Severe Pneumonia Patients Research Articles

Investigation of Microbial Etiology in Endotracheal Aspirate Samples of Severe Pneumonia Patients by Multiplex PCR and Culture Method

Objectives: The probability of detecting viral and atypical agents in pneumonia patients has increased with the molecular methods used in recent years. We aimed to investigate pneumonia pathogens in endotracheal aspiration samples (ETA) of patients with severe community-acquired (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) by multiplex polymerase chain reaction (m-PCR) and culture method. Methods: A prospective study was performed between December 2019 and October 2020. Patients 18 years and older with pneumonia followed in ICU on the mechanical ventilator were included. COVID-19 patients were excluded. Patients were grouped as CAP, HAP, and VAP. Two ETA samples were obtained from patients within 48 hours of the pneumonia diagnosis. Respiratory pathogens were investigated in samples by viral-bacterial m-PCR and bacterial culture methods. Results: 74 patients were included in the study. m-PCR of ETA samples achieved pathogen detection in 87.8% of patients compared with 58.1% with culture methods. The most common pathogen detected by m-PCR was Streptococcus pneumoniae in both CAP and HAP patients and Klebsiella spp. in VAP patients. The most common pathogen isolated by culture was Staphylococcus aureus in both CAP and HAP patients and Klebsiella spp. in VAP patients. Atypical pneumonia pathogens were positive for 14.9% of the patients. Atypical pathogens were recovered from 28.5% of CAP patients and 23.1% of HAP patients. Viruses constituted all of the atypical pathogens recovered from HAP patients. No atypical pathogen was found in VAP patients. Conclusion: In this study, S. pneumoniae was the most common pathogen detected with m-PCR, and S. aureus and Klebsiella spp. were the most common pathogens detected with culture. Determination of microbial etiology of lower respiratory tract samples by molecular methods for diagnosing severe CAP and HAP may be beneficial in terms of treatment. Keywords: pneumonia, multiplex PCR, endotracheal aspirate, conventional methods

Impact of COVID-19 pandemic on emergency department length of stay and clinical outcomes of patients with severe pneumonia: A single-center observational study.

We examined the impact of COVID-19 pandemic on the emergency department length of stay (EDLOS) and clinical outcomes of patients with severe pneumonia admitted to the intensive care unit (ICU) through the emergency department (ED). This single-center retrospective observational study included adult patients with pneumonia admitted to the ICU through the ED between January and December 2019 (pre-pandemic) and between March 2020 and February 2021 (during-pandemic). We compared and analyzed the EDLOS by dividing it into pre-, mid-, and post-EDLOS and in-hospital mortality of patients with pneumonia admitted to the ICU according to the time of ED visits before and during the COVID-19 pandemic. Risk factors for in-hospital mortality according to the time of ED visits were analyzed using multiple logistic regression analysis. In total, 227 patients (73 patients pre-pandemic and 154 patients during the pandemic) with pneumonia admitted to the ICU through the ED were analyzed. During the COVID-19 pandemic, pre-, mid-, and post-EDLOS increased (P < .05), and the in-hospital mortality rate increased by 10.4%; however, this was not significant (P = .155). Multivariate logistic regression analysis revealed post-EDLOS (ED waiting time after making ICU admission decision) as an independent risk factor for in-hospital mortality of patients with pneumonia admitted to the ICU, pre-pandemic (odds ratio [OR] = 2.282, 95% confidence interval [CI]: 1.367–3.807, P = .002) and during the pandemic (OR = 1.126, 95% CI: 1.002–1.266, P = .047). Mid-EDLOS (ED time to assess, care, and ICU admission decision) was an independent risk factor for in-hospital mortality of patients with pneumonia admitted to the ICU during the COVID-19 pandemic (OR = 1.835, 95% CI: 1.089–3.092, P = .023). During the pandemic of emerging respiratory infectious diseases, to reduce in-hospital mortality of severe pneumonia patients, it is necessary to shorten the ED waiting time for admission by increasing the number of isolation ICU beds. It is also necessary to accelerate the assessment and care process in the ED, and make prompt decisions regarding admission to the ICU.

An AI based digital-twin for prioritising pneumonia patient treatment.

