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38 results on '"Montgomery, Ruth R."'

1. SenNet recommendations for detecting senescent cells in different tissues

Author

Suryadevara, Vidyani, Hudgins, Adam D., Rajesh, Adarsh, Pappalardo, Alberto, Karpova, Alla, Dey, Amit K., Hertzel, Ann, Agudelo, Anthony, Rocha, Azucena, Soygur, Bikem, Schilling, Birgit, Carver, Chase M., Aguayo-Mazzucato, Cristina, Baker, Darren J., Bernlohr, David A., Jurk, Diana, Mangarova, Dilyana B., Quardokus, Ellen M., Enninga, Elizabeth Ann L., Schmidt, Elizabeth L., Chen, Feng, Duncan, Francesca E., Cambuli, Francesco, Kaur, Gagandeep, Kuchel, George A., Lee, Gung, Daldrup-Link, Heike E., Martini, Helene, Phatnani, Hemali, Al-Naggar, Iman M., Rahman, Irfan, Nie, Jia, Passos, João F., Silverstein, Jonathan C., Campisi, Judith, Wang, Julia, Iwasaki, Kanako, Barbosa, Karina, Metis, Kay, Nernekli, Kerem, Niedernhofer, Laura J., Ding, Li, Wang, Lichao, Adams, Lisa C., Ruiyang, Liu, Doolittle, Madison L., Teneche, Marcos G., Schafer, Marissa J., Xu, Ming, Hajipour, Mohammadjavad, Boroumand, Mozhgan, Basisty, Nathan, Sloan, Nicholas, Slavov, Nikolai, Kuksenko, Olena, Robson, Paul, Gomez, Paul T., Vasilikos, Periklis, Adams, Peter D., Carapeto, Priscila, Zhu, Quan, Ramasamy, Ramalakshmi, Perez-Lorenzo, Rolando, Fan, Rong, Dong, Runze, Montgomery, Ruth R., Shaikh, Sadiya, Vickovic, Sanja, Yin, Shanshan, Kang, Shoukai, Suvakov, Sonja, Khosla, Sundeep, Garovic, Vesna D., Menon, Vilas, Xu, Yanxin, Song, Yizhe, Suh, Yousin, Dou, Zhixun, and Neretti, Nicola

Published
2024
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2. Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality

Author

Gygi, Jeremy P, Maguire, Cole, Patel, Ravi K, Shinde, Pramod, Konstorum, Anna, Shannon, Casey P, Xu, Leqi, Hoch, Annmarie, Jayavelu, Naresh Doni, Haddad, Elias K, Network, IMPACC, Reed, Elaine F, Kraft, Monica, McComsey, Grace A, Metcalf, Jordan P, Ozonoff, Al, Esserman, Denise, Cairns, Charles B, Rouphael, Nadine, Bosinger, Steven E, Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey B, van Bakel, Harm, Wilson, Michael, Eckalbar, Walter L, Maecker, Holden T, Langelier, Charles R, Steen, Hanno, Altman, Matthew C, Montgomery, Ruth R, Levy, Ofer, Melamed, Esther, Pulendran, Bali, Diray-Arce, Joann, Smolen, Kinga K, Fragiadakis, Gabriela K, Becker, Patrice M, Sekaly, Rafick P, Ehrlich, Lauren IR, Fourati, Slim, Peters, Bjoern, Kleinstein, Steven H, and Guan, Leying

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Humans, COVID-19, Male, Longitudinal Studies, SARS-CoV-2, Female, Middle Aged, Severity of Illness Index, Aged, Adult, Cytokines, Multiomics, IMPACC Network, Adaptive immunity, Innate immunity, Medical and Health Sciences, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.RESULTSIncreasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness.CONCLUSIONOur longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).

Published
2024

3. IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

Author

Ozonoff, Al, Ehrlich, Lauren IR, Melamed, Esther, Sesma, Ana Fernandez, Simon, Viviana, Pulendran, Bali, Nadeau, Kari C, Davis, Mark M, McCoey, Grace A, Sekaly, Rafick, Baden, Lindsey R, Levy, Ofer, Schaenman, Joanna, Reed, Elaine F, Shaw, Albert C, Hafler, David A, Montgomery, Ruth R, Kleinstein, Steven H, Becker, Patrice M, Augustine, Alison D, Calfee, Carolyn S, Erle, David J, DeBakey, Michael E, Corry, David B, Kheradmand, Farrah, Atkinson, Mark A, Brakenridge, Scott C, Higuita, Nelson I Agudelo, Metcalf, Jordan P, Hough, Catherine L, Messer, William B, Kraft, Monica, Bime, Chris, Peters, Bjoern, Milliren, Carly E, Syphurs, Caitlin, McEnaney, Kerry, Barton, Brenda, Lentucci, Claudia, Saluvan, Mehmet, Chang, Ana C, Hoch, Annmarie, Albert, Marisa, Shaheen, Tanzia, Kho, Alvin T, Liu, Shanshan, Thomas, Sanya, Chen, Jing, Murphy, Maimouna D, Cooney, Mitchell, Hayati, Arash Nemati, Bryant, Robert, Abraham, James, Jayavelu, Naresh Doni, Presnell, Scott, Jancsyk, Tomasz, Maguire, Cole, Qi, Jingjing, Lee, Brian, Fourati, Slim, Esserman, Denise A, Guan, Leying, Gygi, Jeremy, Pawar, Shrikant, Brito, Anderson, Fragiadakis, Gabriela K, Patel, Ravi, Overton, James A, Vita, Randi, Westendorf, Kerstin, Shannon, Casey P, Tebbutt, Scott J, Thyagarajan, Rama V, Rousseau, Justin F, Wylie, Dennis, Triplett, Todd A, Kojic, Erna, Chinthrajah, Sharon, Ahuja, Neera, Rogers, Angela J, Artandi, Maja, Geng, Linda, Yendewa, George, Powell, Debra L, Kim, James N, Simmons, Brent, Goonewardene, I Michael, Smith, Cecilia M, Martens, Mark, Sherman, Amy C, Walsh, Stephen R, Issa, Nicolas C, Salehi-Rad, Ramin, Dela Cruz, Charles, Farhadian, Shelli, Iwasaki, Akiko, Ko, Albert I, Anderson, Evan J, Mehta, Aneesh K, and Sevransky, Jonathan E

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Coronaviruses, Lung, Emerging Infectious Diseases, Inflammatory and immune system, Good Health and Well Being, Humans, COVID-19, Glycosylation, SARS-CoV-2, Glycosyltransferases, Complement System Proteins, Immunoglobulin M, IMPACC Network
Abstract

The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.

