infection and illness in a wide range of animals, including humans, poultry, and swine, and cause annual epidemics, resulting in thousands of deaths and millions of hospitalizations all over the world. Thus, there is an urgent need to develop novel anti-IAV drugs with high efficiency and low toxicity. In this study, the anti-IAV activity of a marine-derived compound mycophenolic acid methyl ester (MAE) was intensively investigated both in vitro and in vivo. The results showed that MAE inhibited the replication of different influenza A virus strains in vitro with low cytotoxicity. MAE can mainly block some steps of IAV infection post adsorption. MAE may also inhibit viral replication through activating the cellular Akt-mTOR-S6K pathway. Importantly, oral treatment of MAE can significantly ameliorate pneumonia symptoms and reduce pulmonary viral titers, as well as improving the survival rate of mice, and this was superior to the effect of oseltamivir. In summary, the marine compound MAE possesses anti-IAV effects both in vitro and in vivo, which merits further studies for its development into a novel anti-IAV drug in the future.

CT findings of 144 in-hospital patients with influenza pneumonia: A retrospective analysis.

BACKGROUND/PURPOSE: Patients with influenza infection during their period of admission may have worse computed tomography (CT) manifestation according to the clinical status. This study aimed to evaluate the CT findings of in-hospital patients due to clinically significant influenza pneumonia with correlation of clinical presentations. METHODS: In this retrospective, single center case series, 144 patients were included. All in-hospital patients were confirmed influenza infection and underwent CT scan. These patients were divided into three groups according to the clinical status of the most significant management: (1) without endotracheal tube and mechanical ventilator (ETTMV) or extracorporeal membrane oxygenation (ECMO); (2) with ETTMV; (3) with ETTMV and ECMO. Pulmonary opacities were scored according to extent. Spearman rank correlation analysis was used to evaluate the correlation between clinical parameters and CT scores. RESULTS: The predominant CT manifestation of influenza infection was mixed ground-glass opacity (GGO) and consolidation with both lung involvement. The CT scores were all reach significant difference among all three groups (8.73 ± 6.29 vs 12.49 ± 6.69 vs 18.94 ± 4.57, p < 0.05). The chest CT score was correlated with age, mortality, and intensive care unit (ICU) days (all p values were less than 0.05). In addition, the CT score was correlated with peak lactate dehydrogenase (LDH) level and peak C-reactive protein (CRP) level (all p values were less than 0.05). Concomitant bacterial infection had higher CT score than primary influenza pneumonia (13.02 ± 7.27 vs 8.95 ± 5.99, p < 0.05). CONCLUSION: Thin-section chest CT scores correlated with clinical and laboratory parameters in in-hospital patients with influenza pneumonia.

Effect of Aviptadil, a Novel Therapy, on Clinical Outcomes of Patients with Viral-related Severe ARDS: A Retrospective Observational Study.

Background: Dealing with life-threatening viral acute respiratory distress syndrome (ARDS) has always been challenging and with the recent COVID pandemic experience, there is still the need of newer therapies to alleviate mortality. Aviptadil, has shown significant beneficial results in covid. We share our experience with this molecule by doing a retrospective study to evaluate the effect of this drug on clinical outcomes in viral-related Ards patients. Materials and methods: In this study, all patients with severe viral-related Ards received Aviptadil along with the conventional treatment. The oxygen saturation, SpO2/FiO2 (ratio of pulse oximetric saturation to fractional inspired oxygen) (S/F) ratio and PaO2/FiO2 (ratio of arterial oxygen partial pressure to fractional inspired oxygen) (p/f) ratio, before and after completion of the drug were studied. Radiological clearance and time for complete recovery from respiratory failure was noted. All variables pre- and postadministration of the drug were compared. Results: A total of 68 patients with viral pneumonias were admitted to intensive care unit (Icu) and only 6 patients had severe Ards, who received Aviptadil. The mean oxygen saturation significantly improved from 87.86% before the first Aviptadil dose to 93.43% post 3 days of infusion. Similarly, improvement was seen in PaO2 values from 54.32 to 68.4 posttherapy (p-value < 0.004). SpO2/FiO2 (ratio of pulse oximetric saturation to fractional inspired oxygen) ratio hiked from 149 to 336 at the end of the 3 days infusion (p-value < 0.003). RALE scoring system was used for radiological clearance and the mean change in the score was from 6.42 to 2.5 (p-value 0.00). The average length of stay in the Icu was 12.14 days. No adverse effects were noted. Conclusion: Aviptadil has shown to improve the clinical outcomes in patients with severe viral-related ards without any adverse effects. How to cite this article: Sampley S, Bhasin D, Sekhri K, Singh H, Gupta O. Effect of Aviptadil, a Novel Therapy, on Clinical Outcomes of Patients with Viral-related Severe ARDS: A Retrospective Observational Study. Indian J Crit Care Med 2024;28(1):70-74.

Immunomodulatory and antiviral effects of Lycium barbarum glycopeptide on influenza a virus infection.