A digital-twin based three-tiered system is proposed to prioritise patients for urgent intensive care and ventilator support. The deep learning methods are used to build patient-specific digital-twins to identify and prioritise critical cases amongst severe pneumonia patients. The three-tiered strategy is proposed to generate severity indices to: (1) identify urgent cases, (2) assign critical care and mechanical ventilation, and (3) discontinue mechanical ventilation and critical care at the optimal time. The severity indices calculated in the present study are the probability of death and the probability of requiring mechanical ventilation. These enable the generation of patient prioritisation lists and facilitates the smooth flow of patients in and out of Intensive Therapy Units (ITUs). The proposed digital-twin is built on pre-trained deep learning models using data from more than 1895 pneumonia patients. The severity indices calculated in the present study are assessed using the standard benchmark of Area Under Receiving Operating Characteristic Curve (AUROC). The results indicate that the ITU and mechanical ventilation can be prioritised correctly to an AUROC value as high as 0.89. This model may be employed in its current form to COVID-19 patients, but transfer learning with COVID-19 patient data will improve the predictions. The digital-twin model developed and tested is available via accompanying Supplemental material.

重症COVID–19肺炎の急性期の循環動態は比較的安定している～単施設・症例対照研究～(Critically ill patients with novel coronavirus infectious disease (COVID–19) are relatively hemodynamically stable in the acute phase: a single–centered, retrospective, observational study)

ABSTRACTTo clarify the clinical course of severe COVID–19 pneumonia requiring ventilator support, we investigated the difference of SOFA scores between severe COVID–19 pneumonia and severe pneumonia patients before the emergence of COVID–19. In this single–centered, retrospective, observational study, we enrolled 14 COVID–19 patients requiring ventilator management between February 2020 and May 2020 (COVID–19 group) and 14 patients with pneumonia requiring ventilator management between January 2017 to December 2018 (non–COVID–19 group). We investigated demographic data, laboratory values, treatment, and the SOFA scores on Day 0, 1, and 3, with Day 0 being the day of intubation. The mean age of the 14 COVID–19 patients was 68.3 years and there was no difference in comorbidities and in–hospital mortality with the two groups. The mean SOFA scores (COVID–19 vs. non–COVID–19 group) on the day of intubation were 3.0 vs. 3.1 for respiratory system, 0.1 vs. 2.8 for cardiovascular system, 0.5 vs. 0.6 for coagulation, 0.3 vs. 0.6 for hepatobiliary system, 0.8 vs. 1.6 for central nervous system, and 0.4 vs. 1.3 for renal system, respectively. Significant differences were recognized in cardiovascular system (p<0.01) and central nervous system (p=0.049). The SOFA subscores for cardiovascular system remained significantly lower in the COVID group on Day 1 and 3. The rate of patients who used any vasopressors and the median fluid volume on the day of intubation were significantly lower in COVID–19 group. In conclusion, the hemodynamics were seemed to be more stable in severe COVID–19 pneumonia compared to non–COVID–19 severe pneumonia.

Assessment of Antibiotic Use in ICU Patients with Pneumonia Using ATC/DDD as a Quantitative Analysis Method

Background: Pneumonia is an infection of the lung tissue which is mainly caused by bacteria. High utilization and inappropriate use of antibiotics increase resistant bacteria, morbidity, mortality, and treatment cost. Quantitative evaluation becomes one of the indicators to assess the use of antibiotics which is one indicator of the quality of the antimicrobial resistance control program. Objective: This study aimed to evaluate the use of antibiotics an effort to increase the rationality of the use of antibiotics. Methods: This study was a retrospective observational study with a sampling method of time-limited sampling in Universitas Airlangga hospital from January until December 2019. Quantitatively using Anatomical Therapeutic Chemical (ATC)/Defined Daily Dose (DDD). Result: The samples obtained were 68 severe pneumonia patients who met the inclusion criteria. From the result of the study, there were 13 types of antibiotics used for pneumonia therapy, and the three most used were Levofloxacin, Ceftriaxone, and Meropenem, with a total of all antibiotics 73.64 DDD/100 patients-days. Most useful is parenteral Levofloxacin at 21.92 DDD/100 patient-days, Ceftriaxone at 20.45 DDD/100 patient-days and Meropenem at 14.29 DDD/100 patient-days. Conclusion: The DDD value indicates high antibiotic usage, but high antibiotic use does not imply unreasonable drug use, so we must undertake a qualitative review of antibiotic use.