Published
2024

4. Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study

Author

Ozonoff, Al, Jayavelu, Naresh Doni, Liu, Shanshan, Melamed, Esther, Milliren, Carly E., Qi, Jingjing, Geng, Linda N., McComsey, Grace A., Cairns, Charles B., Baden, Lindsey R., Schaenman, Joanna, Shaw, Albert C., Samaha, Hady, Seyfert-Margolis, Vicki, Krammer, Florian, Rosen, Lindsey B., Steen, Hanno, Syphurs, Caitlin, Dandekar, Ravi, Shannon, Casey P., Sekaly, Rafick P., Ehrlich, Lauren I. R., Corry, David B., Kheradmand, Farrah, Atkinson, Mark A., Brakenridge, Scott C., Higuita, Nelson I. Agudelo, Metcalf, Jordan P., Hough, Catherine L., Messer, William B., Pulendran, Bali, Nadeau, Kari C., Davis, Mark M., Sesma, Ana Fernandez, Simon, Viviana, van Bakel, Harm, Kim-Schulze, Seunghee, Hafler, David A., Levy, Ofer, Kraft, Monica, Bime, Chris, Haddad, Elias K., Calfee, Carolyn S., Erle, David J., Langelier, Charles R., Eckalbar, Walter, Bosinger, Steven E., Peters, Bjoern, Kleinstein, Steven H., Reed, Elaine F., Augustine, Alison D., Diray-Arce, Joann, Maecker, Holden T., Altman, Matthew C., Montgomery, Ruth R., Becker, Patrice M., and Rouphael, Nadine

Published
2024
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6. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study

Author

Ozonoff, Al, Schaenman, Joanna, Jayavelu, Naresh Doni, Milliren, Carly E, Calfee, Carolyn S, Cairns, Charles B, Kraft, Monica, Baden, Lindsey R, Shaw, Albert C, Krammer, Florian, van Bakel, Harm, Esserman, Denise A, Liu, Shanshan, Sesma, Ana Fernandez, Simon, Viviana, Hafler, David A, Montgomery, Ruth R, Kleinstein, Steven H, Levy, Ofer, Bime, Christian, Haddad, Elias K, Erle, David J, Pulendran, Bali, Nadeau, Kari C, Davis, Mark M, Hough, Catherine L, Messer, William B, Higuita, Nelson I Agudelo, Metcalf, Jordan P, Atkinson, Mark A, Brakenridge, Scott C, Corry, David, Kheradmand, Farrah, Ehrlich, Lauren IR, Melamed, Esther, McComsey, Grace A, Sekaly, Rafick, Diray-Arce, Joann, Peters, Bjoern, Augustine, Alison D, Reed, Elaine F, Altman, Matthew C, Becker, Patrice M, Rouphael, Nadine, Bime, Chris, McEnaney, Kerry, Barton, Brenda, Lentucci, Claudia, Saluvan, Mehmet, Chang, Ana C, Hoch, Annmarie, Albert, Marisa, Shaheen, Tanzia, Kho, Alvin T, Thomas, Sanya, Chen, Jing, Murphy, Maimouna D, Cooney, Mitchell, Presnell, Scott, and Fragiadakis, Gabriela K

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Genetics, Clinical Research, Infectious Diseases, Lung, Emerging Infectious Diseases, Prevention, Coronaviruses, Good Health and Well Being, COVID-19, Creatinine, Female, Hospitalization, Humans, Male, Phenotype, Prospective Studies, RNA, Viral, SARS-CoV-2, Severity of Illness Index, Troponin, Post-Acute COVID-19 Syndrome, Viral load, Antibody, IMPACC study group members, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundBetter 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.MethodsImmunophenotyping 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.FindingsThe 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.InterpretationIntegration 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.FundingNIH.

Published
2022

7. Activated sputum eosinophils associated with exacerbations in children on mepolizumab

Author

Wilson, Gabriella E., Knight, James, Liu, Qing, Shelar, Ashish, Stewart, Emma, Wang, Xiaomei, Yan, Xiting, Sanders, Joshua, Visness, Cynthia, Gill, Michelle, Gruchalla, Rebecca, Liu, Andrew H., Kattan, Meyer, Khurana Hershey, Gurjit K., Togias, Alkis, Becker, Patrice M., Altman, Matthew C., Busse, William W., Jackson, Daniel J., Montgomery, Ruth R., and Chupp, Geoffrey L.

Published
2024
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8. “Deficiency in ELF4, X-Linked”: a Monogenic Disease Entity Resembling Behçet’s Syndrome and Inflammatory Bowel Disease

Author

Olyha, Sam J., O’Connor, Shannon K., Kribis, Marat, Bucklin, Molly L., Uthaya Kumar, Dinesh Babu, Tyler, Paul M., Alam, Faiad, Jones, Kate M., Sheikha, Hassan, Konnikova, Liza, Lakhani, Saquib A., Montgomery, Ruth R., Catanzaro, Jason, Du, Hongqiang, DiGiacomo, Daniel V., Rothermel, Holly, Moran, Christopher J., Fiedler, Karoline, Warner, Neil, Hoppenreijs, Esther P.A.H., van der Made, Caspar I., Hoischen, Alexander, Olbrich, Peter, Neth, Olaf, Rodríguez-Martínez, Alejandro, Lucena Soto, José Manuel, van Rossum, Annemarie M.C., Dalm, Virgil A.S.H., Muise, Aleixo M., and Lucas, Carrie L.

Published
2024
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9. Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection

Author

Boada, Patrick, Fatou, Benoit, Belperron, Alexia A, Sigdel, Tara K, Smolen, Kinga K, Wurie, Zainab, Levy, Ofer, Ronca, Shannon E, Murray, Kristy O, Liberto, Juliane M, Rashmi, Priyanka, Kerwin, Maggie, Montgomery, Ruth R, Bockenstedt, Linda K, Steen, Hanno, and Sarwal, Minnie M

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Biotechnology, Vector-Borne Diseases, Emerging Infectious Diseases, Biodefense, West Nile Virus, Rare Diseases, Infectious Diseases, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Humans, West Nile Fever, West Nile virus, Proteome, Proteomics, Lyme Disease, serum proteomics, acute-phase response, immune system, localized and disseminated stage, asymptomatic infection, Lyme disease, longitudinal analysis, Immunology, Biochemistry and cell biology, Genetics
Abstract

