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151. Awake Proning as an Adjunctive Therapy for Refractory Hypoxemia in Non-Intubated Patients with COVID-19 Acute Respiratory Failure : Guidance from an International Group of Healthcare Workers

Author

Stilma, Willemke, Åkerman, Eva, Artigas, Antonio, Bentley, Andrew, Bos, Lieuwe D., Bosman, Thomas J. C., de Bruin, Hendrik, Brummaier, Tobias, Buiteman-Kruizinga, Laura A., Carcò, Francesco, Chesney, Gregg, Chu, Cindy, Dark, Paul, Dondorp, Arjen M., Gijsbers, Harm J. H., Gilder, Mary Ellen, Grieco, Domenico L., Inglis, Rebecca, Laffey, John G., Landoni, Giovanni, Lu, Weihua, Maduro, Lisa M. N., McGready, Rose, McNicholas, Bairbre, de Mendoza, Diego, Morales-Quinteros, Luis, Nosten, Francois, Papali, Alfred, Paternoster, Gianluca, Paulus, Frederique, Pisani, Luigi, Prud'homme, Eloi, Ricard, Jean-Damien, Roca, Oriol, Sartini, Chiara, Scaravilli, Vittorio, Schultz, Marcus J., Sivakorn, Chaisith, Spronk, Peter E., Sztajnbok, Jaques, Trigui, Youssef, Vollman, Kathleen M., van der Woude, Margaretha C. E., Stilma, Willemke, Åkerman, Eva, Artigas, Antonio, Bentley, Andrew, Bos, Lieuwe D., Bosman, Thomas J. C., de Bruin, Hendrik, Brummaier, Tobias, Buiteman-Kruizinga, Laura A., Carcò, Francesco, Chesney, Gregg, Chu, Cindy, Dark, Paul, Dondorp, Arjen M., Gijsbers, Harm J. H., Gilder, Mary Ellen, Grieco, Domenico L., Inglis, Rebecca, Laffey, John G., Landoni, Giovanni, Lu, Weihua, Maduro, Lisa M. N., McGready, Rose, McNicholas, Bairbre, de Mendoza, Diego, Morales-Quinteros, Luis, Nosten, Francois, Papali, Alfred, Paternoster, Gianluca, Paulus, Frederique, Pisani, Luigi, Prud'homme, Eloi, Ricard, Jean-Damien, Roca, Oriol, Sartini, Chiara, Scaravilli, Vittorio, Schultz, Marcus J., Sivakorn, Chaisith, Spronk, Peter E., Sztajnbok, Jaques, Trigui, Youssef, Vollman, Kathleen M., and van der Woude, Margaretha C. E.

Abstract

Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6-12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.

Published
2021

152. Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study

Author

Botta, Michela, Tsonas, Anissa M., Pillay, Janesh, Boers, Leonoor S., Algera, Anna Geke, Bos, Lieuwe D. J., Dongelmans, Dave A., Hollmann, Marcus W., Horn, Janneke, Vlaar, Alexander P. J., Schultz, Marcus J., Neto, Ary Serpa, Paulus, Frederique, PRoVENT-COVID Collaborative Group, Bergmans, Dennis, Botta, Michela, Tsonas, Anissa M., Pillay, Janesh, Boers, Leonoor S., Algera, Anna Geke, Bos, Lieuwe D. J., Dongelmans, Dave A., Hollmann, Marcus W., Horn, Janneke, Vlaar, Alexander P. J., Schultz, Marcus J., Neto, Ary Serpa, Paulus, Frederique, PRoVENT-COVID Collaborative Group, and Bergmans, Dennis

Abstract

Background Little is known about the practice of ventilation management in patients with COVID-19. We aimed to describe the practice of ventilation management and to establish outcomes in invasively ventilated patients with COVID-19 in a single country during the first month of the outbreak.Methods PRoVENT-COVID is a national, multicentre, retrospective observational study done at 18 intensive care units (ICUs) in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The primary outcome was a combination of ventilator variables and parameters over the first 4 calendar days of ventilation: tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and ICU complications. Patient-centred outcomes were ventilator-free days at day 28, duration of ventilation, duration of ICU and hospital stay, and mortality. PRoVENT-COVID is registered at ClinicalTrials.gov (NCT04346342).Findings Between March 1 and April 1, 2020, 553 patients were included in the study. Median tidal volume was 6.3 mL/kg predicted bodyweight (IQR 5.7-7.1), PEEP was 14.0 cm H2O (IQR 11.0-15.0), and driving pressure was 14.0 cm H 2O (11.2-16.0). Median respiratory system compliance was 31.9 mL/cm H 2O (26.0-39.9). Of the adjunctive treatments for refractory hypoxaemia, prone positioning was most often used in the first 4 days of ventilation (283 [53%] of 530 patients). The median number of ventilator-free days at day 28 was 0 (IQR 0-15); 186 (35%) of 530 patients had died by day 28. Predictors of 28-day mortality were gender, age, tidal volume, respiratory system compliance, arterial pH, and heart rate on the first day of invasive ventilation.Interpretation In patient

Published
2021

153. Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts

Author

Bos, Lieuwe D. J., Sjoding, Michael, Sinha, Pratik, Bhavani, Sivasubramanium, Lyons, Patrick G., Bewley, Alice F., Botta, Michela, Tsonas, Anissa M., Neto, Ary Serpa, Schultz, Marcus J., Dickson, Robert P., Paulus, Frederique, PRoVENT-COVID Collaborative Group, Bergmans, Dennis, Bos, Lieuwe D. J., Sjoding, Michael, Sinha, Pratik, Bhavani, Sivasubramanium, Lyons, Patrick G., Bewley, Alice F., Botta, Michela, Tsonas, Anissa M., Neto, Ary Serpa, Schultz, Marcus J., Dickson, Robert P., Paulus, Frederique, PRoVENT-COVID Collaborative Group, and Bergmans, Dennis

Abstract

Background Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches.Methods PRoVENT-COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342.Findings Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent dass analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO(2), pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 pat

Published
2021

154. A lower global lung ultrasound score is associated with higher likelihood of successful extubation in invasively ventilated COVID-19 patients

Author

Pierrakos, Charalampos, Lieveld, Arthur, Pisani, Luigi, Smit, Marry M.R., Heldeweg, Micah, Hagens, Laura L.A., Smit, Jasper, Haaksma, Mark, Veldhuis, Lars, Schmidt, Robin Walburgh, Errico, Giacomo, Marinelli, Valentina, Attou, Rachid, David, Cristina, Zimatore, Claudio, Murgolo, Francesco, Grasso, Salvatore, Mirabella, Lucia, Cinnella, Gilda, De Bels, David, Schultz, Marcus M.J., Tuinman, Pieter Roel, Bos, Lieuwe D J L.D., Pierrakos, Charalampos, Lieveld, Arthur, Pisani, Luigi, Smit, Marry M.R., Heldeweg, Micah, Hagens, Laura L.A., Smit, Jasper, Haaksma, Mark, Veldhuis, Lars, Schmidt, Robin Walburgh, Errico, Giacomo, Marinelli, Valentina, Attou, Rachid, David, Cristina, Zimatore, Claudio, Murgolo, Francesco, Grasso, Salvatore, Mirabella, Lucia, Cinnella, Gilda, De Bels, David, Schultz, Marcus M.J., Tuinman, Pieter Roel, and Bos, Lieuwe D J L.D.

Abstract

Lung ultrasound (LUS) can be used to assess loss of aeration, which is associated with outcome in patients with coronavirus disease 2019 (COVID-19) presenting to the emergency department. We hypothesized that LUS scores are associated with outcome in critically ill COVID-19 patients receiving invasive ventilation. This retrospective international multicenter study evaluated patients with COVID-19-related acute respiratory distress syndrome (ARDS) with at least one LUS study within 5 days after invasive mechanical ventilation initiation. The global LUS score was calculated by summing the 12 regional scores (range 0-36). Pleural line abnormalities and subpleural consolidations were also scored. The outcomes were successful liberation from the ventilator and intensive care mortality within 28 days, analyzed with multistate, competing risk proportional hazard models. One hundred thirty-seven patients with COVID-19-related ARDS were included in our study. The global LUS score was associated with successful liberation from mechanical ventilation (hazard ratio [HR]: 0.91 95% confidence interval [CI] 0.87-0.96; P 5 0.0007) independently of the ARDS severity, but not with 28 days mortality (HR: 1.03; 95% CI 0.97-1.08; P 5 0.36). Subpleural consolidation and pleural line abnormalities did not add to the prognostic value of the global LUS score. Examinations within 24 hours of intubation showed no prognostic value. To conclude, a lower global LUS score 24 hours after invasive ventilation initiation is associated with increased probability of liberation from the mechanical ventilator COVID-19 ARDS patients, independently of the ARDS severity., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2021

155. Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Harvard--MIT Program in Health Sciences and Technology. Laboratory for Computational Physiology, Serpa Neto, Ary, Deliberato, Rodrigo O, Johnson, Alistair E W, Bos, Lieuwe D, Amorim, Pedro, Pereira, Silvio M, Cazati, Denise C, Cordioli, Ricardo L, Correa, Thiago D, Pollard, Tom J, Schettino, Guilherme P P, Timenetsky, Karina T, Celi, Leo A, Pelosi, Paolo, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Harvard--MIT Program in Health Sciences and Technology. Laboratory for Computational Physiology, Serpa Neto, Ary, Deliberato, Rodrigo O, Johnson, Alistair E W, Bos, Lieuwe D, Amorim, Pedro, Pereira, Silvio M, Cazati, Denise C, Cordioli, Ricardo L, Correa, Thiago D, Pollard, Tom J, Schettino, Guilherme P P, Timenetsky, Karina T, Celi, Leo A, and Pelosi, Paolo

Abstract

Purpose Mechanical power (MP) may unify variables known to be related to development of ventilator-induced lung injury. The aim of this study is to examine the association between MP and mortality in critically ill patients receiving invasive ventilation for at least 48 h. Methods This is an analysis of data stored in the databases of the MIMIC–III and eICU. Critically ill patients receiving invasive ventilation for at least 48 h were included. The exposure of interest was MP. The primary outcome was in-hospital mortality. Results Data from 8207 patients were analyzed. Median MP during the second 24 h was 21.4 (16.2–28.1) J/min in MIMIC-III and 16.0 (11.7–22.1) J/min in eICU. MP was independently associated with in-hospital mortality [odds ratio per 5 J/min increase (OR) 1.06 (95% confidence interval (CI) 1.01–1.11); p = 0.021 in MIMIC-III, and 1.10 (1.02–1.18); p = 0.010 in eICU]. MP was also associated with ICU mortality, 30-day mortality, and with ventilator-free days, ICU and hospital length of stay. Even at low tidal volume, high MP was associated with in-hospital mortality [OR 1.70 (1.32–2.18); p < 0.001] and other secondary outcomes. Finally, there is a consistent increase in the risk of death with MP higher than 17.0 J/min. Conclusion High MP of ventilation is independently associated with higher in-hospital mortality and several other outcomes in ICU patients receiving invasive ventilation for at least 48 h.

