Derivation and External Validation of a Simple Prediction Rule for the Development of Respiratory Failure in Hospitalized Patients With Influenza

BACKGROUND: Influenza viruses cause seasonal epidemics worldwide with a significant morbimortality burden. Clinical spectrum of Influenza is wide, being respiratory failure (RF) one of its most severe complications. This study aims to elaborate a clinical prediction rule of RF in hospitalized Influenza patients.METHODS: a prospective cohort study was conducted during two consecutive Influenza seasons (December 2016 - March 2017 and December 2017 - April 2018) including hospitalized adults with confirmed A or B Influenza infection. A prediction rule was derived using logistic regression and recursive partitioning, followed by internal cross-validation. External validation was performed on a retrospective cohort in a different hospital between December 2018 - May 2019. RESULTS: Overall, 707 patients were included in the derivation cohort and 285 in the validation cohort. RF rate was 6.8% and 11.6%, respectively. Chronic obstructive pulmonary disease, immunosuppression, radiological abnormalities, respiratory rate, lymphopenia, lactate dehydrogenase and C-reactive protein at admission were associated with RF. A four category-grouped seven point-score was derived including radiological abnormalities, lymphopenia, respiratory rate and lactate dehydrogenase. Final model area under the curve was 0.796 (0.714-0.877) in the derivation cohort and 0.773 (0.687-0.859) in the validation cohort (p<0.001 in both cases). The predicted model showed an adequate fit with the observed results (Fisher’s test p>0.43). CONCLUSION: we present a simple, discriminating, well-calibrated rule for an early prediction of the development of RF in hospitalized Influenza patients, with proper performance in an external validation cohort. This tool can be helpful in patient´s stratification during seasonal Influenza epidemics.

Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis

Background: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. Methods: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Results: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65–1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03–1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71–0.96) but may have little or no effect on mortality (RR: 1.08, 0.51–2.31). Conclusions: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.

Clinical case of successful treatment of COVID-19 infection manifested with B-cell acute lymphoblastic leukemia

The novel corona virus disease 2019 (covid-19) is currently a global threat. Cancer patients constitute a group that is at high risk of covid-19 infection with a more severe disease course and higher mortality rate. Case description. We report a case of covid-19 occurring concurrently with B-cell acute lymphoblastic leukemia (all) in a young male patient. After verification of the morphological and immunophenotypic profiles of leukemia, the patient receivedall treatment (all-2009 protocol) with concurrent administration of antiviral and antibacterial drugs, as well as immunoglobin replacement therapy. Neutropenia caused by cytostatic treatment led to the progression of lung damage and respiratory failure, which required the withdrawal of cytostatic drugs. The patient was transferred to the intensive care department, where dexamethasone therapy as well as antibacterial and antifungal therapy was continued. Since the lung damage reached 75 % and respiratory failure began to increase, non-invasive ventilation of the lungs was started. Clinical and hematological remission with hematologic recovery and subsequent pneumonia regression was achieved. However, long-term persistence of the virus was observed, and therefore the strategy for treating acute lymphoblastic leukemia was revised. Maintenance therapy with mercaptopurine and methotrexate was administered. After elimination of the virus on the 56th day from the initial positive test, therapy according to the all-2009 protocol was continued. Conclusion. The tactics of treating cancer patients with hemoblastosis during a pandemic should be selected individually with an assessment of the potential benefits and risk of life-threatening complications.

Early Measurement of ROX Index in Intermediary Care Unit Is Associated with Mortality in Intubated COVID-19 Patients: A Retrospective Study

COVID-19 patients often present with rapidly progressing acute hypoxemic respiratory failure, requiring orotracheal intubation with different prognostic issues. However, ICU specialists lack predictive tools to stratify these patients. We conducted a single-center cross-sectional retrospective study to evaluate if the ROX index, measured under non-invasive oxygenation support, can predict ICU mortality in a COVID-19 intubated patient cohort. This study took place in the division of intensive care at the Geneva University Hospitals (Geneva, Switzerland). We included all consecutive adult patients treated by non-invasive oxygenation support and requiring intubation for acute respiratory failure due to COVID-19 between 9 September 2020 and 30 March 2021, corresponding to the second local surge of COVID-19 cases. Baseline demographic data, comorbidities, median ROX between H0 and H8, and clinical outcomes were collected. Overall, 82 patients were intubated after failing a non-invasive oxygenation procedure. Women represented 25.6% of the whole cohort. Median age and median BMI were 70 (60–75) years and 28 (25–33), respectively. Before intubation, the median ROX between H0 and H8 was 6.3 (5.0–8.2). In a multivariate analysis, the median ROX H0–H8 was associated with ICU mortality as a protective factor with an odds ratio (95% CI) = 0.77 (0.60–0.99); p < 0.05. In intubated COVID-19 patients treated initially by non-invasive oxygenation support for acute respiratory failure, the median ROX H0–H8 could be an interesting predictive factor associated with ICU mortality.

Fatality Case in a Tuberculous Meningoencephalitis Patient Coinfected with COVID-19

: Tuberculous meningoencephalitis (TBM) is the most severe, life-threatening form of tuberculosis that contributes to as much as 5% of cases of extrapulmonary tuberculosis. Emerging at the end of 2019, COVID-19 has been shown to affect various organs, including the brain. In this case report, a 21-year-old woman diagnosed with TBM, being in the intensive phase of tuberculous therapy, came with dysphagia and dysphonia as new complaints felt one day before admission accompanied by a positive meningeal sign, diplopia, and cephalgia, which became heavier after previously getting better. Cough and fever followed this complaint two days before admission. About the laboratory results, the PCR was positive for COVID-19, and CT scans showed increased leptomeningeal enhancement when compared with CT scan one month earlier. The patient received intravenous dexamethasone, anti-tuberculosis drugs, phenytoin, aspirin, oseltamivir, and hydroxychloroquine. The patient died four days after being hospitalized due to respiratory failure. This case report shows the coinfection of COVID-19 and TBM resulting in a poor tuberculosis treatment response and outcome.

Aviptadil: Class Effect of a Synthetic Vasoactive Intestinal Peptide as a Treatment Option in Patients with COVID-19 with Severe Respiratory Failure

Despite dynamic drug and vaccine development processes to reduce the disease burden of COVID-19, the treatment options are still very limited. Vasoactive intestinal peptide (VIP) has a diversified physiological action with specific features of lung protection-related activities. VIP inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gene replication in human monocytes and the viral replication in Calu-3 cells, thus further reducing the generation of proinflammatory mediators. Aviptadil, a synthetic form of VIP, is the only pulmonary therapeutic agent to have been granted ‘fast track’ status by the U.S. Food and Drug Administration (FDA) and to be allowed into both Phase II and III clinical trials. Initial binding of Aviptadil with non-structural protein (nsp) 10 and nsp16, which may inhibit the 2’-O-methyltransferase activity of the SARS-CoV-2 nsp10 and nsp16 complex. Aviptadil has already proved to be an effective option in the treatment of severe respiratory failures due to sepsis and other related lung injuries. Interim analysis results of this drug used in respiratory failure caused by SARS-CoV-2 has evolved a new hope in regard to safety and efficacy. The final results from a recently completed trial, as well as all currently ongoing trials, will clarify the class effect of this drug in the treatment of COVID-19 in future days.