COVID-19 Related Respiratory Failure Research Articles

Health related quality of life, physical function, and cognitive performance in mechanically ventilated COVID-19 patients: A long term follow-up study

BackgroundSurvivors of severe COVID-19 related respiratory failure may experience durable functional impairments. We aimed at investigating health-related quality of life (HR-QoL), physical functioning, fatigue, and cognitive outcomes in COVID-19 patients who received invasive mechanical ventilation (IMV). MethodsCase-series, prospective, observational cohort study at 18 months from hospital discharge. Patients referring to the Intensive Care Unit (ICU) of Humanitas Research Hospital (Milan, Italy) were recruited if they needed IMV due to COVID-19 related respiratory failure. After 18 months, these patients underwent the 6-min walking test (6MWT), the Italian version of the 5-level EQ-5D questionnaire (EQ-5D-5L), the Functional Assessment of Chronic Illness Therapy – Fatigue questionnaire (FACIT-F), the Trail Making Test-B (TMT-B) and the Montreal Cognitive Assessment-BLIND test (MoCA-BLIND). Results105 patients were studied. The population's age was 60 ± 10 years on average, with a median Frailty Scale of 2 (Hodgson et al., 2017; Carenzo et al., 2021a [2,3]). EQ-VAS was 80 [70–90] out of 100, walked distance was 406 [331–465] meters, corresponding to about 74 ± 19,1% of the predicted value. FACIT-F score was 43 [36–49] out of 52, and MoCa-BLIND score was 19 (DeSalvo et al., 2006; von Elm et al., 2008; Herdman et al., 2011; Scalone et al., 2015 [16-20]) out of 22. The median TMT-B time was 90 [62–120] seconds. We found a possible age and gender specific effect on HR-QoL and fatigue. ConclusionsAfter 18 months from ICU discharge, survivors of severe COVID-19 respiratory failure experience a moderate reduction in HR-QoL, and a severe reduction in physical functioning. Fatigue prevalence is higher in younger patients and in females. Finally, cognitive impairment was present at a low frequency.

Biomarker Analysis Provides Evidence for Host Response Homogeneity in Patients With COVID-19

BackgroundThe exploration of subphenotypes in hospitalized COVID-19 patients has garnered substantial attention. Most existing studies operate under the assumption of heterogeneity in COVID-19 patient populations and this assumption can lead to erroneous conclusions. Research QuestionDo plasma biomarker profiles reflective of various pathophysiological pathways provide evidence for heterogeneity in hospitalized patients with COVID-19? Study Design and MethodsThis is a secondary analysis of two prospective observational studies of adult patients hospitalized with COVID-19 related respiratory failure in the general ward and intensive care unit (ICU) of two medical centers and with 44 host response biomarkers available. Parsimonious models were used to allocate and validate ARDS inflammatory subphenotypes. Novel biological subphenotypes were identified using latent profile analysis (LPA) and hierarchical clustering. Heterogeneity of treatment effect (HTE) for corticosteroids was assessed using an interaction term in a logistic regression model. ResultsThe cohort consisted of 162 patients admitted to the ICU and 464 to the ward. Using the parsimonious models in ICU patientsonly 3.1-13% of patients were classified as hyperinflammatory subphenotype. Using de novo subphenotyping techniques, neither clustering or LPA revealed significant evidence for heterogeneity in the ward (p = 0.11-0.13), ICU (p = 0.23-0.88) or combined cohort (p = 0.05-0.88). Adding clinical variables did not alter results in the ICU or combined cohort. Using the combined approach in the ward cohort, indices provided borderline significance for two subphenotypes, and there was good agreement between clustering and LPA (87.9%), but no HTE for corticosteroids was observed between these two classes (p = 0.198). InterpretationSystemic inflammatory subphenotypes derived from ARDS patients do not reflect the variation in severity of COVID-19. Empirical evidence, derived from cluster analysis or latent profile analysis, offers limited support for biological heterogeneity in COVID-19.

Cannula associated deep vein thromboses in COVID-19 patients supported with VV ECMO.

VV ECMO is increasingly used as a rescue strategy for hypercarbic and hypoxic respiratory failure refractory to conventional management, and more than 14,000 patients with COVID-19 related respiratory failure have been supported with VV ECMO to date. One of the known complications of VV ECMO support is the development of cannula-associated deep vein thromboses (CaDVT). The purpose of this study was to identify the incidence of CaDVT in COVID-19 patients supported with VV ECMO as compared to non-COVID-19 patients. We hypothesized that due to the hypercoagulable state and longer duration of VV ECMO support required for patients with COVID-19, a higher incidence of CaDVT would be observed in these patients. This is a single center, retrospective observational study. About 291 non-trauma adult patients who were cannulated for VV ECMO and managed at our institution from January 1, 2014 to January 10, 2022 were included. The primary outcome was the presence of CaDVT 24 h after decannulation in COVID-19 versus non-COVID-19 patients. Our secondary outcome was continued presence of DVT on follow up imaging. CaDVT were defined as venous thrombi detected at prior cannulation sites. Both groups had a high incidence of CaDVT. There was no significant difference in the incidence of CaDVT in COVID-19 patients compared to non-COVID-19 patients (95% vs 88%, p = 0.13). Patients with COVID-19 had an increased incidence of persistent CaDVT on repeat imaging (78% vs 56%, p = 0.03). Given the high number of post-decannulation CaDVT in both groups, routine screening should be a part of post ECMO care in both populations. Repeat venous duplex ultrasound should be performed to assess for the need for ongoing treatment given the high incidence of CaDVT that persisted on repeat duplex scans.

