Noninvasive respiratory support for COVID-19 patients: when, for whom, and how?

The significant mortality rate and prolonged ventilator days associated with invasive mechanical ventilation (IMV) in patients with severe COVID-19 have incited a debate surrounding the use of noninvasive respiratory support (NIRS) (i.e., HFNC, CPAP, NIV) as a potential treatment strategy. Central to this debate is the role of NIRS in preventing intubation in patients with mild respiratory disease and the potential beneficial effects on both patient outcome and resource utilization. However, there remains valid concern that use of NIRS may prolong time to intubation and lung protective ventilation in patients with more advanced disease, thereby worsening respiratory mechanics via self-inflicted lung injury. In addition, the risk of aerosolization with the use of NIRS has the potential to increase healthcare worker (HCW) exposure to the virus. We review the existing literature with a focus on rationale, patient selection and outcomes associated with the use of NIRS in COVID-19 and prior pandemics, as well as in patients with acute respiratory failure due to different etiologies (i.e., COPD, cardiogenic pulmonary edema, etc.) to understand the potential role of NIRS in COVID-19 patients. Based on this analysis we suggest an algorithm for NIRS in COVID-19 patients which includes indications and contraindications for use, monitoring recommendations, systems-based practices to reduce HCW exposure, and predictors of NIRS failure. We also discuss future research priorities for addressing unanswered questions regarding NIRS use in COVID-19 with the goal of improving patient outcomes.

Observational study of changes in utilization and outcomes in mechanical ventilation in COVID-19

Background The role of non-invasive ventilation (NIV) in severe COVID-19 remains a matter of debate. Therefore, the utilization and outcome of NIV in COVID-19 in an unbiased cohort was determined. Aim The aim was to provide a detailed account of hospitalized COVID-19 patients requiring non-invasive ventilation during their hospital stay. Furthermore, differences of patients treated with NIV between the first and second wave are explored. Methods Confirmed COVID-19 cases of claims data of the Local Health Care Funds with non-invasive and/or invasive mechanical ventilation (MV) in the spring and autumn pandemic period in 2020 were comparable analysed. Results Nationwide cohort of 17.023 cases (median/IQR age 71/61–80 years, 64% male) 7235 (42.5%) patients primarily received IMV without NIV, 4469 (26.3%) patients received NIV without subsequent intubation, and 3472 (20.4%) patients had NIV failure (NIV-F), defined by subsequent endotracheal intubation. The proportion of patients who received invasive MV decreased from 75% to 37% during the second period. Accordingly, the proportion of patients with NIV exclusively increased from 9% to 30%, and those failing NIV increased from 9% to 23%. Median length of hospital stay decreased from 26 to 21 days, and duration of MV decreased from 11.9 to 7.3 days. The NIV failure rate decreased from 49% to 43%. Overall mortality increased from 51% versus 54%. Mortality was 44% with NIV-only, 54% with IMV and 66% with NIV-F with mortality rates steadily increasing from 62% in early NIV-F (day 1) to 72% in late NIV-F (>4 days). Conclusions Utilization of NIV rapidly increased during the autumn period, which was associated with a reduced duration of MV, but not with overall mortality. High NIV-F rates are associated with increased mortality, particularly in late NIV-F.

Duration of invasive mechanical ventilation prior to extracorporeal membrane oxygenation is not associated with survival in acute respiratory distress syndrome caused by coronavirus disease 2019

Background Duration of invasive mechanical ventilation (IMV) prior to extracorporeal membrane oxygenation (ECMO) affects outcome in acute respiratory distress syndrome (ARDS). In coronavirus disease 2019 (COVID-19) related ARDS, the role of pre-ECMO IMV duration is unclear. This single-centre, retrospective study included critically ill adults treated with ECMO due to severe COVID-19-related ARDS between 01/2020 and 05/2021. The primary objective was to determine whether duration of IMV prior to ECMO cannulation influenced ICU mortality. Results During the study period, 101 patients (mean age 56 [SD ± 10] years; 70 [69%] men; median RESP score 2 [IQR 1–4]) were treated with ECMO for COVID-19. Sixty patients (59%) survived to ICU discharge. Median ICU length of stay was 31 [IQR 20.7–51] days, median ECMO duration was 16.4 [IQR 8.7–27.7] days, and median time from intubation to ECMO start was 7.7 [IQR 3.6–12.5] days. Fifty-three (52%) patients had a pre-ECMO IMV duration of > 7 days. Pre-ECMO IMV duration had no effect on survival (p = 0.95). No significant difference in survival was found when patients with a pre-ECMO IMV duration of < 7 days (< 10 days) were compared to ≥ 7 days (≥ 10 days) (p = 0.59 and p = 1.0). Conclusions The role of prolonged pre-ECMO IMV duration as a contraindication for ECMO in patients with COVID-19-related ARDS should be scrutinised. Evaluation for ECMO should be assessed on an individual and patient-centred basis.

