ABSTRACT
Background: Evidence of cerebrovascular complications in Coronavirus disease 2019 (COVID-19) requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO) is limited. The aim of our study is to characterize the prevalence and risk factors of stroke secondary to COVID-19 in patients on V-V ECMO. Methods: We analyzed prospectively collected observational data of adults from 380 institutions of 53 countries in the COVID-19 Critical Care Consortium (COVID Critical) registry. We used univariable and multivariable survival modeling to identify risk factors for stroke during ECMO. Cox proportional hazards and Fine-Gray models were used, with death and discharge treated as competing risks. Results: 595 patients (median age [IQR]: 51 years [42-59]; male: 70.8%) had V-V ECMO support. Forty-three patients (7.2%) suffered strokes, 83.7% of which were hemorrhagic. In multivariable survival analysis, obesity [adjusted Hazard Ratio (aHR)=2.19, 95% CI=1.05–4.59] and use of vasopressors before ECMO (aHR=2.37, 95% CI =1.08–5.22) were associated with an increased risk of stroke. Relative ΔPaCO2 of negative 26% and relative ΔPaO2 of positive 24% at 48-hours of ECMO initiation were observed in stroke patients in comparison to relative ΔPaCO2 of negative 17% and relative ΔPaO2 of positive 7% in the non-stroke group. Patients with acute stroke had a 79% in-hospital mortality compared with a 45% mortality for stroke-free patients.Conclusion: Our study highlights the association of obesity and pre-ECMO vasopressor use with the development of stroke in COVID-19 patients on V-V ECMO. Also, the importance of relative decrease in PaCO2 and moderate hyperoxia within 48-hours after ECMO initiation were additional risk factors.
Subject(s)
COVID-19ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes govern this remain unknown. In this study, we investigated the landscape of cardiac tissues collected at rapid autopsy from SARS-CoV-2, pH1N1, and control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by gamma-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of Interferon-stimulated genes (ISGs), in particular interferon and complement pathways, when compared with COVID-19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health.
Subject(s)
Coronavirus Infections , COVID-19 , Cardiovascular DiseasesABSTRACT
Background. Robust biomarkers that predict disease outcomes amongst COVID19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. Methods. We conducted a multi cohort observational study to investigate the biology and the prognostic role of interferon alpha inducible protein 27 (IFI27) in COVID19 patients. Findings. We show that IFI27 is expressed in the respiratory tract of COVID19 patients and elevated IFI27 expression is associated with the presence of a high viral load. We further demonstrate that systemic host response, as measured by blood IFI27 expression, is associated with COVID19 severity. For clinical outcome prediction (e.g. respiratory failure), IFI27 expression displays a high positive (0.83) and negative (0.95) predictive value, outperforming all other known predictors of COVID19 severity. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 swine influenza virus infection, IFI27 like genes were highly upregulated in the blood samples of severely infected patients. Interpretation. These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet to be discovered respiratory virus.
Subject(s)
Infections , Hematologic Diseases , Tumor Virus Infections , COVID-19 , Respiratory InsufficiencyABSTRACT
ImportanceThere is a paucity of data that can be used to guide the management of critically ill patients with coronavirus disease 2019 (COVID-19). Global collaboration offers the best chance of obtaining these data, at scale and in time. In the absence of effective therapies, insights derived from real-time observational data will be a crucial means of improving outcomes. ObjectiveIn response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a research and data-sharing collaborative has been assembled to harness the cumulative experience of intensive care units (ICUs) worldwide. The resulting observational study provides a platform to rapidly disseminate detailed data and insights. DesignThe COVID-19 Critical Care Consortium observational study is an international, multicenter, prospective, observational study of patients with confirmed or suspected SARSCoV-2 infection admitted to ICUs. SettingThis is an evolving, open-ended study that commenced on January 1st, 2020 and currently includes more than 350 sites in over 48 countries. The study enrolls patients at the time of ICU admission and follows them to the time of death, hospital discharge, or 28 days post-ICU admission, whichever occurs last. ParticipantsAll subjects, without age limit, requiring admission to an ICU for SARS-CoV-2 infection, confirmed by real-time polymerase chain reaction (PCR) and/or next-generation sequencing or with high clinical suspicion of the infection. Patients admitted to an ICU for any other reason are excluded. Main outcomes and measuresKey data, collected via an electronic case report form devised in collaboration with the ISARIC/SPRINT-SARI networks, include: patient demographic data and risk factors, clinical features, severity of illness and respiratory failure, need for non-invasive and/or mechanical ventilation and/or extracorporeal membrane COVID-19 CCC observational study protocol oxygenation (ECMO), and associated complications, as well as data on adjunctive therapies. Final outcomes of in-hospital death, discharge or continuing admissions at 28 days. DiscussionThis large-scale, observational study of COVID-19 in the critically ill will provide rapid international characterization. Open-ended accrual will increase the power to answer hypothesis-led questions over time. Several sub-studies have already been initiated, examining hemostasis, neurological, cardiac, and long-term outcomes.