Citations 2
Immune checkpoint dysregulation in COVID-19 pathogenesis and disease severity.
Villalba, Julian A. , Shih, Angela , Alba, George A. , Loyola-Rodríguez, Georgina, Alcántara, Ismael Ramírez, Ferreira, Luíz Carlos de Lima , Stigliano, Egidio, Hirschbühl, Klaus , Argueta, Allan , Ackermann, Maximillian , Werlein, Christopher , Uribe‐Uribe, Norma , Vázquez-Benítez, Greissy, Tzankov, Alexandar , Stalder, Anna K. , Francesqui, Joel , Osborn, Michael , Hanley, Brian , Johnston, Robert, Lacy, J. Matthew , Marshall, Desiree A. , Schwensen, Hanna Ferløv , Okudela, Koji , Flikweert, Antine, Iles, Linda , d’Amati, Giulia , Träger, Lene Hoffmann , Çınar, Hüseyin, Aguiar, Diego , Dolhnokoff, Marisa, Chilosi, Marco , Salmon, I, Colville‐Ebeling, Bonnie, Poissy, Julien , Haahr, Martha Kirstine , Reyes, Fabiola, Parry, Blair A. , Garlin, Michelle, Hilburn, Caroline F., ELLIOTT, G. A., Rosas, Iván O. , Sade-Feldman, Moshe , Hacohen, Nir , Baden, Lindsey R. , Li, Jonathan Z. , Schaller, Tina , Gigli, L, Macciò, Umberto , Yick, David C.Y., Bruni, Barbara, Pernazza, Angelina , Mauad, Thaís , Dubini, Alessandra, Hartmann, Arndt, Remmelink, Myriam , Aviles, Alexis J., Barth, Jamie L., Boyraz, Bariş , Araujo-Medina, Milagros, Mendez-Pena, Javier E., Chebib, Ivan , Hung, Yin P. , Rosales, Ivy A. , Smith, Rex-Neal, Hung, Yin P , Tzankov, Alexandar , Li, Yijia , Poli, Sergio , Kunitoki, Keiko , Mehta, Arnav , Santana, Monique Freire , Lacerda, Marcus , Dell’Aquila, Marco , Arena, Vincenzo , Calabrese, Fiorella , Pezzuto, Federica , Märkl, Bruno , Lozano, Maria, Jonigk, Danny David , Pomara, Cristoforo , Salerno, Monica , Salas, Clara , Martínez, Daniel, Parra-Medina, Rafael Santiago , Bradley, Benjamin T. , Chen, Sonja , Varga, Zsuzsanna , Steinestel, Konrad , Harper, Holly , Aiolfi, Alberto , Scendoni, Roberto , Fabro, Alexandre Todorovic , Doglioni, Claudio , Rossi, Giulio , Poletti, Venerino , Herrmann, Martin , Pugh, Matthew , Yan, Lei , Gentili, Matteo , Garlin, Michelle A., Lo, Ying‐Chun , Elliott, Grant, Martínez, Leonardo , Stone, James R. , Colvin, Robert B. , Goldberg, Marcia B. , Filbin, Michael R. , Mino-Kenudson, Mari A. , Kröncke, Thomas J. , Gigli, Laura Álvarez, Sessa, Francesco , Caltabiano, Rosario , Menter, Thomas , Sellarés, Jacobo , Storgaard, Merete , Hamilton‐Dutoit, Stephen , Dannheim, Katelyn , Witte, Hanno Maximilian , Bona, Davide , Leth, Peter Mygind , Banner, Jytte , Batah, Sabrina Setembre , Silva, Luiz Fernando Ferraz da , Duarte‐Neto, Amaro Nunes , Saldiva, Paulo Hilário Nascimento , Munoz, Luis Enrique , Jensen, T. , Brøchner, Christian Beltoft , Gibier, Jean‐Baptiste , Gilbert, Andrea , Madrigal, Emilio , Ly, Amy , Hariri, Lida P. , Caldwell, Nicholas J
No container title available | October 2, 2024 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Accumulating evidence suggests dysregulated immune checkpoint (IC) signaling can exacerbate COVID-19 severity, but the role of these molecules in the pathogenesis of fatal COVID-19-related diffuse alveolar damage (DAD) remains elusive. Understanding how IC proteins influence acute lung injury due to COVID-19 can provide insights into potential therapeutic strategies to modulate immune responses and improve patient outcomes. Here, in a single-center autopsy cohort, we determined the cellular localization of ICs in lung tissue from cases of fatal COVID-19, DAD-comparators, and non-fibrotic controls by using immunohistochemistry, and investigated their association with clinical outcomes. We expanded our findings by performing analyses of publicly available single-cell RNA sequencing datasets from patients with fatal COVID-19 and non-fibrotic controls. We demonstrated the presence of protein-protein interaction networks of ICs in the lung cellular niche by performing transcriptomic profiling of lung tissue-derived RNA counts from patients with fatal COVID-19. Further, we leveraged data from the largest international, multi-center COVID-19 autopsy cohort and validated that, among patients with fatal COVID-19, those with higher PD-L1/CD274 expression in lung endothelial cells had more rapid clinical deterioration. Lastly, in a cohort of individuals with early COVID-19, IC plasma protein levels were elevated in those with persistent SARS-CoV-2 RNAemia and adverse clinical outcomes. Collectively, our data provide unique pathological insights into the role of IC dysregulation and differential disease severity in COVID-19.
Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II
Tumlin, James A., Murugan, Raghavan , Deane, Adam M. , Ostermann, Marlies , Busse, Laurence W. , Ham, Kealy R., Szerlip, Harold M. , Prowle, John R. , Bihorac, Azra , Finkel, Kevin W., Zarbock, Alexander , Lynch, S., Jensen, Jeff, Kroll, Stew, Chawla, Lakhmir S. , Tidmarsh, George F., Karvellas, Constantine , Frendl, György , English, Shane , Grimaldi, David , Hite, R. Duncan , Camporota, Luigi , Young, Paul J. , Bihari, Shailesh , Bersten, Andrew D. , Karvellas, Constantine , Kashani, Kianoush , Forni, Lui G. , Lynch, Shannan J., Bellomo, Rinaldo , Bihorac, Azra , Ostermann, Marlies , Deane, Adam M , Young, Paul J , Poissy, Julien
Critical Care Medicine | March 6, 2018 | Volume: 46 | Issue: 6 | Pages: 949-957
Objective: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. Design: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. Setting: ICUs. Patients: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo ( n = 45 and n = 60, respectively). Interventions: IV angiotensin II or placebo. Measurements and Main Results: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%–67%) and 30% (95% CI, 19%–41%) in patients treated with angiotensin II and placebo ( p = 0.012), respectively. By day 7, 38% (95% CI, 25%–54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%–27%) placebo ( p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%–68%) and 22% (95% CI, 12%–34%) of patients treated with angiotensin II and placebo ( p = 0.001), respectively. Conclusions: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.