ANALYSIS OF ESTONIAN ECMO REGISTRY DATA OF COVID OUTBRAKE 2020 TO 2022

We launched Estonian nationwide ECMO registry in 2021 including data of all patients supported with ECLS in both ECMO centres - Tartu University Hospital and North Estonia Medical Centre. For the completeness of Registry all retrospective data were added back from 2009. Dataset includes patient demographics, diagnoses, ICU-, hospital- and 12 month survival, ECLS details and complications. To date, the registry contains data of 301 patients. Since January 2020, 65 confirmed Covid-19 patients have received ECLS support: VV-ECMO was used 55, ECCO2R 7, VA support 1 and eCPR in 2 instances. The primary outcome in our analysis was in-hospital death. Secondary outcome was to compare in-hospital mortality and length of stay of Covid-confirmed patients to the 54 non-Covid ARDS patients treated with VV-ECMO. <b>Findings:</b> Data for 55 adult patients with Covid-19 who received VV-ECMO support were available and included to this study. Of these 19(34.5%) were discharged home or to rehabilitation centre, 6(10.9%) were still in hospital at a time of analysis and 22(40.0%) died. One patient was bridged to successful lung transplantation. We also supported two pregnant patients with good maternal and neonatal outcomes. Comparing hospital mortality of Covid-confirmed cases to 54 non-Covid adult ARDS patients, hospital mortality was similar between the groups - 44.9% (22/49) and 46.2% (34/52) respectively. For those who were discharged alive, hospital LOS was longer for Covid-confirmed cases compared to non-Covid patients (mean 59 vs 50 days, respectively). <b>Interpretation:</b> In patients with Covid-19 who received ECMO, observed outcome supports existing recommendations to consider use of ECMO in refractory Covid-19 related respiratory failure when performed in experienced centres. Registry can also be used to coordinate ECMO beds, equipment and personnel as resources become constrained. We constantly monitored availability of ECMO beds and agreed on common indications for VV ECMO in covid patients. Further analysis will concentrate on 12 month survival and functional outcome.

COV1: Cannula-Associated Deep Vein Thromboses are Prevalent in COVID-19 Veno-venous Extracorporeal Membrane Oxygenation Patients

Background: Patients with severe COVID-19 related respiratory failure may require veno-venous extracorporeal membrane oxygenation (VV ECMO). After decannulation, patients on VV ECMO have historically had high percentages of cannula-associated deep vein thrombosis (CaDVT). Due to their hypercoagulable state and prolonged course on VV ECMO, we hypothesized that patients with COVID-19 would experience a higher rate of CaDVT when compared to their non-COVID-19 counterparts. We also described the association between location and size of cannula in the development of CaDVTs. Methods: This was a single center retrospective review of patients ≥ 18 years old who were treated with VV ECMO and decannulated from January 1, 2014, to January 10, 2022. Patients who were placed on VV ECMO due to trauma and patients who were cannulated for veno-arterial ECMO were excluded. Patients were managed in a dedicated Lung Rescue Unit and anticoagulated with a heparin infusion at a goal partial thromboplastin time (aPTT) of 45-55 or 60-80 depending on the presence of clotting complications. Post-decannulation venous duplexes were performed 24 hours after decannulation and if positive for DVT, performed again in 2 weeks. Univariate and multivariate analyses were conducted to analyze our primary outcome of the development of CaDVT. Results: A total of 291 patients met our inclusion criteria: 76 COVID-19 VV ECMO patients and 215 non-COVID-19 VV ECMO patients. Decannulated COVID-19 VV ECMO patients had a significantly higher body mass index (BMI) (35.8, 32.9, p= 0.03) and length of ECMO run (hours) (660, 312, p< 0.001) than their non-COVID-19 counterparts. Most decannulated patients in both groups received post-decannulation duplexes (96%, 99%, p= 0.45). COVID-19 and non-COVID-19 patients decannulated from VV ECMO both experienced high incidences of CaDVT on initial post-decannulation ultrasound (95%, 88%, p= 0.13). COVID-19 patients were more likely to have multiple CaDVTs (32%, 11%, p< 0.001). Patients with COVID-19 experienced a higher rate of right common femoral CaDVT (47%, 17%, p< 0.001) and a higher percentage of 25 French drainage cannula CaDVT (48%, 18%, p< 0.001). COVID-19 VV ECMO patients had a significantly higher incidence of persistent CaDVT on repeat ultrasound (78%, 56%, p= 0.03). A logistic regression was performed with all decannulated patients. Age, BMI, hours on ECMO, COVID-19 status, and size and location of ECMO cannulas did not predict the presence of DVT. Conclusion: Both COVID-19 and non-COVID-19 VV ECMO patients had high rates of CaDVTs. The utilization of VV ECMO in COVID-19 respiratory failure was associated with a higher incidence of CaDVTs on repeat ultrasound as compared to patients with non-COVID-19 related respiratory failure. Regular post-decannulation screening, treatment, and follow up imaging should be performed. Further investigation into the effect of anticoagulation strategy is needed.

Directed Hypercapnia for Weaning From ECMO to Mechanical Ventilation—Progress or Just a Process?

