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2. Generalisable long COVID subtypes: Findings from the NIH N3C and RECOVER programmes

Author

Reese, Justin T, Blau, Hannah, Casiraghi, Elena, Bergquist, Timothy, Loomba, Johanna J, Callahan, Tiffany J, Laraway, Bryan, Antonescu, Corneliu, Coleman, Ben, Gargano, Michael, Wilkins, Kenneth J, Cappelletti, Luca, Fontana, Tommaso, Ammar, Nariman, Antony, Blessy, Murali, TM, Caufield, J Harry, Karlebach, Guy, McMurry, Julie A, Williams, Andrew, Moffitt, Richard, Banerjee, Jineta, Solomonides, Anthony E, Davis, Hannah, Kostka, Kristin, Valentini, Giorgio, Sahner, David, Chute, Christopher G, Madlock-Brown, Charisse, Haendel, Melissa A, Robinson, Peter N, Consortium, N3C, Spratt, Heidi, Visweswaran, Shyam, Flack, Joseph Eugene, Yoo, Yun Jae, Gabriel, Davera, Alexander, G Caleb, Mehta, Hemalkumar B, Liu, Feifan, Miller, Robert T, Wong, Rachel, Hill, Elaine L, Consortium, RECOVER, Thorpe, Lorna E, and Divers, Jasmin

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Networking and Information Technology R&D (NITRD), Precision Medicine, Machine Learning and Artificial Intelligence, Emerging Infectious Diseases, Infectious Diseases, Coronaviruses, Good Health and Well Being, Humans, COVID-19, Disease Progression, Post-Acute COVID-19 Syndrome, SARS-CoV-2, N3C Consortium, RECOVER Consortium, Human Phenotype Ontology, Long COVID, Machine learning, Precision medicine, Semantic similarity, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundStratification of patients with post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies. However, long COVID is incompletely understood and characterised by a wide range of manifestations that are difficult to analyse computationally. Additionally, the generalisability of machine learning classification of COVID-19 clinical outcomes has rarely been tested.MethodsWe present a method for computationally modelling PASC phenotype data based on electronic healthcare records (EHRs) and for assessing pairwise phenotypic similarity between patients using semantic similarity. Our approach defines a nonlinear similarity function that maps from a feature space of phenotypic abnormalities to a matrix of pairwise patient similarity that can be clustered using unsupervised machine learning.FindingsWe found six clusters of PASC patients, each with distinct profiles of phenotypic abnormalities, including clusters with distinct pulmonary, neuropsychiatric, and cardiovascular abnormalities, and a cluster associated with broad, severe manifestations and increased mortality. There was significant association of cluster membership with a range of pre-existing conditions and measures of severity during acute COVID-19. We assigned new patients from other healthcare centres to clusters by maximum semantic similarity to the original patients, and showed that the clusters were generalisable across different hospital systems. The increased mortality rate originally identified in one cluster was consistently observed in patients assigned to that cluster in other hospital systems.InterpretationSemantic phenotypic clustering provides a foundation for assigning patients to stratified subgroups for natural history or therapy studies on PASC.FundingNIH (TR002306/OT2HL161847-01/OD011883/HG010860), U.S.D.O.E. (DE-AC02-05CH11231), Donald A. Roux Family Fund at Jackson Laboratory, Marsico Family at CU Anschutz.

Published
2023

3. Metformin is associated with reduced COVID-19 severity in patients with prediabetes

Author

Chan, Lauren E, Casiraghi, Elena, Laraway, Bryan, Coleman, Ben, Blau, Hannah, Zaman, Adnin, Harris, Nomi L, Wilkins, Kenneth, Antony, Blessy, Gargano, Michael, Valentini, Giorgio, Sahner, David, Haendel, Melissa, Robinson, Peter N, Bramante, Carolyn, Reese, Justin, and consortium, on behalf of the N3C