Association of TNF-α, TGF-β1, amphiregulin, IL-2, and EGFR WITH pulmonary fibrosis in COVID-19

Pulmonary fibrosis is a well-recognized sequela associated with coronavirus disease 2019 (COVID-19), however the mechanism is yet to be clearly understood. The study was designed to evaluate the association of TNF-α, TGF- β1, amphiregulin, IL-2, and EGFR with pulmonary fibrosis after COVID-19 pneumonia. Non-severe, severe, and critical COVID-19 pneumonia patients were included in this study after the patients agreed and gave written informed consent. Blood samples were analyzed with the ELISA method for cytokine examination. The non-contrast chest CT scan was performed after patients were discharged from hospital. Seventy-nine patients with a mean age of 54 years (57 % men, 43 % women) were fully evaluated. Pulmonary fibrosis was found in 74 patients (93.7 %). Serum levels of TGF-β1 60.55 pg/mL (11.42–2001.16), TNF-α 13.31 pg/mL (3.54–200.32), EGFR 14.9 pg/mL(6.4–53.6), IL-2 12.41 pg/mL(11–14.13), amphiregulin 156.5 pg/mL (21.7–1234). Serum levels of TNF-α increase according to the severity of clinical classification. A significant association between serum levels of TGF-β1, TNF- α, and pulmonary fibrosis with rs-0.247, p = 0.027; rs 0.259, p = 0.046 was found. According to this study, TNF-α and TGF-β1 potentially participate in the process of pulmonary fibrosis in COVID-19.

The relationship between lung fibrosis, the epidermal growth factor receptor, and disease outcomes in COVID-19 pneumonia: a postmortem evaluation.

The aim of this study was to examine the relationship between the severity of fibrosis in lung tissue and epidermal growth factor receptor (EGFR) positivity in patients who died due to COVID-19 pneumonia, demographic characteristics, comorbidities, biochemical values, and treatments received. Fifty patients who died from COVID-19 pneumonia were included in the study. Demographic data for the patients, laboratory tests, thorax computerized tomography findings, comorbidities, length of stay in the intensive care unit (ICU), intubation times, and treatments given were noted. Postmortem Tru-cut lung biopsy was performed. EGFR positivity was examined and grouped as negative, mild, moderate, and severe. Data were analyzed statistically. EGFR involvement was negative in 11 (22%), mild in 20 (40%), moderate in 13 (26%), and severe in 6 (12%) patients. The mean C-reactive protein (CRP) values, D-dimer values, and mean length of stay in the ICU were found to be significantly different between the groups (p = 0.024; p = 0.003; p = 0.016, respectively). Methylprednisolone dose and the presence of comorbidity did not differ significantly in EGFR involvement (p = 0.79; p = 0.98, respectively). CRP and D-dimer values can be used as a guide to assess the severity of pulmonary fibrosis that develops in severe COVID-19 pneumonia patients. The dose of methylprednisolone used does not make a significant difference in the severity of fibrosis.Trail registration: Clinical Trials.gov identifier date and number 01/13/2022 NCT05290441.

Clinical profile analysis and nomogram for predicting in-hospital mortality among elderly severe community-acquired pneumonia patients with comorbid cardiovascular disease: a retrospective cohort study