Published
2021

156. Lung Ultrasound Assessment of Focal and Non-focal Lung Morphology in Patients With Acute Respiratory Distress Syndrome

Author

Pierrakos, Charalampos, Smit, Marry M.R., Pisani, Luigi, Paulus, Frederique, Schultz, Marcus M.J., Constantin, Jean Michel, Chiumello, Davide, Mojoli, Francesco, Mongodi, Silvia, Bos, Lieuwe D J L.D., Pierrakos, Charalampos, Smit, Marry M.R., Pisani, Luigi, Paulus, Frederique, Schultz, Marcus M.J., Constantin, Jean Michel, Chiumello, Davide, Mojoli, Francesco, Mongodi, Silvia, and Bos, Lieuwe D J L.D.

Abstract

Background: The identification of phenotypes based on lung morphology can be helpful to better target mechanical ventilation of individual patients with acute respiratory distress syndrome (ARDS). We aimed to assess the accuracy of lung ultrasound (LUS) methods for classification of lung morphology in critically ill ARDS patients under mechanical ventilation. Methods: This was a post hoc analysis on two prospective studies that performed LUS and chest computed tomography (CT) scanning at the same time. Expert panels from the two participating centers separately developed two LUS methods for classifying lung morphology based on LUS aeration scores from a 12-region exam (Amsterdam and Lombardy method). Moreover, a previously developed LUS method based on anterior LUS scores was tested (Piedmont method). Sensitivity and specificity of all three LUS methods was assessed in the cohort of the other center(s) by using CT as the gold standard for classification of lung morphology. Results: The Amsterdam and Lombardy cohorts consisted of 32 and 19 ARDS patients, respectively. From these patients, 23 (45%) had focal lung morphology while others had non-focal lung morphology. The Amsterdam method could classify focal lung morphology with a sensitivity of 77% and a specificity of 100%, while the Lombardy method had a sensitivity and specificity of 100 and 61%. The Piedmont method had a sensitivity and specificity of 91 and 75% when tested on both cohorts. With both the Amsterdam and Lombardy method, most patients could be classified based on the anterior regions alone. Conclusion: LUS-based methods can accurately classify lung morphology in invasively ventilated ARDS patients compared to gold standard chest CT. The anterior LUS regions showed to be the most discriminant between focal and non-focal lung morphology, although accuracy increased moderately when lateral and posterior LUS regions were integrated in the method., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2021

157. Assessment of the Effect of Recruitment Maneuver on Lung Aeration Through Imaging Analysis in Invasively Ventilated Patients: A Systematic Review

Author

Pierrakos, Charalampos, Smit, Marry M.R., Hagens, Laura L.A., Heijnen, Nanon N.F.L., Hollmann, Markus M.W., Schultz, Marcus M.J., Paulus, Frederique, Bos, Lieuwe D J L.D., Pierrakos, Charalampos, Smit, Marry M.R., Hagens, Laura L.A., Heijnen, Nanon N.F.L., Hollmann, Markus M.W., Schultz, Marcus M.J., Paulus, Frederique, and Bos, Lieuwe D J L.D.

Abstract

Background: Recruitment maneuvers (RMs) have heterogeneous effects on lung aeration and have adverse side effects. We aimed to identify morphological, anatomical, and functional imaging characteristics that might be used to predict the RMs on lung aeration in invasively ventilated patients. Methods: We performed a systemic review. Studies included invasively ventilated patients who received an RM and in whom re-aeration was examined with chest computed tomography (CT), electrical impedance tomography (EIT), and lung ultrasound (LUS) were included. Results: Twenty studies were identified. Different types of RMs were applied. The amount of re-aerated lung tissue after an RM was highly variable between patients in all studies, irrespective of the used imaging technique and the type of patients (ARDS or non-ARDS). Imaging findings suggesting a non-focal morphology (i.e. radiologic findings consistent with attenuations with diffuse or patchy loss of aeration) were associated with higher likelihood of recruitment and lower chance of overdistention than a focal morphology (i.e. radiological findings suggestive of lobar or segmental loss of aeration). This was independent of the used imaging technique but only observed in patients with ARDS. In patients without ARDS, the results were inconclusive. Conclusions: ARDS patients with imaging findings suggestive of non-focal morphology show most re-aeration of previously consolidated lung tissue after RMs. The role of imaging techniques in predicting the effect of RMs on re-aeration in patients without ARDS remains uncertain., SCOPUS: re.j, info:eu-repo/semantics/published

Published
2021

158. Dead space estimates may not be independently associated with 28-day mortality in COVID-19 ARDS

Author

Infection & Immunity, Medische Staf Intensive Care, Morales-Quinteros, Luis, Neto, Ary Serpa, Artigas, Antonio, Blanch, Lluis, Botta, Michela, Kaufman, David A, Schultz, Marcus J, Tsonas, Anissa M, Paulus, Frederique, Bos, Lieuwe D, PRoVENT-COVID Study Group, Infection & Immunity, Medische Staf Intensive Care, Morales-Quinteros, Luis, Neto, Ary Serpa, Artigas, Antonio, Blanch, Lluis, Botta, Michela, Kaufman, David A, Schultz, Marcus J, Tsonas, Anissa M, Paulus, Frederique, Bos, Lieuwe D, and PRoVENT-COVID Study Group

Published
2021

159. Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study

Author

Infection & Immunity, Medische Staf Intensive Care, Botta, Michela, Tsonas, Anissa M, Pillay, Janesh, Boers, Leonoor S, Algera, Anna Geke, Bos, Lieuwe D J, Dongelmans, Dave A, Hollmann, Marcus W, Horn, Janneke, Vlaar, Alexander P J, Schultz, Marcus J, Neto, Ary Serpa, Paulus, Frederique, PRoVENT-COVID Collaborative Group, Infection & Immunity, Medische Staf Intensive Care, Botta, Michela, Tsonas, Anissa M, Pillay, Janesh, Boers, Leonoor S, Algera, Anna Geke, Bos, Lieuwe D J, Dongelmans, Dave A, Hollmann, Marcus W, Horn, Janneke, Vlaar, Alexander P J, Schultz, Marcus J, Neto, Ary Serpa, Paulus, Frederique, and PRoVENT-COVID Collaborative Group

Published
2021

161. Awake Proning as an Adjunctive Therapy for Refractory Hypoxemia in Non-Intubated Patients with COVID-19 Acute Respiratory Failure: Guidance from an International Group of Healthcare Workers

Author

Stilma, Willemke, primary, Åkerman, Eva, additional, Artigas, Antonio, additional, Bentley, Andrew, additional, Bos, Lieuwe D., additional, Bosman, Thomas J. C., additional, de Bruin, Hendrik, additional, Brummaier, Tobias, additional, Buiteman-Kruizinga, Laura A., additional, Carcò, Francesco, additional, Chesney, Gregg, additional, Chu, Cindy, additional, Dark, Paul, additional, Dondorp, Arjen M., additional, Gijsbers, Harm J. H., additional, Gilder, Mary Ellen, additional, Grieco, Domenico L., additional, Inglis, Rebecca, additional, Laffey, John G., additional, Landoni, Giovanni, additional, Lu, Weihua, additional, Maduro, Lisa M. N., additional, McGready, Rose, additional, McNicholas, Bairbre, additional, de Mendoza, Diego, additional, Morales-Quinteros, Luis, additional, Nosten, Francois, additional, Papali, Alfred, additional, Paternoster, Gianluca, additional, Paulus, Frederique, additional, Pisani, Luigi, additional, Prud’homme, Eloi, additional, Ricard, Jean-Damien, additional, Roca, Oriol, additional, Sartini, Chiara, additional, Scaravilli, Vittorio, additional, Schultz, Marcus J., additional, Sivakorn, Chaisith, additional, Spronk, Peter E., additional, Sztajnbok, Jaques, additional, Trigui, Youssef, additional, Vollman, Kathleen M., additional, and van der Woude, Margaretha C. E., additional

Published
2021
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162. Clinical features and prognostic factors in Covid-19: A prospective cohort study

Author

de Bruin, Sanne, primary, Bos, Lieuwe D., additional, van Roon, Marian A., additional, Tuip-de Boer, Anita M., additional, Schuurman, Alex R., additional, Koel-Simmelinck, Marleen J.A., additional, Bogaard, Harm Jan, additional, Tuinman, Pieter Roel, additional, van Agtmael, Michiel A., additional, Hamann, Jörg, additional, Teunissen, Charlotte E., additional, Wiersinga, W. Joost, additional, (Koos) Zwinderman, A.H., additional, Brouwer, Matthijs C., additional, van de Beek, Diederik, additional, Vlaar, Alexander P.J., additional, van Agtmael, Michiel, additional, Algera, Anne Geke, additional, Appelman, Brent, additional, van Baarle, Frank, additional, Bax, Diane, additional, Beudel, Martijn, additional, Bomers, Marije, additional, Bonta, Peter, additional, Bos, Lieuwe, additional, Botta, Michela, additional, de Brabander, Justin, additional, de Bree, Godelieve, additional, de Bruin, Sanne, additional, Buis, David T.P., additional, Bugiani, Marianna, additional, Bulle, Esther, additional, Chouchane, Osoul, additional, Cloherty, Alex, additional, de Rotte, Maurits C.F.J., additional, Dijkstra, Mirjam, additional, Dongelmans, Dave A., additional, Dujardin, Romein W.G., additional, Elbers, Paul, additional, Fleuren, Lucas, additional, Geerlings, Suzanne, additional, Geijtenbeek, Theo, additional, Girbes, Armand, additional, Goorhuis, Bram, additional, Grobusch, Martin P., additional, Hafkamp, Florianne, additional, Hagens, Laura, additional, Hamann, Jorg, additional, Harris, Vanessa, additional, Hemke, Robert, additional, Hermans, Sabine M., additional, Heunks, Leo, additional, Hollmann, Markus, additional, Horn, Janneke, additional, Hovius, Joppe W., additional, de Jong, Menno D., additional, Koning, Rutger, additional, Lim, Endry H.T., additional, van Mourik, Niels, additional, Nellen, Jeannine, additional, Nossent, Esther J., additional, Paulus, Frederique, additional, Peters, Edgar, additional, Piña-Fuentes, Dan A.I., additional, van der Poll, Tom, additional, Preckel, Bennedikt, additional, Prins, Jan M., additional, Raasveld, Jorinde, additional, Reijnders, Tom, additional, Schinkel, Michiel, additional, Schrauwen, Femke A.P., additional, Schultz, Marcus J., additional, Schuurmans, Alex, additional, Schuurmans, Jaap, additional, Sigaloff, Kim, additional, Slim, Marleen A., additional, Smeele, Patrick, additional, Smit, Marry, additional, Stijnis, Cornelis S., additional, Stilma, Willemke, additional, Teunissen, Charlotte, additional, Thoral, Patrick, additional, Tsonas, Anissa M., additional, Tuinman, Pieter R., additional, van der Valk, Marc, additional, Veelo, Denise, additional, Volleman, Carolien, additional, de Vries, Heder, additional, Vught, Lonneke A., additional, van Vugt, Michèle, additional, Wouters, Dorien, additional, and Zwinderman, A.H (Koos), additional

Published
2021
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163. Association between dexamethasone treatment and the host response in COVID-19 patients admitted to the general ward.

