Survivors Of Acute Respiratory Distress Syndrome Research Articles

Medium-Term Disability and Long-Term Functional Impairment Persistence in Survivors of Severe COVID-19 ARDS: Clinical and Physiological Insights

Background: Although the medium- and long-term sequelae of survivor of acute respiratory distress syndrome (ARDS) of any cause have been documented, little is known about how COVID-19-induced ARDS affects functional disability and exercise components. Our aims were to examine the medium-term disability in severe COVID-19-associated ARDS survivors, delineate pathophysiological changes contributing to their exercise intolerance, and explore its utility in predicting long-term functional impairment persistence.Methods: We studied 108 consecutive subjects with severe COVID-19 ARDS who remained alive 6 months after ICU discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. Functional evaluation included spirometry, plethysmography, muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was assessed through an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional impairments.Results: At 6 months after ICU discharge, a notable dissociation between morphological and clinical-functional sequelae was identified. Moderate-severe disability was present in 47% of patients and these subjects had greater limitation of ventilatory mechanics and gas exchange, as well as greater symptomatic perception during exercise and a probable associated cardiac limitation. Female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume were independently associated with the presence of moderate-severe functional disability, which in turn was related to higher frequency and greater intensity of dyspnea and worse quality of life. Out of the 71 patients with reduced lung volumes or diffusion capacity at 6 months post-ICU discharge, only 19 maintained a restrictive disorder associated with gas exchange impairment at 24 months post-discharge. In these patients, 6-month values for diffusion membrane component, maximal oxygen uptake, ventilatory equivalent for CO2, and dead space to tidal volume ratio were identified as independent risk factors for persistence of long-term functional sequelae.Conclusions: Less than half of survivors of COVID-19 ARDS have moderate-severe disability in the medium term, identifying several risk factors. In turn, diffusion membrane component and exercise tolerance at 6-month ICU discharge are independently associated with the persistence of long-term functional sequelae.

P311 KO Mice are Protected from Experimentally Induced Lung Fibrosis

Pulmonary fibrosis (PF) is a fatal chronic interstitial lung disease and one of the most irreversible forms of tissue/organ fibrosis. Idiopathic pulmonary fibrosis is a very progressive disease accompanied by inflammatory damage with a median survival of less than 5 years. Etiology of IPF is still elusive with potential reasons being genetic predisposition and environmental exposures including particulates, radiation, and SARS-CoV-2. Recent studies indicate that about 50% of COVID19 associated acute respiratory distress syndrome survivors develop PF. There are very limited treatment options with no curative therapies available for PF apart from invasive lung transplantation. P311 is an 8 kDa protein previously shown to have a key role in lung regeneration. As P311 overexpression in fibroblasts induced myofibroblast phenotype, we hypothesized that P311 has a role in tissue fibrosis. We induced PF by intra-tracheally instilling bleomycin (BL) in P311 knockout (KO) mice and wild type (WT, C57BL/6) control mice and collected lungs after 2-5 weeks. P311 KO mice showed significantly less fibrosis. After intra-tracheal instillation of BL, the lungs of P311 KO mice (D21) had significantly reduced number of myofibroblasts as indicated by reduced SM α-actin expression and collagen deposition as indicated by Masson trichrome staining compared to their WT counterparts. We further observed reduced levels of TGF-β1-3 and Smad-2 and -3 along with decreased epithelial to mesenchymal transdifferentiation markers in the lungs of bleomycin treated P311 KOs compared to WT controls. Further bronchoalveolar lavage fluid (BALF) was collected (D14) and utilized to determine the pulmonary inflammation by determining the total and different immune cell populations in the BALF and lung samples by FACS analysis. Even though we saw a significant increase in the BALF cellularity, we did not observe significant changes in T-cell, macrophage, and neutrophil numbers between WT and P311KOs. However, lung cell isolates showed significantly increased CD3 and CD4 positive cells indicating increased T-cells and helper T-cells in fibrotic P311KO lungs compared to WT lungs. In conclusion, bleomycin administration resulted in lung fibrosis in WT mice, but P311 KO mice are protected. This study was partially supported by research funding to KB, from American Lung Association, DA-196629-N. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.

BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1α, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).

Long-term outcomes of survivors with influenza A H1N1 virus-induced severe pneumonia and ARDS: a single-center prospective cohort study.

Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS). This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument. A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening. The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.

Tackling Brain and Muscle Dysfunction in Acute Respiratory Distress Syndrome Survivors: National Heart, Lung, and Blood Institute Workshop Report.

Acute respiratory distress syndrome (ARDS) is associated with long-term impairments in brain and muscle function that significantly impact the quality of life of those who survive the acute illness. The mechanisms underlying these impairments are not yet well understood, and evidence-based interventions to minimize the burden on patients remain unproven. The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health assembled a workshop in April 2023 to review the state of the science regarding ARDS-associated brain and muscle dysfunction, to identify gaps in current knowledge, and to determine priorities for future investigation. The workshop included presentations by scientific leaders across the translational science spectrum and was open to the public as well as the scientific community. This report describes the themes discussed at the workshop as well as recommendations to advance the field toward the goal of improving the health and wellbeing of ARDS survivors.

Healthcare Burden and Resource Utilization After Pediatric Acute Respiratory Distress Syndrome: A Secondary Analysis of the Collaborative Pediatric Critical Care Research Network Acute Respiratory Distress Syndrome Study.

To describe family healthcare burden and health resource utilization in pediatric survivors of acute respiratory distress syndrome (ARDS) at 3 and 9 months. Secondary analysis of a prospective multisite cohort study. Eight academic PICUs in the United States (2019-2020). Critically ill children with ARDS and follow-up survey data collected at 3 and/or 9 months after the event. None. We evaluated family healthcare burden, a measure of healthcare provided by families at home, and child health resource use including medication use and emergency department (ED) and hospital readmissions during the initial 3- and 9-month post-ARDS using proxy-report. Using multivariable logistic regression, we evaluated patient characteristics associated with family healthcare burden at 3 months. Of 109 eligible patients, 74 (68%) and 63 patients (58%) had follow-up at 3- and 9-month post-ARDS. At 3 months, 46 families (62%) reported healthcare burden including (22%) with unmet care coordination needs. At 9 months, 33 families (52%) reported healthcare burden including 10 families (16%) with unmet care coordination needs. At month 3, 61 patients (82%) required prescription medications, 13 patients (18%) had ED visits and 16 patients (22%) required hospital readmission. At month 9, 41 patients (65%) required prescription medications, 19 patients (30%) had ED visits, and 16 (25%) required hospital readmission were reported. Medication use was associated with family healthcare burden at both 3 and 9 months. In a multivariable analysis, preillness functional status and chronic conditions were associated with healthcare burden at month 3 but illness characteristics were not. Pediatric ARDS survivors report high rates of healthcare burden and health resource utilization at 3- and 9-month post-ARDS. Future studies should assess the impact of improved care coordination to simplify care (e.g., medication management) and improve family burden.

Long-term cognitive dysfunction after COVID ARDS

Background: COVID-19 acute respiratory distress syndrome (C-ARDS) survivors suffer from long-term physical complications. However, at the time of this study limited data are available on possible long-term cognitive impairment. Objectives: We hypothesized that COVID-19 ICU patients perform worse on cognitive tasks 6 months after admission, in comparison to reference values of a healthy population. Design: Two-center cohort study with a six months’ time horizon. Patients: Patients admitted to the ICU for COVID-19 associated respiratory failure between March and June 2020. Setting: Post-ICU follow up. Methods and main outcome measures: The primary measure was the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) score (with lower values indicating worse global cognition). The secondary outcome measure was the Trail Making Test (TMT) Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive functions). The Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE, on a scale from 1.0 to 5.0, with 5.0 indicating severe cognitive impairment) was taken for not patients not fluent in Dutch. Results: 117 COVID-19 patients were admitted to the ICU, of whom 32 patients (27%) died within 6 months. 67/85 (79%) patients participated in the cohort study. COVID-19 survivors had lower total RBANS cognition scores than the age-adjusted population norms (n=45). Fifteen (33%) patients had a global cognition score 1.5 SD below the population means. RBANS-subscale performance showed that both memory (immediate and delayed recall) and attention were at minus 1 SD below normative means, while language and visuospatial cognition were unaffected. Median TMT B score was 40 (IQR 10-65) (n=45). There were elevated scores of the short form IQCODE (mean 3.4 (SD 0.4). Conclusions: Our results suggests that COVID-19 ARDS negatively affects long-term cognitive function. Trial registration: ClinicalTrials.gov NCT04593069.

