Genetic clues to COVID-19 severity: exploring the stromal cell-derived factor-1/CXCL12 rs2839693 polymorphism in adult Egyptians.

BACKGROUND: A novel corona virus called SARS-CoV-2 was identified at the end of December 2019, and the illness induced by it was designated as coronavirus disease 2019 (COVID-19). Severity of the disease could vary significantly since most of the infected individuals experience mild to moderate respiratory symptoms and recover without specialized care. Genetic polymorphisms have implications in influencing the varying degrees of COVID-19 severity. This study aims to assess the potential association between the CXCL12 rs2839693 polymorphism and the severity of COVID-19 in Assiut University Quarantine Hospital during the period from May 2022 to August 2022. METHODS: The present study is a cross-sectional study and is applied to 300 COVID-19 patients confirmed by RT-PCR admitted to Assiut University Quarantine Hospital from May 2022 to August 2022. Based on the clinical symptoms, the recruited participants had been divided into two groups. Group I involved mild or moderate cases; Group II involved severe or critical conditions. The rs2839693 polymorphism was detected by real time PCR using TaqMan assay probe. RESULTS: The frequency of the T allele and the TT genotype was significantly higher in the severe or critical group compared with the mild or moderate group (p value < 0.001). C-reactive protein (CRP) and D-dimers are significantly elevated in the combined variants (CT + TT) and the TT compared with the CC (P value 0.006 and 0.017 respectively) and the CC,CT genotypes (p value 0.019 and 0.002 respectively). The combined variants (CT + TT) of CXCL12 were found to be independent predictors to severe or critical COVID-19 risk with P value = < 0.001, OR = 3.034& 95% CI = 1.805-5.098. CONCLUSION: Our findings revealed that CXCL12 rs2839693 had a role in the development and seriousness of COVID-19. Patients with the TT genotype or the T allele at increased risk developed severe or critical rather than mild or moderate disease.

Effect of high-flow nasal cannula versus non-invasive ventilation in preventing re-intubation in high-risk chronic obstructive pulmonary disease patients: A randomised controlled trial.

Background: Currently, a high-flow nasal cannula (HFNC) has been shown to improve extubation outcomes. However, there is a lack of evidence on the utilisation of HFNC in high-risk chronic obstructive pulmonary disease (COPD) patients. This study aimed to compare the effectiveness of HFNC versus non-invasive ventilation (NIV) in preventing re-intubation following planned extubation in high-risk COPD patients. Patients and Methods: In this prospective, randomised, controlled trial, 230 mechanically ventilated COPD patients at high risk for re-intubation who fulfilled the criteria for planned extubation were enrolled. Post-extubation blood gases and vital signs at 1, 24, and 48 hours were recorded. The primary outcome was the re-intubation rate within 72 hours. Secondary outcomes included post-extubation respiratory failure, respiratory infection, intensive care unit and hospital length of stay, and mortality rate at 60 days. Results: 230 patients after planned extubation were randomly allocated to receive either HFNC (n = 120) or NIV (n = 110). Re-intubation within 72 hours was significantly lower in the high-flow group: 8 patients (6.6%) versus 23 patients (20.9%) in the NIV group {absolute difference, 14.3% [95% confidence interval (CI), 10.9-16.3]; P = 0.001}. The frequency of post-extubation respiratory failure was less in patients assigned to HFNC than in those allocated NIV (25% vs. 35.4%) [absolute difference, 10.4% (95% CI, 2.4-14.3); P = 0.001]. There was no significant difference between the two groups regarding reasons for respiratory failure after extubation. It was observed that the 60-day mortality rate was lower in patients who received HFNC than in those assigned to NIV (5% vs. 13.6%) [absolute difference, 8.6 (95% CI, 4.3 to 9.10); P = 0.001]. Conclusion: The use of HFNC after extubation appears to be superior to NIV in reducing the risk of re-intubation within 72 hours and 60-day mortality in high-risk COPD patients.

Markers of inflammasome activation in Coronavirus disease 2019 (COVID-19) Egyptian patients: Impact on disease severity.