In this issue of The Annals of Thoracic Surgery, Kluis and colleagues1Kluis A. Shih E. Squiers J.J. et al.Directed hypercapnia as a strategy to wean extracorporeal membrane oxygenation in COVID-19 pneumonia.Ann Thorac Surg. 2022; 114: e307-e309Abstract Full Text Full Text PDF Scopus (1) Google Scholar report a single-institution experience with 5 cases of severe COVID-19 acute respiratory distress syndrome (ARDS) with hypercarbic respiratory failure using directed hypercapnia as a strategy to wean patients from venovenous extracorporeal membrane oxygenation (ECMO). The authors instituted a directed hypercapnia approach in combination with metabolically compensated respiratory acidosis to terminate long-term ECMO support and to reduce associated morbidity and mortality. Five patients were successfully weaned off ECMO. One patient with preexisting kidney disease requiring renal replacement therapy ultimately died of refractory acidosis and sepsis. ECMO duration ranged from 56 to 167 days, highlighting the extended duration of support. More than 13,000 cases of COVID-19 requiring ECMO have been reported to the Extracorporeal Life Support Organization registry with a 47% in-hospital mortality.2Extracorporeal Life Support OrganizationELSO live registry dashboard of ECMO patient data.https://www.elso.org/Registry/ELSOLiveRegistryDashboard.aspxDate accessed: March 20, 2022Google Scholar Early use of ECMO for COVID-19 resulted in poor outcomes, with many clinicians discouraging this application.3Henry B.M. Lippi G. Poor survival with extracorporeal membrane oxygenation in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19): pooled analysis of early reports.J Crit Care. 2020; 58: 27-28Crossref PubMed Scopus (144) Google Scholar As the pandemic progressed, ECMO use increased rapidly, and more recent data suggest similar outcomes to non-COVID ARDS.4Barbaro R.P. MacLaren G. Boonstra P.S. et al.Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry.Lancet. 2020; 396: 1071-1078Abstract Full Text Full Text PDF PubMed Scopus (420) Google Scholar Much of the management of ECMO and mechanical ventilation has been extrapolated from non-COVID ARDS populations. Whereas most centers use lung-protective ventilation, there are no standard guidelines for ventilator management in this setting. Institutional demands and experiences often dictate the pathway of care. The authors report an ECMO weaning protocol that successfully liberated patients from this high-risk, resource-intensive therapy, allowing discharge from a tertiary center to long-term acute rehabilitation facilities. At the individual patient level, this may translate into decreases in the morbidity and mortality associated with prolonged ECMO. At the health system level, the economic and resource allocation benefits associated with freeing up intensive care beds, staff, and resources could be immense. This protocol could be particularly valuable during high infectivity periods when the health system is significantly strained. Certain considerations temper enthusiasm for widespread adoption of this protocol. Individualized care is essential, and recovery is the primary aim. As reported, all survivors remain on assist-control ventilation, and long-term outcomes, including prospects for eventual ventilator liberation, are unknown. Patients may have been better served with sedative reduction, extubation, and ambulation on ECMO. In addition, proponents of directed hypercapnia must ensure that protocols do not restrict evaluation for lung transplantation. Outcomes from ECMO bridging to transplantation have improved because of better patient selection and protocolized management approaches. As highlighted in a recent US nationwide analysis published in the New England Journal of Medicine, lung transplantation is an important option for refractory COVID-19 ARDS or post-COVID fibrosis, with promising early outcomes including 95% 3-month survival in more than 200 recipients.5Roach A. Chikwe J. Catarino P. et al.Lung transplantation for Covid-19–related respiratory failure in the United States.N Engl J Med. 2022; 386: 1187-1188Crossref PubMed Scopus (24) Google Scholar Notwithstanding, there will likely be a role for directed hypercapnia in this population, which will be further delineated as more research is performed. Directed Hypercapnia as a Strategy to Wean Extracorporeal Membrane Oxygenation in COVID-19 PneumoniaThe Annals of Thoracic SurgeryVol. 114Issue 5PreviewCoronavirus disease 2019 pneumonia with respiratory failure refractory to maximum medical therapy has been successfully managed with venovenous extracorporeal membrane oxygenation. This report describes a process of using directed hypercapnia in 5 patients to wean them from prolonged extracorporeal support secondary to refractory hypercarbic respiratory failure. Full-Text PDF

POTENTIAL ROLE OF A SINGLE NUCLEOTIDE POLYMORPHISM OF NOD-LIKE RECEPTOR-X1 IN COVID-19 SUSCEPTIBILITY

TYPE: Abstract TOPIC: Chest Infections PURPOSE: COVID-19 is the leading cause of death in the United States for the last two years. Host susceptibility and pre-existing co-morbidities plays role in dictating COVID19 pathogenesis. Mitochondrial nucleotide-binding oligomerization domain-like Receptor X1(NLRX1) is an atypical NLR which plays a critical role in connecting innate immune responses with a variety of viral infections. Up to 30% of the general population carries rs10790286 single nucleotide polymorphism (SNP) of NLRX1 which can potentially alter susceptibility to COVID19. We aim to study an association of this SNP in NLRX1 with COVID19 infection. METHODS: We investigated 64 subjects with positive COVID19 PCR test admitted to the hospital with hypoxic respiratory failure. After written consent, blood was drawn, and genotyping assay was performed. Fischer exact test was used to assess the expression data with controls. RESULTS: No statistical difference was found for NLRX1 polymorphism and COVID19 susceptibility (p = 0.499). Similarly, no significant association between NLRX1 SNP and 30-day mortality was observed (p = 0.746). CONCLUSIONS: rs10790286 SNP of the NXLR1 gene is not associated with increased susceptibility and mortality for COVID19 related respiratory failure. CLINICAL IMPLICATIONS: Further research is needed to determine host susceptibility at molecular level for COVID19 related respiratory failure. DISCLOSURE: Funding: NIH R01 ES031253 (SH), NIGMS U54GM104942 (SH Pilot PI). KEYWORD: COVID-19

Global scientific outputs of extracorporeal membrane oxygenation in COVID-19: A bibliometric overview.