TRENDS IN CHOLESTEROL AND LIPOPROTEINS ARE ASSOCIATED WITH ACUTE RESPIRATORY DISTRESS SYNDROME INCIDENCE AND DEATH AMONG SEPSIS PATIENTS.

Objective: Compare changes in cholesterol and lipoprotein levels occurring in septic patients with and without acute respiratory distress syndrome (ARDS) and by survivorship. Methods: We reanalyzed data from prospective sepsis studies. Cholesterol and lipoprotein levels were analyzed using univariate testing to detect changes between septic patients with or without ARDS, and among ARDS survivors compared with nonsurvivors at enrollment (first 24 h of sepsis) and 48 to 72 h later. Results: 214 patients with sepsis were included of whom 48 had ARDS and 166 did not have ARDS. Cholesterol and lipoproteins among septic ARDS versus non-ARDS showed similar enrollment levels. However, 48 to 72 h after enrollment, change in median total cholesterol (48/72 h - enrollment) was significantly different between septic ARDS (-4, interquartile range [IQR] -23.5, 6.5, n = 35) and non-ARDS (0, -10.0, 17.5, P = 0.04; n = 106). When compared by ARDS survivorship, ARDS nonsurvivors (n = 14) had lower median total cholesterol levels (75.5, IQR 68.4, 93.5) compared with ARDS survivors (113.0, IQR 84.0, 126.8, P = 0.022), and lower median enrollment low-density lipoprotein cholesterol (LDL-C) levels (27, IQR 19.5-34.5) compared with ARDS survivors (43, IQR 27-67, P = 0.013; n = 33). Apolipoprotein A-I levels were also significantly lower in ARDS nonsurvivors (n = 14) (87.6, IQR 76.45-103.64) compared with ARDS survivors (130.0, IQR 73.25-165.47, P = 0.047; n = 33). At 48 to 72 h, for ARDS nonsurvivors, median levels of low-density lipoprotein cholesterol (9.0, IQR 4.3, 18.0; n = 10), LDL-C (17.0, IQR 5.0, 29.0; n = 9), and total cholesterol (59.0, 45.3, 81.5; n = 10) were significantly lower compared with ARDS survivors' (n = 25) levels of low-density lipoprotein cholesterol (20.0, IQR 12.0-39.0, P = 0.014), LDL-C (42.0, IQR 27.0-58.0, P = 0.019), and total cholesterol (105.0, IQR 91.0, 115.0, P = 0.003). Conclusions: Change in total cholesterol was different in septic ARDS versus non-ARDS. Total cholesterol, LDL-C, and apolipoprotein A-I levels were lower in ARDS nonsurvivors compared with survivors. Future studies of dysregulated cholesterol metabolism in septic ARDS patients are needed to understand biology and links to potential therapies.

Functional recovery in a cohort of ECMO and non-ECMO acute respiratory distress syndrome survivors