There are conflicting data regarding the relationship between coronavirus disease 2019 (COVID-19) severity and Caspase-1 (Casp-1), interleukin-1ß (IL-1ß), and IL-18. Our study sought to quantify the levels of IL-18, IL-1ß, and Casp-1 as indicators for inflammasome activation in COVID-19 patients at Assiut University Hospitals and to correlate their levels with parameters of disease severity in COVID-19 patients. Serum levels of Casp-1, IL-1ß and IL-18 were measured in 63 COVID-19 patients and 26 normal controls by an enzyme linked immunosorbent assay (ELISA). Also, arterial blood gas analysis and laboratory parameters including hemoglobin, platelets, lymphocyte count, liver function test, kidney function test, C-reactive protein (CRP), D-dimer, ferritin and LDH were estimated. Serum levels of Casp-1, IL-1ß and IL-18 were significantly higher in the COVID-19 group as compared to controls (p= 0.04, p=0.001 and p=0.03, respectively). Although the three markers were higher in the severe group, yet only IL-1ß showed a significant difference as compared to the non-severe group (p=0.04). IL-18 had significant positive correlations with CRP and ferritin (p = 0.04 and p = 0.02, respectively). IL-1ß was positively correlated with alanine aminotransferase. Casp-1 had significant positive correlations with CRP and lactate dehydrogenase (p=0.045 and p=0.001, respectively). Patients showed weak positive correlations between serum level of Casp-1 and each of IL-1ß and IL-18. Also, a strong positive correlation was found between IL-1ß and IL-18 (p < 0.0001). In conclusion, inflammasome activation was a hallmark in COVID-19 patients. The markers of activation were positively correlated with many parameters of inflammation, may suggest their important roles in the pathophysiology of the disease and its progression. IL-1ß was the only marker to be correlated with disease severity and therefore may be suggested as a potential marker for identifying severe COVID-19 patients.

Direct Extubation to High-Flow Nasal Cannula versus Noninvasive Ventilation in Obese Subjects.

BACKGROUND: Patients who are obese have a higher risk of acute respiratory failure after extubation in the ICU. This study aimed to compare the extubation of subjects who were critically ill and obese to high-flow nasal cannula (HFNC) versus noninvasive ventilation (NIV) to determine whether HFNC can aid in reducing postextubation respiratory failure and the re-intubation rate. METHODS: In this randomized controlled trial, subjects who were obese, defined as individuals with a body mass index ≥ 30 kg/m2, were randomly assigned to receive HFNC (n = 60) versus 60 subjects treated with NIV applied immediately after extubation. The primary outcome was the incidence of postextubation respiratory failure and re-intubation rate within 72 h. Secondary outcomes included oxygenation, breathing frequency, subjective dyspnea, ICU and hospital length of stay, and ICU mortality at day 28. RESULTS: Compared with NIV, HFNC reduced the risk of respiratory failure by 8.4%, 95% CI 6.2-12.8%. Even though the rate of re-intubation was lower in the HFNC group versus in the NIV group, no statistical significance was observed (11.6% vs 16.6%; difference 5%, 95% CI 2.5%-8.2%). In 48-h periods and 72 h after extubation, the mean PaO2 /FIO2 significantly increased in the HFNC group compared with the NIV group. Both groups had low dyspnea levels 72 h after extubation. No difference was detected between the groups in breathing frequency. In addition, the 2 groups had no significant difference in ICU and hospital length of stay. The HFNC and NIV groups had comparable hospital mortality rates. The multivariable logistic regression analysis revealed the presence of severe obesity, comorbidities, a higher severity score, and hypercapnia remained as factors associated with an increased risk of re-intubation. CONCLUSIONS: Postextubation application of HFNC may prevent respiratory failure in patients who are obese. (ClinicalTrials.gov registration NCT04035351.).

COVID-19 Infection in Patients with Comorbidities: Clinical and Immunological Insight.