BackgroundResearchers have linked cardiovascular disease (CVD) with advancing age; however, how it drives disease progression in elderly severe community acquired pneumonia (SCAP) patients is still unclear. This study aims to identify leading risk predictors of in-hospital mortality in elderly SCAP patients with CVD, and construct a comprehensive nomogram for providing personalized prediction.Patients and methodsThe study retrospectively enrolled 2365 elderly patients identified SCAP. Among them, 413 patients were found to have CVD. The LASSO regression and multivariate logistic regression analysis were utilized to select potential predictors of in-hospital mortality in elderly SCAP patients with CVD. By incorporating these features, a nomogram was then developed and subjected to internal validations. Discrimination, calibration, and clinical use of the nomogram were assessed via C-index, calibration curve analysis, and decision plot.ResultsCompared with patients without CVD, elderly SCAP patients with CVD had a significant poor outcome. Further analysis of the CVD population identified 7 independent risk factors for in-hospital mortality in elderly SCAP patients, including age, the use of vasopressor, numbers of primary symptoms, body temperature, monocyte, CRP and NLR. The nomogram model incorporated these 7 predictors showed sufficient predictive accuracy, with the C-index of 0.800 (95% CI 0.758–0.842). High C-index value of 0.781 was obtained in the internal validation via bootstrapping validation. Moreover, the calibration curve indicative a good consistency of risk prediction, and the decision curve manifested that the nomogram had good overall net benefits.ConclusionAn integrated nomogram was developed to facilitate the personalized prediction of in-hospital mortality in elderly SCAP patients with CVD.

Pulmonary cavitation in follow-up COVID 2019 cases: An etiological perspective

BackgroundThe current COVID-19 pandemic is an ongoing global healthcare challenge that has caused morbidity and mortality at unprecedented levels. Since the post-COVID pulmonary complications are evolving and challenging, a study was carried out to assess pulmonary cavitation in follow-up COVID cases from an etiological perspective. The aim of this study was to assess the incidence of pulmonary cavitation and describe its etiology and evolution in moderate and severe post-COVID pneumonia patients. MethodsA prospective observational study of all patients admitted to our institution with moderate or severe COVID pneumonia was carried out. Some of these patients again became symptomatic after discharge and developed pulmonary cavitation on imaging. Results6.2% (n = 37) out of 589 patients admitted to our institution with moderate or severe COVID pneumonia developed pulmonary cavitation on follow-up. We describe the imaging characteristics of post-COVID cavitation and present these patients' clinical, laboratory, and microbiological parameters. ConclusionCavitary lung disease in patients with moderate to severe COVID-19 disease is not uncommon, and an etiological workup is necessary to institute timely and correct therapy.

Effect of treatment regimens in severe COVID pneumonia at an Indian tertiary care hospital: An observational, real-world study

BackgroundCorticosteroids have attracted attention as a treatment option for severe Coronavirus disease (COVID-19). However, published data on steroid therapy is debatable, and real-world data is lacking. This study evaluated the effect of treatment regimens, especially Pulse steroid therapy (Injection Methyl Prednisolone 250 mg iv once a day for three days) in severe-COVID-19 pneumonia at an Indian tertiary care hospital. MethodsThis observational cross-sectional study included severe COVID-19 pneumonia patients aged >18 years, requiring assisted ventilation. As part of the hospital protocol, patients received either pulse steroid therapy, remdesivir or tocilizumab in addition to the recommended steroid doses i.e., injection of dexamethasone 6 mg iv once a day. The association of factors and treatment regimens to patient outcomes was evaluated. ResultsData of eighty-three patients were assessed, majority being above 60 years (n = 30, 36.14%) and males (n = 45/83, 54.21%). The commonest comorbidities were hypertension (n = 26), diabetes (n = 23) and obesity (n = 19), fifty-five patients (66.26%) reported at least one comorbidity. Sixty-one patients (73.49%) had received pulse steroid regimen, forty-eight patients (57.83%) were administered remdesivir-based regimen while twelve patients (14.46%) had received tocilizumab treatment. 54.1% patients managed with pulse steroid regimens were discharged after treatment, statistically similar to remdesivir-managed subgroup (62.5%, p > 0.05). On sub-group analysis, pulse steroids showed better outcomes in young males with no comorbidities. No comorbidity had significant relationship with patient outcomes (p > 0.05). ConclusionPulse steroid therapy is an effective therapy in management of patients with severe COVID-19 pneumonia in a real-world setting, with better outcomes in young males without comorbidities. Pulse steroids can be considered a viable option for severe-COVID-19 pneumonia management.

Respiratory technologists in the frontlines against COVID-19.