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Good Health and Well Being, Female, Humans, Metformin, Retrospective Studies, COVID-19, Prediabetic State, Polycystic Ovary Syndrome, Hypoglycemic Agents, Thyroxine, N3C consortium, Glycemia, Polycystic ovary syndrome, Prediabetes, Public Health and Health Services, Psychology, Endocrinology & Metabolism, Clinical sciences, Public health, Clinical and health psychology
Abstract

AimsStudies suggest that metformin is associated with reduced COVID-19 severity in individuals with diabetes compared to other antihyperglycemics. We assessed if metformin is associated with reduced incidence of severe COVID-19 for patients with prediabetes or polycystic ovary syndrome (PCOS), common diseases that increase the risk of severe COVID-19.MethodsThis observational, retrospective study utilized EHR data from 52 hospitals for COVID-19 patients with PCOS or prediabetes treated with metformin or levothyroxine/ondansetron (controls). After balancing via inverse probability score weighting, associations with COVID-19 severity were assessed by logistic regression.ResultsIn the prediabetes cohort, when compared to levothyroxine, metformin was associated with a significantly lower incidence of COVID-19 with "mild-ED" or worse (OR [95% CI]: 0.636, [0.455-0.888]) and "moderate" or worse severity (0.493 [0.339-0.718]). Compared to ondansetron, metformin was associated with lower incidence of "mild-ED" or worse severity (0.039 [0.026-0.057]), "moderate" or worse (0.045 [0.03-0.069]), "severe" or worse (0.183 [0.077-0.431]), and "mortality/hospice" (0.223 [0.071-0.694]). For PCOS, metformin showed no significant differences in severity compared to levothyroxine, but was associated with a significantly lower incidence of "mild-ED" or worse (0.101 [0.061-0.166]), and "moderate" or worse (0.094 [0.049-0.18]) COVID-19 outcome compared to ondansetron.ConclusionsMetformin use is associated with less severe COVID-19 in patients with prediabetes or PCOS.

Published
2022

5. The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19

Author

Rogers, Angela J, Wentworth, Deborah, Phillips, Andrew, Shaw-Saliba, Katy, Dewar, Robin L, Aggarwal, Neil R, Babiker, Abdel G, Chang, Weizhong, Dharan, Nila J, Davey, Victoria J, Higgs, Elizabeth S, Gerry, Norman, Ginde, Adit A, Hayanga, JW Awori, Highbarger, Helene, Highbarger, Jeroen L, Jain, Mamta K, Kan, Virginia, Kim, Kami, Lallemand, Perrine, Leshnower, Bradley G, Lutaakome, Joseph K, Matthews, Gail, Mourad, Ahmad, Mylonakis, Eleftherios, Natarajan, Ven, Padilla, Maria L, Pandit, Lavannya M, Paredes, Roger, Pett, Sarah, Ramachandruni, Srikanth, Rehman, M Tauseef, Sherman, Brad T, Files, D Clark, Brown, Samuel M, Matthay, Michael A, Thompson, B Taylor, Neaton, James D, Lane, H Clifford, Lundgren, Jens D, Sahner, David, Tierney, John, Vogel, Susan E, Herpin, Betsey R, Smolskis, Mary C, McKay, Laura A, Cahill, Kelly, Crew, Page, Sardana, Ratna, Raim, Sharon Segal, Hensely, Lisa, Lorenzo, Johsua, Mock, Rebecca, Zuckerman, Judith, Atri, Negin, Miller, Mark, Vallee, David, Chung, Lucy, Kang, Nayon, and Barrett, Kevin

Subjects
Prevention, Vaccine Related, Emerging Infectious Diseases, Infectious Diseases, Clinical Research, Lung, Biodefense, Inflammatory and immune system, Infection, Good Health and Well Being, Adult, COVID-19, Cross-Sectional Studies, Humans, Male, Nucleocapsid, SARS-CoV-2, ACTIV-3/TICO Study Group, Clinical Sciences, Public Health and Health Services
Abstract

