Comparison between high-flow nasal cannula and noninvasive ventilation in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are important treatment approaches for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the differential impact of HFNC versus NIV on clinical outcomes of COVID-19 is uncertain. OBJECTIVES: We assessed the effects of HFNC versus NIV (interface or mode) on clinical outcomes of COVID-19. METHODS: We searched PubMed, EMBASE, Web of Science, Scopus, MedRxiv, and BioRxiv for randomized controlled trials (RCTs) and observational studies (with a control group) of HFNC and NIV in patients with COVID-19-related AHRF published in English before February 2022. The primary outcome of interest was the mortality rate, and the secondary outcomes were intubation rate, PaO2/FiO2, intensive care unit (ICU) length of stay (LOS), hospital LOS, and days free from invasive mechanical ventilation [ventilator-free day (VFD)]. RESULTS: In all, 23 studies fulfilled the selection criteria, and 5354 patients were included. The mortality rate was higher in the NIV group than the HFNC group [odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.51-0.84, p = 0.0008, I2 = 60%]; however, in this subgroup, no significant difference in mortality was observed in the NIV-helmet group (OR = 1.21, 95% CI: 0.63-2.32, p = 0.57, I2 = 0%) or NIV-continuous positive airway pressure (CPAP) group (OR = 0.77, 95% CI: 0.51-1.17, p = 0.23, I2 = 65%) relative to the HFNC group. There were no differences in intubation rate, PaO2/FiO2, ICU LOS, hospital LOS, or days free from invasive mechanical ventilation (VFD) between the HFNC and NIV groups. CONCLUSION: Although mortality was lower with HFNC than NIV, there was no difference in mortality between HFNC and NIV on a subgroup of helmet or CPAP group. Future large sample RCTs are necessary to prove our findings. REGISTRATION: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022321997).

Role of LL-37 in thrombotic complications in patients with COVID-19.

Blood clot formation induced by dysfunctional coagulation is a frequent complication of coronavirus disease 2019 (COVID-19) and a high-risk factor for severe illness and death. Neutrophil extracellular traps (NETs) are implicated in COVID-19-induced immunothrombosis. Furthermore, human cathelicidin, a NET component, can perturb the interaction between the SARS-CoV-2 spike protein and its ACE2 receptor, which mediates viral entry into cells. At present, however, the levels of cathelicidin antimicrobial peptides after SARS-CoV-2 infection and their role in COVID-19 thrombosis formation remain unclear. In the current study, we analyzed coagulation function and found a decrease in thrombin time but an increase in fibrinogen level, prothrombin time, and activated partial thromboplastin time in COVID-19 patients. In addition, the cathelicidin antimicrobial peptide LL-37 was upregulated by the spike protein and significantly elevated in the plasma of patients. Furthermore, LL-37 levels were negatively correlated with thrombin time but positively correlated with fibrinogen level. In addition to platelet activation, cathelicidin peptides enhanced the activity of coagulation factors, such as factor Xa (FXa) and thrombin, which may induce hypercoagulation in diseases with high cathelicidin peptide levels. Injection of cathelicidin peptides promoted the formation of thrombosis, whereas deletion of cathelicidin inhibited thrombosis in vivo. These results suggest that cathelicidin antimicrobial peptide LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in COVID-19 patients by activating coagulation factors.

Effectiveness of the use of a high-flow nasal cannula to treat COVID-19 patients and risk factors for failure: a meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread globally, and many patients with severe cases have received oxygen therapy through a high-flow nasal cannula (HFNC). OBJECTIVES: We assessed the efficacy of HFNC for treating patients with COVID-19 and risk factors for HFNC failure. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of randomized controlled trials (RCTs) and observational studies of HFNC in patients with COVID-19 published in English from January 1st, 2020 to August 15th, 2021. The primary aim was to assess intubation, mortality, and failure rates in COVID-19 patients supported by HFNC. Secondary aims were to compare HFNC success and failure groups and to describe the risk factors for HFNC failure. RESULTS: A total of 25 studies fulfilled selection criteria and included 2851 patients. The intubation, mortality, and failure rates were 0.44 (95% confidence interval (CI): 0.38-0.51, I2 = 84%), 0.23 (95% CI: 0.19-0.29, I2 = 88%), and 0.47 (95% CI: 0.42-0.51, I2 = 56%), respectively. Compared to the success group, age, body mass index (BMI), Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, D-dimer, lactate, heart rate, and respiratory rate were higher and PaO2, PaO2/FiO2, ROX index (the ratio of SpO2/FiO2 to respiratory rate), ROX index after the initiation of HFNC, and duration of HFNC were lower in the failure group (all Ps < 0.05). There were also more smokers and more comorbidities in the failure group (all Ps < 0.05). Pooled odds ratios (ORs) revealed that older age (OR: 1.04, 95% CI: 1.01-1.07, P = 0.02, I2 = 88%), a higher white blood cell (WBC) count (OR: 1.06, 95% CI: 1.01-1.12, P = 0.02, I2 = 0%), a higher heart rate (OR: 1.42, 95% CI: 1.15-1.76, P < 0.01, I2 = 0%), and a lower ROX index(OR: 0.61, 95% CI: 0.39-0.95, P = 0.03, I2 = 93%) after the initiation of HFNC were all significant risk factors for HFNC failure. CONCLUSIONS: HFNC is an effective way of providing respiratory support in the treatment of COVID-19 patients. Older age, a higher WBC count, a higher heart rate, and a lower ROX index after the initiation of HFNC are associated with an increased risk of HFNC failure.