Advancement in proteomics methods for interrogating biological samples has helped identify disease biomarkers for early diagnostics and unravel underlying molecular mechanisms of disease. Herein, we examined the serum proteomes of 23 study participants presenting with one of two common arthropod-borne infections: Lyme disease (LD), an extracellular bacterial infection or West Nile virus infection (WNV), an intracellular viral infection. The LC/MS based serum proteomes of samples collected at the time of diagnosis and during convalescence were assessed using a depletion-based high-throughput shotgun proteomics (dHSP) pipeline as well as a non-depleting blotting-based low-throughput platform (MStern). The LC/MS integrated analyses identified host proteome responses in the acute and recovery phases shared by LD and WNV infections, as well as differentially abundant proteins that were unique to each infection. Notably, we also detected proteins that distinguished localized from disseminated LD and asymptomatic from symptomatic WNV infection. The proteins detected in both diseases with the dHSP pipeline identified unique and overlapping proteins detected with the non-depleting MStern platform, supporting the utility of both detection methods. Machine learning confirmed the use of the serum proteome to distinguish the infection from healthy control sera but could not develop discriminatory models between LD and WNV at current sample numbers. Our study is the first to compare the serum proteomes in two arthropod-borne infections and highlights the similarities in host responses even though the pathogens and the vectors themselves are different.

Published
2022

10. Early cellular and molecular signatures correlate with severity of West Nile virus infection

Author

Lee, Ho-Joon, Zhao, Yujiao, Fleming, Ira, Mehta, Sameet, Wang, Xiaomei, Wyk, Brent Vander, Ronca, Shannon E., Kang, Heather, Chou, Chih-Hung, Fatou, Benoit, Smolen, Kinga K., Levy, Ofer, Clish, Clary B., Xavier, Ramnik J., Steen, Hanno, Hafler, David A., Love, J. Christopher, Shalek, Alex K., Guan, Leying, Murray, Kristy O., Kleinstein, Steven H., and Montgomery, Ruth R.

Published
2023
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11. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

Author

Abraham, James, Adkisson, Michael, Albert, Marisa, Altamirano, Luz Torres, Alvarenga, Bonny, Anderson, Matthew L., Anderson, Evan J., Arnett, Azlann, Asashima, Hiromitsu, Atkinson, Mark A., Baden, Lindsey R., Barton, Brenda, Beach, Katherine, Beagle, Elizabeth, Becker, Patrice M., Bell, Matthew R., Bernui, Mariana, Bime, Christian, Boddapati, Arun Kumar, Booth, J. Leland, Borresen, Brittney, Brakenridge, Scott C., Bristow, Laurel, Bryant, Robert, Calfee, Carolyn S., Carreño, Juan Manuel, Carrillo, Sidney, Chak, Suzanna, Chang, Iris, Connors, Jennifer, Conway, Michelle, Corry, David B., Cowan, David, Croen, Brett, Dela Cruz, Charles S., Cusimano, Gina, Eaker, Lily, Edwards, Carolyn, Ehrlich, Lauren I.R., Elashoff, David, Erickson, Heidi, Erle, David J., Farhadian, Shelli, Farrugia, Keith, Fatou, Benoit, Fernandes, Andrea, Fernandez-Sesma, Ana, Fragiadakis, Gabriela K., Furukawa, Sara, Geltman, Janelle N., Ghale, Rajani, Bermúdez González, Maria Carolina, Goonewardene, I. Michael, Guerrero, Estella Sanchez, Guirgis, Faheem W., Hafler, David A., Hamilton, Sydney, Harris, Paul, Hayati, Arash Nemati, Hendrickson, Carolyn M., Agudelo Higuita, Nelson I., Hodder, Thomas, Holland, Steven M., Hough, Catherine L., Huerta, Christopher, Hurley, Kerin C., Hutton, Scott R., Iwasaki, Akiko, Jauregui, Alejandra, Jha, Meenakshi, Johnson, Brandi, Joyner, David, Kangelaris, Kirsten N., Kelly, Geoffrey, Khalil, Zain, Khan, Zenab, Kheradmand, Farrah, Kim, James N., Kimura, Hiroki, Ko, Albert I., Kohr, Bernard, Kraft, Monica, Krummel, Matthew, Kutzler, Michele A., Lasky-Su, Jessica, Lee, Serena, Lee, Deanna, Leipold, Michael, Lentucci, Claudia, Leroux, Carolyn, Lin, Edward, Liu, Shanshan, Love, Christina, Lu, Zhengchun, Maliskova, Lenka, Manning, Brittany Roth, Manohar, Monali, Martens, Mark, McComsey, Grace A., McEnaney, Kerry, McLin, Renee, Melamed, Esther, Melnyk, Nataliya, Mendez, Kevin, Messer, William B., Metcalf, Jordan P., Michelotti, Gregory, Mick, Eran, Mohanty, Subhasis, Mosier, Jarrod, Mulder, Lubbertus C.F., Murphy, Maimouna, Nadeau, Kari R.C., Nelson, Ebony, Nelson, Allison, Nguyen, Viet, Oberhaus, Jordan, Panganiban, Bernadine, Pellegrini, Kathryn L., Pickering, Harry C., Powell, Debra L., Presnell, Scott, Pulendran, Bali, Rahman, Adeeb H., Rashid, Ahmad Sadeed, Raskin, Ariel, Reed, Elaine F., Ribeiro, Susan Pereira, Rivera, Adreanne M., Rogers, Jacob E., Rogers, Angela, Rogowski, Brandon, Rooks, Rebecca, Rosenberg-Hasson, Yael, Rothman, Jessica, Rousseau, Justin F., Salehi-Rad, Ramin, Saluvan, Mehmet, Samaha, Hady, Schaenman, Joanna, Schunk, Ron, Semenza, Nicholas C., Sen, Subha, Sevransky, Jonathan, Seyfert-Margolis, Vicki, Shaheen, Tanzia, Shaw, Albert C., Sieg, Scott, Siegel, Sarah A.R., Sigal, Natalia, Siles, Nadia, Simmons, Brent, Simon, Viviana, Singh, Gagandeep, Sinko, Lauren, Smith, Cecilia M., Smolen, Kinga K., Song, Li-Zhen, Srivastava, Komal, Sullivan, Peter, Syphurs, Caitlin, Tcheou, Johnstone, Tegos, George P., Tharp, Greg K., Tong, Alexandra, Tsitsiklis, Alexandra, Ungaro, Ricardo F., Vaysman, Tatyana, Viode, Arthur, Vita, Randi, Wang, Xiaomei, Ward, Alyssa, Ward, Dawn C., Willmore, Andrew, Woloszczuk, Kyra, Wong, Kari, Woodruff, Prescott G., Xu, Leqi, van Haren, Simon, van de Guchte, Adriana, Zhao, Yujiao, Diray-Arce, Joann, Fourati, Slim, Doni Jayavelu, Naresh, Patel, Ravi, Maguire, Cole, Chang, Ana C., Dandekar, Ravi, Qi, Jingjing, Lee, Brian H., van Zalm, Patrick, Schroeder, Andrew, Chen, Ernie, Konstorum, Anna, Brito, Anderson, Gygi, Jeremy P., Kho, Alvin, Chen, Jing, Pawar, Shrikant, Gonzalez-Reiche, Ana Silvia, Hoch, Annmarie, Milliren, Carly E., Overton, James A., Westendorf, Kerstin, Cairns, Charles B., Rouphael, Nadine, Bosinger, Steven E., Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey, Grubaugh, Nathan D., van Bakel, Harm, Wilson, Michael, Rajan, Jayant, Steen, Hanno, Eckalbar, Walter, Cotsapas, Chris, Langelier, Charles R., Levy, Ofer, Altman, Matthew C., Maecker, Holden, Montgomery, Ruth R., Haddad, Elias K., Sekaly, Rafick P., Esserman, Denise, Ozonoff, Al, Augustine, Alison D., Guan, Leying, Peters, Bjoern, and Kleinstein, Steven H.

