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1. Proteomic characterization of acute kidney injury in patients hospitalized with SARS-CoV2 infection

Author

Paranjpe, Ishan, Jayaraman, Pushkala, Su, Chen-Yang, Zhou, Sirui, Chen, Steven, Thompson, Ryan, Del Valle, Diane Marie, Kenigsberg, Ephraim, Zhao, Shan, Jaladanki, Suraj, Chaudhary, Kumardeep, Ascolillo, Steven, Vaid, Akhil, Gonzalez-Kozlova, Edgar, Kauffman, Justin, Kumar, Arvind, Paranjpe, Manish, Hagan, Ross O., Kamat, Samir, Gulamali, Faris F., Xie, Hui, Harris, Joceyln, Patel, Manishkumar, Argueta, Kimberly, Batchelor, Craig, Nie, Kai, Dellepiane, Sergio, Scott, Leisha, Levin, Matthew A., He, John Cijiang, Suarez-Farinas, Mayte, Coca, Steven G., Chan, Lili, Azeloglu, Evren U., Schadt, Eric, Beckmann, Noam, Gnjatic, Sacha, Merad, Miram, Kim-Schulze, Seunghee, Richards, Brent, Glicksberg, Benjamin S., Charney, Alexander W., and Nadkarni, Girish N.

Published
2023
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2. Circulating proteins to predict COVID-19 severity

Author

Su, Chen-Yang, Zhou, Sirui, Gonzalez-Kozlova, Edgar, Butler-Laporte, Guillaume, Brunet-Ratnasingham, Elsa, Nakanishi, Tomoko, Jeon, Wonseok, Morrison, David R., Laurent, Laetitia, Afilalo, Jonathan, Afilalo, Marc, Henry, Danielle, Chen, Yiheng, Carrasco-Zanini, Julia, Farjoun, Yossi, Pietzner, Maik, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Moussa, Yara, DeLuca, Chantal, Duggan, Naomi, Schurr, Erwin, Brassard, Nathalie, Durand, Madeleine, Del Valle, Diane Marie, Thompson, Ryan, Cedillo, Mario A., Schadt, Eric, Nie, Kai, Simons, Nicole W., Mouskas, Konstantinos, Zaki, Nicolas, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Marvin, Robert, Cheng, Esther, Tuballes, Kevin, Argueta, Kimberly, Scott, Ieisha, Greenwood, Celia M. T., Paterson, Clare, Hinterberg, Michael A., Langenberg, Claudia, Forgetta, Vincenzo, Pineau, Joelle, Mooser, Vincent, Marron, Thomas, Beckmann, Noam D., Kim-schulze, Seunghee, Charney, Alexander W., Gnjatic, Sacha, Kaufmann, Daniel E., Merad, Miriam, and Richards, J. Brent

Published
2023
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3. Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae

Author

Thompson, Ryan C., Simons, Nicole W., Wilkins, Lillian, Cheng, Esther, Del Valle, Diane Marie, Hoffman, Gabriel E., Cervia, Carlo, Fennessy, Brian, Mouskas, Konstantinos, Francoeur, Nancy J., Johnson, Jessica S., Lepow, Lauren, Le Berichel, Jessica, Chang, Christie, Beckmann, Aviva G., Wang, Ying-chih, Nie, Kai, Zaki, Nicholas, Tuballes, Kevin, Barcessat, Vanessa, Cedillo, Mario A., Yuan, Dan, Huckins, Laura, Roussos, Panos, Marron, Thomas U., Glicksberg, Benjamin S., Nadkarni, Girish, Heath, James R., Gonzalez-Kozlova, Edgar, Boyman, Onur, Kim-Schulze, Seunghee, Sebra, Robert, Merad, Miriam, Gnjatic, Sacha, Schadt, Eric E., Charney, Alexander W., and Beckmann, Noam D.

Published
2023
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4. Anti-Integrin αvβ6 Autoantibodies Are a Novel Biomarker That Antedate Ulcerative Colitis

Author

Abreu, Maria, Beck, Paul, Bernstein, Charles, Croitoru, Kenneth, Dieleman, Leo, Feagan, Brian, Griffiths, Anne, Guttman, David, Jacobson, Kevan, Kaplan, Gilaad, Krause, Denis O., Madsen, Karen, Marshall, John, Moayyedi, Paul, Ropeleski, Mark, Seidman, Ernest, Silverberg, Mark, Snapper, Scott, Stadnyk, Andy, Steinhart, Hillary, Surette, Michael, Turner, Dan, Walters, Thomas, Vallance, Bruce, Aumais, Guy, Bitton, Alain, Cino, Maria, Critch, Jeff, Denson, Lee, Deslandres, Colette, El-Matary, Wael, Herfarth, Hans, Higgins, Peter, Huynh, Hien, Hyams, Jeff, Mack, David, McGrath, Jerry, Otley, Anthony, Panancionne, Remo, Shapiro, Jason, Shah, Samir, Leleiko, Neal S., Livanos, Alexandra E., Dunn, Alexandra, Fischer, Jeremy, Ungaro, Ryan C., Turpin, Williams, Lee, Sun-Ho, Rui, Shumin, Del Valle, Diane Marie, Jougon, Julia J., Martinez-Delgado, Gustavo, Riddle, Mark S., Murray, Joseph A., Laird, Renee M., Torres, Joana, Agrawal, Manasi, Magee, Jared S., Dervieux, Thierry, Gnjatic, Sacha, Sheppard, Dean, Sands, Bruce E., Porter, Chad K., Petralia, Francesca, Colombel, Jean-Frederic, and Mehandru, Saurabh

Published
2023
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5. A methylation clock model of mild SARS‐CoV‐2 infection provides insight into immune dysregulation

Author

Mao, Weiguang, Miller, Clare M, Nair, Venugopalan D, Ge, Yongchao, Amper, Mary Anne S, Cappuccio, Antonio, George, Mary‐Catherine, Goforth, Carl W, Guevara, Kristy, Marjanovic, Nada, Nudelman, German, Pincas, Hanna, Ramos, Irene, Sealfon, Rachel S G, Soares‐Schanoski, Alessandra, Vangeti, Sindhu, Vasoya, Mital, Weir, Dawn L, Zaslavsky, Elena, Barcessat, Vanessa, Tuballes, Kevin, Del Valle, Diane Marie, Nie, Kai, Xie, Hui, Chung, Grace, Patel, Manishkumar, Harris, Jocelyn, Argueta, Kimberly, Fehr, Jacques, Gruberg, Barr, Zaki, Nicholas, Kim‐Schulze, Seunghee, Gnjatic, Sacha, Merad, Miriam, Letizia, Andrew G, Troyanskaya, Olga G, Sealfon, Stuart C, and Chikina, Maria

Published
2023
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6. Neutralizing Anti-Granulocyte Macrophage-Colony Stimulating Factor Autoantibodies Recognize Post-Translational Glycosylations on Granulocyte Macrophage-Colony Stimulating Factor Years Before Diagnosis and Predict Complicated Crohn’s Disease

Author

Mortha, Arthur, Remark, Romain, Del Valle, Diane Marie, Chuang, Ling-Shiang, Chai, Zhi, Alves, Inês, Azevedo, Catarina, Gaifem, Joana, Martin, Jerome, Petralia, Francesca, Tuballes, Kevin, Barcessat, Vanessa, Tai, Siu Ling, Huang, Hsin-Hui, Laface, Ilaria, Jerez, Yeray Arteaga, Boschetti, Gilles, Villaverde, Nicole, Wang, Mona D., Korie, Ujunwa M., Murray, Joseph, Choung, Rok-Seon, Sato, Takahiro, Laird, Renee M., Plevy, Scott, Rahman, Adeeb, Torres, Joana, Porter, Chad, Riddle, Mark S., Kenigsberg, Ephraim, Pinho, Salomé S., Cho, Judy H., Merad, Miriam, Colombel, Jean-Frederic, and Gnjatic, Sacha