Discriminant models for the prediction of postponed viral shedding time and disease progression in COVID-19.

BACKGROUND: COVID-19 infection can cause life-threatening respiratory disease. This study aimed to fully characterize the clinical features associated with postponed viral shedding time and disease progression, then develop and validate two prognostic discriminant models. METHODS: This study included 125 hospitalized patients with COVID-19, for whom 44 parameters were recorded, including age, gender, underlying comorbidities, epidemiological features, laboratory indexes, imaging characteristics and therapeutic regimen, et al. Fisher's exact test and Mann-Whitney test were used for feature selection. All models were developed with fourfold cross-validation, and the final performances of each model were compared by the Area Under Receiving Operating Curve (AUROC). After optimizing the parameters via L2 regularization, prognostic discriminant models were built to predict postponed viral shedding time and disease progression of COVID-19 infection. The test set was then used to detect the predictive values via assessing models' sensitivity and specificity. RESULTS: Sixty-nine patients had a postponed viral shedding time (> 14 days), and 28 of 125 patients progressed into severe cases. Six and eleven demographic, clinical features and therapeutic regimen were significantly associated with postponed viral shedding time and disease progressing, respectively (p < 0.05). The optimal discriminant models are: y1 (postponed viral shedding time) = - 0.244 + 0.2829x1 (the interval from the onset of symptoms to antiviral treatment) + 0.2306x4 (age) + 0.234x28 (Urea) - 0.2847x34 (Dual-antiviral therapy) + 0.3084x38 (Treatment with antibiotics) + 0.3025x21 (Treatment with Methylprednisolone); y2 (disease progression) = - 0.348-0.099x2 (interval from Jan 1st,2020 to individualized onset of symptoms) + 0.0945x4 (age) + 0.1176x5 (imaging characteristics) + 0.0398x8 (short-term exposure to Wuhan) - 0.1646x19 (lymphocyte counts) + 0.0914x20 (Neutrophil counts) + 0.1254x21 (Neutrphil/lymphocyte ratio) + 0.1397x22 (C-Reactive Protein) + 0.0814x23 (Procalcitonin) + 0.1294x24 (Lactic dehydrogenase) + 0.1099x29 (Creatine kinase).The output ≥ 0 predicted postponed viral shedding time or disease progressing to severe/critical state. These two models yielded the maximum AUROC and faired best in terms of prognostic performance (sensitivity of78.6%, 75%, and specificity of 66.7%, 88.9% for prediction of postponed viral shedding time and disease severity, respectively). CONCLUSION: The two discriminant models could effectively predict the postponed viral shedding time and disease severity and could be used as early-warning tools for COVID-19.

Clinical characteristics and outcome analysis of 8 cases with COVID-19

Objective: To investigate the clinical characteristics and outcome of patients with COVID-19 in Shenyang. Method: Data including clinical characteristics, outcome and laboratory index were obtained and analyzed in eight patients who were diagnosed with COVID-19 and admitted to the First hospital of China Medical University between January 21, 2020 to February 8, 2020.

The efficacy and tolerance of prone positioning in non-intubation patients with acute hypoxemic respiratory failure and ARDS: a meta-analysis.

BACKGROUND AND AIMS: The application of prone positioning with acute hypoxemic respiratory failure (AHRF) or acute respiratory distress syndrome (ARDS) in non-intubation patients is increasing gradually, applying prone positioning for more high-flow nasal oxygen therapy (HFNC) and non-invasive ventilation (NIV) patients. This meta-analysis evaluates the efficacy and tolerance of prone positioning combined with non-invasive respiratory support in patients with AHRF or ARDS. METHODS: We searched randomized controlled trials (RCTs) (prospective or retrospective cohort studies, RCTs and case series) published in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 1 July 2020. We included studies that compared prone and supine positioning with non-invasive respiratory support in awake patients with AHRF or ARDS. The meta-analyses used random effects models. The methodological quality of the RCTs was evaluated using the Newcastle-Ottawa quality assessment scale. RESULTS: A total of 16 studies fulfilled selection criteria and included 243 patients. The aggregated intubation rate and mortality rate were 33% [95% confidence interval (CI): 0.26-0.42, I2 = 25%], 4% (95% CI: 0.01-0.07, I2 = 0%), respectively, and the intolerance rate was 7% (95% CI: 0.01-0.12, I2 = 5%). Prone positioning increased PaO2/FiO2 [mean difference (MD) = 47.89, 95% CI: 28.12-67.66; p < 0.00001, I2 = 67%] and SpO2 (MD = 4.58, 95% CI: 1.35-7.80, p = 0.005, I2 = 97%), whereas it reduced respiratory rate (MD = -5.01, 95% CI: -8.49 to -1.52, p = 0.005, I2 = 85%). Subgroup analyses demonstrated that the intubation rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 34% and 21%, respectively; and the mortality rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 6% and 0%, respectively. PaO2/FiO2 and SpO2 were significantly improved in COVID-19 patients and non-COVID-19 patients. CONCLUSION: Prone positioning could improve the oxygenation and reduce respiratory rate in both COVID-19 patients and non-COVID-19 patients with non-intubated AHRF or ARDS.The reviews of this paper are available via the supplemental material section.