AimAlthough the number of global studies on ECMO, which is an important support system in the treatment of COVID-19 related respiratory failure, has increased in recent months, there is still no bibliometric study on the use of ECMO in COVID-19 in the literature. The aim of this study is to analyze the scientific articles on the use of ECMO in COVID-19 by statistical and bibliometric methods.MethodArticles published between 2019–2022 about the use of ECMO in COVID-19 were obtained from the Web of Science (WoS) database and analyzed using statistical and bibliometric methods. Spearman correlation coefficient was used for correlation studies. Network visualization maps were used to identify effe analysis and trending topics.ResultsA total of 1197 publications were found. 758 (63.3%) of these publications were articles. The top 3 contributing countries to the literature were USA (257, 33.9%), Germany (102, 13.4%) and Japan (87, 11.5%). The top 3 most active institutions were League of European Research Universities (90), Harvard University (50), and Udice French Research Universities (39). The top 3 journals with the highest count of publications were ASAIO Journal (n = 36), Frontiers in Medicine (22), and Perfusion-UK (n = 20). According to the average count of citations per article, the most influential journals were JAMA (1319), Intensive Care Medicine (327), and Lancet (95.7), respectively. We have shared a summary of 758 articles in this comprehensive bibliometric study on the use of ECMO in COVID-19.ConclusionIt can be said that the use of ECMO in COVID-19 has been the trending topic recently and most of the studies are from countries in the ELSO Awards of Excellence list which indicates that the follow-up of ECMO in certain centers and teams can also be influencing the publications. This article can be a useful resource for clinicians, scientists, and students concerning global output for ECMO use in COVID-19.

Successful Treatment of COVID-19 Patient on ECMO Using Mesenchymal Stromal Cells (MSC)-Derived Exosomes: A Case Report

IntroductionThe use of mesenchymal stromal cells (MSC) was recently proposed as a promising intervention for COVID-19 related respiratory failure (RF). Prior studies have suggested that its larger size might lead to entrapment in extracorporeal membrane oxygenation (ECMO), affect circuit function, and attenuate its efficacy. We present a successful case of a severe COVID-19 patient treated with MSC-derived exosomes while receiving veno-venous (VV) ECMO support.Case Report41-year-old unvaccinated obese White male with no past medical history presenting with shortness of breath and a +COVID-19 nasopharyngeal test was admitted receiving high-flow nasal cannula (HFNC), remdesivir, and dexamethasone (Day 1), followed by intubation (day 5), and a peripheral VV ECMO insertion (day 10) due to worsening RF. We used bivalirudin for post-ECMO anticoagulation. Subsequently, he received the first cycle of MSC-derived exosomes on alternative days (day 1, 3, & 5) between days 13-17, followed by the second cycle between days 34-38. After administration of exosomes, the plasma concentration of inflammatory markers reduced, including a decrease of 77% for ferritin, 74% for CRP, and 62% for procalcitonin in approximately one week, along with consistent improvement of PaO2/FiO2 ratio. ECMO membrane oxygenator was exchanged on day 23 at the time of tracheostomy. After successful weaning, ECMO decannulation was performed on day 47, and the patient was discharged home on day 61.SummaryECMO has emerged as a supportive strategy for patients with severe COVID-19 related RF. The patient's inflammatory response has been implicated in the pathophysiology of lung failure. Multiple pharmacological methods are employed to control the severity of this inflammatory response, thus preventing progression to the fibrotic stage of the disease. In our experience, MSC-derived exosomes neither resulted in any side effects nor impaired the function of ECMO and might have enhanced the recovery of the patient.

A low-cost, highly functional, emergency use ventilator for the COVID-19 crisis.

Respiratory failure complicates most critically ill patients with COVID-19 and is characterized by heterogeneous pulmonary parenchymal involvement, profound hypoxemia and pulmonary vascular injury. The high incidence of COVID-19 related respiratory failure has exposed critical shortages in the supply of mechanical ventilators, and providers with the necessary skills to treat. Traditional mass-produced ventilators rely on an internal compressor and mixer to moderate and control the gas mixture delivered to a patient. However, the current emergency has energized the pursuit of alternative designs, enabling greater flexibility in supply chain, manufacturing, storage, and maintenance considerations. To achieve this, we hypothesized that using the medical gasses and flow interruption strategy would allow for a high performance, low cost, functional ventilator. A low-cost ventilator designed and built-in accordance with the Emergency Use guidance from the US Food and Drug Administration (FDA) is presented wherein pressurized medical grade gases enter the ventilator and time limited flow interruption determines the ventilator rate and tidal volume. This simple strategy obviates the need for many components needed in traditional ventilators, thereby dramatically shortening the time from storage to clinical deployment, increasing reliability, while still providing life-saving ventilatory support. The overall design philosophy and its applicability in this new crisis is described, followed by both bench top and animal testing results used to confirm the precision, safety and reliability of this low cost and novel approach to mechanical ventilation. The ventilator meets and exceeds the critical requirements included in the FDA emergency use guidelines. The ventilator has received emergency use authorization from the FDA.