Published
2022
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8. Correction: The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals

Author

Butler-Laporte, Guillaume, Gonzalez-Kozlova, Edgar, Su, Chen-Yang, Zhou, Sirui, Nakanishi, Tomoko, Brunet-Ratnasingham, Elsa, Morrison, David, Laurent, Laetitia, Aflalo, Jonathan, Aflalo, Marc, Henry, Danielle, Chen, Yiheng, Carrasco-Zanini, Julia, Farjoun, Yossi, Pietzner, Maik, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Moussa, Yara, DeLuca, Chantal, Duggan, Naomi, Schurr, Erwin, Brassard, Nathalie, Durand, Madeleine, Del Valle, Diane Marie, Thompson, Ryan, Cedillo, Mario A., Schadt, Eric, Nie, Kai, Simons, Nicole W., Mouskas, Konstantinos, Zaki, Nicolas, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Marvin, Robert, Cheng, Esther, Tuballes, Kevin, Argueta, Kimberly, Scott, Ieisha, Greenwood, Celia M. T., Paterson, Clare, Hinterberg, Michael, Langenberg, Claudia, Forgetta, Vincenzo, Mooser, Vincent, Marron, Thomas, Beckmann, Noam D., Kenigsberg, Ephraim, Charney, Alexander W., Kim-schulze, Seunghee, Merad, Miriam, Kaufmann, Daniel E., Gnjatic, Sacha, and Richards, J. Brent

Published
2022
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9. The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals

Author

Butler-Laporte, Guillaume, Gonzalez-Kozlova, Edgar, Su, Chen-Yang, Zhou, Sirui, Nakanishi, Tomoko, Brunet-Ratnasingham, Elsa, Morrison, David, Laurent, Laetitia, Afilalo, Jonathan, Afilalo, Marc, Henry, Danielle, Chen, Yiheng, Carrasco-Zanini, Julia, Farjoun, Yossi, Pietzner, Maik, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Moussa, Yara, DeLuca, Chantal, Duggan, Naomi, Schurr, Erwin, Brassard, Nathalie, Durand, Madeleine, Del Valle, Diane Marie, Thompson, Ryan, Cedillo, Mario A., Schadt, Eric, Nie, Kai, Simons, Nicole W., Mouskas, Konstantinos, Zaki, Nicolas, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Marvin, Robert, Cheng, Esther, Tuballes, Kevin, Argueta, Kimberly, Scott, Ieisha, Greenwood, Celia M. T., Paterson, Clare, Hinterberg, Michael, Langenberg, Claudia, Forgetta, Vincenzo, Mooser, Vincent, Marron, Thomas, Beckmann, Noam, Kenigsberg, Ephraim, Charney, Alexander W., Kim-schulze, Seunghee, Merad, Miriam, Kaufmann, Daniel E., Gnjatic, Sacha, and Richards, J Brent

Published
2022
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10. An inflammatory cytokine signature predicts COVID-19 severity and survival

Author

Del Valle, Diane Marie, Kim-Schulze, Seunghee, Huang, Hsin-Hui, Beckmann, Noam D., Nirenberg, Sharon, Wang, Bo, and Lavin, Yonit

Subjects
Cytokines -- Physiological aspects, Biological sciences, Health
Abstract

Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-[alpha] and IL-1[beta] in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-[alpha] levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-[alpha] serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-[alpha] levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. Elevated levels of serum IL-6 and TNF-[alpha] at the time of hospitalization are independent and significant predictors of clinical outcome in two cohorts of patients with COVID-19., Author(s): Diane Marie Del Valle [sup.1] [sup.2] [sup.3] , Seunghee Kim-Schulze [sup.1] [sup.2] [sup.3] [sup.4] , Hsin-Hui Huang [sup.5] [sup.6] [sup.7] , Noam D. Beckmann [sup.8] , Sharon Nirenberg [sup.8] [...]

Published
2020
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11. Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children

Author

Beckmann, Noam D., Comella, Phillip H., Cheng, Esther, Lepow, Lauren, Beckmann, Aviva G., Tyler, Scott R., Mouskas, Konstantinos, Simons, Nicole W., Hoffman, Gabriel E., Francoeur, Nancy J., Del Valle, Diane Marie, Kang, Gurpawan, Do, Anh, Moya, Emily, Wilkins, Lillian, Le Berichel, Jessica, Chang, Christie, Marvin, Robert, Calorossi, Sharlene, Lansky, Alona, Walker, Laura, Yi, Nancy, Yu, Alex, Chung, Jonathan, Hartnett, Matthew, Eaton, Melody, Hatem, Sandra, Jamal, Hajra, Akyatan, Alara, Tabachnikova, Alexandra, Liharska, Lora E., Cotter, Liam, Fennessy, Brian, Vaid, Akhil, Barturen, Guillermo, Shah, Hardik, Wang, Ying-chih, Sridhar, Shwetha Hara, Soto, Juan, Bose, Swaroop, Madrid, Kent, Ellis, Ethan, Merzier, Elyze, Vlachos, Konstantinos, Fishman, Nataly, Tin, Manying, Smith, Melissa, Xie, Hui, Patel, Manishkumar, Nie, Kai, Argueta, Kimberly, Harris, Jocelyn, Karekar, Neha, Batchelor, Craig, Lacunza, Jose, Yishak, Mahlet, Tuballes, Kevin, Scott, Ieisha, Kumar, Arvind, Jaladanki, Suraj, Agashe, Charuta, Thompson, Ryan, Clark, Evan, Losic, Bojan, Peters, Lauren, Roussos, Panagiotis, Zhu, Jun, Wang, Wenhui, Kasarskis, Andrew, Glicksberg, Benjamin S., Nadkarni, Girish, Bogunovic, Dusan, Elaiho, Cordelia, Gangadharan, Sandeep, Ofori-Amanfo, George, Alesso-Carra, Kasey, Onel, Kenan, Wilson, Karen M., Argmann, Carmen, Bunyavanich, Supinda, Alarcón-Riquelme, Marta E., Marron, Thomas U., Rahman, Adeeb, Kim-Schulze, Seunghee, Gnjatic, Sacha, Gelb, Bruce D., Merad, Miriam, Sebra, Robert, Schadt, Eric E., and Charney, Alexander W.

Published
2021
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12. Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection

Author

Jayaraman, Pushkala, primary, Rajagopal, Madhumitha, additional, Paranjpe, Ishan, additional, Liharska, Lora, additional, Suarez-Farinas, Mayte, additional, Thompson, Ryan, additional, Del Valle, Diane Marie, additional, Beckmann, Noam, additional, Oh, Wonsuk, additional, Gulamali, Faris F, additional, Kauffman, Justin, additional, Gonzalez-Kozlova, Edgar, additional, Dellepiane, Sergio, additional, Vasquez-Rios, George, additional, Vaid, Akhil, additional, Jiang, Joy, additional, Chen, Annie, additional, Sakhuja, Ankit, additional, Chen, Steven, additional, Kenigsberg, Ephraim, additional, He, John Cijiang, additional, Coca, Steven G, additional, Chan, Lili, additional, Schadt, Eric, additional, Merad, Miram, additional, Kim-Schulze, Seunghee, additional, Gnjatic, Sacha, additional, Tsalik, Ephraim, additional, Langley, Raymond, additional, Charney, Alexander W, additional, and Nadkarni, Girish N, additional

Published
2023
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14. Anti-Integrin αvβ6 Autoantibodies Are a Novel Biomarker That Antedate Ulcerative Colitis