Pulmonary Hypertension at Admission predicts ICU Mortality in Elderly Critically ill with Severe COVID-19 Pneumonia: retrospective cohort study

BackgroundPoint-of-care ultrasound (POCUS) is a useful diagnostic tool for non-invasive assessment of critically ill patients. Mortality of elderly patients with COVID-19 pneumonia is high and there is still scarcity of definitive predictors. Aim of our study was to assess the prediction value of combined lung and heart POCUS data on mortality of elderly critically ill patients with severe COVID-19 pneumonia.MethodsThis was a retrospective observational study. Data of patients older than 70 years, with severe COVID-19 pneumonia admitted to 25-bed mixed, level 3, intensive care unit (ICU) was analyzed retrospectively. POCUS was performed at admission; our parameters of interest were pulmonary artery systolic pressure (PASP) and presence of diffuse B-line pattern (B-pattern) on lung ultrasound.ResultsBetween March 2020 and February 2021, 117 patients aged 70 years or more (average age 77±5 years) were included. Average length of ICU stay was 10.7±8.9 days. High-flow oxygenation, non-invasive ventilation and invasive mechanical ventilation were at some point used to support 36/117 (31%), 39/117 (33%) and 75/117 (64%) patients respectively. ICU mortality was 50.9%. ICU stay was shorter in survivors (8.8±8.3 vs 12.6±9.3 days, p=0.02). PASP was lower in ICU survivors (32.5±9.8 vs. 40.4±14.3 mmHg, p=0.024). B-pattern was more often detected in non-survivals (35/59 (59%) vs. 19/58 (33%), p=0.005). PASP and B-pattern at admission were both univariate predictors of mortality. PASP at admission was an independent predictor of ICU (OR 1.0683, 95%CI: 1.0108-1.1291, p=0.02) and hospital (OR 1.0813, 95%CI 1.0125-1.1548, p=0.02) mortality. Ventilator associated pneumonia (VAP) was a strong predictor of ICU and hospital mortality.ConclusionsPASP at admission is an independent predictor of ICU and hospital mortality of elderly patients with severe COVID-19 pneumonia. During ICU stay development of VAP was a strong predictor of ICU and hospital mortality.

Benefits of Home-Based Exercise Training Following Critical SARS-CoV-2 Infection: A Case Report

In the current scenario, in which an elevated number of COVID-19 survivors present with severe physical deconditioning, exercise intolerance, persistent symptoms, and other post-acute consequences, effective rehabilitation strategies are of utmost relevance. In this study, we report for the first time the effect of home-based exercise training (HBET) in a survivor patient from critical COVID-19 illness. A 67-year-old woman who had critical COVID-19 disease [71 days of hospitalization, of which 49 days were in the intensive care unit (ICU) with invasive mechanical ventilation due to respiratory failure] underwent a 10-week HBET aiming to recovering overall physical condition. Before and after the intervention, we assessed cardiopulmonary parameters, skeletal muscle strength and functionality, fatigue severity, and self-reported persistent symptoms. At baseline (3 months after discharge), she presented with severe impairment in cardiorespiratory functional capacity (&lt;50% age predicted VO2peak). After the intervention, remarkable improvements in VO2peak (from 10.61 to 15.48 mL·kg−1·min−1, Δ: 45.9%), oxygen uptake efficiency slope (OUES; from 1.0 to 1.3 L·min−1, Δ: 30.1%), HR/VO2 slope (from 92 to 52 bpm·L−1, Δ: −43.5%), the lowest VE/VCO2 ratio (from 35.4 to 32.9 L·min−1, Δ: −7.1%), and exertional dyspnea were observed. In addition, handgrip strength (from 22 to 27 kg, Δ: 22.7%), 30-s Sit-to-Stand (30-STS; from 14 to 16 repetitions, Δ:14.3%), Timed-Up-and-Go (TUG; from 8.25 to 7.01 s, Δ: −15%) performance and post-COVID functional status (PCFS) score (from 4 to 2) were also improved from baseline to post-intervention. Self-reported persistent symptoms were also improved, and Fatigue Severity Scale (FSS) score decreased (from 4 to 2.7) from baseline to post-intervention. This is the first evidence that a semi-supervised, HBET program may be safe and potentially effective in improving cardiorespiratory and physical functionality in COVID-19 survivors. Controlled studies are warranted to confirm these findings.