BackgroundThe mortality benefit of VV-ECMO in ARDS has been extensively studied, but the impact on long-term functional outcomes of survivors is poorly defined. We aimed to assess the association between ECMO and functional outcomes in a contemporaneous cohort of survivors of ARDS.MethodsMulticenter retrospective cohort study of ARDS survivors who presented to follow-up clinic. The primary outcome was FVC% predicted. Univariate and multivariate regression models were used to evaluate the impact of ECMO on the primary outcome.ResultsThis study enrolled 110 survivors of ARDS, 34 of whom were managed using ECMO. The ECMO cohort was younger (35 [28, 50] vs. 51 [44, 61] years old, p < 0.01), less likely to have COVID-19 (58% vs. 96%, p < 0.01), more severely ill based on the Sequential Organ Failure Assessment (SOFA) score (7 [5, 9] vs. 4 [3, 6], p < 0.01), dynamic lung compliance (15 mL/cmH20 [11, 20] vs. 27 mL/cmH20 [23, 35], p < 0.01), oxygenation index (26 [22, 33] vs. 9 [6, 11], p < 0.01), and their need for rescue modes of ventilation. ECMO patients had significantly longer lengths of hospitalization (46 [27, 62] vs. 16 [12, 31] days, p < 0.01) ICU stay (29 [19, 43] vs. 10 [5, 17] days, p < 0.01), and duration of mechanical ventilation (24 [14, 42] vs. 10 [7, 17] days, p < 0.01). Functional outcomes were similar in ECMO and non-ECMO patients. ECMO did not predict changes in lung function when adjusting for age, SOFA, COVID-19 status, or length of hospitalization.ConclusionsThere were no significant differences in the FVC% predicted, or other markers of pulmonary, neurocognitive, or psychiatric functional recovery outcomes, when comparing a contemporaneous clinic-based cohort of survivors of ARDS managed with ECMO to those without ECMO.

Association between Acute Respiratory Distress Syndrome Due to COVID-19 and Long-Term Sleep and Circadian Sleep-Wake Disorders.

Current studies agree on the impact of sleep and circadian rest-activity rhythm alterations in acute respiratory distress syndrome (ARDS) survivors. However, research on the duration of this impact is scarce. In this study, we evaluate the impact of ARDS on the sleep and circadian rest-activity rhythm of COVID-19 survivors twelve months after hospital discharge. This is a prospective study including COVID-19 survivors with and without ARDS during hospitalization. Data was collected four and twelve months after hospital discharge. The interventions included one-week wrist actigraphy and a home sleep apnea test (HSAT), and evaluations were conducted according to the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and insomnia severity index (ISI). Fifty-two patients were evaluated (ARDS = 31 and non-ARDS = 21); they had a median age of 49.0 [39.0;57.2] years and 53.8% were male. After twelve months, 91.3% presented poor sleep quality, 58.7% presented insomnia, 50% presented daytime somnolence, and 37% presented comorbid insomnia and obstructive sleep apnea (COMISA). No significant improvement was observed in relation to sleep or the circadian rest-activity rhythm between four and twelve months. A tendency of poor sleep quality, insomnia, daytime somnolence, and COMISA was observed. Finally, there was no significant impact on the circadian rest-activity rhythm between four and twelve months or between the groups.

Functional Capacity in COVID-19 related Acute Respiratory Distress Syndrome Survivors

Background/Purpose:: The aim of this retrospective study is to determine the functional capacity, global muscle weakness and quality of life in COVID-19 survivors. Acute respiratory distress syndrome survivors frequently develop impaired physical function, quality of life, and muscle weakness.&#x0D; Methods: Acute respiratory distress syndrome survivors related to COVID-19 underwent standardized physical clinical evaluation, Medical Research Council-sumscore, hand-grip strength, 6-minute walk test, 5 repetition-chair-stand test, timed up and go test and Short form-36 evaluation following 4-6 weeks after hospital discharge in Physical Medicine and Rehabilitation Outpatient Clinic.&#x0D; Results: Fifteen patients (10 men, 5 women) with median age 69 years and length of intensive care unit stay 10 days were analyzed. There were impairments in 6-minute walk test, 5 repetition-chair-stand test, hand-grip strength and, Role-physical, Role-emotional and Social functioning domains of Short form-36. 6-minute walk distance was negatively correlated with timed up and go. SF-physical functioning was positively correlated with hand-grip strength, Medical Research Council-sumscore and 5 repetition-chair-stand. SF-general health was positively correlated with hand-grip strength.&#x0D; Conclusion: There were varying degrees of functional impairment in survivors. Therefore, it could add advantage to assess these patients after nearly 4-6 weeks following discharge in order to ascertain rehabilitation needs and giving appropriate therapies.

