Advanced Pulmonary and Cardiac Support of COVID-19 Patients: Emerging Recommendations From ASAIO-a Living Working Document.

The severe acute respiratory syndrome-CoV-2 is an emerging viral pathogen responsible for the global coronavirus disease 2019 pandemic resulting in significant human morbidity and mortality. Based on preliminary clinical reports, hypoxic respiratory failure complicated by acute respiratory distress syndrome is the leading cause of death. Further, septic shock, late-onset cardiac dysfunction, and multiorgan system failure are also described as contributors to overall mortality. Although extracorporeal membrane oxygenation and other modalities of mechanical cardiopulmonary support are increasingly being utilized in the treatment of respiratory and circulatory failure refractory to conventional management, their role and efficacy as support modalities in the present pandemic are unclear. We review the rapidly changing epidemiology, pathophysiology, emerging therapy, and clinical outcomes of coronavirus disease 2019; and based on these data and previous experience with artificial cardiopulmonary support strategies, particularly in the setting of infectious diseases, provide consensus recommendations from American Society for Artificial Internal Organs. Of note, this is a living document, which will be updated periodically, as additional information and understanding emerges.

Multi-institutional Analysis of 505 Patients With Coronavirus Disease-2019 Supported With Extracorporeal Membrane Oxygenation: Predictors of Survival.

BACKGROUND: We reviewed our experience with 505 patients with confirmed coronavirus disease-2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) at 45 hospitals and estimated risk factors for mortality. METHODS: A multi-institutional database was created and used to assess all patients with COVID-19 who were supported with ECMO. A Bayesian mixed-effects logistic regression model was estimated to assess the effect on survival of multiple potential risk factors for mortality, including age at cannulation for ECMO as well as days between diagnosis of COVID-19 and intubation and days between intubation and cannulation for ECMO. RESULTS: Median time on ECMO was 18 days (interquartile range, 10-29 days). All 505 patients separated from ECMO: 194 patients (38.4%) survived and 311 patients (61.6%) died. Survival with venovenous ECMO was 184 of 466 patients (39.5%), and survival with venoarterial ECMO was 8 of 30 patients (26.7%). Survivors had lower median age (44 vs 51 years, P < .001) and shorter median time interval from diagnosis to intubation (7 vs 11 days, P = .001). Adjusting for several confounding factors, we estimated that an ECMO patient intubated on day 14 after the diagnosis of COVID-19 vs day 4 had a relative odds of survival of 0.65 (95% credible interval, 0.44-0.96; posterior probability of negative effect, 98.5%). Age was also negatively associated with survival: relative to a 38-year-old patient, we estimated that a 57-year-old patient had a relative odds of survival of 0.43 (95% credible interval, 0.30-0.61; posterior probability of negative effect, >99.99%). CONCLUSIONS: ECMO facilitates salvage and survival of select critically ill patients with COVID-19. Survivors tend to be younger and have shorter time from diagnosis to intubation. Survival of patients supported with only venovenous ECMO was 39.5%.

Multi-institutional Analysis of 200 COVID-19 Patients Treated With Extracorporeal Membrane Oxygenation: Outcomes and Trends.

BACKGROUND: The role of extracorporeal membrane oxygenation (ECMO) in the management of patients with COVID-19 continues to evolve. The purpose of this analysis is to review our multi-institutional clinical experience involving 200 consecutive patients at 29 hospitals with confirmed COVID-19 supported with ECMO. METHODS: This analysis includes our first 200 COVID-19 patients with complete data who were supported with and separated from ECMO. These patients were cannulated between March 17 and December 1, 2020. Differences by mortality group were assessed using χ2 tests for categoric variables and Kruskal-Wallis rank sum tests and Welch's analysis of variance for continuous variables. RESULTS: Median ECMO time was 15 days (interquartile range, 9 to 28). All 200 patients have separated from ECMO: 90 patients (45%) survived and 110 patients (55%) died. Survival with venovenous ECMO was 87 of 188 patients (46.3%), whereas survival with venoarterial ECMO was 3 of 12 patients (25%). Of 90 survivors, 77 have been discharged from the hospital and 13 remain hospitalized at the ECMO-providing hospital. Survivors had lower median age (47 versus 56 years, P < .001) and shorter median time from diagnosis to ECMO cannulation (8 versus 12 days, P = .003). For the 90 survivors, adjunctive therapies on ECMO included intravenous steroids (64), remdesivir (49), convalescent plasma (43), anti-interleukin-6 receptor blockers (39), prostaglandin (33), and hydroxychloroquine (22). CONCLUSIONS: Extracorporeal membrane oxygenation facilitates survival of select critically ill patients with COVID-19. Survivors tend to be younger and have a shorter duration from diagnosis to cannulation. Substantial variation exists in drug treatment of COVID-19, but ECMO offers a reasonable rescue strategy.

Renal Considerations in COVID-19: Biology, Pathology, and Pathophysiology.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Multi-institutional Analysis of 100 Consecutive Patients with COVID-19 and Severe Pulmonary Compromise Treated with Extracorporeal Membrane Oxygenation: Outcomes and Trends Over Time.