Background The COVID-19 pandemic overwhelmed healthcare resources globally, but especially those of resource-limited countries. Strategies to supplement the number of healthcare workers attending COVID-19 patients had to be implemented. Several institutions used non-respiratory clinicians to work in COVID-19 wards. At Universitas Academic Hospital (UAH), Bloemfontein, South Africa, respiratory technologists were requested to assist with managing the oxygen supportive care of patients with severe COVID-19 and respiratory failure. Objectives To highlight the contribution that respiratory technologists made in the management of severe COVID-19 pneumonia patients by describing the baseline characteristics and mortality of patients with COVID-19, whose oxygen supportive care was managed primarily by respiratory technologists at UAH. Methods This was a retrospective study. The investigators extracted data from the hospital files of all adult patients admitted with severe COVID-19 to UAH and where respiratory technologists were involved in their care between 1 January and 31 December 2020. Results A total of 781 patients were admitted to UAH, of whom 106 fulfilled the inclusion criteria. The majority of the patients were female (n=68; 64.1%), and the median age (interquartile range (IQR)) was 59.5 (51 - 68) years. Hypertension (n=69; 65.1%) and diabetes mellitus (n=39; 36.8%) were the most frequent comorbidities. At the time of admission, the median oxygen saturation was 92% and the median respiratory rate oxygenation (ROX) index was 3.2. The median length of stay was 7 days and the mortality was 41.5%. Conclusion The clinical characteristics and mortality of patients whose oxygen support was managed by respiratory technologists were similar to those in previously reported studies from resource-limited settings. Respiratory technologists can form a valuable addition to the front-line team when clinicians and nurses are faced with overwhelming patient numbers in subsequent COVID-19 surges and where the mainstay of treatment is oxygen supportive care.

Low BALF CD4 T cells count is associated with extubation failure and mortality in critically ill covid-19 pneumonia

Background Critically ill COVID-19 pneumonia is one of the main causes of extubation failure and mortality. Understanding clinical characteristics, laboratory profiles and bronchoalveolar lavage fluid (BALF) immunopathology may help improve outcomes in critically ill COVID-19 pneumonia. We aimed to describe clinical characteristics, laboratory profiles and BALF immunopathology based on lung severity in critically ill COVID-19 pneumonia patients. Materials and methods Forty critically ill severe pneumonia patients requiring invasive mechanical ventilation in Cipto Mangunkusumo General (National Tertiary Referral Hospital), Indonesia within November 2020–January 2021 were enrolled in this study. Early BALF collection was performed after patients’ intubation. Clinical characteristics, laboratory profiles and BALF biomarkers (sTREM-1, alveolar macrophage amount and function, IL-6, IL-17, CD4 T-cells, Tregs, SP-A and Caspase-3) were observed and analysed. Outcomes were measured based on extubation failure (within 19 days) and 28-days mortality. Univariate and bivariate analyses were performed. Results Early bronchoscopy was performed in an average of 4 h (SD = 0.82) after patients’ intubation. Twenty-three and twenty-two patients had extubation failure (within 19 days) and 28-days mortality, respectively. In the baseline clinical characteristics of critically ill COVID-19 patients, we found no significant differences in the extubation and mortality status groups. In the laboratory profiles of critically ill COVID-19 patients, we found no significant differences in the extubation status groups. In critically ill COVID-19 pneumonia patients, there was a significant high D-dimer levels in survived group (p = .027), a significant low BALF CD4 T-cells count in the right lung (p = .001) and a significant low BALF CD4 T-cells count (p = .010 and p = .018) in severely affected lung with extubation failure and mortality. Conclusions BALF CD4 T-cells count evaluation of severely affected lung is associated with early extubation failure and mortality in critically ill COVID-19 pneumonia patients. KEY MESSAGE Few studies have been conducted during the peak COVID-19 period analysing combined bronchoalveolar lavage fluid (BALF) immunopathology biomarkers within four hours of intubation to assess extubation failure and mortality. In this study, we reported eight BALF immunopathology biomarkers (sTREM-1, alveolar macrophage, IL-6, IL-17, CD4 T-cells, Tregs, SP-A and Caspase-3). We found significantly low BALF CD4 T-cells count in the right lung, and low BALF CD4 T-cells count in severely affected lung of critically ill COVID-19 pneumonia patients in extubation failure and mortality.