Exosomal miR-17-5p, miR-146a-3p, and miR-223-3p Correlate with Radiologic Sequelae in Survivors of COVID-19-Related Acute Respiratory Distress Syndrome.

We investigated the association between circulating microRNAs (miRNAs) potentially involved in the lung inflammatory process and fibrosis development among COVID-19-related acute respiratory distress syndrome (ARDS) survivors. At 4 ± 2 months from clinical recovery, COVID-19-related ARDS survivors matched for age, sex, and clinical characteristics underwent chest high-resolution computerized tomography (HRCT) and were selected based on imaging pattern evolution into fully recovered (N = normal), pulmonary opacities (PO) and fibrosis-like lesions (FL). Based on the previous literature, we performed plasma miRNA profiling of exosomal miRNAs belonging to the NLRP3-inflammasome platform with validated (miR-17-5p, miR-223-3p) and putative targets (miR-146a-5p), miRNAs involved in the post-transcriptional regulation of acute phase cytokines (miR128-3p, miR3168, miR125b-2-3p, miR106a-5p), miRNAs belonging to the NLRP4-inflammasome platform (miR-141-3p) and miRNAs related to post-transcriptional regulation of the fibrosis process (miR-21-5p). miR-17-5p, miR-223-3p, and miR-146a-5p were significantly down-regulated in patients with FL when compared to patients with PO. miR-146a-5p was also down-regulated in patients with FL than in N. The expression of the remaining miRNAs did not differ by group. In patients with long-term pulmonary radiological sequelae following COVID-19-related ARDS, a down-regulation of miR-17-5p, miR-146a-3p, and miR-223-3p correlated to fibrosis development in patients showing persistent hyper-reactivity to inflammatory stimulation. Our results support the hypothesis that NLRP3-Inflammasome could be implicated in the process of fibrotic evolution of COVID-19-associated ARDS.

Screening Out False Participants in Research Recruitment from Social Media Groups.

Social media-based groups offer a rich opportunity for nurse researchers to connect with potential study participants. However, as the authors discovered from recruitment of acute respiratory distress syndrome survivors in social media-based survivorship groups, there is a risk of enrollment of both false and duplicate participants. Nurse researchers should adopt best practices to screen out false participants and prevent duplicate participation. Lessons learned from recruitment in social media groups include avoiding the use of survey links, requiring video interviews or home visits for confirmation of identity, adoption of strategic screening questions, and avoidance of international groups (unless the aim is to recruit foreign nationals). Adoption of these practices can help to ensure that the data collected from group patrons are trustworthy. Nurses who read research and adopt findings into practice should critically examine if researchers implemented strategies to screen out false and duplicate participants to protect data integrity.

Trajectories of quality of life, return to work, psychopathology, and disability in survivors of the acute respiratory distress syndrome (ARDS): A three-year prospective cohort study (DACAPO)

PurposeDescribe the long-term development of outcomes for survivors of the Acute Respiratory Distress Syndrome (ARDS). Material and MethodsA cohort study with N = 877 ARDS survivors was conducted. Health related quality of life (HRQoL, Physical and Mental Component Scale: PCS, MCS of the SF-12), return to work (RtW), panic disorder, depressive symptoms (PHQD), and post-traumatic-stress-disorder (PTSD, PTSS-14) were assessed at 3, 6, 12, 24, and 36 months after discharge from ICU. ResultsPCS, MCS, and RtW increased during the first 12 months [e.g. PCS: Md = 36 (IQR 31–43) at 3 months, Md = 42 (IQR 34–52) at 12 months; MCS: Md = 44 (IQR 32–54) at 3 months, Md = 47 (IQR 33–57) at 12 months, RtW = 23.2% at 3 months, 54.5% at 12 months], and remained relatively stable afterwards. Proportion of major depressive syndrome decreased from 3 (14.2%) to 36 months (8.9%). Proportions of panic disorder (5.3% to 7.4%) and PTSD (27.1% to 32.6%) varied only slightly. ConclusionsMost of recovery in HRQoL and RtW occur during the first 12 months, after which a plateau is reached, indicating a chronification for many patients. Contrary to this, however, psychopathological symptoms remain stable, except for depressive symptoms. [200 words].

