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1. A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling

Author

Jason A. Hackney, Haridha Shivram, Jason Vander Heiden, Chris Overall, Luz Orozco, Xia Gao, Eugene Kim, Nathan West, Aditi Qamra, Diana Chang, Arindam Chakrabarti, David F. Choy, Alexis J. Combes, Tristan Courau, Gabriela K. Fragiadakis, Arjun Arkal Rao, Arja Ray, Jessica Tsui, Kenneth Hu, Nicholas F. Kuhn, Matthew F. Krummel, David J. Erle, Kirsten Kangelaris, Aartik Sarma, Zoe Lyon, Carolyn S. Calfee, Prescott G. Woodruff, Rajani Ghale, Eran Mick, Ashley Byrne, Beth Shoshana Zha, Charles Langelier, Carolyn M. Hendrickson, Monique G.P. van der Wijst, George C. Hartoularos, Tianna Grant, Raymund Bueno, David S. Lee, John R. Greenland, Yang Sun, Richard Perez, Anton Ogorodnikov, Alyssa Ward, Chun Jimmie Ye, Thiru Ramalingam, Jacqueline M. McBride, Fang Cai, Anastasia Teterina, Min Bao, Larry Tsai, Ivan O. Rosas, Aviv Regev, Sharookh B. Kapadia, Rebecca N. Bauer, Carrie M. Rosenberger, Yumiko Abe-Jones, Michael Adkisson, K. Mark Ansel, Saurabh Asthana, Alexander Beagle, Sharvari Bhide, Cathy Cai, Saharai Caldera, Maria Calvo, Sidney A. Carrillo, Suzanna Chak, Stephanie Christenson, Zachary Collins, Spyros Darmanis, Angela Detweiler, Catherine DeVoe, Walter Eckalbar, Jeremy Giberson, Ana Gonzalez, Gracie Gordon, Paula Hayakawa Serpa, Alejandra Jauregui, Chayse Jones, Serena Ke, Divya Kushnoor, Tasha Lea, Deanna Lee, Aleksandra Leligdowicz, Yale Liu, Salman Mahboob, Lenka Maliskova, Michael Matthay, Elizabeth McCarthy, Priscila Muñoz-Sandoval, Norma Neff, Viet Nguyen, Nishita Nigam, Randy Parada, Maira Phelps, Logan Pierce, Priya Prasad, Sadeed Rashid, Gabriella Reeder, Nicklaus Rodriguez, Bushra Samad, Andrew Schroeder, Cole Shaw, Alan Shen, Austin Sigman, Pratik Sinha, Matthew Spitzer, Sara Sunshine, Kevin Tang, Luz Torres Altamirano, Alexandra Tsitsiklis, Erden Tumurbaatar, Vaibhav Upadhyay, Alexander Whatley, Andrew Willmore, Michael Wilson, Juliane Winkler, Kristine Wong, Kimberly Yee, Michelle Yu, Mingyue Zhou, and Wandi S. Zhu

Subjects
Clinical genetics, Molecular medicine, Immune response, Science
Abstract

Summary: Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

Published
2023
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2. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study