Impact of time to intubation on mortality and pulmonary sequelae in critically ill patients with COVID-19: a prospective cohort study

Question We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. Materials and methods Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. Results We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29–4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42–4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of − 10.77 (95% CI − 18.40 to − 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89–2.13]) and a greater TSS (+ 4.35 [95% CI 2.41–6.27]) in the chest CT scan. Conclusions Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies treatment for COVID-19 patients: a meta-analysis

Objective: We performed a meta analysis in order to determine safety of granulocyte macrophage colony stimulating factor (GM CSF) antibodies on COVID 19. Methods: We searched from the Cochrane Library, PubMed, Embase, biorxiv and medrxiv databases beginning in the COVID-19 outbreak on December 1, 2019 until August 29, 2021. The primary outcomes included death, the incidence of invasive mechanical ventilation (IMV), ventilation requirement, and secondary infection. Results: 6 eligible literature involving 1501 COVID 19 patients were recruited, and they were divided into experimental group (n = 736) and control group (n = 765). Using a random effect model, we found that the GM CSF antibodies treatment was associated with a 3.8-26.9% decline of the risk of mortality[odd ratio (OR) = 0.06, 95% confidence interval (CI): -0.11, -0.01, p =0.02], a 5.3-28.7% reduction of incidence of IMV [OR = 0.51, 95% CI: 0.28, 0.95, p =0.03], and a 23.3-50.0% enhancement of ventilation improvement [OR = 11.70, 95% CI: 1.99, 68.68, p=0.006]. There were no statistically significant differences in the association between two groups in second infection. Conclusion: Severe COVID 19 patients may benefit from GM CSF antibodies.

Outcomes of COVID-19 infection in patients with chronic kidney disease on maintenance hemodialysis at a COVID hospital in India

Background: Patients with chronic kidney disease (CKD) on hemodialysis are highly vulnerable to COVID-19 infection with a mortality rate higher than the rest of the population. There are several clinical and laboratory parameters that can predict the course and the outcomes in this group of population. Methods: We retrospectively collected the baseline demographic, clinical, in-hospital, and laboratory data of the patients with CKD on maintenance hemodialysis who were admitted to our COVID-19 hospital during the first and the second wave. Results: We obtained data for 35 patients from the first and 5 patients from the second wave. The analysis of the data for 35 patients from the first wave revealed shortness of breath (62.9%), and fever (54.3%) being the most common presenting symptoms, and the majority of the patients (57.2 %) presented with moderate to severe disease at admission with 57 % had bilateral lung infiltrates, and required oxygen support (65.7%) at admission. The comparison of clinical and laboratory markers between survivors (27 patients, 77.1%) and non-survivors (8 patients, 22.9%) revealed an older age, severe disease at presentation, invasive mechanical ventilation, baseline severe lymphocytopenia, high serum glutamic oxaloacetic transaminase, blood urea, and inflammatory markers like Interleukin-6 and procalcitonin, fibrinogen and low albumin in non survivors. Conclusions: The older age, severe disease at presentation, the requirement of invasive mechanical ventilation, raised baseline Interleukin-6, procalcitonin, serum glutamic oxaloacetic transaminase, blood urea and a low albumin level could be valuable predictors of poor outcomes.

Comorbidities as Risk Factors for Severe Disease in Hospitalized Elderly COVID-19 Patients by Different Age-Groups in Japan

<b><i>Introduction:</i></b> Old age is an independent risk factor (RF) for severe COVID-19; evidence for clinico-epidemiological characteristics among elderly COVID-19 patients is scarce. We aimed to analyze clinical and epidemiological characteristics and comorbidities associated with COVID-19 inpatients in age-stratified populations of an elderly COVID-19 cohort. <b><i>Methods:</i></b> We conducted a retrospective cohort study, using nationwide registry data of COVID-19 patients hospitalized before October 31, 2020 (major information entered in the registry as of December 28, 2020). Participants were divided by age according to the Japan Geriatrics Society and the Japan Gerontological Society: pre-old (65–74 years), old (75–89 years), and super-old (≥90 years). Multivariable logistic regression (MLR) analyses were conducted to identify stratified risk and relationships with comorbidities associated with worse outcomes in different age-groups of elderly patients. Demographics and supportive care were evaluated by category. <b><i>Results:</i></b> Data of 4,701 patients from 444 hospitals were included. Most patients (79.3%) had at least one comorbidity; the proportion of patients with hypertension was high in all categories. The proportion of patients with dementia, cardiovascular disease, and cerebrovascular disease increased with age. The percentage of patients who underwent invasive mechanical ventilation/extracorporeal membrane oxygenation was lower in the super-old group. In total, 11.5% of patients died (5.3%, pre-old; 15.2%, old; and 22.4%, super-old). MLR showed that the risk of critical illness differed among age-groups. Male sex was a significant RF in all ages. Collagen disease, moderate to severe renal disorder, and dialysis were significant RFs in older patients, while hematological malignancies and metastatic tumors were more important RFs for severe disease in relatively younger patients. Most of the RFs for critical illnesses were associated with death. <b><i>Conclusion:</i></b> Differences in the epidemiological and clinical characteristics among the different age-groups were found.