AIM: Our study's objectives were to study the clinical and laboratory characteristics that may serve as biomarkers for predicting disease severity, IL-10 levels, and frequencies of different T cell subsets in comorbid COVID-19 patients. METHODS: Sixty-two hospitalized COVID-19 patients with comorbidities were assessed clinically and radiologically. Blood samples were collected to assess the T lymphocyte subsets by flow cytometry and IL-10 levels by ELISA. RESULTS: The most common comorbidities observed in COVID-19 patients were diabetes mellitus (DM), hypertension, and malignancies. Common symptoms and signs included fever, cough, dyspnea, fatigue, myalgia, and sore throat. CRP, ferritin, D dimer, LDH, urea, creatinine, and direct bilirubin were significantly increased in patients than controls. Lymphocyte count and CD4+ and CD8+ T-cells were significantly decreased in comorbid COVID-19 patients, and CD25 and CD45RA expression were increased. CD4+ and CD8+ regulatory T cells (Tregs) and IL-10 levels were significantly decreased in patients. CONCLUSIONS: Many parameters were found to be predictive of severity in the comorbid patients in our study. Significant reductions in the levels and activation of CD4+ and CD8+ T-cells were found. In addition, CD4+ and CD8+ Tregs were significant decreased in patients, probably pointing to a prominent role of CD8+ Tregs in dampening CD4+ T-cell activation.

Long-term COVID-19 effects on pulmonary function, exercise capacity, and health status.

BACKGROUND: The long-term effects of respiratory function and related physiological characteristics of coronavirus disease 2019 (COVID-19) survivors have not yet been studied in depth. OBJECTIVE: To examine pulmonary function, exercise capacity, and health-related quality of life among COVID-19 survivors. METHODS: Eighty-five survivors with confirmed COVID-19 were evaluated at the end of 3 and 6 months after disease onset. The assessment included lung function, diffusing capacity, 6-min walk distance (6MWD), and health status by the 36-item Short-Form General Health Survey (SF-36) questionnaire. RESULTS: Totally 85 survivors, 48 (56.5%) were men. The mean (standard deviation) age was 34.6 (9.9) years. Thirteen patients (15.2%) had medical co-morbidities the mean length of hospitalization was 18.5 (5.6) days. 25 (29.4%) required intensive care unit admission, whereas 6 (7%) of them required invasive mechanical ventilation. No significant differences were observed between lung volume parameters. At 6 months, there was a significant reduction in diffusing capacity for carbon monoxide (DLCO), P = 0.02*. 25 (29.4%) of patients had impaired DLCO ≤80% predicted. Regarding 6MWD, a significant increase was noted in 6MWD from 486 ± 72 m at 3 months to 526 ± 82 m at 6 months (P = 0.001*). The 6MWD was lower than that for normal controls of the same age groups. There was significant impairment of health status assessed by SF-36 questionnaire among COVID-19 survivors at 6 months as compared with controls of the same age groups. There were significant positive correlations between lung function parameters (FVC, VC, FEV1, and DlCO) with several SF-36 domains. CONCLUSION: In discharged survivors with COVID-19, 23.5% had significant impairment of diffusion capacity abnormality of lung function. The exercise capacity and health status were considerably lower than that of a normal population after 6 months postinfection.

Assessment of community psycho-behavioral responses during the outbreak of novel coronavirus (2019-nCoV): a cross-sectional study.

The novel coronavirus 2019 (2019-nCoV) is a public health emergency of international concern resulting in adverse psychological impacts during the epidemic. METHODS: From 1 to 10 April 2020, we conducted an online survey. The online survey collected information on demographic data, precautionary measures against (2019-nCoV), self-health evaluation, knowledge, and concerns about (2019-nCoV), and appraisal of crisis management. The psychological impact was assessed by the General Anxiety Disorder 7-item (GAD-7) scale. The designed questionnaire was answered by participants, and collected data were statistically analyzed. RESULTS: This study included 1200 respondents. In total, 80% of respondents rated the psychological impact; 18% reported minimal anxiety; 34% reported mild anxiety, and 48% with moderate anxiety symptoms. A large proportion (74%) believed that they were very or somewhat likely to contract (2019-nCoV) while only (35%) believed they were unlikely to survive if they contracted the disease. (58%) of the respondents, practiced the precautionary measures directed against person-to-person droplet spread. Respondents with a moderate level of anxiety were most likely to take comprehensive precautionary measures against the infection. Also, older, female, more educated people as well as those who are more likely to contract the infection. CONCLUSIONS: During the outbreak, more than half of the respondents rated the psychological impact as moderate anxiety. Thus, the psychological needs during the outbreak should be addressed appropriately. Our results highlight the need to promote protective personal health practices to interrupt the transmission of the (2019-nCoV) in the community. Therefore, educational public programs about preventive measures should be targeted at the identified groups with low current uptake of precautions.