Sex-differences in the longitudinal recovery of neuromuscular function in COVID-19 associated acute respiratory distress syndrome survivors.

Patients admitted to the intensive care unit (ICU) following severe acute respiratory syndrome 2 (SARS-CoV-2) infection may have muscle weakness up to 1 year or more following ICU discharge. However, females show greater muscle weakness than males, indicating greater neuromuscular impairment. The objective of this work was to assess sex differences in longitudinal physical functioning following ICU discharge for SARS-CoV-2 infection. We performed longitudinal assessment of physical functioning in two groups: 14 participants (7 males, 7 females) in the 3-to-6 month and 28 participants (14 males, 14 females) in the 6-to-12 month group following ICU discharge and assessed differences between the sexes. We examined self-reported fatigue, physical functioning, compound muscle action potential (CMAP) amplitude, maximal strength, and the neural drive to the tibialis anterior muscle. We found no sex differences in the assessed parameters in the 3-to-6-month follow-up, indicating significant weakness in both sexes.Sex differences emerged in the 6-to-12-month follow-up. Specifically, females exhibited greater impairments in physical functioning, including lower strength, walking lower distances, and high neural input even 1 year following ICU-discharge. Females infected by SARS-CoV-2 display significant impairments in functional recovery up to 1 year following ICU discharge. The effects of sex should be considered in post-COVID neurorehabilitation.

Post intensive care syndrome in survivors of COVID-19 who required mechanical ventilation during the third wave of the pandemic: A prospective study

BackgroundPost intensive care syndrome is defined as the presence of any impairment affecting the physical, psychiatric, or cognitive domains as a result of critical illnesses. ObjectivesTo explore functional, cognitive and psychological outcomes at 30 days post hospital discharge among survivors of COVID-19–associated acute respiratory distress syndrome, who required mechanical ventilation. MethodsProspective cohort study. We included adult patients with COVID-19–associated acute respiratory distress syndrome, invasively ventilated in two ICUs in Buenos Aires. We measured functional, cognitive and psychological impairments with Barthel index, Montreal Cognitive Assessment test, Patient Health Questionnaire-9 and General Anxiety Disorder-7. Primary outcome was post-intensive care syndrome. Secondary outcome was mortality at 60 days. ResultsWe admitted 40 patients, median age was 69 (60–75) and mostly male (75%). Mortality at 60 days was 37%. Cox regression analysis identified diabetes and Apache II as independent predictors of mortality. Out of 22 patients studied, 14 (64%) developed PICS after discharge. With a physical, cognitive and psychological impairment in 64%, 41% and 32% of patients, respectively. Obesity, days of mechanical ventilation, Apache II, vasopressors use, delirium duration and cumulative midazolam dose were associated with functional dependence. ConclusionsWe identified a high prevalence of functional, cognitive and mental impairment at 30 days after hospital discharge in COVID-19–associated acute respiratory distress syndrome survivors, invasively ventilated. The physical domain was the most frequently affected. These findings suggest the need for long-term follow-up of this population.

Exosomal miRNAs targeting NLRP3 inflammasome platform are associated with radiologic sequelae in survivors of COVID-19-associated acute respiratory distress syndrome