Author

Livanos, Alexandra E., primary, Dunn, Alexandra, additional, Fischer, Jeremy, additional, Ungaro, Ryan C., additional, Turpin, Williams, additional, Lee, Sun-Ho, additional, Rui, Shumin, additional, Del Valle, Diane Marie, additional, Jougon, Julia J., additional, Martinez-Delgado, Gustavo, additional, Riddle, Mark S., additional, Murray, Joseph A., additional, Laird, Renee M., additional, Torres, Joana, additional, Agrawal, Manasi, additional, Magee, Jared S., additional, Dervieux, Thierry, additional, Gnjatic, Sacha, additional, Sheppard, Dean, additional, Sands, Bruce E., additional, Porter, Chad K., additional, Croitoru, Kenneth, additional, Petralia, Francesca, additional, Colombel, Jean-Frederic, additional, Mehandru, Saurabh, additional, Abreu, Maria, additional, Beck, Paul, additional, Bernstein, Charles, additional, Dieleman, Leo, additional, Feagan, Brian, additional, Griffiths, Anne, additional, Guttman, David, additional, Jacobson, Kevan, additional, Kaplan, Gilaad, additional, Krause, Denis O., additional, Madsen, Karen, additional, Marshall, John, additional, Moayyedi, Paul, additional, Ropeleski, Mark, additional, Seidman, Ernest, additional, Silverberg, Mark, additional, Snapper, Scott, additional, Stadnyk, Andy, additional, Steinhart, Hillary, additional, Surette, Michael, additional, Turner, Dan, additional, Walters, Thomas, additional, Vallance, Bruce, additional, Aumais, Guy, additional, Bitton, Alain, additional, Cino, Maria, additional, Critch, Jeff, additional, Denson, Lee, additional, Deslandres, Colette, additional, El-Matary, Wael, additional, Herfarth, Hans, additional, Higgins, Peter, additional, Huynh, Hien, additional, Hyams, Jeff, additional, Mack, David, additional, McGrath, Jerry, additional, Otley, Anthony, additional, Panancionne, Remo, additional, Shapiro, Jason, additional, Shah, Samir, additional, and Leleiko, Neal S., additional

Published
2023
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15. Additional file 3 of The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals

Author

Butler-Laporte, Guillaume, Gonzalez-Kozlova, Edgar, Su, Chen-Yang, Zhou, Sirui, Nakanishi, Tomoko, Brunet-Ratnasingham, Elsa, Morrison, David, Laurent, Laetitia, Afilalo, Jonathan, Afilalo, Marc, Henry, Danielle, Chen, Yiheng, Carrasco-Zanini, Julia, Farjoun, Yossi, Pietzner, Maik, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Moussa, Yara, DeLuca, Chantal, Duggan, Naomi, Schurr, Erwin, Brassard, Nathalie, Durand, Madeleine, Del Valle, Diane Marie, Thompson, Ryan, Cedillo, Mario A., Schadt, Eric, Nie, Kai, Simons, Nicole W., Mouskas, Konstantinos, Zaki, Nicolas, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Marvin, Robert, Cheng, Esther, Tuballes, Kevin, Argueta, Kimberly, Scott, Ieisha, Greenwood, Celia M. T., Paterson, Clare, Hinterberg, Michael, Langenberg, Claudia, Forgetta, Vincenzo, Mooser, Vincent, Marron, Thomas, Beckmann, Noam, Kenigsberg, Ephraim, Charney, Alexander W., Kim-schulze, Seunghee, Merad, Miriam, Kaufmann, Daniel E., Gnjatic, Sacha, and Richards, J Brent

Abstract

Additional file 3: Protein correlation heatmaps.

Published
2022
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16. Shift of lung macrophage composition is associated with COVID-19 disease severity and recovery

Author

Chen, Steven T., Park, Matthew D., Del Valle, Diane Marie, Buckup, Mark, Tabachnikova, Alexandra, Simons, Nicole W., Mouskas, Konstantinos, Lee, Brian, Geanon, Daniel, D’Souza, Darwin, Dawson, Travis, Marvin, Robert, Nie, Kai, Thompson, Ryan C., Zhao, Zhen, LeBerichel, Jessica, Chang, Christie, Jamal, Hajra, Chaddha, Udit, Mathews, Kusum, Acquah, Samuel, Brown, Stacey-Ann, Reiss, Michelle, Harkin, Timothy, Feldmann, Marc, Powell, Charles A., Hook, Jaime L., Kim-Schulze, Seunghee, Rahman, Adeeb H., Brown, Brian D., Beckmann, Noam D., Gnjatic, Sacha, Kenigsberg, Ephraim, Charney, Alexander W., and Merad, Miriam

Subjects
Macrophages, Macrophages, Alveolar, COVID-19, Humans, Lung, Article, Monocytes
Abstract

Although it has been more than 2 years since the start of the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 continues to be a worldwide health crisis. Despite the development of preventive vaccines, therapies to treat COVID-19 and other inflammatory diseases remain a major unmet need in medicine. Our study sought to identify drivers of disease severity and mortality to develop tailored immunotherapy strategies to halt disease progression. We assembled the Mount Sinai COVID-19 Biobank, which was composed of almost 600 hospitalized patients followed longitudinally through the peak of the pandemic in 2020. Moderate disease and survival were associated with a stronger antigen presentation and effector T cell signature. In contrast, severe disease and death were associated with an altered antigen presentation signature, increased numbers of inflammatory immature myeloid cells, and extrafollicular activated B cells that have been previously associated with autoantibody formation. In severely ill patients with COVID-19, lung tissue-resident alveolar macrophages not only were drastically depleted but also had an altered antigen presentation signature, which coincided with an influx of inflammatory monocytes and monocyte-derived macrophages. In addition, we found that the size of the alveolar macrophage pool correlated with patient outcome and that alveolar macrophage numbers and functionality were restored to homeostasis in patients who recovered from COVID-19. These data suggest that local and systemic myeloid cell dysregulation are drivers of COVID-19 severity and modulation of alveolar macrophage numbers and activity in the lung may be a viable therapeutic strategy for the treatment of critical inflammatory lung diseases.

Published
2022

17. Additional file 6 of The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals

Author

Butler-Laporte, Guillaume, Gonzalez-Kozlova, Edgar, Su, Chen-Yang, Zhou, Sirui, Nakanishi, Tomoko, Brunet-Ratnasingham, Elsa, Morrison, David, Laurent, Laetitia, Afilalo, Jonathan, Afilalo, Marc, Henry, Danielle, Chen, Yiheng, Carrasco-Zanini, Julia, Farjoun, Yossi, Pietzner, Maik, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Moussa, Yara, DeLuca, Chantal, Duggan, Naomi, Schurr, Erwin, Brassard, Nathalie, Durand, Madeleine, Del Valle, Diane Marie, Thompson, Ryan, Cedillo, Mario A., Schadt, Eric, Nie, Kai, Simons, Nicole W., Mouskas, Konstantinos, Zaki, Nicolas, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Marvin, Robert, Cheng, Esther, Tuballes, Kevin, Argueta, Kimberly, Scott, Ieisha, Greenwood, Celia M. T., Paterson, Clare, Hinterberg, Michael, Langenberg, Claudia, Forgetta, Vincenzo, Mooser, Vincent, Marron, Thomas, Beckmann, Noam, Kenigsberg, Ephraim, Charney, Alexander W., Kim-schulze, Seunghee, Merad, Miriam, Kaufmann, Daniel E., Gnjatic, Sacha, and Richards, J Brent

Abstract

Additional file 6: Mount Sinai investigators.