Author

Al Ozonoff, Joanna Schaenman, Naresh Doni Jayavelu, Carly E. Milliren, Carolyn S. Calfee, Charles B. Cairns, Monica Kraft, Lindsey R. Baden, Albert C. Shaw, Florian Krammer, Harm van Bakel, Denise A. Esserman, Shanshan Liu, Ana Fernandez Sesma, Viviana Simon, David A. Hafler, Ruth R. Montgomery, Steven H. Kleinstein, Ofer Levy, Christian Bime, Elias K. Haddad, David J. Erle, Bali Pulendran, Kari C. Nadeau, Mark M. Davis, Catherine L. Hough, William B. Messer, Nelson I. Agudelo Higuita, Jordan P. Metcalf, Mark A. Atkinson, Scott C. Brakenridge, David Corry, Farrah Kheradmand, Lauren I.R. Ehrlich, Esther Melamed, Grace A. McComsey, Rafick Sekaly, Joann Diray-Arce, Bjoern Peters, Alison D. Augustine, Elaine F. Reed, Matthew C. Altman, Patrice M. Becker, Nadine Rouphael, Chris Bime, Mark M Davis, Kerry McEnaney, Brenda Barton, Claudia Lentucci, Mehmet Saluvan, Ana C. Chang, Annmarie Hoch, Marisa Albert, Tanzia Shaheen, Alvin T. Kho, Sanya Thomas, Jing Chen, Maimouna D. Murphy, Mitchell Cooney, Scott Presnell, Gabriela K. Fragiadakis, Ravi Patel, Leying Guan, Jeremy Gygi, Shrikant Pawar, Anderson Brito, Zain Khalil, Cole Maguire, Slim Fourati, James A. Overton, Randi Vita, Kerstin Westendorf, Ramin Salehi-Rad, Aleksandra Leligdowicz, Michael A. Matthay, Jonathan P. Singer, Kirsten N. Kangelaris, Carolyn M. Hendrickson, Matthew F. Krummel, Charles R. Langelier, Prescott G. Woodruff, Debra L. Powell, James N. Kim, Brent Simmons, I. Michael Goonewardene, Cecilia M. Smith, Mark Martens, Jarrod Mosier, Hiroki Kimura, Amy C. Sherman, Stephen R. Walsh, Nicolas C. Issa, Charles Dela Cruz, Shelli Farhadian, Akiko Iwasaki, Albert I. Ko, Sharon Chinthrajah, Neera Ahuja, Angela J. Rogers, Maja Artandi, Sarah A.R. Siegel, Zhengchun Lu, Douglas A. Drevets, Brent R. Brown, Matthew L. Anderson, Faheem W. Guirgis, Rama V. Thyagarajan, Justin F. Rousseau, Dennis Wylie, Johanna Busch, Saurin Gandhi, Todd A. Triplett, George Yendewa, Olivia Giddings, Evan J. Anderson, Aneesh K. Mehta, Jonathan E. Sevransky, Bernard Khor, Adeeb Rahman, Daniel Stadlbauer, Jayeeta Dutta, Hui Xie, Seunghee Kim-Schulze, Ana Silvia Gonzalez-Reiche, Adriana van de Guchte, Keith Farrugia, Zenab Khan, Holden T. Maecker, David Elashoff, Jenny Brook, Estefania Ramires-Sanchez, Megan Llamas, Adreanne Rivera, Claudia Perdomo, Dawn C. Ward, Clara E. Magyar, Jennifer A. Fulcher, Yumiko Abe-Jones, Saurabh Asthana, Alexander Beagle, Sharvari Bhide, Sidney A. Carrillo, Suzanna Chak, Rajani Ghale, Ana Gonzalez, Alejandra Jauregui, Norman Jones, Tasha Lea, Deanna Lee, Raphael Lota, Jeff Milush, Viet Nguyen, Logan Pierce, Priya A. Prasad, Arjun Rao, Bushra Samad, Cole Shaw, Austin Sigman, Pratik Sinha, Alyssa Ward, Andrew Willmore, Jenny Zhan, Sadeed Rashid, Nicklaus Rodriguez, Kevin Tang, Luz Torres Altamirano, Legna Betancourt, Cindy Curiel, Nicole Sutter, Maria Tercero Paz, Gayelan Tietje-Ulrich, Carolyn Leroux, Jennifer Connors, Mariana Bernui, Michel A. Kutzler, Carolyn Edwards, Edward Lee, Edward Lin, Brett Croen, Nicholas C. Semenza, Brandon Rogowski, Nataliya Melnyk, Kyra Woloszczuk, Gina Cusimano, Mathew R. Bell, Sara Furukawa, Renee McLin, Pamela Marrero, Julie Sheidy, George P. Tegos, Crystal Nagle, Nathan Mege, Kristen Ulring, Vicki Seyfert-Margolis, Michelle Conway, Dave Francisco, Allyson Molzahn, Heidi Erickson, Connie Cathleen Wilson, Ron Schunk, Bianca Sierra, Trina Hughes, Kinga Smolen, Michael Desjardins, Simon van Haren, Xhoi Mitre, Jessica Cauley, Xiaofang Li, Alexandra Tong, Bethany Evans, Christina Montesano, Jose Humberto Licona, Jonathan Krauss, Jun Bai Park Chang, Natalie Izaguirre, Omkar Chaudhary, Andreas Coppi, John Fournier, Subhasis Mohanty, M. Catherine Muenker, Allison Nelson, Khadir Raddassi, Michael Rainone, William E. Ruff, Syim Salahuddin, Wade L. Schulz, Pavithra Vijayakumar, Haowei Wang, Elsio Wunder Jr., H. Patrick Young, Yujiao Zhao, Miti Saksena, Deena Altman, Erna Kojic, Komal Srivastava, Lily Q. Eaker, Maria C. Bermúdez-González, Katherine F. Beach, Levy A. Sominsky, Arman R. Azad, Juan Manuel Carreño, Gagandeep Singh, Ariel Raskin, Johnstone Tcheou, Dominika Bielak, Hisaaki Kawabata, Lubbertus CF Mulder, Giulio Kleiner, Alexandra S. Lee, Evan Do Do, Andrea Fernandes, Monali Manohar, Thomas Hagan, Catherine A. Blish, Hena Naz Din, Jonasel Roque, Samuel Yang, Amanda Brunton, Peter E. Sullivan, Matthew Strnad, Zoe L. Lyski, Felicity J. Coulter, J. Leland Booth, Lauren A. Sinko, Lyle L. Moldawer, Brittany Borresen, Brittney Roth-Manning, Li-Zhen Song, Ebony Nelson, Megan Lewis-Smith, Jacob Smith, Pablo Guaman Tipan, Nadia Siles, Sam Bazzi, Janelle Geltman, Kerin Hurley, Gio Gabriele, Scott Sieg, Tatyana Vaysman, Laurel Bristow, Laila Hussaini, Kieffer Hellmeister, Hady Samaha, Andrew Cheng, Christine Spainhour, Erin M. Scherer, Brandi Johnson, Amer Bechnak, Caroline R. Ciric, Lauren Hewitt, Erin Carter, Nina Mcnair, Bernadine Panganiban, Christopher Huerta, Jacob Usher, and Susan Pereira Ribeiro