BackgroundLevels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19.ObjectiveTo evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2.DesignCross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge.Setting114 centers in 10 countries.ParticipantsAdults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms.MeasurementsBaseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively.ResultsPlasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity.LimitationsPlasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available.ConclusionElevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients.Primary funding sourceU.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Published
2022

6. Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study

Author

Sahner, David, Tierney, John, Vogel, Susan E., Herpin, Betsey R., Smolskis, Mary C., McKay, Laura A., Cahill, Kelly, Crew, Page, Sardana, Ratna, Raim, Sharon Segal, Hensely, Lisa, Lorenzo, Johsua, Mock, Rebecca, Zuckerman, Judith, Atri, Negin, Miller, Mark, Vallee, David, Chung, Lucy, Kang, Nayon, Barrett, Kevin, Adam, Stacey J., Read, Sarah, Draghia-Akli, Ruxandra, Currier, Judy, Hughes, Eric, Harrigan, Rachel H., Amos, Laura, Carlsen, Amy, Carter, Anita, Collins, Gary, Davis, Bionca, Denning, Eileen, DuChene, Alain, Eckroth, Kate, Engen, Nicole, Frase, Alex, Gandits, Greg, Grund, Birgit, Harrison, Merrie, Hurlbut, Nancy, Kaiser, Payton, Koopmeiners, Joseph, Larson, Gregg, Meger, Sue, Mistry, Shweta Sharma, Murray, Thomas, Nelson, Ray, Quan, Kien, Quan, Siu Fun, Reilly, Cavan, Siegel, Lianne, Thompson, Greg, Vock, David, Walski, Jamie, Gelijns, Annetine C., Moskowitz, Alan J., Bagiella, Emilia, Moquete, Ellen, O'Sullivan, Karen, Marks, Mary E., Accardi, Evan, Kinzel, Emily, Burris, Sarah, Bedoya, Gabriela, Gupta, Lola, Overbey, Jessica R., Santos, Milerva, Gillinov, Marc A., Miller, Marissa A., Taddei-Peters, Wendy C., Fenton, Kathleen, Sandkovsky, Uriel, Gottlieb, Robert L., Mack, Michael, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Bettacchi, Christopher, Golden, Kevin, Duhaime, Erin, Ryan, Madison, Tallmadge, Catherine, Estrada, Lorie, Jones, Felecia, Villa, Samatha, Wang, Samatha, Robert, Raven, Coleman, Tanquinisha, Clariday, Laura, Baker, Rebecca, Hurutado-Rodriguez, Mariana, Iram, Nazia, Fresnedo, Michelle, Davis, Allyson, Leonard, Kiara, Ramierez, Noelia, Thammavong, Jon, Duque, Krizia, Turner, Emma, Fisher, Tammy, Robinson, Dianna, Ransom, Desirae, Maldonado, Nicholas, Lusk, Erica, Killian, Aaron, Palacious, Adriana, Solis, Edilia, Jerrow, Janet, Watts, Matthew, Whitacre, Heather, Cothran, Elizabeth, Smith, Peter K., Barkauskas, Christina E., Vekstein, Andrew M., Ko, Emily R., Dreyer, Grace R., Stafford, Neil, Brooks, Megan, Der, Tatyana, Witte, Marie, Gamarallage, Ruwan, Franzone, John, Ivey, Noel, Lumsden, Rebecca H., Mosaly, Nilima, Mourad, Ahmaad, Holland, Thomas L., Motta, Mary, Lane, Kathleen, McGowan, Lauren M., Stout, Jennifer, Aloor, Heather, Bragg, Kennesha