Auto-titrating versus fixed-EPAP intelligent volume-assured pressure support (iVAPS) ventilation in patients with COPD and hypercapnic respiratory failure.

BACKGROUND: Intelligent volume-assured pressure support (iVAPS) is a new noninvasive ventilation (NIV) mode that can automatically adjust pressure support to deliver effective ventilation. Our aim was to compare treatment efficacy and level of satisfaction between auto-titrating expiratory positive airway pressure (auto-EPAP) and fixed expiratory positive airway pressure (fixed-EPAP) during iVAPS treatment in stable hypercapnic chronic obstructive pulmonary disease (COPD) patients. MATERIAL AND METHODS: In this prospective single-blinded, randomized study, 50 patients with chronic stable hypercapnia (COPD) who met the study criteria were randomized into a group I treated with auto-EPAP and a group II who received fixed-EPAP during iVAPS treatment for 5 consecutive days. The patients' characteristics, arterial blood gases, and lung function test were recorded. Numeric rating scale (NRS), dyspnea and comfort scale were obtained. The study subjects were evaluated and followed up after initiating therapy for 5 consecutive days. Outcome measures were recorded at baseline (T0) and after three (T1) and five (T2) days of each consecutive period All parameters were collected and statistically analyzed. RESULT: No significant differences were found regarding age, sex, or BMI between the both groups. It was noted that daytime PaCO2 decreased significantly over the follow-up period in the group I patients treated with auto-EPAP as compared with fixed-EPAP. Regarding the patient comfort and dyspnea during iVAPS treatment, dyspnea sensation was significantly lower with auto-EPAP 7.9 ± 1.8 (T0) vs 3.5 ± 1.1 (T2), p = 0.001 and fixed-EPAP 7.7 ± 1.9 (T0) vs 3.4 ± 1.6 (T2), p = 0.001, but no significance was reached between the both groups. However, auto-EPAP demonstrated significant improvement in comfort when compared with fixed-EPAP modality. However, the overall satisfaction of the patients receiving auto-EPAP modality was significantly increased. Mean tidal volume tended to be higher in auto-EPAP 698 ± 213 mL compared with 628 ± 178 mL in fixed-EPAP (p = 0.001). The air leak was significantly lower in auto-adjusting mode (2.5 ± 1.3 vs 3.7 ± 2.2 L/ min) in fixed-EPAP modality. CONCLUSION: Auto-titrating NIV mode may provide additional benefit in decreasing PaCO2 more efficiently and improve patient comfort and satisfaction.

The utility of HACOR score in predicting failure of high-flow nasal oxygen in acute hypoxemic respiratory failure.

OBJECTIVES: To assess the diagnostic performance of HACOR scoring system using bedside variables and to predict failure of HFNO in patients with acute hypoxemic respiratory failure (AHRF). MATERIAL AND METHODS: 150 patients with AHRF who were receiving HFNO were enrolled in this study; to predict HFNO treatment failure. A scoring scale (HACOR score) consisted of Heart rate (beats/minute), acidosis (assessed by pH), consciousness (assessed by Glasgow coma score), oxygenation, and respiratory rate. Failure was defined as the need for intubation or death. RESULTS: Patients were analyzed according to the success or failure of HFNO. Total 150 patients, of which 100 (66.7%) had a successful treatment while 50 (33.3%) failed with such intervention. There was an improvement in HR and RR, and PaO2/FiO2 within the first hour (T1) in the success group and these parameters continued to improve even after 24 hours (T2) of HFNO treatment. Patients with HFNO failure had a higher HACOR score at initiation and after 1, 12, 24 and 48 hours. Before intubation, the highest value of the HACOR score was reached in the failure group. At 1h of HFNO assessment, the area under the receiver operating characteristic curve was 0.86, showing good predictive power for failure. We found that HACOR score at a cutoff point > 6 had 81.2% sensitivity and 91% specificity, 92.5% positive predictive value, and 71.4% negative predictive value with a diagnostic accuracy was 85%. Furthermore, the overall diagnostic accuracy exceeded 87% when the HACOR score was assessed at 1, 12, 24 or 48 h of HFNO. CONCLUSIONS: The HACOR scale is a clinically useful bedside tool for the prediction of HFNO failure in hypoxemic patients. A HACOR score < 6 after 1 hour of HFNO highlights patients with < 85% risk of failure.