The role of extracorporeal membrane oxygenation (ECMO) in the management of severely ill patients with coronavirus disease 2019 (COVID-19) continues to evolve. The purpose of this study is to review a multi-institutional clinical experience in 100 consecutive patients, at 20 hospitals, with confirmed COVID-19 supported with ECMO. This analysis includes our first 100 patients with complete data who had confirmed COVID-19 and were supported with ECMO. The first patient in the cohort was placed on ECMO on March 17, 2020. Differences by the mortality group were assessed using χ2 tests for categorical variables and Kruskal-Wallis rank-sum tests and Welch's analysis of variance for continuous variables. The median time on ECMO was 12.0 days (IQR = 8-22 days). All 100 patients have since been separated from ECMO: 50 patients survived and 50 patients died. The rate of survival with veno-venous ECMO was 49 of 96 patients (51%), whereas that with veno-arterial ECMO was 1 of 4 patients (25%). Of 50 survivors, 49 have been discharged from the hospital and 1 remains hospitalized at the ECMO-providing hospital. Survivors were generally younger, with a lower median age (47 versus 56.5 years, p = 0.014). In the 50 surviving patients, adjunctive therapies while on ECMO included intravenous steroids (26), anti-interleukin-6 receptor blockers (26), convalescent plasma (22), remdesivir (21), hydroxychloroquine (20), and prostaglandin (15). Extracorporeal membrane oxygenation may facilitate salvage and survival of selected critically ill patients with COVID-19. Survivors tend to be younger. Substantial variation exists in the drug treatment of COVID-19, but ECMO offers a reasonable rescue strategy.

Big Data Analytics + Virtual Clinical Semantic Network (vCSN): An Approach to Addressing the Increasing Clinical Nuances and Organ Involvement of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has revealed deep gaps in our understanding of the clinical nuances of this extremely infectious viral pathogen. In order for public health, care delivery systems, clinicians, and other stakeholders to be better prepared for the next wave of SARS-CoV-2 infections, which, at this point, seems inevitable, we need to better understand this disease-not only from a clinical diagnosis and treatment perspective-but also from a forecasting, planning, and advanced preparedness point of view. To predict the onset and outcomes of a next wave, we first need to understand the pathologic mechanisms and features of COVID-19 from the point of view of the intricacies of clinical presentation, to the nuances of response to therapy. Here, we present a novel approach to model COVID-19, utilizing patient data from related diseases, combining clinical understanding with artificial intelligence modeling. Our process will serve as a methodology for analysis of the data being collected in the ASAIO database and other data sources worldwide.

Extracorporeal Membrane Oxygenation in the Treatment of Severe Pulmonary and Cardiac Compromise in Coronavirus Disease 2019: Experience with 32 Patients.

As coronavirus disease 2019 (COVID-19) cases surge worldwide, an urgent need exists to enhance our understanding of the role of extracorporeal membrane oxygenation (ECMO) in the management of severely ill patients with COVID-19 who develop acute respiratory and cardiac compromise refractory to conventional therapy. The purpose of this manuscript is to review our initial clinical experience in 32 patients with confirmed COVID-19 treated with ECMO. A multi-institutional registry and database was created and utilized to assess all patients who were supported with ECMO provided by SpecialtyCare. Data captured included patient characteristics, pre-COVID-19 risk factors and comorbidities, confirmation of COVID-19 diagnosis, features of ECMO support, specific medications utilized to treat COVID-19, and short-term outcomes through hospital discharge. This analysis includes all of our patients with COVID-19 supported with ECMO, with an analytic window starting March 17, 2020, when our first COVID-19 patient was placed on ECMO, and ending April 9, 2020. During the 24 days of this study, 32 consecutive patients with COVID-19 were placed on ECMO at nine different hospitals. As of the time of analysis, 17 remain on ECMO, 10 died before or shortly after decannulation, and five are alive and extubated after removal from ECMO, with one of these five discharged from the hospital. Adjunctive medication in the surviving patients while on ECMO was as follows: four of five survivors received intravenous steroids, three of five survivors received antiviral medications (Remdesivir), two of five survivors were treated with anti-interleukin-6-receptor monoclonal antibodies (Tocilizumab or Sarilumab), and one of five survivors received hydroxychloroquine. Analysis of these 32 COVID-19 patients with severe pulmonary compromise supported with ECMO suggests that ECMO may play a useful role in salvaging select critically ill patients with COVID-19. Additional patient experience and associated clinical and laboratory data must be obtained to further define the optimal role of ECMO in patients with COVID-19 and acute respiratory distress syndrome (ARDS). These initial data may provide useful information to help define the best strategies to care for these challenging patients and may also provide a framework for much-needed future research about the use of ECMO to treat patients with COVID-19.

Advanced Pulmonary and Cardiac Support of COVID-19 Patients: Emerging Recommendations From ASAIO-A "Living Working Document".

The severe acute respiratory syndrome (SARS)-CoV-2 is an emerging viral pathogen responsible for the global coronavirus disease 2019 (COVID)-19 pandemic resulting in significant human morbidity and mortality. Based on preliminary clinical reports, hypoxic respiratory failure complicated by acute respiratory distress syndrome is the leading cause of death. Further, septic shock, late-onset cardiac dysfunction, and multiorgan system failure are also described as contributors to overall mortality. Although extracorporeal membrane oxygenation and other modalities of mechanical cardiopulmonary support are increasingly being utilized in the treatment of respiratory and circulatory failure refractory to conventional management, their role and efficacy as support modalities in the present pandemic are unclear. We review the rapidly changing epidemiology, pathophysiology, emerging therapy, and clinical outcomes of COVID-19; and based on these data and previous experience with artificial cardiopulmonary support strategies, particularly in the setting of infectious diseases, provide consensus recommendations from ASAIO. Of note, this is a "living document," which will be updated periodically, as additional information and understanding emerges.