Influenza is caused by a respiratory virus and has a major global impact on human health. Influenza A viruses in particular are highly pathogenic to humans and have caused multiple pandemics. An important consequence of infection is viral pneumonia, and with serious complications of excessive inflammation and tissue damage. Therefore, simultaneously reducing direct damage caused by virus infection and relieving indirect damage caused by excessive inflammation would be an effective treatment strategy. Lycium barbarum glycopeptide (LbGp) is a mixture of five highly branched polysaccharide-protein conjuncts (LbGp1-5) isolated from Lycium barbarum fruit. LbGp has pro-immune activity that is 1-2 orders of magnitude stronger than that of other plant polysaccharides. However, there are few reports on the immunomodulatory and antiviral activities of LbGp. In this study, we evaluated the antiviral and immunomodulatory effects of LbGp in vivo and in vitro and investigated its therapeutic effect on H1N1-induced viral pneumonia and mechanisms of action. In vitro, cytokine secretion, NF-κB p65 nuclear translocation, and CD86 mRNA expression in LPS-stimulated RAW264.7 cells were constrained by LbGp treatment. In A549 cells, LbGp can inhibit H1N1 infection by blocking virus attachment and entry action. In vivo experiments confirmed that administration of LbGp can effectively increase the survival rate, body weight and decrease the lung index of mice infected with H1N1. Compared to the model group, pulmonary histopathologic symptoms in lung sections of mice treated with LbGp were obviously alleviated. Further investigation revealed that the mechanism of LbGp in the treatment of H1N1-induced viral pneumonia includes reducing the viral load in lung, regulating the phenotype of pulmonary macrophages, and inhibiting excessive inflammation. In conclusion, LbGp exhibits potential curative effects against H1N1-induced viral pneumonia in mice, and these effects are associated with its good immuno-regulatory and antiviral activities.

COVID-19 does not influence functional status after ARDS therapy.

RATIONALE: Health-related quality of life after surviving acute respiratory distress syndrome has come into focus in recent years, especially during the coronavirus disease 2019 pandemic. OBJECTIVES: A total of 144 patients with acute respiratory distress syndrome caused by COVID-19 or of other origin were recruited in a randomized multicenter trial. METHODS: Clinical data during intensive care treatment and data up to 180 days after study inclusion were collected. Changes in the Sequential Organ Failure Assessment score were used to quantify disease severity. Disability was assessed using the Barthel index on days 1, 28, 90, and 180. MEASUREMENTS: Mortality rate and morbidity after 180 days were compared between patients with and without COVID-19. Independent risk factors associated with high disability were identified using a binary logistic regression. MAIN RESULTS: The SOFA score at day 5 was an independent risk factor for high disability in both groups, and score dynamic within the first 5 days significantly impacted disability in the non-COVID group. Mortality after 180 days and impairment measured by the Barthel index did not differ between patients with and without COVID-19. CONCLUSIONS: Resolution of organ dysfunction within the first 5 days significantly impacts long-term morbidity. Acute respiratory distress syndrome caused by COVID-19 was not associated with increased mortality or morbidity.

Early Detection of Aspergillus Species in Lower Respiratory Tract is Associated with Higher Mortality in Viral Community-Acquired Pneumonia: A Multicenter Prospective Cohort Study in China.

PURPOSE: Community-acquired pneumonia (CAP) is a leading cause of adult mortality worldwide and poses a significant global burden. Previous studies have indicated a tendency for viral pneumonia, particularly severe influenza virus pneumonia, to be complicated by Aspergillus superinfection. However, the clinical features and prognostic implications of Aspergillus detection in early-onset viral CAP remain unclear. METHODS: We conducted a prospective multicenter observational cohort study in China involving CAP patients. Adult patients with CAP from six hospitals were enrolled between January 2017 and October 2018. Within 72 h of admission, lower respiratory tract specimens, including sputum and alveolar lavage fluid, were collected. Comprehensive pathogenic testing, utilizing molecular biology techniques, was performed on the collected specimens, encompassing bacteria, atypical pathogens, viruses, and fungi. Patient clinical data were collected through a unified electronic medical record website system. RESULTS: A total of 382 adult CAP patients were included in the study. The viral detection rate was 38% (145/382), with Aspergillus identified in 11.0% (16/145) of viral CAP cases. Mortality among Aspergillus-positive patients was significantly higher (25%, 4/16) compared to Aspergillus-negative patients (5.4%, 7/129) in viral CAP (P = 0.021). Multivariable logistic regression models demonstrated that the presence of Aspergillus at admission might increase the mortality risk in viral CAP [OR (95%CI) = 7.34 (0.92-58.65), P = 0.06]. Furthermore, Aspergillus-positive patients exhibited a significantly lower lymphocyte count than Aspergillus-negative patients (P = 0.047). CONCLUSION: Positive detection of Aspergillus in lower respiratory tract specimens might be associated with higher mortality in early-onset viral CAP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03093220. Registered retrospectively on 28 March 2017.

A Real Time Method for Distinguishing COVID-19 Utilizing 2D-CNN and Transfer Learning.