P486 Treatment-emergent COVID-19 infections in ozanimod ulcerative colitis and multiple sclerosis clinical trials

BackgroundOzanimod, a sphingosine 1-phosphate (S1P) receptor S1P1 and S1P5 modulator, is approved in the United States for moderately to severely active ulcerative colitis (UC) and in multiple countries for relapsing multiple sclerosis (MS). We describe COVID-19 outcomes in ozanimod-treated UC or MS patients (pts) in active phase 3 open-label extension (OLE) studies.MethodsA database search identified COVID-19 infection reports in ozanimod-treated pts with UC in the True North OLE and MS in the DAYBREAK OLE. The analysis period was November 1, 2019 to either August 31, 2021 (UC) or May 10, 2021 (MS). The last COVID-19 event from all pts with ≥1 event was analyzed.ResultsAmong 2792 ozanimod-treated pts with UC or MS, 258 developed COVID-19 (confirmed: 215); thus, the incidence in these clinical trial settings was 9.2% during the analysis periods. Most pts with confirmed cases (193/215 [89.8%]) had nonserious infections not requiring hospitalization or meeting other International Conference on Harmonisation criteria for a serious event. Of 611 ozanimod-treated pts with UC, 68 (11.1%) developed COVID-19 (confirmed: 55; Fig 1). A majority of UC pts with confirmed cases (45/55 [81.8%]) had nonserious COVID-19; most (54/55 [98.2%]) recovered (2 with sequalae) and 1 was recovering at data cutoff. One UC pt with confirmed COVID-19 discontinued ozanimod (1.8%), 23 temporarily interrupted it (41.8%), and 31 had no change to treatment (56.4%). No COVID-19‒related deaths were reported in UC pts. Of 2181 ozanimod-treated pts with MS, 190 (8.7%) developed COVID-19 (confirmed: 160; Fig 2). Most MS pts with confirmed COVID-19 (148/160 [92.5%]) had nonserious cases; most (158/160 [98.8%]) recovered (5 with sequelae) (Fig 1). No MS pts with confirmed cases discontinued ozanimod, 61 temporarily interrupted it (38.1%), and 99 had no change to treatment (61.9%). Outcomes in 13 additional UC pts (Fig 1) and 30 additional MS pts (Fig 2) with suspected COVID-19 were similar to those with confirmed cases. There were 3 COVID-19‒related deaths in the MS program. One pt died from a presumed pulmonary embolism; this pt had received high-dose corticosteroids for MS relapse immediately before COVID-19 symptom onset. Another pt died from suspected COVID-19‒related respiratory failure. One tetraplegic, cachectic pt died from a lung abscess following COVID-19 infection.ConclusionIn the UC and MS OLE studies, most pts with confirmed COVID-19 had nonserious infections, recovered, and did not require ozanimod discontinuation. There were 3 deaths in MS patients (case-fatality rate 1.6% in MS, 1.2% overall).

Awake Prone Positioning for Acute Hypoxaemic Respiratory Failure in COVID-19

Prone positioning has been demonstrated to significantly reduce mortality in invasively ventilated patients with moderate to severe acute respiratory distress syndrome through several physiological mechanisms, including optimization of ventilation and perfusion and a reduction in ventilator-associated lung injury. The marked increase of hospitalisation rates of patients with acute hypoxaemic respiratory failure during the COVID-19 pandemic, and associated strain on healthcare resources, led to interest in the use of prone positioning in conscious self-ventilating, or “awake”, patients, as an adjunct to the provision of oxygen therapy and respiratory support. The adoption of this technique was with the intent of reducing the likelihood of progressive respiratory failure and thus the need for invasive mechanical ventilation. In this review we summarize the background, physiological mechanisms and current evidence for the use of awake prone positioning in both COVID-19 related hypoxaemic respiratory failure and that attributed to other aetiologies. Whilst several studies note an improvement in respiratory parameters including oxygenation, the effect on clinically important outcomes such as rates of intubation and mortality remain unclear. The evidence base beyond COVID-19 related respiratory failure remains constrained and there is a paucity of evidence to help identify those most likely to benefit from this therapy. There remains no agreed consensus on how to implement awake prone positioning and significant variation exists in practice. Several clinical questions should be the focus for future research studies of this treatment modality including how to identify early responders and non-responders to therapy.

Factors Associated with 90-Day Mortality in Invasively Ventilated Patients with COVID-19 in Marseille, France.