Author

de Brabander, Justin, Michels, Erik H. A., van Linge, Christine C. A., Chouchane, Osoul, Douma, Renée A., Reijnders, Tom D. Y., Schuurman, Alex R., van Engelen, Tjitske S. R., Amsterdam UMC COVID-19 biobank study group, van Agtmael, Michiel A., Algera, Anne Geke, Appelman, Brent, van Baarle, Frank E. H. P., Bax, Diane J. C., Beudel, Martijn, Bogaard, Harm Jan, Bomers, Marije, Bonta, Peter I., Bos, Lieuwe D. J., and Botta, Michela

Subjects
COVID-19, DEXAMETHASONE, HOSPITAL patients, ENDOTHELIAL cells, INTERLEUKIN-1
Abstract

Dexamethasone improves clinical outcomes in COVID-19 patients requiring supplementary oxygen. We investigated possible mechanisms of action by comparing sixteen plasma host response biomarkers in general ward patients before and after implementation of dexamethasone as standard of care. 48 patients without and 126 patients with dexamethasone treatment were sampled within 48 h of admission. Endothelial cell and coagulation activation biomarkers were comparable. Dexamethasone treatment was associated with lower plasma interleukin (IL)-6 and IL-1 receptor antagonist levels, whilst other inflammation parameters were not affected. These data argue against modification of vascular-procoagulant responses as an early mechanism of action of dexamethasone in COVID-19. [ABSTRACT FROM AUTHOR]

Published
2022
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165. Impact of a gap junction protein alpha 4 variant on clinical disease phenotype in F508del homozygous patients with cystic fibrosis

Author

Horn, Tabea, Ludwig, Michael, Eickmeier, Olaf, Neerinex, Anne H., Maitland-van der Zee, Anke H., Smaczny, Christina, Wagner, Thomas O. F., Schubert, Ralf, Zielen, Stefan, Majoor, Christof, Bos, Lieuwe D., Schmitt-Grohé, Sabina, Pulmonology, Paediatric Pulmonology, AII - Inflammatory diseases, APH - Personalized Medicine, Amsterdam institute for Infection and Immunity, Intensive Care Medicine, and ACS - Heart failure & arrhythmias

Subjects
cystic fibrosis, lung disease phenotype, phenotype/genotype relation, precision medicine, gap junction protein alpha 4-genotype, Genetics, Molecular Medicine, lung function, ddc:610, inflammatory markers, F508del homozygous, Genetics (clinical)
Abstract

Background: Lung disease phenotype varies widely even in the F508del (homozygous) genotype. Leukocyte-driven inflammation is important for pulmonary disease pathogenesis in cystic fibrosis (CF). Blood cytokines correlate negatively with pulmonary function in F508del homozygous patients, and gap junction proteins (GJA) might be related to the influx of blood cells into the lung and influence disease course. We aimed to assess the relationship between GJA1/GJA4 genotypes and the clinical disease phenotype. Methods: One-hundred-and-sixteen homozygous F508del patients (mean age 27 years, m/f 66/50) were recruited from the CF centers of Bonn, Frankfurt, and Amsterdam. Sequence analysis was performed for GJA1 and GJA4. The clinical disease course was assessed over 3 years using pulmonary function tests, body mass index, Pseudomonas aeruginosa colonization, diabetes mellitus, survival to end-stage lung disease, blood and sputum inflammatory markers. Results: Sequence analysis revealed one clinically relevant single nucleotide polymorphism. In this GJA4 variant (rs41266431), homozygous G variant carriers (n = 84/116; 72.4%) had poorer pulmonary function (FVC% pred: mean 78/86, p < 0.040) and survival to end-stage lung disease was lower (p < 0.029). The frequency of P. aeruginosa colonization was not influenced by the genotype, but in those chronically colonized, those with the G/G genotype had reduced pulmonary function (FVC% pred: mean 67/80, p < 0.049). Serum interleukin-8 (median: 12.4/6.7 pg/ml, p < 0.052) and sputum leukocytes (2305/437.5 pg/ml, p < 0.025) were higher for the G/G genotype. Conclusions: In carriers of the A allele (27.6%) the GJA4 variant is associated with significantly better protection against end-stage lung disease and superior pulmonary function test results in F508del homozygous patients. This SNP has the potential of a modifier gene for phenotyping severity of CF lung disease, in addition to the CFTR genotype. Clinical Trial Registration: The study was registered with ClinicalTrials.gov, number NCT04242420, retrospectively on January 24th, 2020.

Published
2020

166. PRactice of VENTilation in Patients with Novel Coronavirus Disease (PRoVENT-COVID): rationale and protocol for a national multicenter observational study in The Netherlands

Author

Boers, Noor S, Botta, Michela, Tsonas, Annisa M, Algera, Anna Geke, Pillay, Janesh, Dongelmans, Dave A, Horn, Janneke, Vlaar, Alexander P J, Hollmann, Markus W, Bos, Lieuwe D J, Paulus, Frederique, Neto, Ary Serpa, Schultz, Marcus J, de Klerk, Eline S., Lectoraat Critical Care, Urban Vitality, Faculteit Gezondheid, Intensive Care Medicine, Graduate School, AII - Inflammatory diseases, ACS - Microcirculation, Anesthesiology, ACS - Heart failure & arrhythmias, Nursing, ACS - Atherosclerosis & ischemic syndromes, APH - Quality of Care, ACS - Pulmonary hypertension & thrombosis, and ACS - Diabetes & metabolism

Subjects
medicine.medical_specialty, medicine.medical_treatment, mechanical ventilation, critical care medicine, Hypoxemia, law.invention, 03 medical and health sciences, the coronavirus disease 2019 (COVID-19), 0302 clinical medicine, law, Intensive care, Health care, Pandemic, medicine, Extracorporeal membrane oxygenation, 030212 general & internal medicine, Mechanical ventilation, ventilator-free days, business.industry, SARS-CoV-2, General Medicine, EVOLUTION, Study Protocal, 030228 respiratory system, Emergency medicine, Ventilation (architecture), Observational study, medicine.symptom, business
Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic is rapidly expanding across the world, with more than 100,000 new cases each day as of end-June 2020. Healthcare workers are struggling to provide the best care for COVID-19 patients. Approaches for invasive ventilation vary widely between and within countries and new insights are acquired rapidly. We aim to investigate invasive ventilation practices and outcome in COVID-19 patients in the Netherlands.Methods: PRoVENT-COVID ('study of PRactice of VENTilation in COVID-19') is an investigator-initiated national, multicenter observational study to be undertaken in intensive care units (ICUs) in The Netherlands. Consecutive COVID-19 patients aged 18 years or older, who are receiving invasive ventilation in the participating ICUs, are to be enrolled during a 10-week period, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cmH2O) during the first 3 days of ventilation. Secondary outcomes include other ventilatory variables, use of rescue therapies for refractory hypoxemia such as prone positioning and extracorporeal membrane oxygenation, use of sedatives, vasopressors and inotropes; daily cumulative fluid balances; acute kidney injury; ventilator-free days and alive at day 28 (VFD-28), duration of ICU and hospital stay, and ICU, hospital and 90-day mortality.Discussion: PRoVENT-COVID will be the largest observational study to date, with high density ventilatory data and major outcomes. There is urgent need for a better understanding of ventilation practices, and the effects of ventilator settings on outcomes in COVID-19 patients. The results of PRoVENT-COVID will be rapidly disseminated through electronic presentations, such as webinars and electronic conferences, and publications in international peer-reviewed journals. Access to source data will be made available through local, regional and national anonymized datasets on request, and after agreement of the PRoVENT-COVID steering committee.Trial Registration: PRoVENT-COVID is registered at clinicaltrials.gov (identifier NCT04346342).

Published
2020

167. Additional file 1 of Acute respiratory distress syndrome subphenotypes and therapy responsive traits among preclinical models: protocol for a systematic review and meta-analysis

Author

Carla, Adrien, Pereira, Bruno, Boukail, Hanifa, Audard, Jules, Pinol-Domenech, Nathalie, Carvalho, Manuela De, Blondonnet, Raiko, Ruoyang Zhai, Morand, Dominique, Lambert, Céline, Sapin, Vincent, Ware, Lorraine B., Calfee, Carolyn S., Bastarache, Julie A., Laffey, John G., Juffermans, Nicole P., Bos, Lieuwe D., Artigas, Antonio, Rocco, Patricia R. M., Matthay, Michael A., McAuley, Daniel F., Jean-Michel Constantin, and Jabaudon, Matthieu

Subjects
Data_FILES
Abstract

Additional file 1. Representative Search Strategy.

Published
2020
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168. Additional file 2 of Acute respiratory distress syndrome subphenotypes and therapy responsive traits among preclinical models: protocol for a systematic review and meta-analysis

Author

Carla, Adrien, Pereira, Bruno, Boukail, Hanifa, Audard, Jules, Pinol-Domenech, Nathalie, Carvalho, Manuela De, Blondonnet, Raiko, Ruoyang Zhai, Morand, Dominique, Lambert, Céline, Sapin, Vincent, Ware, Lorraine B., Calfee, Carolyn S., Bastarache, Julie A., Laffey, John G., Juffermans, Nicole P., Bos, Lieuwe D., Artigas, Antonio, Rocco, Patricia R. M., Matthay, Michael A., McAuley, Daniel F., Jean-Michel Constantin, and Jabaudon, Matthieu

Abstract

Additional file 2. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) checklist.

Published
2020
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169. Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Author

