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1.
Ann Am Thorac Soc ; 18(4): 698-708, 2021 04.
Article in English | MEDLINE | ID: covidwho-1186616

ABSTRACT

Patients hospitalized for pneumonia are at high risk for mortality. Effective therapies are therefore needed. Recent randomized clinical trials suggest that systemic steroids can reduce the length of hospital stays among patients hospitalized for pneumonia. Furthermore, preliminary findings from a feasibility study demonstrated that early treatment with a combination of an inhaled corticosteroid and a bronchodilator can improve oxygenation and reduce risk of respiratory failure in patients at risk of acute respiratory distress syndrome. Whether such a combination administered early is effective in reducing acute respiratory failure (ARF) among patients hospitalized with pneumonia is unknown. Here we describe the ARREST Pneumonia (Arrest Respiratory Failure due to Pneumonia) trial designed to address this question. ARREST Pneumonia is a two-arm, randomized, double-blinded, placebo-controlled trial designed to test the efficacy of a combination of an inhaled corticosteroid and a ß-agonist compared with placebo for the prevention of ARF in hospitalized participants with severe pneumonia. The primary outcome is ARF within 7 days of randomization, defined as a composite endpoint of intubation and mechanical ventilation; need for high-flow nasal cannula oxygen therapy or noninvasive ventilation for >36 hours (each alone or combined); or death within 36 hours of being placed on respiratory support. The planned enrollment is 600 adult participants at 10 academic medical centers. In addition, we will measure selected plasma biomarkers to better understand mechanisms of action. The trial is funded by the U.S. National Heart Lung and Blood Institute.Clinical trial registered with www.clinicaltrials.gov (NCT04193878).


Subject(s)
COVID-19 , Pneumonia , Respiratory Insufficiency , Adult , Humans , Respiration, Artificial , Respiratory Insufficiency/therapy , SARS-CoV-2
2.
Respir Care ; 66(6): 891-896, 2021 06.
Article in English | MEDLINE | ID: covidwho-1171336

ABSTRACT

BACKGROUND: There is a persistent concern over the risk of respiratory pathogen transmission, including SARS-CoV-2, via the formation of aerosols (ie, a suspension of microdroplets and residual microparticles after evaporation) generated during high-flow nasal cannula (HFNC) oxygen therapy in critically ill patients. This concern is fueled by limited available studies on this subject. In this study, we tested our hypothesis that HFNC treatment is not associated with increased aerosol formation as compared to conventional oxygen therapy. METHODS: We used laser light scattering and a handheld particle counter to detect and quantify aerosols in healthy subjects and in adults with acute respiratory disease, including COVID-19, during HFNC or conventional oxygen therapy. RESULTS: The use of HFNC was not associated with increased formation of aerosols as compared to conventional oxygen therapy in both healthy subjects (n = 3) and subjects with acute respiratory disease, including COVID-19 (n = 17). CONCLUSIONS: In line with scarce previous clinical and experimental findings, our results indicate that HFNC itself does not result in overall increased aerosol formation as compared to conventional oxygen therapy. This suggests there is no increased risk of respiratory pathogen transmission to health care workers during HFNC.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Adult , Aerosols , Cannula , Critical Illness , Humans , Oxygen Inhalation Therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , SARS-CoV-2
3.
Open Forum Infect Dis ; 8(3): ofab019, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1155800

ABSTRACT

BACKGROUND: Impaired immune response has been reported to be the cause of the development of coronavirus disease 2019 (COVID-19)-related respiratory failure. Further studies are needed to understand the immunopathogenesis and to enable an improved stratification of patients who are at risk for critical illness. METHODS: Thirty-two severely ill patients hospitalized with COVID-19 were recruited in our center at the University Hospital Heidelberg. We performed a comprehensive analysis of immune phenotype, cytokine, and chemokine profiling and leukocyte transcripts in patients with severe COVID-19 and compared critically ill patients who required mechanical ventilation and high-flow oxygen therapy and noncritically ill patient who received low-flow oxygen therapy. RESULTS: Critically ill patients exhibited low levels of CD8 T cells and myeloid dendritic cells. We noted a pronounced CCR6+ TH17 phenotype in CD4 central memory cells and elevated circulating levels of interleukin-17 in the critical group. Gene expression of leukocytes derived from critically ill patients was characterized by an upregulation of proinflammatory cytokines and reduction of interferon (IFN)-responsive genes upon stimulation with Toll-like receptor 7/8 agonist. When correlating clinical improvement and immune kinetics, we found that CD8 T-cell subsets and myeloid dendritic cells significantly increased after disconnection from the ventilator. CONCLUSION: Critical illness was characterized by a TH17-mediated response and dysfunctional IFN-associated response, indicating an impaired capacity to mount antiviral responses during severe acute respiratory syndrome coronavirus 2 severe infection.