Published
2022
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18. Additional file 1 of The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals

Author

Butler-Laporte, Guillaume, Gonzalez-Kozlova, Edgar, Su, Chen-Yang, Zhou, Sirui, Nakanishi, Tomoko, Brunet-Ratnasingham, Elsa, Morrison, David, Laurent, Laetitia, Afilalo, Jonathan, Afilalo, Marc, Henry, Danielle, Chen, Yiheng, Carrasco-Zanini, Julia, Farjoun, Yossi, Pietzner, Maik, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Moussa, Yara, DeLuca, Chantal, Duggan, Naomi, Schurr, Erwin, Brassard, Nathalie, Durand, Madeleine, Del Valle, Diane Marie, Thompson, Ryan, Cedillo, Mario A., Schadt, Eric, Nie, Kai, Simons, Nicole W., Mouskas, Konstantinos, Zaki, Nicolas, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Marvin, Robert, Cheng, Esther, Tuballes, Kevin, Argueta, Kimberly, Scott, Ieisha, Greenwood, Celia M. T., Paterson, Clare, Hinterberg, Michael, Langenberg, Claudia, Forgetta, Vincenzo, Mooser, Vincent, Marron, Thomas, Beckmann, Noam, Kenigsberg, Ephraim, Charney, Alexander W., Kim-schulze, Seunghee, Merad, Miriam, Kaufmann, Daniel E., Gnjatic, Sacha, and Richards, J Brent

Abstract

Additional file 1: List of immunity-related proteins measured.

Published
2022
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19. Additional file 2 of The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals

Author

Butler-Laporte, Guillaume, Gonzalez-Kozlova, Edgar, Su, Chen-Yang, Zhou, Sirui, Nakanishi, Tomoko, Brunet-Ratnasingham, Elsa, Morrison, David, Laurent, Laetitia, Afilalo, Jonathan, Afilalo, Marc, Henry, Danielle, Chen, Yiheng, Carrasco-Zanini, Julia, Farjoun, Yossi, Pietzner, Maik, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Moussa, Yara, DeLuca, Chantal, Duggan, Naomi, Schurr, Erwin, Brassard, Nathalie, Durand, Madeleine, Del Valle, Diane Marie, Thompson, Ryan, Cedillo, Mario A., Schadt, Eric, Nie, Kai, Simons, Nicole W., Mouskas, Konstantinos, Zaki, Nicolas, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Marvin, Robert, Cheng, Esther, Tuballes, Kevin, Argueta, Kimberly, Scott, Ieisha, Greenwood, Celia M. T., Paterson, Clare, Hinterberg, Michael, Langenberg, Claudia, Forgetta, Vincenzo, Mooser, Vincent, Marron, Thomas, Beckmann, Noam, Kenigsberg, Ephraim, Charney, Alexander W., Kim-schulze, Seunghee, Merad, Miriam, Kaufmann, Daniel E., Gnjatic, Sacha, and Richards, J Brent

Abstract

Additional file 2: Sample code for the generalized additive models.

Published
2022
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20. Additional file 5 of The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals

Author

Butler-Laporte, Guillaume, Gonzalez-Kozlova, Edgar, Su, Chen-Yang, Zhou, Sirui, Nakanishi, Tomoko, Brunet-Ratnasingham, Elsa, Morrison, David, Laurent, Laetitia, Afilalo, Jonathan, Afilalo, Marc, Henry, Danielle, Chen, Yiheng, Carrasco-Zanini, Julia, Farjoun, Yossi, Pietzner, Maik, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Moussa, Yara, DeLuca, Chantal, Duggan, Naomi, Schurr, Erwin, Brassard, Nathalie, Durand, Madeleine, Del Valle, Diane Marie, Thompson, Ryan, Cedillo, Mario A., Schadt, Eric, Nie, Kai, Simons, Nicole W., Mouskas, Konstantinos, Zaki, Nicolas, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Marvin, Robert, Cheng, Esther, Tuballes, Kevin, Argueta, Kimberly, Scott, Ieisha, Greenwood, Celia M. T., Paterson, Clare, Hinterberg, Michael, Langenberg, Claudia, Forgetta, Vincenzo, Mooser, Vincent, Marron, Thomas, Beckmann, Noam, Kenigsberg, Ephraim, Charney, Alexander W., Kim-schulze, Seunghee, Merad, Miriam, Kaufmann, Daniel E., Gnjatic, Sacha, and Richards, J Brent

Abstract

Additional file 5: Inferred protein levels over time.

Published
2022
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22. The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals

Author

Butler-Laporte, Guillaume, Gonzalez-Kozlova, Edgar, Su, Chen-Yang, Zhou, Sirui, Nakanishi, Tomoko, Brunet-Ratnasingham, Elsa, Morrison, David, Laurent, Laetitia, Afilalo, Jonathan, Afilalo, Marc, Henry, Danielle, Chen, Yiheng, Carrasco-Zanini, Julia, Farjoun, Yossi, Pietzner, Maik, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Moussa, Yara, DeLuca, Chantal, Duggan, Naomi, Schurr, Erwin, Brassard, Nathalie, Durand, Madeleine, Del Valle, Diane Marie, Thompson, Ryan, Cedillo, Mario A, Schadt, Eric, Nie, Kai, Simons, Nicole W, Mouskas, Konstantinos, Zaki, Nicolas, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Marvin, Robert, Cheng, Esther, Tuballes, Kevin, Argueta, Kimberly, Scott, Ieisha, Greenwood, Celia M T, Paterson, Clare, Hinterberg, Michael, Langenberg, Claudia, Forgetta, Vincenzo, Mooser, Vincent, Marron, Thomas, Beckmann, Noam, Kenigsberg, Ephraim, Charney, Alexander W, Kim-Schulze, Seunghee, Merad, Miriam, Kaufmann, Daniel E, Gnjatic, Sacha, Richards, J Brent, Rezk, Nardin [0000-0001-5358-7704], Richards, J Brent [0000-0002-3746-9086], and Apollo - University of Cambridge Repository

Subjects
Proteomics, Somascan, Immunity, Covid-19
Abstract

IntroductionSevere COVID-19 leads to important changes in circulating immune-related proteins. To date it has been difficult to understand their temporal relationship and identify cytokines that are drivers of severe COVID-19 outcomes and underlie differences in outcomes between sexes. Here, we measured 147 immune-related proteins during acute COVID-19 to investigate these questions.MethodsWe measured circulating protein abundances using the SOMAscan nucleic acid aptamer panel in two large independent hospital-based COVID-19 cohorts in Canada and the United States. We fit generalized additive models with cubic splines from the start of symptom onset to identify protein levels over the first 14 days of infection which were different between severe cases and controls, adjusting for age and sex. Severe cases were defined as individuals with COVID-19 requiring invasive or non-invasive mechanical respiratory support.Results580 individuals were included in the analysis. Mean subject age was 64.3 (sd 18.1), and 47% were male. Of the 147 proteins, 69 showed a significant difference between cases and controls (p -4). Three clusters were formed by 108 highly correlated proteins that replicated in both cohorts, making it difficult to determine which proteins have a true causal effect on severe COVID-19. Six proteins showed sex differences in levels over time, of which 3 were also associated with severe COVID-19: CCL26, IL1RL2, and IL3RA, providing insights to better understand the marked differences in outcomes by sex.ConclusionsSevere COVID-19 is associated with large changes in 69 immune-related proteins. Further, five proteins were associated with sex differences in outcomes. These results provide direct insights into immune-related proteins that are strongly influenced by severe COVID-19 infection.