Background: There is limited understanding of the pathophysiology of post-acute pulmonary sequelae in COVID-19-associated acute respiratory distress syndrome (ARDS). We aimed at investigating the association of circulating microRNAs (miRNAs) involved in post-transcriptional regulation of NLRP3-inflammasome pathways and lung radiological features among COVID-19- associated ARDS survivors. Methods: We evaluated COVID-19-associated ARDS survivors at 4±2 months from clinical recovery. Patients were selected based on imaging pattern evolution according to chest high-resolution computerized tomography (HRCT) findings into “fully recovered” (FR), “pulmonary opacities” (PO) and “fibrosis-like lesions” (FL) according to radiological appearance. Plasma miRNA profiling was performed using real time quantitative polymerase chain reaction (RT-qPCR). The exosomal expression of NLRP3 inflammasome related miRNAs (miR-17-5p, miR-223-3p, miR-146a-5p) was evaluated. Results: 31 patients (33% men, mean age 60±6 years, mean BMI 31.1±6.6 Kg/m2) were selected for the present study. No statistically significant differences between FR, PO and FL patterns were observed according to clinical features. NLRP3-inflammasome-related miRNAs such as miR-17-5p, miR-223-3p and miR-146a-5p were significantly up-regulated in patients with PO when compared to patients with FL. miR-146a-5p was also up-regulated in patients with FL than in FR. Conclusions: In patients with long-term pulmonary radiological sequelae following COVID71 19- associated ARDS, a down-regulation of miRNAs inhibiting NLRP3 (miR-17-5p, miR-146a72 3p and miR-223-3p) correlated to fibrosis development in patients showing persistent hyper-reactivity to inflammatory stimulation. NLRP3-Inflammasome-related miRNAs could be a possible therapeutic target to prevent the fibrotic evolution of COVID-19-associated ARDS.

Post-intensive care syndrome and pulmonary fibrosis in patients surviving ARDS-pneumonia of COVID-19 and non-COVID-19 etiologies

The purpose was to examine patient-centered outcomes and the occurrence of lung fibrotic changes on Chest computed tomography (CT) imaging following pneumonia-related acute respiratory distress syndrome (ARDS). We sought to investigate outpatient clinic chest CT imaging in survivors of COVID19-related ARDS and non-COVID-related ARDS, to determine group differences and explore relationships between lung fibrotic changes and functional outcomes. A retrospective practice analysis of electronic health records at an ICU Recovery Clinic in a tertiary academic medical center was performed in adult patients surviving ARDS due to COVID-19 and non-COVID etiologies. Ninety-four patients with mean age 53 ± 13 and 51% male were included (n = 64 COVID-19 and n = 30 non-COVID groups). There were no differences for age, sex, hospital length of stay, ICU length of stay, mechanical ventilation duration, or sequential organ failure assessment (SOFA) scores between the two groups. Fibrotic changes visualized on CT imaging occurred in a higher proportion of COVID-19 survivors (70%) compared to the non-COVID group (43%, p < 0.001). Across both groups, patients with fibrotic changes (n = 58) were older, had a lower BMI, longer hospital and ICU LOS, lower mean RASS scores, longer total duration of supplemental oxygen. While not statistically different, patients with fibrotic changes did have reduced respiratory function, worse performance on the six-minute walk test, and had high occurrences of anxiety, depression, emotional distress, and mild cognitive impairment regardless of initial presenting diagnosis. Patients surviving pneumonia-ARDS are at high risk of impairments in physical, emotional, and cognitive health related to Post-Intensive Care Syndrome. Of clinical importance, pulmonary fibrotic changes on chest CT occurred in a higher proportion in COVID-ARDS group; however, no functional differences were measured in spirometry or physical assessments at ICU follow-up. Whether COVID infection imparts a unique recovery is not evident from these data but suggest that long-term follow up is necessary for all survivors of ARDS.

Quantitative image analysis in COVID-19 acute respiratory distress syndrome: a cohort observational study.