Bastard, P., Zhang, Q., Michailidis, E., Hoffmann, H.H., Zhang, Y., Dorgham, Karim, Philippot, Q., Rosain, J., Béziat, V., Manry, J., Shaw, E., Haljasmägi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A.A., Belot, A., Kallaste, A., Catherinot, E., Tandjaoui-Lambiotte, Y., Le Pen, J., Kerner, G., Bigio, B., Seeleuthner, Y., Yang, R., Bolze, A., Spaan, A.N., Delmonte, O.M., Abers, M.S., Aiuti, A., Casari, G., Lampasona, V., Piemonti, L., Ciceri, F., Bilguvar, K., Lifton, R.P., Vasse, M., Smadja, D.M., Migaud, M., Hadjadj, J., Terrier, B., Duffy, D., Quintana-Murci, L., van de Beek, D., Roussel, L., Vinh, D.C., Tangye, S., Haerynck, F., Dalmau, D., Martinez-Picado, J., Brodin, P., Nussenzweig, M.C., Boisson-Dupuis, S., Rodríguez-Gallego, C., Vogt, G., Mogensen, T.H., Oler, A.J., Gu, J., Burbelo, P.D., Cohen, J.I., Biondi, A., Bettini, L.R., DÁngio, M., Bonfanti, P., Rossignol, P., Mayaux, J., Rieux-Laucat, F., Husebye, E.S., Fusco, F., Ursini, M.V., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Castagnoli, R., Montagna, D., Licari, A., Marseglia, G.L., Duval, X., Ghosn, J., Tsang, J.S., Goldbach-Mansky, R., Kisand, K., Lionakis, M.S., Puel, A., Zhang, S.Y., Holland, S.M., Gorochov, G., Jouanguy, E., Rice, C.M., Cobat, A., Notarangelo, L.D., Abel, L., Su, H.C., Casanova, J.L., Arias, A.A., Boisson, B., Boucherit, S., Bustamante, J., Chbihi, M., Chen, J., Chrabieh, M., Kochetkov, T., Le Voyer, T., Liu, D., Nemirovskaya, Y., Ogishi, M., Papandrea, D., Patissier, C., Rapaport, F., Roynard, M., Vladikine, N., Woollett, M., Zhang, P., Kashyap, A., Ding, L., Bosticardo, M., Wang, Q., Ochoa, S., Liu, H., Chauvin, S.D., Stack, M., Koroleva, G., Bansal, N., Dalgard, C.L., Snow, A.L., Abad Capa, Jorge, Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Amoura, Z., Antolí, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinières, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, Mireia, Borie, R., Bousfiha, A.A., Bouvattier, C., Boyarchuk, O., Bueno, M.R.P., Agra, J.J.C., Calimli, S., Capra, R., Carrabba, M., Casasnovas, Carlos, Caseris, M., Castelle, M., Castelli, F., de Vera, M.C., Castro, M.V., Chalumeau, M., Charbit, B., Cheng, M.P., Clavé, P., Clotet, B., Codina, A., Colkesen, F., Colobrán Oriol, Roger, Comarmond, C., Corsico, A.G., Darley, D.R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Di Sabatino, A., Diehl, J.L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M.F., Flores, Carlos, Francois, B., Fumadó, V., Solis, B.G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Goffard, J.C., Gok, F., González-Montelongo, R., Guerder, A., Gul, Y., Guner, S.N., Gut, M., Halwani, R., Hammarström, L., Hatipoglu, N., Hernandez-Brito, E., Holanda-Peña, M.S., Horcajada, J.P., Hraiech, S., Humbert, L., Iglesias, A.D., Íñigo-Campos, A., Jamme, M., Arranz, M.J., Jordan, I., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K.K., Keles, S., Demirkol, Y.K., Klocperk, A., Król, Z.J., Kuentz, P., Kwan, Y.W.M., Lagier, J.C., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Linglart, A., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Luyt, C.E., Lye, D.C., Mansouri, D., Marjani, M., Pereira, J.M., Martin, A., Pueyo, D.M., Marzana, I., Mathian, A., Matos, L.R.B., Matthews, G.V., Mège, J.L., Melki, I., Meritet, J.F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melián, A.M., Martinez, A.M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Muñoz-Barrera, A., Nafati, C., Neves, J.F., Ng, L.F.P., Medina, Y.N., Cuadros, E.N., Gonzalo Ocejo-Vinyals, J., Orbak, Z., Oualha, M., Ozcelik, T., Hammarström, Q.P., Parizot, C., Pascreau, T., Paz-Artal, E., de Diego, R.P., Philippe, A., Philippota, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A.S., Reisli, I., Ricart, P., Richard, J.C., Rivet, N., Rivière, J.G., Blanch, G.R., Rodrigo, C., Rodriguez-Gallego, C., Rodríguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Rozenberg, F., del Prado, M.Y.R., Riera, J.S., Sanchez, O., Sánchez-Ramón, S., Schluter, A., Schmidt, M., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L.M., Sene, D., Senoglu, S., Seppänen, M.R.J., Ilovich, A.S., Shahrooei, M., Smadja, D., Sobh, A., Moreno, X.S., Solé-Violán, J., Soler, C., Soler-Palacín, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiottea, Y., Taupin, J.L., Tavernier, S.J., Thumerelle, C., Tomasoni, G., Toubiana, J., Alvarez, J.T., Trouillet-Assanta, S., Troya, J., Tucci, A., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., van Den Rym, A.M., Vandernoot, I., Vatansev, H., Vélez-Santamaria, V., Viel, S., Vilain, C., Vilaire, M.E., Vincent, A., Voiriot, G., Vuotto, F., Yosunkaya, A., Young, B.E., Yucel, F., Zannad, F., Zatz, M., Belota, A., Foti, Giuseppe, Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Bole-Feysot, C., Lyonnet, S., Masson, C., Nitschke, P., Pouliet, A., Schmitt, Y., Tores, F., Zarhrate, M., Abela, L., Andrejak, C., Angoulvant, F., Bachelet, D., Basmaci, R., Behillil, S., Beluze, M., Benkerrou, D., Bhavsar, K., Bompart, F., Bouadma, L., Bouscambert, M., Caralp, M., Cervantes-Gonzalez, M., Chair, A., Coelho, A., Couffignal, C., Couffin-Cadiergues, S., D'ortenzio, E., da Silveira, C., Debray, M.P., Deplanque, D., Descamps, D., Desvallées, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Eloy, P., Enouf, V.V.E., Espérou, H., Esposito-Farese, M., Etienne, M., Ettalhaoui, N., Gault, N., Gaymard, A., Gigante, T., Gorenne, I., Guedj, J., Hoctin, A., Hoffmann, I., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Khalil, A., Khan, C., Laouénan, C., Laribi, S., Le, M., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lescure, F.X., Lévy, Y., Levy-Marchal, C., Lina, B., Lingas, G., Lucet, J.C., Malvy, D., Mambert, M., Mentré, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puéchal, O., Rosa-Calatrava, M., Rossignol, B., Roy, C., Schneider, M., Semaille, C., Mohammed, N.S., Tagherset, L., Tardivon, C., Tellier, M.C., Téoulé, F., Terrier, O., Timsit, J.F., Treoux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Abelc, L., Alcover, A., Aschard, H., Astrom, K., Bousso, P., Bruhns, P., Cumano, A., Demangel, C., Deriano, L., Santo, J.D., Dromer, F., Eberl, G., Enninga, J., Fellay, Jacques, Gomperts-Boneca, I., Hasan, M., Hercberg, S., Lantz, O., Patin, E., Pellegrini, S., Pol, S., Rausell, A., Rogge, L., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M.N., Albert, M.L., Alavoine, L., Amat, K.K.A., Bielicki, J., Bruijning, P., Burdet, C., Caumes, E., Charpentier, C., Coignard, B., Costa, Y., Damond, F., Dechanet, A., Delmas, C., Ecobichon, J.L., Enouf, V., Frezouls, W., Houhou, N., Ilic-Habensus, E., Kikoine, J., Lebeaux, D., Leclercq, A., Lehacaut, J., Letrou, S., Manchon, P., Mandic, M., Meghadecha, M., Motiejunaite, J., Nouroudine, M., Piquard, V., Postolache, A., Quintin, C., Rexach, J., Roufai, L., Terzian, Z., Thy, M., Vignali, V., van Agtmael, M., Algera, A.G., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bos, Lieuwe D, Botta, M., de Brabander, J., Bree, G., Brouwer, M.C., de Bruin, S., Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Elbers, P., Fleuren, L., Geerlings, S., Geerts, B., Geijtenbeek, T., Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M.W., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., van Mourik, N., Nellen, J., Paulus, F., Peters, E., van der Poll, T., Preckel, B., Prins, J.M., Raasveld, J., Reijnders, T., Schinkel, M., Schultz, M.J., Schuurman, A., Sigaloff, K., Smit, M., Stijnis, C.S., Stilma, Willemke, Teunissen, C., Thoral, P., Tsonas, A., van der Valk, M., Veelo, D., Vlaar, A.P.J., de Vries, H., van Vugt, M., Joost