Published
2021

23. Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection

Author

Paranjpe, Ishan, primary, Jayaraman, Pushkala, additional, Su, Chen-Yang, additional, Zhou, Sirui, additional, Chen, Steven, additional, Thompson, Ryan, additional, Del Valle, Diane Marie, additional, Kenigsberg, Ephraim, additional, Zhao, Shan, additional, Jaladanki, Suraj, additional, Chaudhary, Kumardeep, additional, Ascolillo, Steven, additional, Vaid, Akhil, additional, Kumar, Arvind, additional, Kozlova, Edgar, additional, Paranjpe, Manish, additional, O’Hagan, Ross, additional, Kamat, Samir, additional, Gulamali, Faris F., additional, Kauffman, Justin, additional, Xie, Hui, additional, Harris, Joceyln, additional, Patel, Manishkumar, additional, Argueta, Kimberly, additional, Batchelor, Craig, additional, Nie, Kai, additional, Dellepiane, Sergio, additional, Scott, Leisha, additional, Levin, Matthew A, additional, He, John Cijiang, additional, Suarez-Farinas, Mayte, additional, Coca, Steven G, additional, Chan, Lili, additional, Azeloglu, Evren U, additional, Schadt, Eric, additional, Beckmann, Noam, additional, Gnjatic, Sacha, additional, Merad, Miram, additional, Kim-Schulze, Seunghee, additional, Richards, Brent, additional, Glicksberg, Benjamin S, additional, Charney, Alexander W, additional, and Nadkarni, Girish N, additional

Published
2021
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24. Quantitative chest CT combined with plasma cytokines predict outcomes in COVID-19 patients

Author

Carbonell, Guillermo, primary, Del Valle, Diane Marie, additional, Gonzalez-Kozlova, Edgar E, additional, Marinelli, Brett, additional, Klein, Emma, additional, El Homsi, Maria, additional, Stocker, Daniel, additional, Chung, Michael, additional, Bernheim, Adam, additional, Simons, Nicole, additional, Xiang, Jiani, additional, Nirenberg, Sharon, additional, Kovatch, Patricia, additional, Lewis, Sara, additional, Merad, Miriam, additional, Gnjatic, Sacha, additional, and Taouli, Bachir, additional

Published
2021
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25. Anti–GM-CSF autoantibodies promote a “pre-diseased” state in Crohn’s Disease

Author

Mortha, Arthur, primary, Remark, Romain, additional, Del Valle, Diane Marie, additional, Chuang, Ling-Shiang, additional, Chai, Zhi, additional, Alves, Inês, additional, Azevedo, Catarina, additional, Gaifem, Joana, additional, Martin, Jerome, additional, Tuballes, Kevin, additional, Barcessat, Vanessa, additional, Tai, Siu Ling, additional, Huang, Hsin-Hui, additional, Laface, Ilaria, additional, Jerez, Yeray Arteaga, additional, Boschetti, Gilles, additional, Villaverde, Nicole, additional, Wang, Mona D., additional, Korie, Ujunwa M., additional, Murray, Joseph, additional, Choung, Rok-Seon, additional, Sato, Takahiro, additional, Laird, Renee M., additional, Plevy, Scot, additional, Rahman, Adeeb, additional, Torres, Joana, additional, Porter, Chad, additional, Riddle, Mark S., additional, Kenigsberg, Ephraim, additional, Pinho, Salomé S., additional, Cho, Judy H., additional, Merad, Miriam, additional, Colombel, Jean-Frederic, additional, and Gnjatic, Sacha, additional

Published
2021
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26. Immune Landscape Associated with Response to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Relapsed/Refractory Hodgkin Lymphoma (E4412 Phase 1)

Author

Diefenbach, Catherine S, Gonzalez-Kozlova, Edgar, Del Valle, Diane Marie, Huang, Hsin-Hui, Jegede, Opeyemi, Barcessat, Vanessa, Tuballes, Kevin, Kelly, Geoffrey, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Argueta, Kimberly, Nie, Kai, Moravec, Radim, Altreuter, Jennifer, Duose, Dzifa Yawa, Kahl, Brad S., Ansell, Stephen M, Yu, Joyce, Cerami, Ethan, Lindsay, James, Wistuba, Ignacio, Kim-Schulze, Seunghee, and Gnjatic, Sacha

Published
2023
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27. A shift in lung macrophage composition is associated with COVID-19 severity and recovery.

Author

Chen, Steven T., Park, Matthew D., Del Valle, Diane Marie, Buckup, Mark, Tabachnikova, Alexandra, Thompson, Ryan C., Simons, Nicole W., Mouskas, Konstantinos, Lee, Brian, Geanon, Daniel, D'Souza, Darwin, Dawson, Travis, Marvin, Robert, Nie, Kai, Zhao, Zhen, LeBerichel, Jessica, Chang, Christie, Jamal, Hajra, Akturk, Guray, and Chaddha, Udit

Subjects
COVID-19, ALVEOLAR macrophages, MYELOID cells, ANTIGEN presentation, AUTOANTIBODIES, COVID-19 pandemic, B cells, MACROPHAGES
Abstract

Although it has been more than 2 years since the start of the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 continues to be a worldwide health crisis. Despite the development of preventive vaccines, therapies to treat COVID-19 and other inflammatory diseases remain a major unmet need in medicine. Our study sought to identify drivers of disease severity and mortality to develop tailored immunotherapy strategies to halt disease progression. We assembled the Mount Sinai COVID-19 Biobank, which was composed of almost 600 hospitalized patients followed longitudinally through the peak of the pandemic in 2020. Moderate disease and survival were associated with a stronger antigen presentation and effector T cell signature. In contrast, severe disease and death were associated with an altered antigen presentation signature, increased numbers of inflammatory immature myeloid cells, and extrafollicular activated B cells that have been previously associated with autoantibody formation. In severely ill patients with COVID-19, lung tissue–resident alveolar macrophages not only were drastically depleted but also had an altered antigen presentation signature, which coincided with an influx of inflammatory monocytes and monocyte-derived macrophages. In addition, we found that the size of the alveolar macrophage pool correlated with patient outcome and that alveolar macrophage numbers and functionality were restored to homeostasis in patients who recovered from COVID-19. These data suggest that local and systemic myeloid cell dysregulation are drivers of COVID-19 severity and modulation of alveolar macrophage numbers and activity in the lung may be a viable therapeutic strategy for the treatment of critical inflammatory lung diseases. Modulation of macrophages: Understanding why some individuals develop severe disease after SARS-CoV-2 infection remains a high priority. Here, Chen et al. evaluated factors associated with disease severity and survival in samples from 600 individuals hospitalized with COVID-19 during 2020. The authors found that severe disease and death were associated with altered antigen presentation signatures, as well as a distinct macrophage profile in the peripheral blood. They also studied lung macrophages, finding that those with severe COVID-19 had increased inflammatory monocytes and monocyte-derived macrophage infiltration, with a corresponding decrease in the alveolar macrophage population. Together, these data suggest that restoring macrophage homeostasis may be a strategy for treating COVID-19. [ABSTRACT FROM AUTHOR]

Published
2022
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28. A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward

Author

Wang, Bo, primary, Van Oekelen, Oliver, additional, Mouhieddine, Tarek H., additional, Del Valle, Diane Marie, additional, Richter, Joshua, additional, Cho, Hearn Jay, additional, Richard, Shambavi, additional, Chari, Ajai, additional, Gnjatic, Sacha, additional, Merad, Miriam, additional, Jagannath, Sundar, additional, Parekh, Samir, additional, and Madduri, Deepu, additional

Published
2020
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29. An inflammatory cytokine signature helps predict COVID-19 severity and death