Chest-X-ray-based scoring, total leukocyte count, and neutrophil-to-lymphocyte ratio to predict in-hospital mortality in COVID-19 patients: a retrospective study

Background: The objective of this study was to assess the demographical characteristic, laboratory and radiological findings associated with COVID-19 mortality in hospitalized patients and also to co-relate neutrophil-to-lymphocyte ratio (NLR) and chest x-ray (CXR) score with severity of the disease.Methods: This is a retrospective study done in Bowring and Lady Curzon hospital between the period of May 2021 to July 2021. 100 patients who were tested positive for SARS-CoV2 with RT-PCR were taken for the study after fulfilling the inclusion criteria. On day 1 of admission, routine blood investigations including CBC with differential count and chest X ray is taken. From the above said data, NLR and CXR score is calculated and a comparison is made to determine severity and in-hospital mortality between mild, moderate and severe COVID pneumonia patients. This study is being carried out after obtaining institutional ethical committee approval clearance. All analysis were performed using SPSS software version 10.Results: The sample size studied was 100. The mean age of patients was 28.3 in mild, 49.9 in moderate and 62.6 in severe COVID patients. Among these 67% were males and 33% were females. It was noted that, leukocytosis (mean-13245), neutrophilia (mean-83.05%), lymphocytopenia (mean-10.45%) and chest X-ray score (mean-4.98) was seen among severe group with p value being significant.Conclusions: TLC, NLR and CXR score were significantly different between severe and non-severe patients, so assessment of these simple parameters may help identify high risk COVID-19 patients at an early stage in a resource limited setting from the data retrieved from our hospital, NLR and CXR Score showed an acceptable efficiency to separate COVID-19 patients among severe and non-severe patients with a significant p value thereby helping in triaging the patients and need for early ICU needs.

Weaker Response to XueBiJing Treatment in Severe Community-Acquired Pneumonia Patients With Higher Body Mass Index or Hyperglycemia: A Post Hoc Analysis of a Randomized Controlled Trial.

Background: Overweight and hyperglycemia might result in poor prognosis in patients with severe community-acquired pneumonia (SCAP). XueBiJing treatment could significantly improve the outcomes of patients with SCAP. We investigated the efficacy of XueBiJing injection in patients with SCAP stratified by body mass index (BMI) and fasting blood glucose (FBG). Methods: This is a post hoc analysis of XueBiJing trial, a large prospective, randomized, controlled study conducted in 33 hospitals in China. We compared data from non-overweight (BMI <24 kg/m2, n = 425) vs. overweight (BMI ≥24 kg/m2, n = 250) patients as well as non-hyperglycemia (FBG <7 mmol/L, n = 315) vs. hyperglycemia (FBG ≥7 mmol/L, n = 360) patients with XueBiJing, 100 ml, q12 h, or a visually indistinguishable placebo treatment for 5–7 days. Results: Among patients with BMI <24 kg/m2 (n = 425), 33 (15.3%), XueBiJing recipients and 52 (24.9%) placebo recipients (p = 0.0186) died within 28 days. Among patients with BMI ≥24 kg/m2 (n = 250), XueBiJing recipients still had lower mortality (XueBiJing 16.9% vs. placebo 24.2%; p = 0.2068) but without significantly statistical difference. For the FBG group, patients with FBG <7 mmol/L (n = 315), 18 (11.2%) XueBiJing recipients and 32 (20.8%) placebo recipients (p = 0.030) died within 28 days. Among patients with FBG ≥7 mmol/L (n = 360), XueBiJing recipients still had lower mortality (XueBiJing 20.2% vs. placebo 27.8%; p = 0.120) but without significantly statistical difference. The total duration of the ICU stay and the duration of mechanical ventilation were similar in both groups (p > 0.05). Conclusion: Overweight or hyperglycemia might weaken the efficacy of XueBiJing injection in the treatment of SCAP as indicated by the significant elevated risk of 28-day mortality. Additional studies are needed to validate our findings and to further understand the underlying mechanisms.

Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study

BackgroundExisting clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19.MethodsThe MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging.ResultsSeven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 109/L vs. 1.78 × 109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients.ConclusionsOur trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population.Trial Registration: MEXCOVID, NCT04276987.