Objectives: To describe clinical characteristics and management of intensive care units (ICU) patients with laboratory-confirmed COVID-19 and to determine 90-day mortality after ICU admission and associated risk factors. Methods: This observational retrospective study was conducted in six intensive care units (ICUs) in three university hospitals in Marseille, France. Between 10 March and 10 May 2020, all adult patients admitted in ICU with laboratory-confirmed SARS-CoV-2 and respiratory failure were eligible for inclusion. The statistical analysis was focused on the mechanically ventilated patients. The primary outcome was the 90-day mortality after ICU admission. Results: Included in the study were 172 patients with COVID-19 related respiratory failure, 117 of whom (67%) received invasive mechanical ventilation. 90-day mortality of the invasively ventilated patients was 27.4%. Median duration of ventilation and median length of stay in ICU for these patients were 20 (9–33) days and 29 (17–46) days. Mortality increased with the severity of ARDS at ICU admission. After multivariable analysis was carried out, risk factors associated with 90-day mortality were age, elevated Charlson comorbidity index, chronic statins intake and occurrence of an arterial thrombosis. Conclusion: In this cohort, age and number of comorbidities were the main predictors of mortality in invasively ventilated patients. The only modifiable factor associated with mortality in multivariate analysis was arterial thrombosis.

CLINICAL ATTRIBUTES AND RISK FACTORS FOR MECHANICAL VENTILATION AMONG PATIENTS WITH COVID-19 IN A COMMUNITY HOSPITAL SETTING: A PROPENSITY-MATCHED ANALYSIS

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Covid-19 caused by the novel SARS-CoV-2 has emerged as a global health crisis with various clinical complications. Covid-19 related respiratory manifestations have been reported as mild, moderate to severe including acute lung injury and acute respiratory distress syndrome necessitating non-invasive forms of oxygenation to mechanical ventilation (MV). MV patients frequently undergo prolonged hospitalizations with substantial morbidity and mortality. We sought to evaluate risk factors for MV in our cohort. METHODS: We conducted a retrospective cohort study of patients admitted in our institution from March 1st to June 21st2020, to assess risk factors for Covid-19 related respiratory failure requiring MV. The original cohort encompassed 166 MV and 503 non MV patients. Information from our hospital medical records was extracted, which included demographics, presenting symptoms, past medical history, vital signals, and laboratory data and need for MV. We propensity matched 166 MV with a concurrent cohort of non MV patients in our institution. Covariates applied in matching included age, gender, race, and body mass index (BMI). The admission clinical attributes and laboratory parameters were analyzed, along with outcomes. RESULTS: The mean age of our matched cohort was 63.8 years. Mechanically Ventilated patients had a higher incidence of tachycardia (heart rate > 125) (p <.001), elevated respiratory rate > 24 cycles per minute (p <.001), fever > 97.8 F (Temperature > (p = .037), shortness of breath (p = .001), and headaches (p = .005). In addition, mechanically ventilated patients had a lower serum albumin (g/dl) ≤ 3 units (p <. 001), elevated serum creatinine (mg/dl) ≥ 1.135 units (p = .02), elevated serum CRP-HS ≥ 123 units (p = .005), HbA1C (%) > 6.6 units (p = .004), serum lactic acid (mmol/L) > 1.7 units (p = .003), serum LDH U/L > 465 U/L (p <.001), Procalcitonin (ng/ml) > .305 units (p <0.001), SGOT IU/L or AST IU/L ≥ 54 units (p < 0.001), SGPT or ALT IU/L ≥ 41 units (p = .021), and WBC count > 8.4 k/ul (p <.001). Furthermore, tachycardia (OR = 3.98, p = .001), HbA1C (OR = 2.36, p = .008), serum LDH (OR = 1.9, p = .041), and absolute lymphocyte percent ≤ 12 (OR = 1.98, p = .022) predicted mechanical ventilation in all matched patients in our institutional cohort. CONCLUSIONS: Our case series provides clinical characteristics, laboratory parameters, and predictors for mechanical ventilation in matched patients with Covid-19. Elevated heart rate, HbA1C, serum LDH and decreased lymphocyte percentage were predictors for mechanical ventilation. Tachycardia had the highest odds of 3.98. CLINICAL IMPLICATIONS: Several clinical and laboratory parameters can be utilized for evaluating and stratifying Covid-19 patients’ risk for mechanical ventilation. These risk factors will need further validation in other similar cohorts. DISCLOSURES: No relevant relationships by Olawale Akande, source=Web Response No relevant relationships by Olga Badem, source=Web Response No relevant relationships by Premila Bhat, source=Web Response No relevant relationships by Utpal Bhatt, source=Web Response No relevant relationships by Diego Castellon, source=Web Response No relevant relationships by Bhargav Desai, source=Web Response No relevant relationships by Basilides Fermin, source=Web Response No relevant relationships by Shurovi Jafar, source=Web Response No relevant relationships by KELASH KUMAR, source=Web Response No relevant relationships by Juan Martinez Zegarra, source=Web Response No relevant relationships by Tanveer Mir, source=Web Response No relevant relationships by Parvez Mir, source=Web Response No relevant relationships by Luis Morón Mercado, source=Web Response No relevant relationships by Beatriz Omeragic, source=Web Response No relevant relationships by Maxine Orris, source=Web Response No relevant relationships by Priyank Patel, source=Web Response No relevant relationships by Giovanna Ramirez-Barbieri, source=Web Response No relevant relationships by Luis Santana Alcantara, source=Web Response No relevant relationships by Karthik Seetharam, source=Web Response No relevant relationships by Jilan Shah, source=Web Response No relevant relationships by Phanthira Tamsukhin, source=Web Response No relevant relationships by Zeyar Thet, source=Web Response No relevant relationships by Elbia Toribio, source=Web Response No relevant relationships by Thinzar Wai, source=Web Response No relevant relationships by Vamsi Yenugadhati, source=Web Response

Non-Invasive Ventilation in COVID-19 Related Respiratory Failure

Non-invasive ventilation (NIV) refers to the technique of providing mechanical ventilation that does not require definitive airway clearance using an endotracheal tube or tracheostomy. Since its early development in the 1980s, the use of NIV has become increasingly popular in the last three decades. However, its usage on COVID-19 related respiratory failure still lacked guidelines, although several recent studies have shown its benefits. Many aspects, ranging from indications or patient selection, timing to start, understanding the predictor factors of failure, and choosing suitable interfaces, are keys of success for NIV. In principle, each patient has a different condition and should be treated case by case. NIV is not an absolute solution, and intubation can still be the first choice if NIV is deemed less beneficial for the patient.