Author

Del Valle, Diane Marie, primary, Kim-schulze, Seunghee, additional, Hsin-hui, Huang, additional, Beckmann, Noam D, additional, Nirenberg, Sharon, additional, Wang, Bo, additional, Lavin, Yonit, additional, Swartz, Talia, additional, Madduri, Deepu, additional, Stock, Aryeh, additional, Marron, Thomas, additional, Xie, Hui, additional, Patel, Manish Kumar, additional, van Oekelen, Oliver, additional, Rahman, Adeeb, additional, Kovatch, Patricia, additional, Aberg, Judith, additional, Schadt, Eric, additional, Jagannath, Sundar, additional, Mazumdar, Madhu, additional, Charney, Alexander, additional, Firpo-Betancourt, Adolfo, additional, Mendu, Damodara Rao, additional, Jhang, Jeffrey, additional, Reich, David, additional, Sigel, Keith, additional, Cordon-Cardo, Carlos, additional, Feldmann, Marc, additional, Parekh, Samir, additional, Merad, Miriam, additional, and Gnjatic, Sacha, additional

Published
2020
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30. Sampling the host response to SARS-CoV-2 in hospitals under siege

Author

Charney, Alexander W., Simons, Nicole W., Mouskas, Konstantinos, Lepow, Lauren, Cheng, Esther, Le Berichel, Jessica, Chang, Christie, Marvin, Robert, Del Valle, Diane Marie, Calorossi, Sharlene, Lansky, Alona, Walker, Laura, Patel, Manishkumar, Xie, Hui, Yi, Nancy, Yu, Alex, Kang, Gurpawan, Mendoza, Anthony, Liharska, Lora E., Moya, Emily, Hartnett, Matthew, Hatem, Sandra, Wilkins, Lillian, Eaton, Melody, Jamal, Hajra, Tuballes, Kevin, Chen, Steven T., Tabachnikova, Alexandra, Chung, Jonathan, Harris, Jocelyn, Batchelor, Craig, Lacunza, Jose, Yishak, Mahlet, Argueta, Kimberly, Karekar, Neha, Lee, Brian, Kelly, Geoffrey, Geanon, Daniel, Handler, Diana, Leech, John, Stefanos, Hiyab, Dawson, Travis, Scott, Ieisha, Francoeur, Nancy, Johnson, Jessica S., Vaid, Akhil, Glicksberg, Benjamin S., Nadkarni, Girish N., Schadt, Eric E., Gelb, Bruce D., Rahman, Adeeb, Sebra, Robert, Martin, Glenn, Agashe, Charuta, Agrawal, Priyal, Akyatan, Alara, Alesso-Carra, Kasey, Alibo, Eziwoma, Alvarez, Kelvin, Amabile, Angelo, Ascolillo, Steven, Bailey, Rasheed, Begani, Priya, Correra, Paloma Bravo, Brown, Stacey-Ann, Buckup, Mark, Burka, Larissa, Cambron, Lena, Carrara, Gina, Chang, Serena, Chien, Jonathan, Chowdhury, Mashkura, Bozkus, Cansu Cimen, Comella, Phillip, Cosgrove, Dana, Cossarini, Francesca, Cotter, Liam, Dave, Arpit, Dayal, Bheesham, Dhainaut, Maxime, Dornfeld, Rebecca, Dul, Katie, Eber, Nissan, Elaiho, Cordelia, Fabris, Frank, Faith, Jeremiah, Falci, Dominique, Feng, Susie, Fennessy, Brian, Fernandes, Marie, Gangadharan, Sandeep, Grabowska, Joanna, Gyimesi, Gavin, Hamdani, Maha, Herbinet, Manon, Herrera, Elva, Hochman, Arielle, Hoffman, Gabriel E., Hook, Jaime, Horta, Laila, Humblin, Etienne, Karim, Subha, Kim, Jessica, Lebovitch, Dannielle, Lee, Grace, Lee, Gyu Ho, Lee, Jacky, Leventhal, Mike, Lindblad, Katherine, Livanos, Alexandra, Machado, Rosalie, Mahmood, Zafar, Mar, Kelcey, Maskey, Shrisha, Matthews, Paul, Meckel, Katherine, Mehandru, Saurabh, Mercedes, Cynthia, Meyer, Dara, Mollaoglu, Gurkan, Morris, Sarah, Nie, Kai, Nisenholtz, Marjorie, Ofori-Amanfo, George, Onel, Kenan, Ounadjela, Merouane, Patel, Vishwendra, Pruitt, Cassandra, Rathi, Shivani, Redes, Jamie, Reyes-Torres, Ivan, Rodrigues, Alcina, Rodriguez, Alfonso, Roudko, Vladimir, Ruiz, Evelyn, Scalzo, Pearl, Silva, Pedro, Schanoski, Alessandra Soares, Straw, Meghan, Tabachnikova, Sasha, Teague, Collin, Upadhyaya, Bhaskar, Van Der Heide, Verena, Vaninov, Natalie, Wacker, Daniel, Walsh, Hadley, Wilk, C. Matthias, Wilson, Jessica, Wilson, Karen M., Xue, Li, Yeboah, Naa-akomaah, Young, Sabina, Zaks, Nina, Zha, Renyuan, Marron, Thomas, Beckmann, Noam, Kim-Schulze, Seunghee, Gnjatic, Sacha, and Merad, Miriam

Subjects
Siege, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Host response, Sampling (statistics), General Medicine, biology.organism_classification, Virology, General Biochemistry, Genetics and Molecular Biology, Pandemic, Medicine, business, Betacoronavirus
Published
2020
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31. Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis

Author

Shang, Joan, Del Valle, Diane Marie, Britton, Graham J., Mead, K.R., Rajpal, Urvija, Chen-Liaw, Alice, Mogno, Ilaria, Li, Zhihua, Menon, Rajita, Gonzalez-Kozlova, Edgar, Elkrief, Arielle, Peled, Jonathan U., Gonsalves, Tina Ruth, Shah, Neil J., Postow, Michael, Colombel, Jean-Frederic, Gnjatic, Sacha, Faleck, David M., and Faith, Jeremiah J.

Abstract

Immunotherapy-related colitis (irC) frequently emerges as an immune-related adverse event during immune checkpoint inhibitor therapy and is presumably influenced by the gut microbiota. We longitudinally studied microbiomes from 38 ICI-treated cancer patients. We compared 13 ICI-treated subjects who developed irC against 25 ICI-treated subjects who remained irC-free, along with a validation cohort. Leveraging a preclinical mouse model, predisease stools from irC subjects induced greater colitigenicity upon transfer to mice. The microbiota during the first 10 days of irC closely resembled inflammatory bowel disease microbiomes, with reduced diversity, increased Proteobacteria and Veillonella, and decreased Faecalibacterium, which normalized before irC remission. These findings highlight the irC gut microbiota as functionally distinct but phylogenetically similar to non-irC and healthy microbiomes, with the exception of an acute, transient disruption early in irC. We underscore the significance of longitudinal microbiome profiling in developing clinical avenues to detect, monitor, and mitigate irC in ICI therapy cancer patients.

Published
2025
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32. Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae

Author

Thompson, Ryan C., Simons, Nicole W., Wilkins, Lillian, Cheng, Esther, Del Valle, Diane Marie, Hoffman, Gabriel E., Cervia, Carlo, Fennessy, Brian, Mouskas, Konstantinos, Francoeur, Nancy J., Johnson, Jessica S., Lepow, Lauren, Le Berichel, Jessica, Chang, Christie, Beckmann, Aviva G., Wang, Ying-chih, Nie, Kai, Zaki, Nicholas, Tuballes, Kevin, Barcessat, Vanessa, Cedillo, Mario A., Yuan, Dan, Huckins, Laura, Roussos, Panos, Marron, Thomas U., Glicksberg, Benjamin S., Nadkarni, Girish, Heath, James R., Gonzalez-Kozlova, Edgar, Boyman, Onur, Kim-Schulze, Seunghee, Sebra, Robert, Merad, Miriam, Gnjatic, Sacha, Schadt, Eric E., Charney, Alexander W., and Beckmann, Noam D.

Abstract

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.