Background Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury commonly associated with pneumonia, including coronavirus disease-19 (COVID-19). The resultant effect can be persistent lung damage, but its extent is not known. We used quantitative high resolution computed tomography (QHR-CT) lung scans to radiographically characterize the lung damage in COVID-19 ARDS (CARDS) survivors. Methods Patients with CARDS (N=20) underwent QHR-CT lung scans 60 to 90 days after initial diagnosis, while hospitalized at a long-term acute care hospital (LTACH). QHR-CT assessed for mixed disease (QMD), ground glass opacities (QGGO), consolidation (QCON) and normal lung tissue (QNL). QMD was correlated with respiratory support on admission, tracheostomy decannulation and supplementary oxygen need on discharge. Results Sixteen patients arrived with tracheostomy requiring invasive mechanical ventilation. Four patients arrived on nasal oxygen support. Of the patients included in this study 10 had the tracheostomy cannula removed, four remained on invasive ventilation, and two died. QHR-CT showed 45% QMD, 28.1% QGGO, 3.0% QCON and QNL=23.9%. Patients with mandatory mechanical ventilation had the highest proportion of QMD when compared to no mechanical ventilation. There was no correlation between QMD and tracheostomy decannulation or need for supplementary oxygen at discharge. Conclusions Our data shows severe ongoing lung injury in patients with CARDS, beyond what is usually expected in ARDS. In this severely ill population, the extent of mixed disease correlates with mechanical ventilation, signaling formation of interstitial lung disease. QHR-CT analysis can be useful in the post-acute setting to evaluate for interstitial changes in ARDS.

Effects of COVID-19 Acute Respiratory Distress Syndrome ICU Survivor Telemedicine Clinic on Patient Readmission, Pain Perception and Self-Assessed Health Scores: A Randomized, Prospective, Single-Center Exploratory Study.

Post-intensive care syndrome (PICS) affects up to 50% of intensive care unit (ICU) survivors leading to long-term neurocognitive, psychosocial, and physical impairments. Approximately 80% of COVID-19 pneumonia patients who require ICU level care are at elevated risk for developing acute respiratory distress syndrome (ARDS). Survivors of COVID-19 ARDS are at high-risk for unanticipated healthcare utilization post discharge. Common to this group of patients are increased readmission rates, long term decreased mobility, and overall poorer outcomes. Multidisciplinary post-ICU clinics for ICU survivors are usually located in large urban academic medical centers providing in-person consultation. Data is lacking on the feasibility of providing telemedicine post-ICU care for COVID-19 ARDS survivors. We explored the feasibility of instituting a COVID-19 ARDS ICU survivor telemedicine clinic and examined its effect on healthcare utilization post hospital discharge. This randomized, unblinded, single-center, parallel-group exploratory study was conducted at a rural, academic, tertiary-care medical center. Study group (SG) participants underwent a telemedicine visit within 14 days of discharge, during which a six-minute walk test (6MWT), a EuroQoL 5-Dimension (EQ-5D) questionnaire, and vital signs logs (VSL) were reviewed by an intensivist. Additional appointments were arranged as needed based on the outcome of these review and tests. The control group (CG) received a telemedicine visit within six weeks of discharge and completed the EQ-5D questionnaire; additional care was provided as needed based on findings in this telemedicine visit. Both SG (n=20) and CG (n=20) participants had similar baseline characteristics and dropout rate (10%). Among SG participants, 72.2% agreed to follow up in the pulmonary clinic compared to 50.0% of CG participants (P=.31). Unanticipated visits to the emergency department were 11.1% in the SG compared to 5.6% CG (not sig.). The rate of pain/discomfort was noted to be 66.7% in the SG compared to 61.1% in the CG (P=.72). The anxiety/depression rate was 72.2% vs. 61.1% (P=.59) in the SG compared to the CG. Participants' self-assessed health rating scores was M=73.9, SD 16.1 in the SG compared to M=70.6, SD 20.9 in the CG (P=.59). Both primary care physicians (PCPs) and participants in the SG perceived the telemedicine clinic as a favorable model for post-discharge critical illness follow-up in an open-ended questionnaire regarding care. This exploratory study found no statistically significant results in reducing healthcare utilization post-discharge and health related quality of life. However, PCPs and patients perceived telemedicine as a feasible and favorable model for post-discharge care among COVID-19 ICU survivors to facilitate expedited subspecialty assessment, decrease unanticipated post-discharge healthcare utilization, and reduce PICS. Further investigation is warranted to determine the feasibility of incorporating telemedicine-based post-hospitalization follow-up for all medical ICU survivors which may show improvement in healthcare utilization in a larger population.