Axonal polineuropathy associated with Sars-CoV 2 infection: a case report.

World healthcare systems are dealing with the pandemic of the severe Coronavirus disease 19 (Covid-19). Covid-19 neurological manifestations affecting both central and peripheral nervous systems have been reported. We describe the case of 44-year-old patient, who was admitted to our Rehabilitation Unit after discharge from intensive care unit for severe Covid-19 related respiratory failure. Neurophysiological investigation revealed an axonal polineuropathy with impairment both of sensory and motor component. He underwent a comprehensive rehabilitation treatment, including breathing exercises and motor rehabilitation. Despite rapid and effective diagnosis and customized progressive rehabilitation treatment, significant improvement in sensory-motor abnormalities has begun but distal complete recovery was not achieved. Indeed, complete indipendence during walking has been partially reached: patient constantly needs two sticks and wears two ankle-foot orthosis during ambulatory function. Nowadays, exploring the neurologic manifestations of Covid-19 may represent a step towards better understanding the virus, preventing longterm sequela and rehabilitation concerns.

Effect of prone position on respiratory parameters, intubation and death rate in COVID-19 patients: systematic review and meta-analysis

Prone position (PP) is known to improve oxygenation and reduce mortality in COVID-19 patients. This systematic review and meta-analysis aimed to determine the effects of PP on respiratory parameters and outcomes. PubMed, EMBASE, ProQuest, SCOPUS, Web of Sciences, Cochrane library, and Google Scholar were searched up to 1st January 2021. Twenty-eight studies were included. The Cochran's Q-test and I2 statistic were assessed heterogeneity, the random-effects model was estimated the pooled mean difference (PMD), and a meta-regression method has utilized the factors affecting heterogeneity between studies. PMD with 95% confidence interval (CI) of PaO2/FIO2 Ratio in before–after design, quasi-experimental design and in overall was 55.74, 56.38, and 56.20 mmHg. These values for Spo2 (Sao2) were 3.38, 17.03, and 7.58. PP in COVID-19 patients lead to significantly decrease of the Paco2 (PMD: − 8.69; 95% CI − 14.69 to − 2.69 mmHg) but significantly increase the PaO2 (PMD: 37.74; 95% CI 7.16–68.33 mmHg). PP has no significant effect on the respiratory rate. Based on meta-regression, the study design has a significant effect on the heterogeneity of Spo2 (Sao2) (Coefficient: 12.80; p < 0.001). No significant associations were observed for other respiratory parameters with sample size and study design. The pooled estimate for death rate and intubation rates were 19.03 (8.19–32.61) and 30.68 (21.39–40.75). The prone positioning was associated with improved oxygenation parameters and reduced mortality and intubation rate in COVID-19 related respiratory failure.

Prolonged Effects of the COVID-19 Pandemic on Sleep Medicine Services-Longitudinal Data from the Swedish Sleep Apnea Registry.

The worldwide COVID-19 pandemic has affected the operation of health care systems. The direct impact of obstructive sleep apnea (OSA) on COVID-19 infection outcome remains to be elucidated. However, the coincidence of common risk factors for OSA and severe COVID-19 suggests that patients with OSA receiving positive airway pressure therapy may have an advantage relative to those untreated when confronted with a COVID-19 infection. The ongoing COVID-19 pandemic has led to a substantial reduction of sleep medicine services, and the long-term consequences may be considerable. New strategies for the management of sleep disorders are needed to overcome the current underdiagnosis and delay of treatment.