Published
2022
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33. Author Correction: Sampling the host response to SARS-CoV-2 in hospitals under siege

Author

Charney, Alexander W., Simons, Nicole W., Mouskas, Konstantinos, Lepow, Lauren, Cheng, Esther, Le Berichel, Jessica, Chang, Christie, Marvin, Robert, Del Valle, Diane Marie, Calorossi, Sharlene, Lansky, Alona, Walker, Laura, Patel, Manishkumar, Xie, Hui, Yi, Nancy, Yu, Alex, Kang, Gurpawan, Mendoza, Anthony, Liharska, Lora E., Moya, Emily, Hartnett, Matthew, Hatem, Sandra, Wilkins, Lillian, Eaton, Melody, Jamal, Hajra, Tuballes, Kevin, Chen, Steven T., Tabachnikova, Alexandra, Chung, Jonathan, Harris, Jocelyn, Batchelor, Craig, Lacunza, Jose, Yishak, Mahlet, Argueta, Kimberly, Karekar, Neha, Lee, Brian, Kelly, Geoffrey, Geanon, Daniel, Handler, Diana, Leech, John, Stefanos, Hiyab, Dawson, Travis, Scott, Ieisha, Francoeur, Nancy, Johnson, Jessica S., Vaid, Akhil, Glicksberg, Benjamin S., Nadkarni, Girish N., Schadt, Eric E., Gelb, Bruce D., Rahman, Adeeb, Sebra, Robert, Martin, Glenn, Marron, Thomas, Beckmann, Noam, Kim-Schulze, Seunghee, Gnjatic, Sacha, and Merad, Miriam

Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41591-021-01247-3.

Published
2021
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34. Author Correction: Sampling the host response to SARS-CoV-2 in hospitals under siege

Author

Charney, Alexander W., Simons, Nicole W., Mouskas, Konstantinos, Lepow, Lauren, Cheng, Esther, Le Berichel, Jessica, Chang, Christie, Marvin, Robert, Del Valle, Diane Marie, Calorossi, Sharlene, Lansky, Alona, Walker, Laura, Patel, Manishkumar, Xie, Hui, Yi, Nancy, Yu, Alex, Kang, Gurpawan, Liharska, Lora E., Moya, Emily, Hartnett, Matthew, Hatem, Sandra, Wilkins, Lillian, Eaton, Melody, Jamal, Hajra, Tuballes, Kevin, Chen, Steven T., Chung, Jonathan, Harris, Jocelyn, Batchelor, Craig, Lacunza, Jose, Yishak, Mahlet, Argueta, Kimberly, Karekar, Neha, Lee, Brian, Kelly, Geoffrey, Geanon, Daniel, Handler, Diana, Leech, John, Stefanos, Hiyab, Dawson, Travis, Scott, Ieisha, Francoeur, Nancy, Johnson, Jessica S., Vaid, Akhil, Glicksberg, Benjamin S., Nadkarni, Girish N., Schadt, Eric E., Gelb, Bruce D., Rahman, Adeeb, Sebra, Robert, Martin, Glenn, Marron, Thomas, Beckmann, Noam, Kim-Schulze, Seunghee, Gnjatic, Sacha, and Merad, Miriam

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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35. Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection.

Author

Jayaraman P, Rajagopal M, Paranjpe I, Liharska L, Suarez-Farinas M, Thompson R, Del Valle DM, Beckmann N, Oh W, Gulamali FF, Kauffman J, Gonzalez-Kozlova E, Dellepiane S, Vasquez-Rios G, Vaid A, Jiang J, Chen A, Sakhuja A, Chen S, Kenigsberg E, He JC, Coca SG, Chan L, Schadt E, Merad M, Kim-Schulze S, Gnjatic S, Tsalik E, Langley R, Charney AW, and Nadkarni GN

Abstract

Background: Acute kidney injury (AKI) is common in hospitalized patients with SARS-CoV2 infection despite vaccination and leads to long-term kidney dysfunction. However, peripheral blood molecular signatures in AKI from COVID-19 and their association with long-term kidney dysfunction are yet unexplored., Methods: In patients hospitalized with SARS-CoV2, we performed bulk RNA sequencing using peripheral blood mononuclear cells(PBMCs). We applied linear models accounting for technical and biological variability on RNA-Seq data accounting for false discovery rate (FDR) and compared functional enrichment and pathway results to a historical sepsis-AKI cohort. Finally, we evaluated the association of these signatures with long-term trends in kidney function., Results: Of 283 patients, 106 had AKI. After adjustment for sex, age, mechanical ventilation, and chronic kidney disease (CKD), we identified 2635 significant differential gene expressions at FDR<0.05. Top canonical pathways were EIF2 signaling, oxidative phosphorylation, mTOR signaling, and Th17 signaling, indicating mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Comparison with sepsis associated AKI showed considerable overlap of key pathways (48.14%). Using follow-up estimated glomerular filtration rate (eGFR) measurements from 115 patients, we identified 164/2635 (6.2%) of the significantly differentiated genes associated with overall decrease in long-term kidney function. The strongest associations were 'autophagy', 'renal impairment via fibrosis', and 'cardiac structure and function'., Conclusions: We show that AKI in SARS-CoV2 is a multifactorial process with mitochondrial dysfunction driven by ER stress whereas long-term kidney function decline is associated with cardiac structure and function and immune dysregulation. Functional overlap with sepsis-AKI also highlights common signatures, indicating generalizability in therapeutic approaches., Significance Statement: Peripheral transcriptomic findings in acute and long-term kidney dysfunction after hospitalization for SARS-CoV2 infection are unclear. We evaluated peripheral blood molecular signatures in AKI from COVID-19 (COVID-AKI) and their association with long-term kidney dysfunction using the largest hospitalized cohort with transcriptomic data. Analysis of 283 hospitalized patients of whom 37% had AKI, highlighted the contribution of mitochondrial dysfunction driven by endoplasmic reticulum stress in the acute stages. Subsequently, long-term kidney function decline exhibits significant associations with markers of cardiac structure and function and immune mediated dysregulation. There were similar biomolecular signatures in other inflammatory states, such as sepsis. This enhances the potential for repurposing and generalizability in therapeutic approaches.

Published
2023
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36. Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection.

Author

Paranjpe I, Jayaraman P, Su CY, Zhou S, Chen S, Thompson R, Del Valle DM, Kenigsberg E, Zhao S, Jaladanki S, Chaudhary K, Ascolillo S, Vaid A, Kumar A, Kozlova E, Paranjpe M, O'Hagan R, Kamat S, Gulamali FF, Kauffman J, Xie H, Harris J, Patel M, Argueta K, Batchelor C, Nie K, Dellepiane S, Scott L, Levin MA, He JC, Suarez-Farinas M, Coca SG, Chan L, Azeloglu EU, Schadt E, Beckmann N, Gnjatic S, Merad M, Kim-Schulze S, Richards B, Glicksberg BS, Charney AW, and Nadkarni GN

Abstract

Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Using measurements of ∼4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N= 437), we identified 413 higher plasma abundances of protein targets and 40 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p <0.05). Of these, 62 proteins were validated in an external cohort (p <0.05, N =261). We demonstrate that COVID-AKI is associated with increased markers of tubular injury (NGAL) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p <0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2, trefoil factor 3, transmembrane emp24 domain-containing protein 10, and cystatin-C indicating tubular dysfunction and injury. Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.

Published
2022
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37. Quantitative chest CT combined with plasma cytokines predict outcomes in COVID-19 patients.