Published
2023
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14. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19

Author

Unterman, Avraham, Sumida, Tomokazu S., Nouri, Nima, Yan, Xiting, Zhao, Amy Y., Gasque, Victor, Schupp, Jonas C., Asashima, Hiromitsu, Liu, Yunqing, Cosme, Jr., Carlos, Deng, Wenxuan, Chen, Ming, Raredon, Micha Sam Brickman, Hoehn, Kenneth B., Wang, Guilin, Wang, Zuoheng, DeIuliis, Giuseppe, Ravindra, Neal G., Li, Ningshan, Castaldi, Christopher, Wong, Patrick, Fournier, John, Bermejo, Santos, Sharma, Lokesh, Casanovas-Massana, Arnau, Vogels, Chantal B. F., Wyllie, Anne L., Grubaugh, Nathan D., Melillo, Anthony, Meng, Hailong, Stein, Yan, Minasyan, Maksym, Mohanty, Subhasis, Ruff, William E., Cohen, Inessa, Raddassi, Khadir, Niklason, Laura E., Ko, Albert I., Montgomery, Ruth R., Farhadian, Shelli F., Iwasaki, Akiko, Shaw, Albert C., van Dijk, David, Zhao, Hongyu, Kleinstein, Steven H., Hafler, David A., Kaminski, Naftali, and Dela Cruz, Charles S.

Published
2022
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15. Corrigendum to “Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: results from the IMPACC study” [eBioMedicine 83 (2022) 104208]

Author

Ozonoff, Al, primary, Schaenman, Joanna, additional, Jayavelu, Naresh Doni, additional, Milliren, Carly E., additional, Calfee, Carolyn S., additional, Cairns, Charles B., additional, Kraft, Monica, additional, Baden, Lindsey R., additional, Shaw, Albert C., additional, Krammer, Florian, additional, van Bakel, Harm, additional, Esserman, Denise A., additional, Liu, Shanshan, additional, Sesma, Ana Fernandez, additional, Simon, Viviana, additional, Hafler, David A., additional, Montgomery, Ruth R., additional, Kleinstein, Steven H., additional, Levy, Ofer, additional, Bime, Chris, additional, Haddad, Elias K., additional, Erle, David J., additional, Pulendran, Bali, additional, Nadeau, Kari C., additional, Davis, Mark M., additional, Hough, Catherine L., additional, Messer, William B., additional, Agudelo Higuita, Nelson I., additional, Metcalf, Jordan P., additional, Atkinson, Mark A., additional, Brakenridge, Scott C., additional, Corry, David, additional, Kheradmand, Farrah, additional, Ehrlich, Lauren I.R., additional, Melamed, Esther, additional, McComsey, Grace A., additional, Sekaly, Rafick, additional, Diray-Arce, Joann, additional, Peters, Bjoern, additional, Augustine, Alison D., additional, Reed, Elaine F., additional, Altman, Matthew C., additional, Becker, Patrice M., additional, and Rouphael, Nadine, additional

Published
2023
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16. Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants

Author

Gygi, Jeremy P., primary, Maguire, Cole, additional, Patel, Ravi K., additional, Shinde, Pramod, additional, Konstorum, Anna, additional, Shannon, Casey P., additional, Xu, Leqi, additional, Hoch, Annmarie, additional, Jayavelu, Naresh Doni, additional, Network, IMPACC, additional, Haddad, Elias K., additional, Reed, Elaine F., additional, Kraft, Monica, additional, McComsey, Grace A., additional, Metcalf, Jordan, additional, Ozonoff, Al, additional, Esserman, Denise, additional, Cairns, Charles B., additional, Rouphael, Nadine, additional, Bosinger, Steven E., additional, Kim-Schulze, Seunghee, additional, Krammer, Florian, additional, Rosen, Lindsey B., additional, van Bakel, Harm, additional, Wilson, Michael, additional, Eckalbar, Walter, additional, Maecker, Holden, additional, Langelier, Charles R., additional, Steen, Hanno, additional, Altman, Matthew C., additional, Montgomery, Ruth R., additional, Levy, Ofer, additional, Melamed, Esther, additional, Pulendran, Bali, additional, Diray-Arce, Joann, additional, Smolen, Kinga K., additional, Fragiadakis, Gabriela K., additional, Becker, Patrice M., additional, Augustine, Alison D., additional, Sekaly, Rafick P., additional, Ehrlich, Lauren I. R., additional, Fourati, Slim, additional, Peters, Bjoern, additional, Kleinstein, Steven H., additional, and Guan, Leying, additional

Published
2023
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18. Proteome Analysis for Inflammation Related to Acute and Convalescent Infection

Author

Sigdel, Tara K., primary, Sur, Swastika, additional, Boada, Patrick, additional, McDermott, Suzanne M., additional, Arlehamn, Cecilia S. Lindestam, additional, Murray, Kristy O., additional, Bockenstedt, Linda K., additional, Kerwin, Maggie, additional, Reed, Elaine F., additional, Harris, Eva, additional, Stuart, Ken, additional, Peters, Bjoern, additional, Sesma, Ana, additional, Montgomery, Ruth R., additional, and Sarwal, Minnie M., additional

Published
2023
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19. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination

Author

Asashima, Hiromitsu, primary, Kim, Dongjoo, additional, Wang, Kaicheng, additional, Lele, Nikhil, additional, Buitrago-Pocasangre, Nicholas C., additional, Lutz, Rachel, additional, Cruz, Isabella, additional, Raddassi, Khadir, additional, Ruff, William E., additional, Racke, Michael K., additional, Wilson, JoDell E., additional, Givens, Tara S., additional, Grifoni, Alba, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Kleinstein, Steven H., additional, Montgomery, Ruth R., additional, Shaw, Albert C., additional, Li, Fangyong, additional, Fan, Rong, additional, Hafler, David A., additional, Tomayko, Mary M., additional, and Longbrake, Erin E., additional

Published
2023
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20. Early cellular and molecular signatures correlate with severity of West Nile Virus infection

Author

Lee, Ho-Joon, primary, Zhao, Yujiao, additional, Fleming, Ira, additional, Mehta, Sameet, additional, Wang, Xiaomei, additional, Wyk, Brent Vander, additional, Ronca, Shannon E., additional, Kang, Heather, additional, Chou, Chih-Hung, additional, Fatou, Benoit, additional, Smolen, Kinga K., additional, Levy, Ofer, additional, Clish, Clary B., additional, Xavier, Ramnik J., additional, Steen, Hanno, additional, Hafler, David A., additional, Love, J. Christopher, additional, Shalek, Alex K., additional, Guan, Leying, additional, Murray, Kristy O., additional, Kleinstein, Steven H., additional, and Montgomery, Ruth R., additional

Published
2023
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21. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

Author

Diray-Arce, Joann, primary, Fourati, Slim, additional, Jayavelu, Naresh Doni, additional, Patel, Ravi, additional, Maguire, Cole, additional, Chang, Ana C., additional, Dandekar, Ravi, additional, Qi, Jingjing, additional, Lee, Brian, additional, van Zalm, Patrick, additional, Schroeder, Andrew, additional, Chen, Ernie, additional, Konstorum, Anna, additional, Brito, Anderson, additional, Gygi, Jeremy P., additional, Kho, Alvin, additional, Chen, Jing, additional, Pawar, Shrikant, additional, Gonzalez-Reiche, Ana Silvia, additional, Hoch, Annmarie, additional, Milliren, Carly E., additional, Overton, James A., additional, Westendorf, Kerstin, additional, Cairns, Charles B., additional, Rouphael, Nadine, additional, Bosinger, Steven, additional, Kim-Schulze, Seunghee, additional, Krammer, Florian, additional, Rosen, Lindsey, additional, Grubaugh, Nathan, additional, van Bakel, Harm, additional, Wilson, Michael, additional, Rajan, Jayant, additional, Steen, Hanno, additional, Eckalbar, Walter, additional, Cotsapas, Chris, additional, Langelier, Charles R., additional, Levy, Ofer, additional, Altman, Matthew C., additional, Maecker, Holden, additional, Montgomery, Ruth R., additional, Haddad, Elias K., additional, Sekaly, Rafick P., additional, Esserman, Denise, additional, Ozonoff, Al, additional, Becker, Patrice M., additional, Augustine, Alison D., additional, Guan, Leying, additional, Peters, Bjoern, additional, and Kleinstein, Steven H., additional

Published
2023
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22. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients.

Author

Diray-Arce, Joann, Diray-Arce, Joann, Fourati, Slim, Doni Jayavelu, Naresh, Patel, Ravi, Maguire, Cole, Chang, Ana C, Dandekar, Ravi, Qi, Jingjing, Lee, Brian H, van Zalm, Patrick, Schroeder, Andrew, Chen, Ernie, Konstorum, Anna, Brito, Anderson, Gygi, Jeremy P, Kho, Alvin, Chen, Jing, Pawar, Shrikant, Gonzalez-Reiche, Ana Silvia, Hoch, Annmarie, Milliren, Carly E, Overton, James A, Westendorf, Kerstin, IMPACC Network, Cairns, Charles B, Rouphael, Nadine, Bosinger, Steven E, Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey, Grubaugh, Nathan D, van Bakel, Harm, Wilson, Michael, Rajan, Jayant, Steen, Hanno, Eckalbar, Walter, Cotsapas, Chris, Langelier, Charles R, Levy, Ofer, Altman, Matthew C, Maecker, Holden, Montgomery, Ruth R, Haddad, Elias K, Sekaly, Rafick P, Esserman, Denise, Ozonoff, Al, Becker, Patrice M, Augustine, Alison D, Guan, Leying, Peters, Bjoern, Kleinstein, Steven H, Diray-Arce, Joann, Diray-Arce, Joann, Fourati, Slim, Doni Jayavelu, Naresh, Patel, Ravi, Maguire, Cole, Chang, Ana C, Dandekar, Ravi, Qi, Jingjing, Lee, Brian H, van Zalm, Patrick, Schroeder, Andrew, Chen, Ernie, Konstorum, Anna, Brito, Anderson, Gygi, Jeremy P, Kho, Alvin, Chen, Jing, Pawar, Shrikant, Gonzalez-Reiche, Ana Silvia, Hoch, Annmarie, Milliren, Carly E, Overton, James A, Westendorf, Kerstin, IMPACC Network, Cairns, Charles B, Rouphael, Nadine, Bosinger, Steven E, Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey, Grubaugh, Nathan D, van Bakel, Harm, Wilson, Michael, Rajan, Jayant, Steen, Hanno, Eckalbar, Walter, Cotsapas, Chris, Langelier, Charles R, Levy, Ofer, Altman, Matthew C, Maecker, Holden, Montgomery, Ruth R, Haddad, Elias K, Sekaly, Rafick P, Esserman, Denise, Ozonoff, Al, Becker, Patrice M, Augustine, Alison D, Guan, Leying, Peters, Bjoern, and Kleinstein, Steven H

Abstract

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

Published
2023

23. Featured Cover

Author

Konstorum, Anna, primary, Mohanty, Subhasis, additional, Zhao, Yujiao, additional, Melillo, Anthony, additional, Vander Wyk, Brent, additional, Nelson, Allison, additional, Tsang, Sui, additional, Blevins, Tamara P., additional, Belshe, Robert B., additional, Chawla, Daniel G., additional, Rondina, Matthew T., additional, Gill, Thomas M., additional, Montgomery, Ruth R., additional, Allore, Heather G., additional, Kleinstein, Steven H., additional, and Shaw, Albert C., additional

Published
2023
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24. Platelet response to influenza vaccination reflects effects of aging

Author

Konstorum, Anna, primary, Mohanty, Subhasis, additional, Zhao, Yujiao, additional, Melillo, Anthony, additional, Vander Wyk, Brent, additional, Nelson, Allison, additional, Tsang, Sui, additional, Blevins, Tamara P., additional, Belshe, Robert B., additional, Chawla, Daniel G., additional, Rondina, Matthew T., additional, Gill, Thomas M., additional, Montgomery, Ruth R., additional, Allore, Heather G., additional, Kleinstein, Steven H., additional, and Shaw, Albert C., additional