Subjects
COVID-19, SARS-CoV-2, Viral load, Antibody, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. Methods: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. Findings: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28–3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13–2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63– 4.80) or troponin (OR 1.89; 95% 1.03–3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61–2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96–5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17–2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. Interpretation: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. Funding: NIH.

Published
2022
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3. Discovering Dominant Tumor Immune Archetypes in A Pan-Cancer Census

Author

Alexis J. Combes, Bushra Samad, Jessica Tsui, Nayvin W. Chew, Peter Yan, Gabriella C. Reeder, Divyashree Kushnoor, Alan Shen, Brittany Davidson, Andrea J. Barczak, Michael Adkisson, Austin Edwards, Mohammad Naser, Kevin C. Barry, Tristan Courau, Taymour Hammoudi, Rafael J. Argüello, Arjun Arkal Rao, Adam B. Olshen, Cathy Cai, Jenny Zhan, Katelyn C. Davis, Robin K. Kelley, Jocelyn S. Chapman, Chloe E. Atreya, Amar Patel, Adil I. Daud, Patrick Ha, Aaron A. Diaz, Johannes R. Kratz, Eric A. Collisson, Gabriela K. Fragiadakis, David J. Erle, Alexandre Boissonnas, Saurabh Asthana, Vincent Chan, Matthew F. Krummel, Matthew Spitzer, Lawrence Fong, Amanda Nelson, Raj Kumar, Justin Lee, Arun Burra, Joy Hsu, Caroline Hackett, Karen Tolentino, Jasmine Sjarif, Peter Johnson, Evans Shao, Darrell Abrau, Leonard Lupin, Cole Shaw, Zachary Collins, Tasha Lea, Carlos Corvera, Eric Nakakura, Julia Carnevale, Michael Alvarado, Kimberley Loo, Lawrence Chen, Melissa Chow, Jennifer Grandis, Will Ryan, Ivan El-Sayed, David Jablons, Gavitt Woodard, Maxwell W. Meng, Sima P. Porten, Hideho Okada, Margaret Tempero, Andrew Ko, Kim Kirkwood, Scott Vandenberg, Denise Guevarra, Erica Oropeza, Chris Cyr, Pat Glenn, Jennifer Bolen, Amanda Morton, Walter Eckalbar, University of California [San Francisco] (UC San Francisco), University of California (UC), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Department of Epidemiology and Biostatistics, University of California, San Francisco, and University of California (UC)-University of California (UC)

Subjects
Universities, Computational Biology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Censuses, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Flow Cytometry, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, General Biochemistry, Genetics and Molecular Biology, Article, Cohort Studies, Gene Expression Regulation, Neoplastic, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Neoplasms, Biomarkers, Tumor, Tumor Microenvironment, Cluster Analysis, Humans, San Francisco, RNA-Seq, Transcriptome, ComputingMilieux_MISCELLANEOUS
Abstract

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here "archetypes"-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy.