Author

Carbonell G, Del Valle DM, Gonzalez-Kozlova E, Marinelli B, Klein E, El Homsi M, Stocker D, Chung M, Bernheim A, Simons NW, Xiang J, Nirenberg S, Kovatch P, Lewis S, Merad M, Gnjatic S, and Taouli B

Abstract

Despite extraordinary international efforts to dampen the spread and understand the mechanisms behind SARS-CoV-2 infections, accessible predictive biomarkers directly applicable in the clinic are yet to be discovered. Recent studies have revealed that diverse types of assays bear limited predictive power for COVID-19 outcomes. Here, we harness the predictive power of chest CT in combination with plasma cytokines using a machine learning approach for predicting death during hospitalization and maximum severity degree in COVID-19 patients. Patients (n=152) from the Mount Sinai Health System in New York with plasma cytokine assessment and a chest CT within 5 days from admission were included. Demographics, clinical, and laboratory variables, including plasma cytokines (IL-6, IL-8, and TNF-α) were collected from the electronic medical record. We found that chest CT combined with plasma cytokines were good predictors of death (AUC 0.78) and maximum severity (AUC 0.82), whereas CT quantitative was better at predicting severity (AUC 0.81 vs 0.70) while cytokine measurements better predicted death (AUC 0.70 vs 0.66). Finally, we provide a simple scoring system using plasma IL-6, IL-8, TNF-α, GGO to aerated lung ratio and age as novel metrics that may be used to monitor patients upon hospitalization and help physicians make critical decisions and considerations for patients at high risk of death for COVID-19.

Published
2021
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38. Acute COVID-19 gene-expression profiles show multiple etiologies of long-term sequelae.

Author

Thompson RC, Simons NW, Wilkins L, Cheng E, Del Valle DM, Hoffman GE, Fennessy B, Mouskas K, Francoeur NJ, Johnson JS, Lepow L, Le Berichel J, Chang C, Beckmann AG, Wang YC, Nie K, Zaki N, Tuballes K, Barcessat V, Cedillo MA, Huckins L, Roussos P, Marron TU, Glicksberg BS, Nadkarni G, Gonzalez-Kozlova E, Kim-Schulze S, Sebra R, Merad M, Gnjatic S, Schadt EE, Charney AW, and Beckmann ND

Abstract

Two years into the SARS-CoV-2 pandemic, the post-acute sequelae of infection are compounding the global health crisis. Often debilitating, these sequelae are clinically heterogeneous and of unknown molecular etiology. Here, a transcriptome-wide investigation of this new condition was performed in a large cohort of acutely infected patients followed clinically into the post-acute period. Gene expression signatures of post-acute sequelae were already present in whole blood during the acute phase of infection, with both innate and adaptive immune cells involved. Plasma cells stood out as driving at least two distinct clusters of sequelae, one largely dependent on circulating antibodies against the SARS-CoV-2 spike protein and the other antibody-independent. Altogether, multiple etiologies of post-acute sequelae were found concomitant with SARS-CoV-2 infection, directly linking the emergence of these sequelae with the host response to the virus.

Published
2021
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39. Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children.

Author

Beckmann ND, Comella PH, Cheng E, Lepow L, Beckmann AG, Mouskas K, Simons NW, Hoffman GE, Francoeur NJ, Del Valle DM, Kang G, Moya E, Wilkins L, Le Berichel J, Chang C, Marvin R, Calorossi S, Lansky A, Walker L, Yi N, Yu A, Hartnett M, Eaton M, Hatem S, Jamal H, Akyatan A, Tabachnikova A, Liharska LE, Cotter L, Fennessey B, Vaid A, Barturen G, Tyler SR, Shah H, Wang YC, Sridhar SH, Soto J, Bose S, Madrid K, Ellis E, Merzier E, Vlachos K, Fishman N, Tin M, Smith M, Xie H, Patel M, Argueta K, Harris J, Karekar N, Batchelor C, Lacunza J, Yishak M, Tuballes K, Scott L, Kumar A, Jaladanki S, Thompson R, Clark E, Losic B, Zhu J, Wang W, Kasarskis A, Glicksberg BS, Nadkarni G, Bogunovic D, Elaiho C, Gangadharan S, Ofori-Amanfo G, Alesso-Carra K, Onel K, Wilson KM, Argmann C, Alarcón-Riquelme ME, Marron TU, Rahman A, Kim-Schulze S, Gnjatic S, Gelb BD, Merad M, Sebra R, Schadt EE, and Charney AW

Abstract

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition. By projecting the MIS-C signature onto a co-expression network, we identified disease gene modules and found genes downregulated in MIS-C clustered in a module enriched for the transcriptional signatures of exhausted CD8 + T-cells and CD56 dim CD57 + NK cells. Bayesian network analyses revealed nine key regulators of this module, including TBX21 , a central coordinator of exhausted CD8 + T-cell differentiation. Together, these findings suggest dysregulated cytotoxic lymphocyte response to SARS-Cov-2 infection in MIS-C.

Published
2020
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40. A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward.

Author

Wang B, Van Oekelen O, Mouhieddine TH, Del Valle DM, Richter J, Cho HJ, Richard S, Chari A, Gnjatic S, Merad M, Jagannath S, Parekh S, and Madduri D

Abstract

Background: The COVID-19 pandemic, caused by SARS-CoV-2 virus, has resulted in over 100,000 deaths in the United States. Our institution has treated over 2,000 COVID-19 patients during the pandemic in New York City. The pandemic directly impacted cancer patients and the organization of cancer care. Mount Sinai Hospital has a large and diverse multiple myeloma (MM) population. Herein, we report the characteristics of COVID-19 infection and serological response in MM patients in a large tertiary care institution in New York., Methods: We performed a retrospective study on a cohort of 58 patients with a plasma-cell disorder (54 MM, 4 smoldering MM) who developed COVID-19 between March 1, 2020 and April 30, 2020. We report epidemiological, clinical and laboratory characteristics including persistence of viral detection by polymerase chain reaction (PCR) and anti-SARS-CoV-2 antibody testing, treatments initiated, and outcomes., Results: Of the 58 patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age was 67 years; 52% of patients were male and 63% were non-white. Hypertension (64%), hyperlipidemia (62%), obesity (37%), diabetes mellitus (28%), chronic kidney disease (24%) and lung disease (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age (>70 years), male sex, cardiovascular risk, and patients not in complete remission (CR) or stringent CR were significantly (p<0.05) associated with hospitalization. Among hospitalized patients, laboratory findings demonstrated elevation of traditional inflammatory markers (CRP, ferritin, D-dimer) and a significant (p<0.05) association between elevated inflammatory markers, severe hypogammaglobulinemia, non-white race, and mortality. Ninety-six percent (22/23) of patients developed antibodies to SARS-CoV-2 at a median of 32 days after initial diagnosis. Median time to PCR negativity was 43 (range 19-68) days from initial positive PCR., Conclusions: Drug exposure and MM disease status at the time of contracting COVID-19 had no bearing on mortality. Mounting a severe inflammatory response to SARS-CoV-2 and severe hypogammaglobulinemia were associated with higher mortality. The majority of patients mounted an antibody response to SARS-CoV-2. These findings pave a path to identification of vulnerable MM patients who need early intervention to improve outcome in future outbreaks of COVID-19., Competing Interests: All other authors declare no potential conflict of interest.

Published
2020
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41. An inflammatory cytokine signature helps predict COVID-19 severity and death.

Author

Del Valle DM, Kim-Schulze S, Hsin-Hui H, Beckmann ND, Nirenberg S, Wang B, Lavin Y, Swartz T, Madduri D, Stock A, Marron T, Xie H, Patel MK, van Oekelen O, Rahman A, Kovatch P, Aberg J, Schadt E, Jagannath S, Mazumdar M, Charney A, Firpo-Betancourt A, Mendu DR, Jhang J, Reich D, Sigel K, Cordon-Cardo C, Feldmann M, Parekh S, Merad M, and Gnjatic S

Abstract

The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-α, and IL-1β in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF-α levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.

Published
2020
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