Published
2023
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25. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection

Author

Asashima, Hiromitsu, primary, Mohanty, Subhasis, additional, Comi, Michela, additional, Ruff, William E., additional, Hoehn, Kenneth B., additional, Wong, Patrick, additional, Klein, Jon, additional, Lucas, Carolina, additional, Cohen, Inessa, additional, Coffey, Sarah, additional, Lele, Nikhil, additional, Greta, Leissa, additional, Raddassi, Khadir, additional, Chaudhary, Omkar, additional, Unterman, Avraham, additional, Emu, Brinda, additional, Kleinstein, Steven H., additional, Montgomery, Ruth R., additional, Iwasaki, Akiko, additional, Dela Cruz, Charles S., additional, Kaminski, Naftali, additional, Shaw, Albert C., additional, Hafler, David A., additional, and Sumida, Tomokazu S., additional

Published
2023
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26. Analytical Approaches to Uncover Genetic Associations for Rare Outcomes: Lessons from West Nile Neuroinvasive Disease

Author

Cahill, Megan E. and Montgomery, Ruth R.

Subjects
Incidence, Humans, West Nile virus, Article, West Nile Fever
Abstract

West Nile viral infection causes severe neuroinvasive disease in less than one percent of infected humans. There are no targeted therapeutics for this serious and potentially fatal disease, and to date no vaccine has been approved for humans. With climate change expected to result in rising incidence of West Nile and other related vector-borne viral infections, there is an increasing need to identify those at risk for serious disease and potential leads for therapeutic and vaccine development. Genetic variation, particularly in genes whose products are either directly or indirectly connected to immune response to infections, is a critical avenue of investigation to identify those at higher risk of clinically apparent West Nile infection. Given the small percent of infections that progress to severe disease and the relatively low numbers of reported infections, it is challenging to conduct well-powered studies to identify genetic factors associated with more severe outcomes. In this chapter, we outline several approaches with the objective to take full advantage of all available data in order to identify genetic factors which lead to increased risk of severe West Nile neuroinvasive disease. These methods are generalizable to other conditions with limited cohort size and rare outcomes.

Published
2022
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27. Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection

Author

Boada, Patrick, primary, Fatou, Benoit, additional, Belperron, Alexia A., additional, Sigdel, Tara K., additional, Smolen, Kinga K., additional, Wurie, Zainab, additional, Levy, Ofer, additional, Ronca, Shannon E., additional, Murray, Kristy O., additional, Liberto, Juliane M., additional, Rashmi, Priyanka, additional, Kerwin, Maggie, additional, Montgomery, Ruth R., additional, Bockenstedt, Linda K., additional, Steen, Hanno, additional, and Sarwal, Minnie M., additional

Published
2022
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28. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study

Author

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

Published
2022
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30. Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells

Author

Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Chemistry, Koch Institute for Integrative Cancer Research at MIT, Jiang, Ruoyi, Meng, Hailong, Raddassi, Khadir, Fleming, Ira, Hoehn, Kenneth B, Dardick, Kenneth R, Belperron, Alexia A, Montgomery, Ruth R, Shalek, Alex K, Hafler, David A, Kleinstein, Steven H, Bockenstedt, Linda K, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Chemistry, Koch Institute for Integrative Cancer Research at MIT, Jiang, Ruoyi, Meng, Hailong, Raddassi, Khadir, Fleming, Ira, Hoehn, Kenneth B, Dardick, Kenneth R, Belperron, Alexia A, Montgomery, Ruth R, Shalek, Alex K, Hafler, David A, Kleinstein, Steven H, and Bockenstedt, Linda K

Abstract

The skin lesion erythema migrans (EM) is an initial sign of the Ixodes tick-transmitted Borreliella spirochetal infection known as Lyme disease. T cells and innate immune cells have previously been shown to predominate the EM lesion and promote the reaction. Despite the established importance of B cells and antibodies in preventing infection, the role of B cells in the skin immune response to Borreliella is unknown. Here, we used single-cell RNA-Seq in conjunction with B cell receptor (BCR) sequencing to immunophenotype EM lesions and their associated B cells and BCR repertoires. We found that B cells were more abundant in EM in comparison with autologous uninvolved skin; many were clonally expanded and had circulating relatives. EM-associated B cells upregulated the expression of MHC class II genes and exhibited preferential IgM isotype usage. A subset also exhibited low levels of somatic hypermutation despite a gene expression profile consistent with memory B cells. Our study demonstrates that single-cell gene expression with paired BCR sequencing can be used to interrogate the sparse B cell populations in human skin and reveals that B cells in the skin infection site in early Lyme disease expressed a phenotype consistent with local antigen presentation and antibody production.

Published
2022

31. Platelet response to influenza vaccination reflects effects of aging

Author

Konstorum, Anna, primary, Mohanty, Subhasis, additional, Zhao, Yujiao, additional, Melillo, Anthony, additional, Vander Wyk, Brent, additional, Nelson, Allison, additional, Tsang, Sui, additional, Blevins, Tamara P., additional, Belshe, Robert B., additional, Chawla, Daniel G., additional, Rondina, Matthew T., additional, Montgomery, Ruth R., additional, Allore, Heather G., additional, Kleinstein, Steven H., additional, and Shaw, Albert C., additional

Published
2022
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32. Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology

Author

Phan, Hoang Van, Tsitsiklis, Alexandra, Maguire, Cole P., Haddad, Elias K., Becker, Patrice M., Kim-Schulze, Seunghee, Lee, Brian, Chen, Jing, Hoch, Annmarie, Pickering, Harry, van Zalm, Patrick, Altman, Matthew C., Augustine, Alison D., Calfee, Carolyn S., Bosinger, Steve, Cairns, Charles B., Eckalbar, Walter, Guan, Leying, Jayavelu, Naresh Doni, Kleinstein, Steven H., Krammer, Florian, Maecker, Holden T., Ozonoff, Al, Peters, Bjoern, Rouphael, Nadine, Montgomery, Ruth R., Reed, Elaine, Schaenman, Joanna, Steen, Hanno, Levy, Ofer, Diray-Arce, Joann, and Langelier, Charles R.