Abnormal expression of lncRNA CASC9 in pneumonia children with respiratory failure and its feasible value for the clinical diagnosis of patients

ABSTRACT lncRNA CASC9 expression was involved in a variety of diseases and exerted a protective role against inflammation and sepsis-induced injury. However, the role of CASC9 in severe pneumonia remains unclear. This study aimed to explore the potential diagnostic role of lncRNA CASC9 in severe pneumonia. The CASC9 expression levels were measured by RT-qPCR. The receiver operating characteristic curve (ROC) was conducted to evaluate the clinical diagnostic value of CASC9 in severe pneumonia. LPS-induced human lung fibroblast MRC-5 was used to establish the pneumonia model and then transfected with CASC9 overexpression vectors to evaluate the influence of CASC9 on cell viability and apoptosis. The inflammatory cytokines IL-1β, TNF-α, IL-6 levels were detected using a commercial enzyme-linked immunosorbent assay (ELISA). Pearson correlation analysis was used to explore the correlation between CASC9 expression and clinical data. The relative expression of CASC9 was downregulated in serum samples of severe pneumonia patients. The low expression of CASC9 in severe pneumonia was negatively correlated with several clinical data. The CASC9 had the relatively high area under ROC curve (AUC) values for distinguishing severe pneumonia from pneumonia children and healthy control. The elevated expression of CASC9 accelerated cell viability and diminished apoptosis in LPS-induced MRC-5 cells. The CASC9 expression was decreased in serum samples of severe pneumonia, and upregulation of CASC9 facilitated LPS-induced cell viability and inhibited apoptosis. In summary, CASC9 might be a diagnostic predictor and might act as a crucial regulatory roles in the progression of severe pneumonia.

Sex-Dependent Performance of the Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, Platelet-to-Lymphocyte and Mean Platelet Volume-to-Platelet Ratios in Discriminating COVID-19 Severity.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and mean platelet volume-to-platelet ratio (MPR) are combined hematology tests that predict COVID-19 severity, although with different cut-off values. Because sex significantly impacts immune responses and the course of COVID-19, the ratios could be biased by sex.PurposeThis study aims to evaluate sex-dependent differences in the contribution of NLR, PLR, MLR, and MPR to COVID-19 severity and mortality upon hospital admission using a sample of pneumonia patients with SARS-CoV-2 infection.MethodsThis single-center observational cross-sectional study included 3,280 confirmed COVID-19 cases (CDC 2019-Novel Coronavirus real-time RT-PCR Diagnostic) from Quito (Ecuador). The receiver operating characteristic (ROC) curve analysis was conducted to identify optimal cut-offs of the above parameters when discriminating severe COVID-19 pneumonia and mortality risks after segregation by sex. Severe COVID-19 pneumonia was defined as having PaO2 < 60 mmHg and SpO2 < 94%, whereas non-severe COVID-19 pneumonia was defined as having PaO2 ≥ 60 mmHg and SpO2 ≥ 94%.ResultsThe mortality rate of COVID-19 among men was double that in women. Severe COVID-19 pneumonia and non-surviving patients had a higher level of NLR, MLR, PLR, and MPR. The medians of NLR, MLR, and MPR in men were significantly higher, but PLR was not different between men and women. In men, these ratios had lower cut-offs than in women (NLR: 2.42 vs. 3.31, MLR: 0.24 vs. 0.35, and PLR: 83.9 vs. 151.9). The sensitivity of NLR, MLR, and PLR to predict pneumonia severity was better in men (69–77%), whereas their specificity was enhanced in women compared to men (70–76% vs. 23–48%).ConclusionThese ratios may represent widely available biomarkers in COVID-19 since they were significant predictors for disease severity and mortality although with different performances in men and women.