A UNIQUE CASE OF GUILLAIN-BARRÉ SYNDROME RELATED TO COVID-19 INFECTION

SESSION TITLE: Fellows Critical Care Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: SARS-CoV2 causes a systemic infection, but pulmonary involvement is the main problem linked to SARS-CoV-2 infection(1). Neurological manifestations are increasingly reported in patients affected by COVID-19, including cases of encephalitis, stroke, and Guillain-Barre syndrome (2). We report a unique case of Guillain-Barre syndrome (GBS) in an immunocompromised patient with COVID-19 related respiratory failure who was failing weaning trial repeatedly. CASE PRESENTATION: A 59year old male with the history of splenectomy , Renal transplantation for End stage renal disease came with the chief complaints of confusion for 2 days. On arrival, the patient’s vitals were significant for hypoxia requiring supplemental oxygen via non-rebreather. CT head showed no acute intracranial pathology. His Chest X-ray revealed bilateral chest infiltrates. COVID-19 PCR on nasopharyngeal swab tested positive. His inflammatory markers were elevated and the patient received Convalescent Plasma and Tocilizumab. The patient’s mental status improved over next 3 days and he became oriented to time, place and person. The patient, however, had to be intubated on day 6 for worsening hypoxic respiratory failure. After 12 days of intubation, the patient was placed on weaning trial. He was able to open eyes during sedation breaks, however, was unable to follow commands or move extremities spontaneously or to painful stimuli. Repeat Head CT showed no acute changes. Electromyography revealed demyelinating axonal polyneuropathy. Lumbar puncture studies came out to be significant for elevated protein and minimal cell count (albumin-cytological dissociation). The Meningioencephalitis panel of Cerebrospinal fluid was negative. The patient has just completed five days of treatment with intravenous immunoglobulins. Due to the inability to wean him off the ventilator, he eventually underwent Tracheostomy and Peg tube placement procedure. DISCUSSION: Our case draws attention to the occurrence of GBS in patients with COVID-19 who are immunocompromised and does not experience motor or sensory symptoms before or at the time of intubation. In our case, GBS was suspected when our patient failed weaning trials. The mechanism of GBS in patients with COVID-19 is still unclear. Both SARS and COVID-19 attach to the angiotensin-converting enzyme 2 receptor which is present in cell membranes of numerous human organs including lung, liver, kidney, and nervous system (3). Guillain-Barré syndrome (GBS) is an acute/subacute immune-mediated polyradiculoneuropathy and may occur as a result of molecular mimicry. SARS-CoV-2 is known to cause an excessive immune reaction with an increased level of cytokines leading to extensive tissue damage (2). CONCLUSIONS: This must be known by clinicians as GBS may lead to failure of weaning trials in patient with COVID-19 and needs to be differentiated from a possible ICU-acquired weakness after ICU treatments. Reference #1: Guan WJ, Ni ZY, Hu Y et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Feb 28. doi: 10.1056/NEJMoa2002032. Reference #2: Carod-Artal FJ. Neurological complications of coronavirus and COVID-19. Rev Neurol. 2020;70(9):311-322. doi:10.33588/rn.7009.2020179 Reference #3: Sahin AR, Erdogan A, Mutlu Agaoglu P, Dineri Y, Cakirci AY, Senel ME, et al. 2019 Novel Coronavirus (COVID-Outbreak: A Review of the Current Literature. EJMO 2020;4(1):1-7.14 DISCLOSURES: No relevant relationships by Oleg Epelbaum, source=Web Response No relevant relationships by Anant Jain, source=Web Response No relevant relationships by Hamid Yaqoob, source=Web Response

Prognostic factors in patients admitted to an urban teaching hospital with COVID-19 infection

BackgroundSevere COVID-19 infection results in a systemic inflammatory response (SIRS). This SIRS response shares similarities to the changes observed during the peri-operative period that are recognised to be associated with the development of multiple organ failure.MethodsElectronic patient records for patients who were admitted to an urban teaching hospital during the initial 7-week period of the COVID-19 pandemic in Glasgow, U.K. (17th March 2020—1st May 2020) were examined for routine clinical, laboratory and clinical outcome data. Age, sex, BMI and documented evidence of COVID-19 infection at time of discharge or death certification were considered minimal criteria for inclusion.ResultsOf the 224 patients who fulfilled the criteria for inclusion, 52 (23%) had died at 30-days following admission. COVID-19 related respiratory failure (75%) and multiorgan failure (12%) were the commonest causes of death recorded. Age ≥ 70 years (p < 0.001), past medical history of cognitive impairment (p ≤ 0.001), previous delirium (p < 0.001), clinical frailty score > 3 (p < 0.001), hypertension (p < 0.05), heart failure (p < 0.01), national early warning score (NEWS) > 4 (p < 0.01), positive CXR (p < 0.01), and subsequent positive COVID-19 swab (p ≤ 0.001) were associated with 30-day mortality. CRP > 80 mg/L (p < 0.05), albumin < 35 g/L (p < 0.05), peri-operative Glasgow Prognostic Score (poGPS) (p < 0.05), lymphocytes < 1.5 109/l (p < 0.05), neutrophil lymphocyte ratio (p ≤ 0.001), haematocrit (< 0.40 L/L (male)/ < 0.37 L/L (female)) (p ≤ 0.01), urea > 7.5 mmol/L (p < 0.001), creatinine > 130 mmol/L (p < 0.05) and elevated urea: albumin ratio (< 0.001) were also associated with 30-day mortality.On multivariate analysis, age ≥ 70 years (O.R. 3.9, 95% C.I. 1.4–8.2, p < 0.001), past medical history of heart failure (O.R. 3.3, 95% C.I. 1.2–19.3, p < 0.05), NEWS > 4 (O.R. 2.4, 95% C.I. 1.1–4.4, p < 0.05), positive initial CXR (O.R. 0.4, 95% C.I. 0.2–0.9, p < 0.05) and poGPS (O.R. 2.3, 95% C.I. 1.1–4.4, p < 0.05) remained independently associated with 30-day mortality.Among those patients who tested PCR COVID-19 positive (n = 122), age ≥ 70 years (O.R. 4.7, 95% C.I. 2.0—11.3, p < 0.001), past medical history of heart failure (O.R. 4.4, 95% C.I. 1.2–20.5, p < 0.05) and poGPS (O.R. 2.4, 95% C.I. 1.1–5.1, p < 0.05) remained independently associated with 30-days mortality.ConclusionAge ≥ 70 years and severe systemic inflammation as measured by the peri-operative Glasgow Prognostic Score are independently associated with 30-day mortality among patients admitted to hospital with COVID-19 infection.