Published
2021
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4. Mass cytometry reveals a conserved immune trajectory of recovery in hospitalized COVID-19 patients

Author

Cassandra E. Burnett, Trine Line Hauge Okholm, Iliana Tenvooren, Diana M. Marquez, Stanley Tamaki, Priscila Munoz Sandoval, Andrew Willmore, Carolyn M. Hendrickson, Kirsten N. Kangelaris, Charles R. Langelier, Matthew F. Krummel, Prescott G. Woodruff, Carolyn S. Calfee, David J. Erle, K. Mark Ansel, Matthew H. Spitzer, Ravi Patel, Yumiko Abe-Jones, Saurabh Asthana, Alexander Beagle, Sharvari Bhide, Cathy Cai, Maria Calvo, Sidney A. Carrillo, Suzanna Chak, Zachary Collins, Spyros Darmanis, Gabriela K. Fragiadakis, Rajani Ghale, Jeremy Giberson, Pat Glenn, Ana Gonzalez, Kamir Hiam-Galvez, Alejandra Jauregui, Serena Ke, Tasha Lea, Deanna Lee, Raphael Lota, Leonard Lupin-Jimenez, Viet Nguyen, Nishita Nigam, Logan Pierce, Priya Prasad, Arjun Rao, Sadeed Rashid, Nicklaus Rodriguez, Bushra Samad, Cole Shaw, Austin Sigman, Pratik Sinha, Kevin Tang, Luz Torres Altamirano, Erden Tumurbaatar, Vaibhav Upadhyay, Alyssa Ward, Kristine Wong, Chun Jimmie Ye, Kimberly Yee, and Mingyue Zhou

Subjects
Infectious Diseases, SARS-CoV-2, Immunology, Disease Progression, COVID-19, Humans, Immunology and Allergy, Pneumonia
Abstract

While studies have elucidated many pathophysiological elements of COVID-19, little is known about immunological changes during COVID-19 resolution. We analyzed immune cells and phosphorylated signaling states at single-cell resolution from longitudinal blood samples of patients hospitalized with COVID-19, pneumonia and/or sepsis, and healthy individuals by mass cytometry. COVID-19 patients showed distinct immune compositions and an early, coordinated, and elevated immune cell signaling profile associated with early hospital discharge. Intra-patient longitudinal analysis revealed changes in myeloid and T cell frequencies and a reduction in immune cell signaling across cell types that accompanied disease resolution and discharge. These changes, together with increases in regulatory T cells and reduced signaling in basophils, also accompanied recovery from respiratory failure and were associated with better outcomes at time of admission. Therefore, although patients have heterogeneous immunological baselines and highly variable disease courses, a core immunological trajectory exists that defines recovery from severe SARS-CoV-2 infection.

Published
2022
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5. An Asynchronous, Personalized Learning Platform―Guided Learning Pathways (GLP)

Author

Soheil Sibdari, Cole Shaw, Richard K. Larson, Massachusetts Institute of Technology. Department of Civil and Environmental Engineering, Massachusetts Institute of Technology. Institute for Data, Systems, and Society, Massachusetts Institute of Technology. Office of Digital Learning, Shaw, Cole J, and Larson, Richard Charles

Subjects
Blended learning, Asynchronous learning, Multimedia, Computer science, Active learning (machine learning), Educational technology, Collaborative learning, General Medicine, Personalized learning, computer.software_genre, Robot learning, computer, Synchronous learning
Abstract

The authors propose that personalized learning can be brought to traditional and non-traditional learners through asynchronous learning platform that recommends to individual learners the learning materials best suited for him or her. Such a platform would allow learners to advance towards individual learning goals at their own pace, with learning materials catered to each learner’s interests and motivations. This paper describes the authors’ vision and design for a modular, personalized learning platform called Guided Learning Pathways (GLP), and its characteristics and features. We provide detailed descriptions of and propose frameworks for critical modules like the Content Map, Learning Nuggets, and Recommendation Algorithms. A threaded user scenario is provided for each module to help the reader visualize different aspects of GLP. We discuss work done at MIT to support such a platform.

Published
2014

6. Considerations for Implementing an IP-Based, Video Assessment and Surveillance System

Author

Jack C. Connell, Robert M. Riley, and Cole Shaw

Subjects
Flexibility (engineering), Set (abstract data type), Multimedia, Order (exchange), Computer science, Video tracking, Control (management), Bandwidth (signal processing), Video streaming, computer.software_genre, computer, Physical security
Abstract

The flexibility gained in moving from an analog video system to a digital video system is immeasurable, and the onslaught of new IP-addressable cameras and recording solutions has given security system designers an endless set of options for migrating to a digital video system. Video can be brought up and viewed by any authorized user on the security network, and adding new devices is as easy as plugging them into the security network. However, the change to an IP-based framework also leads to a completely different set of considerations - what kind of bandwidth does the network infrastructure need in order to handle all the video streaming across it? How do you integrate an IP video system into the rest of a physical security system (including entry control, command, control, and communication)? This paper will address these considerations, among others, to help guide security system designers in determining the type of video system best suited for their applications

Published
2006
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