Wiersinga, W., Wouters, D., Zwinderman, A.H., Abelb, L., Iuti, F., Muhsen, S.A., Al-Mulla, F., Anderson, M.S., Bogunovic, D., Bondarenko, A., Bryceson, Y., Bustamante, C.D., Butte, M., Chakravorty, S., Christodoulou, J., Cirulli, E., Condino-Neto, A., Cooper, M.A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Franco, J.L., Gregersen, P.K., Hagin, D., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Itan, Y., Karamitros, T., Kisanda, K., Ku, C.L., Ling, Y., Lucas, C.L., Maniatis, T., Marodi, L., Milner, J.D., Mironska, K., Morio, T., Notarangeloa, L.D., Novelli, G., Novelli, A., O'Farrelly, C., Okada, S., Planas, A.M., Prando, C., Pujol, A., Renia, L., Renieri, A., Sancho-Shimizu, V., Sankaran, V., Barrett, K.S., Snow, A., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., von Bernuth, H., Washington, N., Zawadzki, P., Sua, H.C., Casanovaa, J.L., Rosen, L.B., Universitat Autònoma de Barcelona, Bastard, P., Zhang, Q., Michailidis, E., Hoffmann, H.H., Zhang, Y., Dorgham, Karim, Philippot, Q., Rosain, J., Béziat, V., Manry, J., Shaw, E., Haljasmägi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A.A., Belot, A., Kallaste, A., Catherinot, E., Tandjaoui-Lambiotte, Y., Le Pen, J., Kerner, G., Bigio, B., Seeleuthner, Y., Yang, R., Bolze, A., Spaan, A.N., Delmonte, O.M., Abers, M.S., Aiuti, A., Casari, G., Lampasona, V., Piemonti, L., Ciceri, F., Bilguvar, K., Lifton, R.P., Vasse, M., Smadja, D.M., Migaud, M., Hadjadj, J., Terrier, B., Duffy, D., Quintana-Murci, L., van de Beek, D., Roussel, L., Vinh, D.C., Tangye, S., Haerynck, F., Dalmau, D., Martinez-Picado, J., Brodin, P., Nussenzweig, M.C., Boisson-Dupuis, S., Rodríguez-Gallego, C., Vogt, G., Mogensen, T.H., Oler, A.J., Gu, J., Burbelo, P.D., Cohen, J.I., Biondi, A., Bettini, L.R., DÁngio, M., Bonfanti, P., Rossignol, P., Mayaux, J., Rieux-Laucat, F., Husebye, E.S., Fusco, F., Ursini, M.V., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Castagnoli, R., Montagna, D., Licari, A., Marseglia, G.L., Duval, X., Ghosn, J., Tsang, J.S., Goldbach-Mansky, R., Kisand, K., Lionakis, M.S., Puel, A., Zhang, S.Y., Holland, S.M., Gorochov, G., Jouanguy, E., Rice, C.M., Cobat, A., Notarangelo, L.D., Abel, L., Su, H.C., Casanova, J.L., Arias, A.A., Boisson, B., Boucherit, S., 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Karbuz, A., Yasar, K.K., Keles, S., Demirkol, Y.K., Klocperk, A., Król, Z.J., Kuentz, P., Kwan, Y.W.M., Lagier, J.C., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Linglart, A., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Luyt, C.E., Lye, D.C., Mansouri, D., Marjani, M., Pereira, J.M., Martin, A., Pueyo, D.M., Marzana, I., Mathian, A., Matos, L.R.B., Matthews, G.V., Mège, J.L., Melki, I., Meritet, J.F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melián, A.M., Martinez, A.M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Muñoz-Barrera, A., Nafati, C., Neves, J.F., Ng, L.F.P., Medina, Y.N., Cuadros, E.N., Gonzalo Ocejo-Vinyals, J., Orbak, Z., Oualha, M., Ozcelik, T., Hammarström, Q.P., Parizot, C., Pascreau, T., Paz-Artal, E., de Diego, R.P., Philippe, A., Philippota, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A.S., Reisli, I., Ricart, P., Richard, J.C., Rivet, N., Rivière, J.G., Blanch, G.R., Rodrigo, C., Rodriguez-Gallego, C., Rodríguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Rozenberg, F., del Prado, M.Y.R., Riera, J.S., Sanchez, O., Sánchez-Ramón, S., Schluter, A., Schmidt, M., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L.M., Sene, D., Senoglu, S., Seppänen, M.R.J., Ilovich, A.S., Shahrooei, M., Smadja, D., Sobh, A., Moreno, X.S., Solé-Violán, J., Soler, C., Soler-Palacín, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiottea, Y., Taupin, J.L., Tavernier, S.J., Thumerelle, C., Tomasoni, G., Toubiana, J., Alvarez, J.T., Trouillet-Assanta, S., Troya, J., Tucci, A., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., van Den Rym, A.M., Vandernoot, I., Vatansev, H., Vélez-Santamaria, V., Viel, S., Vilain, C., Vilaire, M.E., Vincent, A., Voiriot, G., Vuotto, F., Yosunkaya, A., Young, B.E., Yucel, F., Zannad, F., Zatz, M., Belota, A., Foti, Giuseppe, Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Bole-Feysot, C., Lyonnet, S., Masson, C., Nitschke, P., Pouliet, A., Schmitt, Y., Tores, F., Zarhrate, M., Abela, L., Andrejak, C., Angoulvant, F., Bachelet, D., Basmaci, R., Behillil, S., Beluze, M., Benkerrou, D., Bhavsar, K., Bompart, F., Bouadma, L., Bouscambert, M., Caralp, M., Cervantes-Gonzalez, M., Chair, A., Coelho, A., Couffignal, C., Couffin-Cadiergues, S., D'ortenzio, E., da Silveira, C., Debray, M.P., Deplanque, D., Descamps, D., Desvallées, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Eloy, P., Enouf, V.V.E., Espérou, H., Esposito-Farese, M., Etienne, M., Ettalhaoui, N., Gault, N., Gaymard, A., Gigante, T., Gorenne, I., Guedj, J., Hoctin, A., Hoffmann, I., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Khalil, A., Khan, C., Laouénan, C., Laribi, S., Le, M., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lescure, F.X., Lévy, Y., Levy-Marchal, C., Lina, B., Lingas, G., Lucet, J.C., Malvy, D., Mambert, M., Mentré, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puéchal, O., Rosa-Calatrava, M., Rossignol, B., Roy, C., Schneider, M., Semaille, C., Mohammed, N.S., Tagherset, L., Tardivon, C., Tellier, M.C., Téoulé, F., Terrier, O., Timsit, J.F., Treoux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Abelc, L., Alcover, A., Aschard, H., Astrom, K., Bousso, P., Bruhns, P., Cumano, A., Demangel, C., Deriano, L., Santo, J.D., Dromer, F., Eberl, G., Enninga, J., Fellay, Jacques, Gomperts-Boneca, I., Hasan, M., Hercberg, S., Lantz, O., Patin, E., Pellegrini, S., Pol, S., Rausell, A., Rogge, L., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M.N., Albert, M.L., Alavoine, L., Amat, K.K.A., Bielicki, J., Bruijning, P., Burdet, C., Caumes, E., Charpentier, C., Coignard, B., Costa, Y., Damond, F., Dechanet, A., Delmas, C., Ecobichon, J.L., Enouf, V., Frezouls, W., Houhou, N., Ilic-Habensus, E., Kikoine, J., Lebeaux, D., Leclercq, A., Lehacaut, J., Letrou, S., Manchon, P., Mandic, M., Meghadecha, M., Motiejunaite, J., Nouroudine, M., Piquard, V., Postolache, A., Quintin, C., Rexach, J., Roufai, L., Terzian, Z., Thy, M., Vignali, V., van Agtmael, M., Algera, A.G., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bos, Lieuwe D, Botta, M., de Brabander, J., Bree, G., Brouwer, M.C., de Bruin, S., Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Elbers, P., Fleuren, L., Geerlings, S., Geerts, B., Geijtenbeek, T., Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M.W., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., van Mourik, N., Nellen, J., Paulus, F., Peters, E., van der Poll, T., Preckel, B., Prins, J.M., Raasveld, J., Reijnders, T., Schinkel, M., Schultz, M.J., Schuurman, A., Sigaloff, K., Smit, M., Stijnis, C.S., Stilma, Willemke, Teunissen, C., Thoral, P., Tsonas, A., van der Valk, M., Veelo, D., Vlaar, A.P.J., de Vries, H., van Vugt, M., Joost Wiersinga, W., Wouters, D., Zwinderman, A.H., Abelb, L., Iuti, F., Muhsen, S.A., Al-Mulla, F., Anderson, M.S., Bogunovic, D., Bondarenko, A., Bryceson, Y., Bustamante, C.D., Butte, M., Chakravorty, S., Christodoulou, J., Cirulli, E., Condino-Neto, A., Cooper, M.A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Franco, J.L., Gregersen, P.K., Hagin, D., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Itan, Y., Karamitros, T., Kisanda, K., Ku, C.L., Ling, Y., Lucas, C.L., Maniatis, T., Marodi, L., Milner, J.D., Mironska, K., Morio, T., Notarangeloa, L.D., Novelli, G., Novelli, A., O'Farrelly, C., Okada, S., Planas, A.M., Prando, C., Pujol, A., Renia, L., Renieri, A., Sancho-Shimizu, V., Sankaran, V., Barrett, K.S., Snow, A., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., von Bernuth, H., Washington, N., Zawadzki, P., Sua, H.C., Casanovaa, J.L., Rosen, L.B., and Universitat Autònoma de Barcelona