A risk scoring system to predict progression to severe pneumonia in patients with Covid-19

Rapid outbreak of coronavirus disease 2019 (Covid-19) raised major concern regarding medical resource constraints. We constructed and validated a scoring system for early prediction of progression to severe pneumonia in patients with Covid-19. A total of 561 patients from a Covid-19 designated hospital in Daegu, South Korea were randomly divided into two cohorts: development cohort (N = 421) and validation cohort (N = 140). We used multivariate logistic regression to identify four independent risk predictors for progression to severe pneumonia and constructed a risk scoring system by giving each factor a number of scores corresponding to its regression coefficient. We calculated risk scores for each patient and defined two groups: low risk (0 to 8 points) and high risk (9 to 20 points). In the development cohort, the sensitivity and specificity were 83.8% and 78.9%. In the validation cohort, the sensitivity and specificity were 70.8% and 79.3%, respectively. The C-statistics was 0.884 (95% CI 0.833–0.934) in the development cohort and 0.828 (95% CI 0.733–0.923) in the validation cohort. This risk scoring system is useful to identify high-risk group for progression to severe pneumonia in Covid-19 patients and can prevent unnecessary overuse of medical care in limited-resource settings.

Based on the Auxiliary Effect of X-Ray in the Treatment of Severe Pneumonia in Children with Arterial and Venous Blood Gas.

Pediatric severe pneumonia clinical is a conceptual term for the diagnosis and treatment of pediatric clinical diseases. At present, domestic and foreign standards for clinical diagnosis of severe pneumonia, which is a childhood disease, are still inconsistent. At present, the first book of the main pediatric medical textbook in the society interprets the clinical definition of severe pneumonia in children as follows: severe pneumonia refers to pulmonary function in heart failure or other comorbidities in other important organs except the lung. This article is based on X-ray medical film and television examinations, through the analysis of arterial and venous blood gas in children with severe pneumonia to play a certain role in adjuvant therapy for children with pneumonia. Prospective clinical studies have found significant changes in the function of auxiliary coagulation and blood fibrinolysis indicators in patients with severe pneumonia in late childhood. The obvious difference between the pretreatment and the late-stage treatment for 1 week and the direct influence on the blood gas quantitative analysis and liver function of advanced patients provide a scientific basis for the diagnosis of typical advanced childhood severe pneumonia patients with adjuvant anticoagulant therapy. The data analysis of the clinical laboratory found that the blood coagulation and fibrinolysis functions of the typical patients with severe pneumonia in the typical late stage of childhood were significantly activated, and the anticoagulant antibody substances were significantly reduced, fibrinolytic coagulation inhibitors and anticoagulants are significantly increased, fibrinolytic activators are significantly reduced, and the body is in a procoagulant state for a long time. Adjuvant anticoagulation therapy through quantitative analysis of blood gas in patients can not only effectively increase the success rate of early treatment of typical late-stage severe pneumonia in children by 64.28% but also significantly reduce the inflammatory coagulation indexes of patients with late-stage severe pneumonia in children. The functions of coagulation, anticoagulation, and coagulation fibrinolysis have been significantly restored. The advantages of X-ray-based adjuvant treatment of severe pneumonia in children with arteriovenous blood gas are good contrast, clear imaging, and clear development of fine lesions or thick parts, and objective records are kept for comparison during review and consultation and discussion. The disadvantage is that the operation is more complicated, and it is not convenient to observe the activity function of the organ.

A study on echocardiography findings in severe COVID-19 pneumonia patients

Background: Whilst the COVID-19 predominantly affects the respiratory tract, it is also observed to cause a wide range of cardiac complications. Accordingly, the ECHO findings range from specific regional wall motion abnormalities to different degrees of global cardiac dysfunction. Thus, there is a need to better understand the interactions between COVID-19 and the cardiac functions.Methods: In this retrospective observational study, 86 subjects admitted with severe COVID-19 pneumonia were considered. Those with pre-existing heart-diseases were excluded. The ECHO parameters were assessed as right heart or left heart abnormalities; they were correlated with Inflammatory markers.Results: Right heart abnormality was the most common finding (51.1%). 23% had combined right and left heart abnormalities, 4.6% had left heart abnormality, rest 21% had a normal 2D-ECHO findings. 55.8% had evidence of pulmonary hypertension. RV dilatation and dysfunction is associated with a pro-thrombotic, inflammatory state reflected by elevation of CRP and D-dimer levels; however, these ECHO findings did not correlate with increase in marker levels (p=0.227, &gt;0.05).Conclusions: RV dysfunction is more common than LV dysfunction among COVID-19 patients. 2D-ECHO findings may serve as a useful guide in optimization and modification of treatment strategies in critically ill COVID-19 patients, but are not independent predictors of mortality (p=0.09, &gt;0.05).