4.
Am J Med Sci ; 361(5): 591-597, 2021 05.
Article in English | MEDLINE | ID: covidwho-973807

ABSTRACT

BACKGROUND: The information on electrocardiographic features of patients with coronavirus disease 2019 (COVID-19) is limited. Our aim was to determine if baseline electrocardiographic features of hospitalized COVID-19 patients are associated with markers of myocardial injury and clinical outcomes. METHODS: In this retrospective, single center cohort study, we included 223 hospitalized patients with laboratory-confirmed COVID-19. Clinical, electrocardiographic and laboratory data were collected and analyzed. Primary composite endpoint of mortality, need for invasive mechanical ventilation, or admission to the intensive care unit was assessed. RESULTS: Forty patients (17.9%) reached the primary composite endpoint. Patients with the primary composite endpoint were more likely to have wide QRS complex (>120 ms) and lateral ST-T segment abnormality. The multivariable Cox regression showed increasing odds of the primary composite endpoint associated with acute respiratory distress syndrome (odds ratio 7.76, 95% CI 2.67-22.59; p < 0.001), acute cardiac injury (odds ratio 3.14, 95% CI 1.26-7.99; p = 0.016), high flow oxygen therapy (odds ratio 2.43, 95% CI 1.05-5.62; p = 0.037) and QRS duration longer than >120 ms (odds ratio 3.62, 95% CI 1.39-9.380; p = 0.008) Patients with a wide QRS complex (>120 ms) had significantly higher median level of troponin T and pro-BNP than those without it. Patients with abnormality of lateral ST-T segment had significantly higher median level of troponin T and pro-BNP than patients without. CONCLUSIONS: The presence of QRS duration longer than 120 ms and lateral ST-T segment abnormality were associated with worse clinical outcomes and higher levels of myocardial injury biomarkers.


Subject(s)
COVID-19 , Electrocardiography , Heart Injuries , Natriuretic Peptide, Brain/blood , Respiration, Artificial , SARS-CoV-2/metabolism , Troponin T/blood , Acute Disease , Adult , Aged , Biomarkers , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , COVID-19/therapy , Disease-Free Survival , Female , Heart/physiopathology , Heart Injuries/blood , Heart Injuries/mortality , Heart Injuries/physiopathology , Heart Injuries/therapy , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate
5.
Eur J Clin Invest ; 51(3): e13435, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-868107

ABSTRACT

OBJECTIVE: This study aimed to investigate the value of high-flow nasal cannula (HNFC) oxygen therapy in treating patients with severe novel coronavirus pneumonia (COVID-19). METHODS: The clinical data of 22 patients with severe COVID-19 were collected. The heart rate (HR), respiratory rate (RR) and oxygenation index (PO2 /FiO2 ) at 0, 6, 24 and 72 hours after treatment were compared between the HFNC oxygen therapy group and the conventional oxygen therapy (COT) group. In addition, the white blood cell (WBC) count, lymphocyte (L) count, C-reactive protein (CRP) and procalcitonin (PCT) were compared before and at 72 hours after oxygen therapy treatment. RESULTS: The differences at 0 hours between the two groups were not statistically significant. Compared with COT group,in the HFNC oxygen therapy group, HR, RR and PaO2 /FiO2 were better at 6 hours after treatment, PaO2 /FiO2 was better at 24 and 72 hours. After 72 hours, L and CRP had improved in the HFNC oxygen therapy group compared with the COT group, but the differences in WBC and PCT were not statistically significant. The length of stay in the intensive care unit (ICU) and the total length of hospitalization was shorter in the HFNC oxygen therapy group than in the COT group. CONCLUSION: Compared with COT, early application of HFNC oxygen therapy in patients with severe COVID-19 can improve oxygenation and RR, and HFNC oxygen therapy can improve the infection indexes of patients and reduce the length of stay in the ICU of patients. Therefore, it has high clinical application value.