Abstract

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

Published
2020

170. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author

Zhang, Q., Liu, Z., Moncada-Velez, M., Chen, J., Ogishi, M., Bigio, B., Yang, R., Arias, A.A., Zhou, Q., Han, J.E., Ugurbil, A.C., Zhang, P., Rapaport, F., Li, J., Spaan, A.N., Boisson, B., Boisson-Dupuis, S., Bustamante, J., Puel, A., Ciancanelli, M.J., Zhang, S.Y., Béziat, V., Jouanguy, E., Abel, L., Cobat, A., Casanova, J.L., Bastard, P., Korol, C., Rosain, J., Philippot, Q., Chbihi, M., Lorenzo, L., Bizien, L., Neehus, A.L., Kerner, G., Seeleuthner, Y., Manry, J., Le Voyer, T., Le Pen, J., Schneider, W.M., Razooky, B.S., Hoffmann, H.H., Michailidis, E., Rice, C.M., Sabli, I.K.D., Hodeib, S., Sancho-Shimizu, V., Bilguvar, K., Ye, J., Maniatis, T., Bolze, A., Zhang, Y., Notarangelo, L.D., Su, H.C., Onodi, F., Korniotis, S., Karpf, L., Soumelis, V., Bonnet-Madin, L., Amara, A., Dorgham, Karim, Gorochov, G., Smith, N., Duffy, D., Moens, L., Meyts, I., Meade, P., Garcia-Sastre, Adolfo, Krammer, F., Corneau, A., Masson, C., Schmitt, Y., Schluter, A., Pujol, A., Khan, T., Marr, N., Fellay, Jacques, Roussel, L., Vinh, D.C., Shahrooei, M., Alosaimi, M.F., Alsohime, F., Hasanato, R., Mansouri, D., Al-Saud, H., Almourfi, F., Al-Mulla, F., Al-Muhsen, S.Z., Al Turki, S., van de Beek, D., Biondi, A., Bettini, L.R., D'Angio, M., Bonfanti, P., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Oler, A.J., Tompkins, M.F., Alba, C., Dalgard, C.L., Vandernoot, I., Smits, G., Goffard, J.C., Migeotte, I., Haerynck, F., Soler-Palacín, P., Martin-Nalda, A., Colobrán Oriol, Roger, Morange, P.E., Keles, S., Çölkesen, F., Ozcelik, T., Yasar, K.K., Senoglu, S., Karabela, Ş.N., Rodríguez-Gallego, C., Novelli, G., Hraiech, S., Tandjaoui-Lambiotte, Y., Duval, X., Laouénan, C., Snow, A., Milner, J.D., Mogensen, T.H., Nussenzweig, M., Lifton, R.P., Foti, Giuseppe, Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Abad Capa, Jorge, Blanco, I., Rodrigo, C., Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Mouly, S., Sene, D., Amoura, Z., Mathian, A., Antolí, A., Blanch, G.R., Riera, J.S., Moreno, X.S., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Lévy, R., Oualha, M., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blandinières, A., Rivet, N., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, Mireia, Clavé, P., Bosteels, C., Lambrecht, B.N., van Braeckel, E., Bousfiha, A.A., Bouvattier, C., Vincent, A., Boyarchuk, O., Bueno, M.R.P., Castro, M.V., Matos, L.R.B., Zatz, M., Agra, J.J.C., Calimli, S., Capra, R., Carrabba, M., Fabio, G., Casasnovas, Carlos, Vélez-Santamaria, V., Caseris, M., Falck, A., Poncelet, G., Castelle, M., Castelli, F., de Vera, M.C., Catherinot, E., Chalumeau, M., Toubiana, J., Charbit, B., Li, Z., Pellegrini, S., Cheng, M.P., Clotet, B., Codina, A., Colkesen, F., Comarmond, C., Dalmau, D., Darley, D.R., Dauby, N., Dauger, S., Le Bourgeois, F., Levy, M., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Diehl, J.L., Dobbelaere, S., Durand, S., Mircher, C., Rebillat, A.S., Vilaire, M.E., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Faivre, L., Fartoukh, M., Faure, M., Arquero, M.F., Flores, Carlos, Francois, B., Fumadó, V., Fusco, F., Ursini, M.V., Solis, B.G., de Diego, R.P., van Den Rym, A.M., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Gok, F., Yosunkaya, A., Thy, M., van Agtmael, M., Bomers, M., Chouchane, O., Geerlings, S., Goorhuis, B., Grobusch, M.P., Harris, V., Hermans, S.M., Hovius, J.W., Nellen, J., Peters, E., van der Poll, T., Prins, J.M., Reijnders, T., Schinkel, M., Sigaloff, K., Stijnis, C.S., van der Valk, M., van Vugt, M., Joost Wiersinga, W., Algera, A.G., van Baarle, F., Bos, Lieuwe D, Botta, M., de Bruin, S., Bulle, E., Elbers, P., Fleuren, L., Girbes, A., Hagens, L., Heunks, L., Horn, J., van Mourik, N., Paulus, F., Raasveld, J., Schultz, M.J., Smit, M., Stilma, Willemke, Thoral, P., Tsonas, A., de Vries, H., Bax, D., Cloherty, A., Beudel, M., Brouwer, M.C., Koning, R., Bogaard, H.J., de Brabander, J., de Bree, G., Bugiani, M., Geerts, B., Hollmann, M.W., Preckel, B., Veelo, D., Geijtenbeek, T., Hafkamp, F., Hamann, J., Hemke, R., de Jong, M.D., Schuurman, A., Teunissen, C., Vlaar, A.P.J., Wouters, D., Zwinderman, A.H., Aiuti, A., Muhsen, S.A., Anderson, M.S., Bogunovic, D., Itan, Y., Cirulli, E., Barrett, K.S., Washington, N., Bondarenko, A., Brodin, P., Bryceson, Y., Bustamante, C.D., Butte, M., Casari, G., Chakravorty, S., Christodoulou, J., Le Mestre, S., Condino-Neto, A., Cooper, M.A., David, A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Franco, J.L., Gregersen, P.K., Hagin, D., Halwani, R., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Karamitros, T., Kisand, K., Ku, C.L., Lau, Y.L., Ling, Y., Lucas, C.L., Marodi, L., Milner, J., Mironska, K., Morio, T., Novelli, A., O'Farrelly, C., Okada, S., Planas, A.M., Prando, C., Quintana-Murci, L., Renia, L., Renieri, A., Sankaran, V., Tangye, S., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., von Bernuth, H., Zawadzki, P., Jing, H., Tung, W., Meguro, K., Shaw, E., Shafer, S., Zheng, L., Zhang, Z., Kubo, S., Chauvin, S.D., Lenardo, M., Luthers, C.R., Bauman, B.M., Lack, J., Karlins, E., Hupalo, D.M., Rosenberger, J., Sukumar, G., Wilkerson, M.D., Zhang, X., Universitat Autònoma Barcelona, Zhang, Q., Liu, Z., Moncada-Velez, M., Chen, J., Ogishi, M., Bigio, B., Yang, R., Arias, A.A., Zhou, Q., Han, J.E., Ugurbil, A.C., Zhang, P., Rapaport, F., Li, J., Spaan, A.N., Boisson, B., Boisson-Dupuis, S., Bustamante, J., Puel, A., Ciancanelli, M.J., Zhang, S.Y., Béziat, V., Jouanguy, E., Abel, L., Cobat, A., Casanova, J.L., Bastard, P., Korol, C., Rosain, J., Philippot, Q., Chbihi, M., Lorenzo, L., Bizien, L., Neehus, A.L., Kerner, G., Seeleuthner, Y., Manry, J., Le Voyer, T., Le Pen, J., Schneider, W.M., Razooky, B.S., Hoffmann, H.H., Michailidis, E., Rice, C.M., Sabli, I.K.D., Hodeib, S., Sancho-Shimizu, V., Bilguvar, K., Ye, J., Maniatis, T., Bolze, A., Zhang, Y., Notarangelo, L.D., Su, H.C., Onodi, F., Korniotis, S., Karpf, L., Soumelis, V., Bonnet-Madin, L., Amara, A., Dorgham, Karim, Gorochov, G., Smith, N., Duffy, D., Moens, L., Meyts, I., Meade, P., Garcia-Sastre, Adolfo, Krammer, F., Corneau, A., Masson, C., Schmitt, Y., Schluter, A., Pujol, A., Khan, T., Marr, N., Fellay, Jacques, Roussel, L., Vinh, D.C., Shahrooei, M., Alosaimi, M.F., Alsohime, F., Hasanato, R., Mansouri, D., Al-Saud, H., Almourfi, F., Al-Mulla, F., Al-Muhsen, S.Z., Al Turki, S., van de Beek, D., Biondi, A., Bettini, L.R., D'Angio, M., Bonfanti, P., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Oler, A.J., Tompkins, M.F., Alba, C., Dalgard, C.L., Vandernoot, I., Smits, G., Goffard, J.C., Migeotte, I., Haerynck, F., Soler-Palacín, P., Martin-Nalda, A., Colobrán Oriol, Roger, Morange, P.E., Keles, S., Çölkesen, F., Ozcelik, T., Yasar, K.K., Senoglu, S., Karabela, Ş.N., Rodríguez-Gallego, C., Novelli, G., Hraiech, S., Tandjaoui-Lambiotte, Y., Duval, X., Laouénan, C., Snow, A., Milner, J.D., Mogensen, T.H., Nussenzweig, M., Lifton, R.P., Foti, Giuseppe, Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Abad Capa, Jorge, Blanco, I., Rodrigo, C., Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Mouly, S., Sene, D., Amoura, Z., Mathian, A., Antolí, A., Blanch, G.R., Riera, J.S., Moreno, X.S., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Lévy, R., Oualha, M., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blandinières, A., Rivet, N., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, Mireia, Clavé, P., Bosteels, C., Lambrecht, B.N., van Braeckel, E., Bousfiha, A.A., Bouvattier, C., Vincent, A., Boyarchuk, O., Bueno, M.R.P., Castro, M.V., Matos, L.R.B., Zatz, M., Agra, J.J.C., Calimli, S., Capra, R., Carrabba, M., Fabio, G., Casasnovas, Carlos, Vélez-Santamaria, V., Caseris, M., Falck, A., Poncelet, G., Castelle, M., Castelli, F., de Vera, M.C., Catherinot, E., Chalumeau, M., Toubiana, J., Charbit, B., Li, Z., Pellegrini, S., Cheng, M.P., Clotet, B., Codina, A., Colkesen, F., Comarmond, C., Dalmau, D., Darley, D.R., Dauby, N., Dauger, S., Le Bourgeois, F., Levy, M., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Diehl, J.L., Dobbelaere, S., Durand, S., Mircher, C., Rebillat, A.S., Vilaire, M.E., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Faivre, L., Fartoukh, M., Faure, M., Arquero, M.F., Flores, Carlos, Francois, B., Fumadó, V., Fusco, F., Ursini, M.V., Solis, B.G., de Diego, R.P., van Den Rym, A.M., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Gok, F., Yosunkaya, A., Thy, M., van Agtmael, M., Bomers, M., Chouchane, O., Geerlings, S., Goorhuis, B., Grobusch, M.P., Harris, V., Hermans, S.M., Hovius, J.W., Nellen, J., Peters, E., van der Poll, T., Prins, J.M., Reijnders, T., Schinkel, M., Sigaloff, K., Stijnis, C.S., van der Valk, M., van Vugt, M., Joost Wiersinga, W., Algera, A.G., van Baarle, F., Bos, Lieuwe D, Botta, M., de Bruin, S., Bulle, E., Elbers, P., Fleuren, L., Girbes, A., Hagens, L., Heunks, L., Horn, J., van Mourik, N., Paulus, F., Raasveld, J., Schultz, M.J., Smit, M., Stilma, Willemke, Thoral, P., Tsonas, A., de Vries, H., Bax, D., Cloherty, A., Beudel, M., Brouwer, M.C., Koning, R., Bogaard, H.J., de Brabander, J., de Bree, G., Bugiani, M., Geerts, B., Hollmann, M.W., Preckel, B., Veelo, D., Geijtenbeek, T., Hafkamp, F., Hamann, J., Hemke, R., de Jong, M.D., Schuurman, A., Teunissen, C., Vlaar, A.P.J., Wouters, D., Zwinderman, A.H., Aiuti, A., Muhsen, S.A., Anderson, M.S., Bogunovic, D., Itan, Y., Cirulli, E., Barrett, K.S., Washington, N., Bondarenko, A., Brodin, P., Bryceson, Y., Bustamante, C.D., Butte, M., Casari, G., Chakravorty, S., Christodoulou, J., Le Mestre, S., Condino-Neto, A., Cooper, M.A., David, A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Franco, J.L., Gregersen, P.K., Hagin, D., Halwani, R., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Karamitros, T., Kisand, K., Ku, C.L., Lau, Y.L., Ling, Y., Lucas, C.L., Marodi, L., Milner, J., Mironska, K., Morio, T., Novelli, A., O'Farrelly, C., Okada, S., Planas, A.M., Prando, C., Quintana-Murci, L., Renia, L., Renieri, A., Sankaran, V., Tangye, S., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., von Bernuth, H., Zawadzki, P., Jing, H., Tung, W., Meguro, K., Shaw, E., Shafer, S., Zheng, L., Zhang, Z., Kubo, S., Chauvin, S.D., Lenardo, M., Luthers, C.R., Bauman, B.M., Lack, J., Karlins, E., Hupalo, D.M., Rosenberger, J., Sukumar, G., Wilkerson, M.D., Zhang, X., and Universitat Autònoma Barcelona

Abstract

Afegiu 653 1_, Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

Published
2020

171. A Higher Fluid Balance in the Days After Septic Shock Reversal Is Associated With Increased Mortality: An Observational Cohort Study

Author

DVF Medisch, Infection & Immunity, van Mourik, Niels, Geerts, Bart F, Binnekade, Jan M, Veelo, Denise P, Bos, Lieuwe D J, Wiersinga, W Joost, van der Poll, Tom, Cremer, Olaf L, Schultz, Marcus J, Vlaar, Alexander P J, DVF Medisch, Infection & Immunity, van Mourik, Niels, Geerts, Bart F, Binnekade, Jan M, Veelo, Denise P, Bos, Lieuwe D J, Wiersinga, W Joost, van der Poll, Tom, Cremer, Olaf L, Schultz, Marcus J, and Vlaar, Alexander P J

Published
2020

172. Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study

Author

Botta, Michela, primary, Tsonas, Anissa M, additional, Pillay, Janesh, additional, Boers, Leonoor S, additional, Algera, Anna Geke, additional, Bos, Lieuwe D J, additional, Dongelmans, Dave A, additional, Hollmann, Marcus W, additional, Horn, Janneke, additional, Vlaar, Alexander P J, additional, Schultz, Marcus J, additional, Neto, Ary Serpa, additional, Paulus, Frederique, additional, van Akkeren, Jesse P., additional, Algoe, Cheetel K., additional, van Amstel, Rombout B., additional, Baur, Onno L., additional, van de Berg, Pablo, additional, van den Berg, Alida E., additional, Bergmans, Dennis C.J.J., additional, van den Bersselaar, Dido I., additional, Bertens, Freke A., additional, Bindels, Alexander J.G.H., additional, de Boer, Milou M., additional, den Boer, Sylvia, additional, Boers, Leonoor S., additional, Bogerd, Margriet, additional, Bos, Lieuwe D.J., additional, Botta, Michela, additional, Breel, Jennifer S., additional, de Bruin, Hendrik, additional, de Bruin, Sanne, additional, Bruna, Caro L., additional, Buiteman-Kruizinga, Laura A., additional, Cremer, Olaf L., additional, Determann, Rogier M., additional, Dieperink, Willem, additional, Dongelmans, Dave A., additional, Franke, Hildegard S., additional, Galek-Aldridge, Michal S., additional, de Graaff, Mart J., additional, Hagens, Laura A., additional, Haringman, Jasper J., additional, van der Heide, Sebastiaan T., additional, van der Heiden, Pim L.J., additional, Heijnen, Nanon F.L., additional, Hiel, Stephan J.P., additional, Hoeijmakers, Lotte L., additional, Hol, Liselotte, additional, Hollmann, Markus W., additional, Hoogendoorn, Marga E., additional, van der Horst, Robrecht, additional, Ie, Evy L.K., additional, Ivanov, Dimitri P., additional, Juffermans, Nicole, additional, Kho, Eline, additional, de Klerk, Eline S., additional, Koopman-van Gemert, Ankie W.M.M., additional, Koopmans, Matty, additional, Kucukcelebi, Songul, additional, Kuiper, Michael A., additional, de Lange, Dylan W., additional, van Mourik, Niels, additional, Nijbroek, Sunny G.L.H., additional, Onrust, Marisa, additional, Oostdijk, Evelien A.N., additional, Pennartz, Charlotte J., additional, Pisani, Luigi, additional, Purmer, Ilse M., additional, Rettig, Thijs C.D., additional, Roozeman, Jan-Paul, additional, Schuijt, Michiel T.U., additional, Schultz, Marcus J., additional, Serpa Neto, Ary, additional, Sleeswijk, Mengalvio E., additional, Smit, Marry R., additional, Spronk, Peter E., additional, Stilma, Willemke, additional, Strang, Aart C., additional, Tsonas, Anissa M., additional, Tuinman, Pieter R., additional, Valk, Christel M.A., additional, Veen-Schra, Felicia L., additional, Veldhuis, Lars I., additional, van Velzen, Patricia, additional, van der Ven, Ward H., additional, Vlaar, Alexander P.J., additional, van Vliet, Peter, additional, van der Voort, Peter H.J., additional, van Welie, Louis, additional, Wesselink, Henrico J.F.T., additional, van der Wier-Lubbers, Hermien H., additional, van Wijk, Bas, additional, Winters, Tineke, additional, Wong, Wing Yi, additional, and van Zanten, Arthur R.H., additional

Published
2021
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175. Development and validation of a point-of-care breath test for octane detection

Author

Hagens, Laura A., primary, Verschueren, Alwin R. M., additional, Lammers, Ariana, additional, Heijnen, Nanon F. L., additional, Smit, Marry R., additional, Nijsen, Tamara M. E., additional, Geven, Inge, additional, Schultz, Marcus J., additional, Bergmans, Dennis C. J. J., additional, Schnabel, Ronny M., additional, and Bos, Lieuwe D. J., additional

Published
2021
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177. Towards a biological definition of ARDS: are treatable traits the solution?