Abstract

Age is a major risk factor for severe coronavirus disease 2019 (COVID-19), yet the mechanisms behind this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host immune response in the blood and the upper airway, as well as the nasal microbiome in a prospective, multicenter cohort of 1031 vaccine-naïve patients hospitalized for COVID-19 between 18 and 96 years old. We performed mass cytometry, serum protein profiling, anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays, and blood and nasal transcriptomics. We found that older age correlated with increased SARS-CoV-2 viral abundance upon hospital admission, delayed viral clearance, and increased type I interferon gene expression in both the blood and upper airway. We also observed age-dependent up-regulation of innate immune signaling pathways and down-regulation of adaptive immune signaling pathways. Older adults had lower naïve T and B cell populations and higher monocyte populations. Over time, older adults demonstrated a sustained induction of pro-inflammatory genes and serum chemokines compared with younger individuals, suggesting an age-dependent impairment in inflammation resolution. Transcriptional and protein biomarkers of disease severity differed with age, with the oldest adults exhibiting greater expression of pro-inflammatory genes and proteins in severe disease. Together, our study finds that aging is associated with impaired viral clearance, dysregulated immune signaling, and persistent and potentially pathologic activation of pro-inflammatory genes and proteins.

Published
2024
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33. PD-1highCXCR5–CD4+peripheral helper T cells promote CXCR3+plasmablasts in human acute viral infection

Author

Asashima, Hiromitsu, Mohanty, Subhasis, Comi, Michela, Ruff, William E., Hoehn, Kenneth B., Wong, Patrick, Klein, Jon, Lucas, Carolina, Cohen, Inessa, Coffey, Sarah, Lele, Nikhil, Greta, Leissa, Raddassi, Khadir, Chaudhary, Omkar, Unterman, Avraham, Emu, Brinda, Kleinstein, Steven H., Montgomery, Ruth R., Iwasaki, Akiko, Dela Cruz, Charles S., Kaminski, Naftali, Shaw, Albert C., Hafler, David A., and Sumida, Tomokazu S.

Abstract

T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4+T cell subsets associated with plasmablast expansion and clinical outcome. Peripheral helper T cells (Tph cells; denoted as PD-1highCXCR5–CD4+T cells) are significantly increased, as are plasmablasts. Tph cells exhibit “B cell help” signatures and induce plasmablast differentiation in vitro. Interestingly, expanded plasmablasts show increased CXCR3expression, which is positively correlated with higher frequency of activated Tph cells and better clinical outcome. Mechanistically, Tph cells help B cell differentiation and produce more interferon γ (IFNγ), which induces CXCR3 expression on plasmablasts. These results elucidate a role for Tph cells in regulating protective B cell response during acute viral infection.

Published
2023
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34. Chronic Viral Reactivation and Associated Host Immune Response and Clinical Outcomes in Acute COVID-19 and Post-Acute Sequelae of COVID-19.

Author

Maguire C, Chen J, Rouphael N, Pickering H, Phan HV, Glascock A, Chu V, Dandekar R, Corry D, Kheradmand F, Baden LR, Selaky R, McComsey GA, Haddad EK, Cairns CB, Pulendran B, Sesma AF, Simon V, Metcalf JP, Agudelo Higuita NI, Messer WB, David MM, Nadeau KC, Kraft M, Bime C, Schaenman J, Erle D, Calfee CS, Atkinson MA, Brackenridge SC, Ehrlich LIR, Montgomery RR, Shaw AC, Hough CL, Geng LN, Hafler DA, Augustine AD, Becker PM, Peters B, Ozonoff A, Kim-Schulze SH, Krammer F, Bosinger S, Eckalbar W, Altman MC, Wilson M, Guan L, Kleinstein SH, Smolen KK, Reed EF, Levy O, Maecker H, Hunt P, Steen H, Diray-Arce J, Langelier CR, and Melamed E

Abstract

Chronic viral infections are ubiquitous in humans, with individuals harboring multiple latent viruses that can reactivate during acute illnesses. Recent studies have suggested that SARS- CoV-2 infection can lead to reactivation of latent viruses such as Epstein-Barr Virus (EBV) and cytomegalovirus (CMV), yet, the extent and impact of viral reactivation in COVID-19 and its effect on the host immune system remain incompletely understood. Here we present a comprehensive multi-omic analysis of viral reactivation of all known chronically infecting viruses in 1,154 hospitalized COVID-19 patients, from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, who were followed prospectively for twelve months. We reveal significant reactivation of Herpesviridae , Enteroviridae , and Anelloviridae families during acute stage of COVID-19 (0-40 days post- hospitalization), each exhibiting distinct temporal dynamics. We also show that viral reactivation correlated with COVID-19 severity, demographic characteristics, and clinical outcomes, including mortality. Integration of cytokine profiling, cellular immunophenotyping, metabolomics, transcriptomics, and proteomics demonstrated virus-specific host responses, including elevated pro-inflammatory cytokines (e.g. IL-6, CXCL10, and TNF), increased activated CD4+ and CD8+ T-cells, and upregulation of cellular replication genes, independent of COVID-19 severity and SARS-CoV-2 viral load. Notably, persistent Anelloviridae reactivation during convalescence (≥3 months post-hospitalization) was associated with Post-Acute Sequelae of COVID-19 (PASC) symptoms, particularly physical function and fatigue. Our findings highlight a remarkable prevalence and potential impact of chronic viral reactivation on host responses and clinical outcomes during acute COVID-19 and long term PASC sequelae. Our data provide novel immune, transcriptomic, and metabolomic biomarkers of viral reactivation that may inform novel approaches to prognosticate, prevent, or treat acute COVID- 19 and PASC.

Published
2024
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35. Host-Microbe Multiomic Profiling Reveals Age-Dependent COVID-19 Immunopathology.

Author

Van Phan H, Tsitsiklis A, Maguire CP, Haddad EK, Becker PM, Kim-Schulze S, Lee B, Chen J, Hoch A, Pickering H, Van Zalm P, Altman MC, Augustine AD, Calfee CS, Bosinger S, Cairns C, Eckalbar W, Guan L, Jayavelu ND, Kleinstein SH, Krammer F, Maecker HT, Ozonoff A, Peters B, Rouphael N, Montgomery RR, Reed E, Schaenman J, Steen H, Levy O, Diray-Arce J, and Langelier CR