Effect of average volume-assured pressure support treatment on health-related quality of life in COPD patients with chronic hypercapnic respiratory failure: a randomized trial.

The long-term effect of average volume-assured pressure support (AVAPS) on health-related quality of life (HRQOL) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure (CHRF) remains unclear. The objective of this study is to identify the long-term effect of AVAPS in COPD patients with CHRF through assessment of HRQOL, exercise tolerance after six months duration. METHODS: In this randomized, controlled, parallel-group study, 40 stable hypercapnic COPD patients were randomized in a 1:1 ratio to receive either spontaneous timed AVAPS (ST/AVAPS) (intervention) or Bilevel positive airway pressure (ST/BiPAP) (control). HRQL was measured with the Short Form 12 Health Survey Questionnaire (SF-12). Exercise tolerance assessed by 6 min walking distance. Analyses were done between groups from baseline to the average of six months measurements. RESULTS: AVAPS led to significant 6 months improvements in several domains of (SF-12) compared to the control group, with the greatest improvement seen in general health [treatment effect of 8.2 points (95% confidence interval [95% CI 3.2 to 11.7; p = 0.001)], vitality (treatment effect 5.4 points [95% CI 1.4 to 9.3]; p = 0.001), physical functioning 5.5 points [95% CI 1.1 to 9.8]; p = 0.001) and bodily pain 5.1 points [95% CI 3.4 to 8.8]; p = 0.002). The physical health summary score improved by 3.7 points (95% CI 1.2 to 5.8; p = 0.001), but no significant improvement in the emotional or social role functioning, mental health subscale was noted. AVAPS also resulted in improvement 6 min walking distance 9.2 points (95% CI - 1 to - 15];p = 0.001). A significant reduction in the daytime (PaCO2) was observed after 6 months in those treated with AVAPS. CONCLUSIONS: In COPD patients with hypercapnic respiratory failure, AVAPS improved exercise tolerance and multiple domains of HRQOL over six months of follow-up, with the significant improvement observed in general health.

Six-minute walk test before and after large-volume paracentesis in cirrhotic patients with refractory ascites: A pilot study.

BACKGROUND/AIMS: Functional impairment is common among cirrhotic patients with refractory ascites, and improvement in functional impairment is an expected issue after paracentesis. The six-minute walk test (6MWT) is considered an objective test for functional activity. No published data have evaluated the 6MWT among cirrhotic patients with refractory ascites before and after large-volume paracentesis. The research aim was to assess the feasibility of performing the 6MWT among cirrhotic patients who had refractory ascites before and after large-volume paracentesis. MATERIALS AND METHODS: Thirty-one cirrhotic inpatients with refractory ascites were subjected to pulmonary function tests (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], FEV1/FVC) and diffusion lung capacity for carbon monoxide (DLCO) before and 48 h after therapeutic large-volume paracentesis. Dyspnoea as assessed by the Borg scale and functional capacity as assessed by the 6MWT were also evaluated. RESULTS: Prior to paracentesis, the mean values of FVC and FEV1 were lower than the predicted values, and a significant increase was observed after paracentesis. There was improvement in the mean DLCO values after paracentesis (P < 0.05). Regarding the 6MWT, significant increases in the walked distance (6MWD) (310.7 ±â€¯73 vs. 348.7 ±â€¯72.3 m) and oxygen saturation after paracentesis (P = 0.001) were observed. Significant improvement in the dyspnoea scale also occurred after paracentesis (P = 0.001). A significant positive correlation between the 6MWD before paracentesis and serum albumin levels was demonstrated (r = 0.373, P = 0.039). CONCLUSION: We found a decrease in pulmonary function and the 6MWD in patients who had refractory ascites, which improved significantly following large-volume paracentesis. The 6MWT is useful in detecting impaired functional capacity among cirrhotic patients.