Author

Bos, Lieuwe D. J., Laffey, John G., Ware, Lorraine B., Heijnen, Nanon F. L., Sinha, Pratik, Patel, Brijesh, Jabaudon, Matthieu, Bastarache, Julie A., McAuley, Daniel F., Summers, Charlotte, Calfee, Carolyn S., and Shankar-Hari, Manu

Subjects
*ADULT respiratory distress syndrome, *PULMONARY edema
Abstract

The pathophysiology of acute respiratory distress syndrome (ARDS) includes the accumulation of protein-rich pulmonary edema in the air spaces and interstitial areas of the lung, variable degrees of epithelial injury, variable degrees of endothelial barrier disruption, transmigration of leukocytes, alongside impaired fluid and ion clearance. These pathophysiological features are different between patients contributing to substantial biological heterogeneity. In this context, it is perhaps unsurprising that a wide range of pharmacological interventions targeting these pathophysiological processes have failed to improve patient outcomes. In this manuscript, our goal is to provide a narrative summary of the potential methods to capture the underlying biological heterogeneity of ARDS and discuss how this information could inform future ARDS redefinitions. We discuss what biological tests are available to identify patients with any of the following predominant biological patterns: (1) epithelial and/or endothelial injury, (2) protein rich pulmonary edema and (3) systemic or within lung inflammatory responses. [ABSTRACT FROM AUTHOR]

Published
2022
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179. Phenotypes and personalized medicine in the acute respiratory distress syndrome

Author

Matthay, Michael A., primary, Arabi, Yaseen M., additional, Siegel, Emily R., additional, Ware, Lorraine B., additional, Bos, Lieuwe D. J., additional, Sinha, Pratik, additional, Beitler, Jeremy R., additional, Wick, Katherine D., additional, Curley, Martha A. Q., additional, Constantin, Jean-Michel, additional, Levitt, Joseph E., additional, and Calfee, Carolyn S., additional

Published
2020
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182. Impact of a Gap Junction Protein Alpha 4 Variant on Clinical Disease Phenotype in F508del Homozygous Patients With Cystic Fibrosis

Author

Horn, Tabea, primary, Ludwig, Michael, additional, Eickmeier, Olaf, additional, Neerinex, Anne H., additional, Maitland-van der Zee, Anke H., additional, Smaczny, Christina, additional, Wagner, Thomas O. F., additional, Schubert, Ralf, additional, Zielen, Stefan, additional, Majoor, Christof, additional, Bos, Lieuwe D., additional, and Schmitt-Grohé, Sabina, additional

Published
2020
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183. A Higher Fluid Balance in the Days After Septic Shock Reversal Is Associated With Increased Mortality: An Observational Cohort Study

Author

van Mourik, Niels, primary, Geerts, Bart F., additional, Binnekade, Jan M., additional, Veelo, Denise P., additional, Bos, Lieuwe D. J., additional, Wiersinga, W. Joost, additional, van der Poll, Tom, additional, Cremer, Olaf L., additional, Schultz, Marcus J., additional, and Vlaar, Alexander P. J., additional

Published
2020
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185. The importance of airway and lung microbiome in the critically ill

Author

Martin-Loeches, Ignacio, primary, Dickson, Robert, additional, Torres, Antoni, additional, Hanberger, Håkan, additional, Lipman, Jeffrey, additional, Antonelli, Massimo, additional, de Pascale, Gennaro, additional, Bozza, Fernando, additional, Vincent, Jean Louis, additional, Murthy, Srinivas, additional, Bauer, Michael, additional, Marshall, John, additional, Cilloniz, Catia, additional, and Bos, Lieuwe D., additional

Published
2020
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187. Lung Microbiota Predict Clinical Outcomes in Critically Ill Patients

Author

Dickson, Robert P., primary, Schultz, Marcus J., additional, van der Poll, Tom, additional, Schouten, Laura R., additional, Falkowski, Nicole R., additional, Luth, Jenna E., additional, Sjoding, Michael W., additional, Brown, Christopher A., additional, Chanderraj, Rishi, additional, Huffnagle, Gary B., additional, Bos, Lieuwe D. J., additional, de Beer, F. M., additional, Bos, L. D., additional, Claushuis, T. A., additional, Glas, G. J., additional, Horn, J., additional, Hoogendijk, A. J., additional, van Hooijdonk, R. T., additional, Huson, M. A., additional, de Jong, M. D., additional, Juffermans, N. P., additional, Lagrand, W. A., additional, van der Poll, T., additional, Scicluna, B., additional, Schouten, L. R., additional, Schultz, M. J., additional, van der Sluijs, K. F., additional, Straat, M., additional, van Vught, L. A., additional, Wieske, L., additional, Wiewel, M. A., additional, and Witteveen, E., additional

Published
2020
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188. Anti-C5a Antibody (IFX-1) Treatment of Severe COVID-19: An Exploratory Phase 2 Randomized Controlled Trial

Author

Vlaar, Alexander P. J., primary, de Bruin, Sanne, additional, Busch, Matthias, additional, Timmermans, Sjoerd, additional, van Zeggeren, Ingeborg E., additional, Koning, Rutger, additional, ter Horst, Liora, additional, Bulle, Esther B., additional, van Baarle, Frank E.H.P., additional, van de Poll, Marcel C.G., additional, Kemper, E. Marleen, additional, van der Horst, Iwan C.C., additional, Schultz, Marcus J., additional, Horn, Janneke, additional, Paulus, Frederique, additional, Bos, Lieuwe D., additional, Wiersinga, W. Joost, additional, Witzenrath, Martin, additional, Rueckinger, Simon, additional, Pilz, Korinna, additional, Brouwer, Matthijs C., additional, Guo, Ren-Feng, additional, Heunks, Leo, additional, van Paassen, Pieter, additional, Riedemann, Niels. C., additional, and van de Beek, Diederik, additional

Published
2020
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191. The INVENT COVID trial: a structured protocol for a randomized controlled trial investigating the efficacy and safety of intravenous imatinib mesylate (Impentri®) in subjects with acute respiratory distress syndrome induced by COVID-19.

Author

Atmowihardjo, Leila, Schippers, Job R., Bartelink, Imke H., Bet, Pierre M., van Rein, Nienke, Purdy, Keith, Cavalla, David, Comberiati, Valérie, McElroy, Andrew, Snape, Sue D., Bogaard, Harm Jan, Heunks, Leo, Juffermans, Nicole, Schultz, Marcus, Tuinman, Pieter R., Bos, Lieuwe D. J., and Aman, Jurjan

Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a disruptive increase in the number of intensive care unit (ICU) admissions with acute respiratory distress syndrome (ARDS). ARDS is a severe, life-threatening medical condition characterized by widespread inflammation and vascular leak in the lungs. Although there is no proven therapy to reduce pulmonary vascular leak in ARDS, recent studies demonstrated that the tyrosine kinase inhibitor imatinib reinforces the endothelial barrier and prevents vascular leak in inflammatory conditions, while leaving the immune response intact.Methods: This is a randomized, double-blind, parallel-group, placebo-controlled, multicenter clinical trial of intravenous (IV) imatinib mesylate in 90 mechanically ventilated subjects with COVID-19-induced ARDS. Subjects are 18 years or older, admitted to the ICU for mechanical ventilation, meeting the Berlin criteria for moderate-severe ARDS with a positive polymerase chain reaction test for SARS-CoV2. Participants will be randomized in a 1:1 ratio to either imatinib (as mesylate) 200 mg bis in die (b.i.d.) or placebo IV infusion for 7 days, or until ICU discharge or death. The primary study outcome is the change in Extravascular Lung Water Index (EVLWi) between day 1 and day 4. Secondary outcome parameters include changes in oxygenation and ventilation parameters, duration of invasive mechanical ventilation, number of ventilator-free days during the 28-day study period, length of ICU stay, and mortality during 28 days after randomization. Additional secondary parameters include safety, tolerability, and pharmacokinetics.Discussion: The current study aims to investigate the efficacy and safety of IV imatinib in mechanically ventilated subjects with COVID-19-related ARDS. We hypothesize that imatinib decreases pulmonary edema, as measured by extravascular lung water using a PiCCO catheter. The reduction in pulmonary edema may reverse hypoxemic respiratory failure and hasten recovery. As pulmonary edema is an important contributor to ARDS, we further hypothesize that imatinib reduces disease severity, reflected by a reduction in 28-day mortality, duration of mechanical ventilation, and ICU length of stay.Trial Status: Protocol version and date: V3.1, 16 April 2021. Recruitment started on 09 March 2021. Estimated recruitment period of approximately 40 weeks.Trial Registration: ClinicalTrials.gov NCT04794088 . Registered on 11 March 2021. [ABSTRACT FROM AUTHOR]

Published
2022
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193. Source-specific host response and outcomes in critically ill patients with sepsis: a prospective cohort study.

Author

Peters-Sengers, Hessel, Butler, Joe M., Uhel, Fabrice, Schultz, Marcus J., Bonten, Marc J., Cremer, Olaf L., Scicluna, Brendon P., van Vught, Lonneke A., van der Poll, Tom, the MARS consortium, de Beer, Friso M., Bos, Lieuwe D. J., Glas, Gerie J., van Hooijdonk, Roosmarijn T. M., Horn, Janneke, Schouten, Laura R. A., Straat, Marleen, Wieske, Luuk, Witteveen, Esther, and Reijnders, Tom D. Y.