Abstract

Age is a major risk factor for severe coronavirus disease-2019 (COVID-19), yet the mechanisms responsible for this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host and viral dynamics in a prospective, multicenter cohort of 1,031 patients hospitalized for COVID-19, ranging from 18 to 96 years of age. We performed blood transcriptomics and nasal metatranscriptomics, and measured peripheral blood immune cell populations, inflammatory protein expression, anti-SARS-CoV-2 antibodies, and anti-interferon (IFN) autoantibodies. We found that older age correlated with an increased SARS-CoV-2 viral load at the time of admission, and with delayed viral clearance over 28 days. This contributed to an age-dependent increase in type I IFN gene expression in both the respiratory tract and blood. We also observed age-dependent transcriptional increases in peripheral blood IFN-γ, neutrophil degranulation, and Toll like receptor (TLR) signaling pathways, and decreases in T cell receptor (TCR) and B cell receptor signaling pathways. Over time, older adults exhibited a remarkably sustained induction of proinflammatory genes (e.g., CXCL6 ) and serum chemokines (e.g., CXCL9) compared to younger individuals, highlighting a striking age-dependent impairment in inflammation resolution. Augmented inflammatory signaling also involved the upper airway, where aging was associated with upregulation of TLR, IL17, type I IFN and IL1 pathways, and downregulation TCR and PD-1 signaling pathways. Metatranscriptomics revealed that the oldest adults exhibited disproportionate reactivation of herpes simplex virus and cytomegalovirus in the upper airway following hospitalization. Mass cytometry demonstrated that aging correlated with reduced naïve T and B cell populations, and increased monocytes and exhausted natural killer cells. Transcriptional and protein biomarkers of disease severity markedly differed with age, with the oldest adults exhibiting greater expression of TLR and inflammasome signaling genes, as well as proinflammatory proteins (e.g., IL6, CXCL8), in severe COVID-19 compared to mild/moderate disease. Anti-IFN autoantibody prevalence correlated with both age and disease severity. Taken together, this work profiles both host and microbe in the blood and airway to provide fresh insights into aging-related immune changes in a large cohort of vaccine-naïve COVID-19 patients. We observed age-dependent immune dysregulation at the transcriptional, protein and cellular levels, manifesting in an imbalance of inflammatory responses over the course of hospitalization, and suggesting potential new therapeutic targets.

Published
2024
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36. Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants.

Author

Gygi JP, Maguire C, Patel RK, Shinde P, Konstorum A, Shannon CP, Xu L, Hoch A, Jayavelu ND, Network I, Haddad EK, Reed EF, Kraft M, McComsey GA, Metcalf J, Ozonoff A, Esserman D, Cairns CB, Rouphael N, Bosinger SE, Kim-Schulze S, Krammer F, Rosen LB, van Bakel H, Wilson M, Eckalbar W, Maecker H, Langelier CR, Steen H, Altman MC, Montgomery RR, Levy O, Melamed E, Pulendran B, Diray-Arce J, Smolen KK, Fragiadakis GK, Becker PM, Augustine AD, Sekaly RP, Ehrlich LIR, Fourati S, Peters B, Kleinstein SH, and Guan L

Abstract

Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes. Increasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, NETosis, and T-cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma immunoglobulins and B cells, as well as dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to the failure of viral clearance in patients with fatal illness. Our longitudinal multi-omics profiling study revealed novel temporal coordination across diverse omics that potentially explain disease progression, providing insights that inform the targeted development of therapies for hospitalized COVID-19 patients, especially those critically ill.

Published
2023
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37. PD-1 high CXCR5 - CD4 + peripheral helper T cells promote CXCR3 + plasmablasts in human acute viral infection.

Author

Asashima H, Mohanty S, Comi M, Ruff WE, Hoehn KB, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein SH, Montgomery RR, Iwasaki A, Dela Cruz CS, Kaminski N, Shaw AC, Hafler DA, and Sumida TS

Subjects
Humans, CD4-Positive T-Lymphocytes, T-Lymphocytes, Helper-Inducer, Plasma Cells metabolism, Receptors, CXCR5, Receptors, CXCR3 metabolism, Programmed Cell Death 1 Receptor metabolism, COVID-19 metabolism
Abstract

T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4 + T cell subsets associated with plasmablast expansion and clinical outcome. Peripheral helper T cells (Tph cells; denoted as PD-1 high CXCR5 - CD4 + T cells) are significantly increased, as are plasmablasts. Tph cells exhibit "B cell help" signatures and induce plasmablast differentiation in vitro. Interestingly, expanded plasmablasts show increased CXCR3 expression, which is positively correlated with higher frequency of activated Tph cells and better clinical outcome. Mechanistically, Tph cells help B cell differentiation and produce more interferon γ (IFNγ), which induces CXCR3 expression on plasmablasts. These results elucidate a role for Tph cells in regulating protective B cell response during acute viral infection., Competing Interests: Declaration of interests D.A.H. has received research funding from Bristol-Myers Squibb, Novartis, Sanofi, and Genentech. He has been a consultant for Bayer Pharmaceuticals, Bristol Myers Squibb, Compass Therapeutics, EMD Serono, Genentech, Juno Therapeutics, Novartis Pharmaceuticals, Proclara Biosciences, Sage Therapeutics, and Sanofi Genzyme. Further information regarding funding is available at https://openpaymentsdata.cms.gov/physician/166753/general-payments. N.K. reports personal fees from Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indalo, Theravance, LifeMax, Three Lake Partners, and RohBar in the last 36 months and Equity in Pliant. N.K. is also a recipient of a grant from Veracyte and non-financial support from Miragen. In addition, N.K. has patents on New Therapies in Pulmonary Fibrosis and ARDS (unlicensed) and Peripheral Blood Gene Expression as biomarkers in IPF (licensed to biotech), all outside the submitted work. S.H.K. receives consulting fees from Northrop Grumman. K.B.H. receives consulting fees from Prellis Biologics., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2023
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38. Analytical Approaches to Uncover Genetic Associations for Rare Outcomes: Lessons from West Nile Neuroinvasive Disease.

Author

Cahill ME and Montgomery RR

Subjects
Humans, Incidence, West Nile Fever complications, West Nile virus genetics
Abstract

West Nile viral infection causes severe neuroinvasive disease in less than 1% of infected humans. There are no targeted therapeutics for this serious and potentially fatal disease, and to date no vaccine has been approved for humans. With climate change expected to result in rising incidence of West Nile and other related vector-borne viral infections, there is an increasing need to identify those at risk for serious disease and potential leads for therapeutic and vaccine development. Genetic variation, particularly in genes whose products are either directly or indirectly connected to immune response to infections, is a critical avenue of investigation to identify those at higher risk of clinically apparent West Nile infection. Given the small percent of infections that progress to severe disease and the relatively low numbers of reported infections, it is challenging to conduct well-powered studies to identify genetic factors associated with more severe outcomes. In this chapter, we outline several approaches with the objective to take full advantage of all available data in order to identify genetic factors which lead to increased risk of severe West Nile neuroinvasive disease. These methods are generalizable to other conditions with limited cohort size and rare outcomes., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2023
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