Subject(s)
COVID-19/therapy , Heart Rate/physiology , Oxygen Inhalation Therapy/methods , Oxygen/blood , Respiratory Rate/physiology , Blood Gas Analysis , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/physiopathology , Cannula , Female , Humans , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Oxygen/administration & dosage , Partial Pressure , Procalcitonin/blood , SARS-CoV-2 , Severity of Illness Index
6.
Int J Infect Dis ; 101: 194-200, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-796226

ABSTRACT

BACKGROUND: Absolute numbers of COVID-19 cases and deaths reported to date in the sub-Saharan Africa (SSA) region have been significantly lower than those across the Americas, Asia and Europe. As a result, there has been limited information about the demographic and clinical characteristics of deceased cases in the region, as well as the impacts of different case management strategies. METHODS: Data from deceased cases reported across SSA through 10 May 2020 and from hospitalized cases in Burkina Faso through 15 April 2020 were analyzed. Demographic, epidemiological and clinical information on deceased cases in SSA was derived through a line-list of publicly available information and, for cases in Burkina Faso, from aggregate records at the Centre Hospitalier Universitaire de Tengandogo in Ouagadougou. A synthetic case population was probabilistically derived using distributions of age, sex and underlying conditions from populations of West African countries to assess individual risk factors and treatment effect sizes. Logistic regression analysis was conducted to evaluate the adjusted odds of survival for patients receiving oxygen therapy or convalescent plasma, based on therapeutic effectiveness observed for other respiratory illnesses. RESULTS: Across SSA, deceased cases for which demographic data were available were predominantly male (63/103, 61.2%) and aged >50 years (59/75, 78.7%). In Burkina Faso, specifically, the majority of deceased cases either did not seek care at all or were hospitalized for a single day (59.4%, 19/32). Hypertension and diabetes were often reported as underlying conditions. After adjustment for sex, age and underlying conditions in the synthetic case population, the odds of mortality for cases not receiving oxygen therapy were significantly higher than for those receiving oxygen, such as due to disruptions to standard care (OR 2.07; 95% CI 1.56-2.75). Cases receiving convalescent plasma had 50% reduced odds of mortality than those who did not (95% CI 0.24-0.93). CONCLUSIONS: Investment in sustainable production and maintenance of supplies for oxygen therapy, along with messaging around early and appropriate use for healthcare providers, caregivers and patients could reduce COVID-19 deaths in SSA. Further investigation into convalescent plasma is warranted until data on its effectiveness specifically in treating COVID-19 becomes available. The success of supportive or curative clinical interventions will depend on earlier treatment seeking, such that community engagement and risk communication will be critical components of the response.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , SARS-CoV-2/physiology , Adolescent , Adult , Africa South of the Sahara , Aged , Antiviral Agents/administration & dosage , Asia/epidemiology , Burkina Faso/epidemiology , COVID-19/epidemiology , COVID-19/therapy , Child , Child, Preschool , Europe/epidemiology , Female , Humans , Immunization, Passive , Infant , Male , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2/drug effects , Young Adult
7.
J Am Coll Emerg Physicians Open ; 2020 May 29.
Article in English | MEDLINE | ID: covidwho-436542

ABSTRACT

OBJECTIVE: All respiratory care represents some risk of becoming an Aerosol Generating Procedure (AGP) during COVID-19 patient management. Personal Protective Equipment (PPE) and Environmental Control/Engineering is advised. High Velocity Nasal Insufflation (HVNI) and High Flow Nasal Cannula (HFNC) deliver High Flow Oxygen (HFO) therapy, established as a competent means of supporting oxygenation for acute respiratory distress patients, including that precipitated by COVID-19. Although unlikely to present a disproportionate particle dispersal risk, AGP from HFO continues to be a concern. Previously, we published a preliminary model. Here, we present a subsequent high-resolution simulation (higher complexity/reliability) to provide a more accurate and precise particle characterization on the effect of surgical masks on patients during HVNI, Low-Flow Oxygen therapy (LFO2), and tidal breathing. METHODS: This in-silico modeling study of HVNI, LFO2, and tidal breathing presents ANSYS Fluent Computational Fluid Dynamics simulations that evaluate the effect of Type I surgical mask use over patient face on particle/droplet behavior. RESULTS: This in-silico modeling simulation study of HVNI (40L∙min-1) with a simulated surgical mask suggests 88.8% capture of exhaled particulate mass in the mask, compared to 77.4% in LFO2 (6L∙min-1) capture, with particle distribution escaping to the room (>1m from face) lower for HVNI+Mask versus LFO2+Mask (8.23% versus 17.2%). The overwhelming proportion of particulate escape was associated with mask-fit designed model gaps. Particle dispersion was associated with lower velocity. CONCLUSIONS: These simulations suggest employing a surgical mask over the HVNI interface may be useful in reduction of particulate mass distribution associated with AGPs.This article is protected by copyright. All rights reserved.

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