Rapid identification of COVID-19 can assist in making decisions for effective treatment and epidemic prevention. The PCR-based test is expert-dependent, is time-consuming, and has limited sensitivity. By inspecting Chest R-ray (CXR) images, COVID-19, pneumonia, and other lung infections can be detected in real time. The current, state-of-the-art literature suggests that deep learning (DL) is highly advantageous in automatic disease classification utilizing the CXR images. The goal of this study is to develop models by employing DL models for identifying COVID-19 and other lung disorders more efficiently. For this study, a dataset of 18,564 CXR images with seven disease categories was created from multiple publicly available sources. Four DL architectures including the proposed CNN model and pretrained VGG-16, VGG-19, and Inception-v3 models were applied to identify healthy and six lung diseases (fibrosis, lung opacity, viral pneumonia, bacterial pneumonia, COVID-19, and tuberculosis). Accuracy, precision, recall, f1 score, area under the curve (AUC), and testing time were used to evaluate the performance of these four models. The results demonstrated that the proposed CNN model outperformed all other DL models employed for a seven-class classification with an accuracy of 93.15% and average values for precision, recall, f1-score, and AUC of 0.9343, 0.9443, 0.9386, and 0.9939. The CNN model equally performed well when other multiclass classifications including normal and COVID-19 as the common classes were considered, yielding accuracy values of 98%, 97.49%, 97.81%, 96%, and 96.75% for two, three, four, five, and six classes, respectively. The proposed model can also identify COVID-19 with shorter training and testing times compared to other transfer learning models.

The protective effect of 999 XiaoErGanMao granules on the lungs and intestines of influenza A virus-infected mice.

CONTEXT: Gastrointestinal symptoms are a common complication of influenza virus infection in children, which the gut-lung axis become involved in its biological progress. The protective effect of 999 XiaoErGanMao granules (XEGMG) on multi-organ injury in viral pneumonia remains unclear. OBJECTIVE: To investigate the therapeutic effect of XEGMG on lungs and intestines injury in A/FM/1/47 (H1N1) influenza virus-infected mice. MATERIALS AND METHODS: Male BALB/c mice were infected with the 2LD50 H1N1 influenza virus and then treated with XEGMG (6 or 12 g/kg) intragastrically once a day for 4 days. The lung and colon samples were then collected for pathological observation, and assays for inflammatory cytokines and intestinal barrier. Mouse feces were collected to evaluate the intestinal microbiota. RESULTS: Treating with XEGMG (12 g/kg) can mitigate body weight loss caused by 2LD50 H1N1 infection. It can also reduce lung index and pathological damage with the decreased inflammatory cytokines such as IL-6 and IL-1ß. Furthermore, XEGMG (12 g/kg) can maintain the goblet cell number in the colons to protect the intestinal barrier and regulate the major flora such as Firmicutes, Bacteroidetes, and Muribaculaceae back to normal. Meanwhile, the expression of IL-17A in the colon tissues was significantly lower in the group of XEGMG (6, 12 g/kg) compared to H1N1 group. DISCUSSION AND CONCLUSIONS: XEGMG can protect against H1N1 invasion involved in gut-lung axis regulation. The results provide new evidence for the protective effect of XEGMG, which is beneficial to vulnerable children.

THE ROLE OF THROMBOSIS RISK SCALES LIKE PROGRESSION PREDICTORS OF COVID-19-ASSOCIATED PNEUMONIA.

OBJECTIVE: The aim: To determine the risk factors for progression by establishing the diagnostic and prognostic role of PPS and ISTH DIC score in patients with COVID-19 required hospitalization. PATIENTS AND METHODS: Materials and methods: Main group was 130 patients with COVID-19, divided depending on the severity into 3 subgroups. Patients were examined twice. On visit 1 and visit 2 (after 7-14 days after hospitalization). Were provided: physical examination, lung ultrasound (LUS), laboratory tests (D-dimer, coagulogram). Were counted PPS and ISTH DIC score. Non-parametrical statistic, ROC analysis. RESULTS: Results: The level of D-dimer was significantly elevated in the examined patients and correlated with the severity of the disease. The number of points on the scales ISTH DIC and Padua had a significant difference between the subgroups. The maximum number of points was obtained by patients of subgroup 3, which indicates the maximum risk of thrombotic complications, as well as DIC. The ROC analysis showed that among coagulation parameters the most sensitive and specific factors associated with the progression of the clinical course is the D-dimer at admission. CONCLUSION: Conclusions: Thus, the determination of D-dimer, fibrinogen, as well as usage of the DIC and Padua scales is a useful tool not only to estimate the severity of COVID-19, but also to predict the prognosis. Thus, the level of D-dimer above 260 ng/ml, as well as the presence of three or more points on the DIC scale and/or five or more points on the Padua scale in patients with COVID-19 during hospitalization significantly increases the risk of progression clinical process.

Antiviral Drugs for Viral Pneumonia.

How to cite this article: Bansal T. Antiviral Drugs for Viral Pneumonia. Indian J Crit Care Med 2023;27(8):600.