Subjects
SEPSIS, CRITICALLY ill, SYSTEMIC inflammatory response syndrome, INTENSIVE care units, COHORT analysis, NEONATAL sepsis, CENTRAL nervous system
Abstract

Purpose: There is limited knowledge on how the source of infection impacts the host response to sepsis. We aimed to compare the host response in sepsis patients with a single, known source at admission (< 24 h) to the intensive care unit. Methods: From the molecular diagnosis and risk stratification of sepsis (MARS) prospective cohort, we measured 16 plasma host response biomarkers reflective of key host response pathways in 621 sepsis patients. In a subgroup (n = 335), blood leukocyte transcriptomes were compared between the sources. Differences in clinical patient profiles and survival were compared in the whole sepsis cohort (n = 2019). Results: The plasma biomarker cohort was categorized into sepsis originating from the respiratory tract (n = 334, 53.8%), abdomen (n = 159, 25.6%), urinary tract (n = 44, 7.1%), cardiovascular (n = 41, 6.6%), central nervous system (CNS) (n = 18, 2.9%), or skin (n = 25, 4%). This analysis revealed stronger inflammatory and cytokine responses, loss of vascular integrity and coagulation activation in abdominal sepsis relative to respiratory. Endothelial cell activation was prominent in urinary, cardiovascular and skin infections, while CNS infection was associated with the least host response aberrations. The leukocyte transcriptional response showed the largest overlap between abdominal and pulmonary infections (76% in common); notable differences between the sources were detected regarding hemostasis, cytokine signaling, innate and adaptive immune, and metabolic transcriptional pathways. After adjustment for confounders, the source of infection remained an independent contributor to 30-day mortality (unadjusted p = 0.001, adjusted p = 0.028). Conclusion: Sepsis heterogeneity is partly explained by source-specific host response dysregulations and should be considered when selecting patients for trials testing immune modulatory drugs. [ABSTRACT FROM AUTHOR]

Published
2022
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194. Estimated dead space fraction and the ventilatory ratio are associated with mortality in early ARDS

Author

Morales-Quinteros, Luis, Schultz, Marcus J., Bringué, Josep, Calfee, Carolyn S., Camprubí, Marta, Cremer, Olaf L., Horn, Janneke, van der Poll, Tom, Sinha, Pratik, Artigas, Antonio, Bos, Lieuwe D., de Beer, Friso M., Glas, Gerie J., Hoogendijk, Arie J., van Hooijdonk, Roosmarijn T., Huson, Mischa A., Scicluna, Brendon, Schouten, Laura R., Straat, Marleen, van Vught, Lonneke A., Wieske, Luuk, Wiewel, Maryse A., Witteveen, Esther, Bonten, Marc J., Frencken, Jos F., van de Groep, Kirsten, Klein Klouwenberg, Peter M., Koster-Brouwer, Maria E., Ong, David S., Varkila, Meri R., Verboom, Diana M., Intensive Care Medicine, ANS - Neuroinfection & -inflammation, Center of Experimental and Molecular Medicine, Infectious diseases, ACS - Heart failure & arrhythmias, Anesthesiology, Graduate School, ACS - Diabetes & metabolism, APH - Quality of Care, Epidemiology and Data Science, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Medical Microbiology and Infection Prevention, AII - Inflammatory diseases, ARD - Amsterdam Reproduction and Development, ACS - Pulmonary hypertension & thrombosis, and ACS - Microcirculation

Subjects
medicine.medical_specialty, ARDS, medicine.medical_treatment, Dead space, Respiratory Dead Space, Prognostication, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Journal Article, medicine, Acute respiratory distress syndrome (ARDS), Intensive care unit, Mortality, Respiratory dead space, Mechanical ventilation, Acute respiratory distress syndrome, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Ventilatory ratio, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Odds ratio, medicine.disease, 030228 respiratory system, Breathing, Cardiology, Prediction, business, Cohort study
Abstract

Background Indirect indices for measuring impaired ventilation, such as the estimated dead space fraction and the ventilatory ratio, have been shown to be independently associated with an increased risk of mortality. This study aimed to compare various methods for dead space estimation and the ventilatory ratio in patients with acute respiratory distress syndrome (ARDS) and to determine their independent values for predicting death at day 30. The present study is a post hoc analysis of a prospective observational cohort study of ICUs of two tertiary care hospitals in the Netherlands. Results Individual patient data from 940 ARDS patients were analyzed. Estimated dead space fraction and the ventilatory ratio at days 1 and 2 were significantly higher among non-survivors (p VD/VT phys] and the ventilatory ratio at day 2 showed independent association with mortality at 30 days (odds ratio 1.28 [95% CI 1.02–1.61], p p VD/VT HB] and Penn State [VD/VT PS] estimations were not associated with mortality. The predicted validity of the estimated dead space fraction and the ventilatory ratio improved the baseline model based on PEEP, PaO2/FiO2, driving pressure and compliance of the respiratory system at day 2 (AUROCC 0.72 vs. 0.69, p Conclusions Estimated methods for dead space calculation and the ventilatory ratio during the early course of ARDS are associated with mortality at day 30 and add statistically significant but limited improvement in the predictive accuracy to indices of oxygenation and respiratory system mechanics at the second day of mechanical ventilation.

Published
2019

195. Targeted treatment of acute respiratory distress syndrome with statins—a commentary on two phenotype stratified re-analysis of randomized controlled trials

Author

Heijnen, Nanon F. L., Bergmans, Dennis C. J. J., Schnabel, Ronny M., Bos, Lieuwe D. J., Hagens, Laura A., Smit, Marry R., Schultz, Marcus J., Nijsen, Tamara, Verschueren, Alwin, Geven, Inge, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Arts Assistenten IC (9), Intensive Care, MUMC+: MA Medische Staf IC (9), and Surgery

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, ARDS, medicine.medical_specialty, SEPSIS, business.industry, MEDLINE, Acute respiratory distress, medicine.disease, Phenotype, Article, law.invention, SUBPHENOTYPES, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Pharmacological interventions, Editorial, Randomized controlled trial, law, Medicine, 030212 general & internal medicine, business, Intensive care medicine
Abstract

BACKGROUND: Precision medicine approaches targeting patients based on disease subtype have transformed approaches to cancer, asthma, and other heterogeneous syndromes. Two distinct subphenotypes of ARDS have been identified in three US-based clinical trials and respond differently to positive end-expiratory pressure and fluid management. It remains unknown if these subphenotypes exist in different populations and respond differently to pharmacotherapies. METHODS: We conducted a secondary analysis using data from 539 patients enrolled in a UK multicenter, placebo-controlled randomized trial of simvastatin for ARDS (HARP-2). Latent class analysis was applied to baseline data without consideration of outcomes to identify subphenotypes. Clinical outcomes were compared across subphenotypes and treatment groups. FINDINGS: A two class (two-subphenotype) model was an improvement over a one class model (p

Published
2019

196. Soluble urokinase plasminogen activator receptor for the prediction of ventilator-associated pneumonia

Author

van Oort, Pouline M., Bos, Lieuwe D.., Póvoa, Pedro, Ramirez, Paula, Torres, Antoni, Artigas Raventós, Antoni, Schultz, Marcus J., Martin-Loeches, Ignacio, Universitat Autònoma de Barcelona, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Graduate School, AII - Inflammatory diseases, ACS - Heart failure & arrhythmias, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, and ACS - Microcirculation

Subjects
BIOMARKER, Pulmonary and Respiratory Medicine, medicine.medical_specialty, lcsh:Medicine, DIAGNOSIS, Gastroenterology, Procalcitonin, law.invention, SUPAR, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, SCORE, Medicine, 030212 general & internal medicine, PROCALCITONIN, Prospective cohort study, Receptor, SEPSIS, Receiver operating characteristic, business.industry, MORTALITY, lcsh:R, Ventilator-associated pneumonia, Original Articles, medicine.disease, Intensive care unit, Pneumonia, SEVERITY, 030228 respiratory system, SuPAR, BIOLOGICAL MARKER, Respiratory Infections, business, CRITICALLY-ILL PATIENTS
Abstract

Introduction Diagnosing ventilator-associated pneumonia (VAP) remains challenging. Soluble urokinase plasminogen activator receptor (suPAR) has prognostic value in critically ill patients with systemic infection. We hypothesised that plasma suPAR levels accurately predict development of VAP. Methods This observational, multicentre, prospective cohort study compared patients at risk for VAP with a control group. Plasma and tracheal aspirate samples were collected. Plasma suPAR levels were measured on the day of diagnosis and 3 days before diagnosis. Results The study included 24 VAP patients and 19 control patients. The suPAR concentration measured 3 days before diagnosis was significantly increased in VAP patients versus matched samples of control patients (area under the receiver operating characteristic curve (AUC) 0.68, 95% CI 0.52–1.00; p=0.04). Similar results were found on the day of diagnosis (AUC 0.77, 95% CI 0.6–0.93; p=0.01). Plasma suPAR was significantly higher in deceased patients (AUC 0.79, 95% CI 0.57–1.00; p, suPAR can be used to diagnose VAP with a fair diagnostic accuracy and has a moderate prognostic accuracy to be used in critically ill ICU patients http://ow.ly/ubmf30nIgZO

Published
2019

197. Predicting the clinical trajectory in critically ill patients with sepsis: A cohort study

Author

Klein Klouwenberg, Peter M. C., Spitoni, Cristian, van der Poll, Tom, Bonten, Marc J., Cremer, Olaf L., Frencken, Jos F., van de Groep, Kirsten, Koster-Brouwer, Marlies E., Ong, David S. Y., Verboom, Diana, de Beer, Friso M., Bos, Lieuwe D. J., Glas, Gerie J., van Hooijdonk, Roosmarijn T. M., Schouten, Laura R. A., Straat, Marleen, Witteveen, Esther, Wieske, Luuk, Hoogendijk, Arie J., Huson, Mischa A., van Vught, Lonneke A., Schultz, Marcus, Center of Experimental and Molecular Medicine, Infectious diseases, AII - Infectious diseases, Anesthesiology, Graduate School, ACS - Heart failure & arrhythmias, ANS - Neuroinfection & -inflammation, Intensive Care Medicine, ACS - Diabetes & metabolism, APH - Quality of Care, Neurology, ANS - Amsterdam Neuroscience, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, ARD - Amsterdam Reproduction and Development, ACS - Pulmonary hypertension & thrombosis, and ACS - Microcirculation

Subjects
medicine.medical_specialty, Epidemiology, Discharged alive, Disease, Research Support, Critical Care and Intensive Care Medicine, law.invention, Sepsis, 03 medical and health sciences, 0302 clinical medicine, law, medicine, Journal Article, Organ failure, Intensive care unit, 030212 general & internal medicine, Non-U.S. Gov't, Outcome, Critically ill, business.industry, Research Support, Non-U.S. Gov't, Organ dysfunction, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, Markov model, Emergency medicine, medicine.symptom, business, Cohort study
Abstract

Background To develop a mathematical model to estimate daily evolution of disease severity using routinely available parameters in patients admitted to the intensive care unit (ICU). Methods Over a 3-year period, we prospectively enrolled consecutive adults with sepsis and categorized patients as (1) being at risk for developing (more severe) organ dysfunction, (2) having (potentially still reversible) limited organ failure, or (3) having multiple-organ failure. Daily probabilities for transitions between these disease states, and to death or discharge, during the first 2 weeks in ICU were calculated using a multi-state model that was updated every 2 days using both baseline and time-varying information. The model was validated in independent patients. Results We studied 1371 sepsis admissions in 1251 patients. Upon presentation, 53 (4%) were classed at risk, 1151 (84%) had limited organ failure, and 167 (12%) had multiple-organ failure. Among patients with limited organ failure, 197 (17%) evolved to multiple-organ failure or died and 809 (70%) improved or were discharged alive within 14 days. Among patients with multiple-organ failure, 67 (40%) died and 91 (54%) improved or were discharged. Treatment response could be predicted with reasonable accuracy (c-statistic ranging from 0.55 to 0.81 for individual disease states, and 0.67 overall). Model performance in the validation cohort was similar. Conclusions This prediction model that estimates daily evolution of disease severity during sepsis may eventually support clinicians in making better informed treatment decisions and could be used to evaluate prognostic biomarkers or perform in silico modeling of novel sepsis therapies during trial design. Clinical trial registration ClinicalTrials.gov NCT01905033

Published
2019

200. Epidemiology and outcomes of source control procedures in critically ill patients with intra-abdominal infection

Author

Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Epi Infectieziekten, MMB, Medische Staf Intensive Care, van de Groep, Kirsten, Verhoeff, Tessa L, Verboom, Diana M, Bos, Lieuwe D, Schultz, Marcus J, Bonten, Marc J M, Cremer, Olaf L, Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Epi Infectieziekten, MMB, Medische Staf Intensive Care, van de Groep, Kirsten, Verhoeff, Tessa L, Verboom, Diana M, Bos, Lieuwe D, Schultz, Marcus J, Bonten, Marc J M, and Cremer, Olaf L

Published
2019

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