M., Toledo, Barvina, McLendon-Arvik, Beth, Bussadori, Barbara, Hollister, Beth A., Griffin, Michelle, Giangiacomo, Dana M., Rodriguez, Vicente, Bokhart, Gordon, Eichman, Sharon M., Parrino, Patrick E., Spindel, Stephen, Bansal, Aditya, Baumgarten, Katherine, Hand, Johnathan, Vonderhaar, Derek, Nossaman, Bobby, Sylvia Laudun, Ames, DeAnna, Broussard, Shane, Hernandez, Nilmo, Isaac, Geralyn, Dinh, Huan, Zheng, Yiling, Tran, Sonny, McDaniel, Hunter, Crovetto, Nicolle, Perin, Emerson, Costello, Briana, Manian, Prasad, Sohail, M. Rizwan, Postalian, Alexander, Hinsu, Punit, Watson, Carolyn, Chen, James, Fink, Melyssa, Sturgis, Lydia, Walker, Kim, Mahon, Kim, Parenti, Jennifer, Kappenman, Casey, Knight, Aryn, Sturek, Jeffrey M., Barros, Andrew, Enfield, Kyle B., Kadl, Alexandra, Green, China J., Simon, Rachel M., Fox, Ashley, Thornton, Kara, Adams, Amy, Badhwar, Vinay, Sharma, Sunil, Peppers, Briana, McCarthy, Paul, Krupica, Troy, Sarwari, Arif, Reece, Rebecca, Fornaresico, Lisa, Glaze, Chad, Evans, Raquel, Di, Fang, Carlson, Shawn, Aucremanne, Tanja, Tennant, Connie, Sutton, Lisa Giblin, Buterbaugh, Sabrina, Williams, Roger, Bunner, Robin, Traverse, Jay H., Rhame, Frank, Huelster, Joshua, Kethireddy, Rajesh, Davies, Irena, Salamanca, Julianne, Majeski, Christine, Skelton, Paige, Zarambo, Maria, Sarafolean, Andrea, Bowdish, Michael E., Borok, Zea, Wald-Dickler, Noah, Hutcheon, Douglass, Towfighi, Amytis, Lee, Mary, Lewis, Meghan R., Spellberg, Brad, Sher, Linda, Sharma, Aniket, Olds, Anna P., Justino, Chris, Loxano, Edward, Romero, Chris, Leong, Janet, Rodina, Valentina, Quesada, Christine, Hamilton, Luke, Escobar, Jose, Leshnower, Brad, Bender, William, Sharifpour, Milad, Miller, Jeffrey, Farrington, Woodrow, Baio, Kim T., McBride, Mary, Fielding, Michele, Mathewson, Sonya, Porte, Kristina, Maton, Missy, Ponder, Chari, Haley, Elisabeth, Spainhour, Christine, Rogers, Susan, Tyler, Derrick, Madathil, Ronson J., Rabin, Joseph, Levine, Andrea, Saharia, Kapil, Tabatabai, Ali, Lau, Christine, Gammie, James S., Peguero, Maya-Loren, McKernan, Kimberly, Audette, Mathew, Fleischmann, Emily, Akbari, Kreshta, Lee, Myounghee, Chi, Andrew, Salehi, Hanna, Pariser, Alan, Nyguyen, Phuong Tran, Moore, Jessica, Gee, Adrienne, Vincent, Shelika, Zuckerman, Richard A., Iribarne, Alexander, Metzler, Sara, Shipman, Samantha, Johnson, Haley, Newton, Crystallee, Parr, Doug, Miller, Leslie, Schelle, Beth, McLean, Sherry, Rothbaum, Howard R., Alvarez, Michael S., Kalan, Shivam P., Germann, Heather H., Hendershot, Jennifer, Moroney, Karen, Herring, Karen, Cook, Sharri, Paul, Pam, Walker-Ignasiak, Rebecca, North, Crystal, Oldmixon, Cathryn, Ringwood, Nancy, Muzikansky, Ariela, Morse, Richard, Fitzgerald, Laura, Morin, Haley D., Brower, Roy G., Reineck, Lora A., Bienstock, Karen, Steingrub, Jay H., Hou, Peter K., Steingrub, Jay S., Tidswell, Mark A., Kozikowski, Lori-Ann, Kardos, Cynthia, DeSouza, Leslie, Romain, Sarah, Thornton-Thompson, Sherell, Talmor, Daniel, Shapiro, Nathan, Andromidas, Konstantinos, Banner-Goodspeed, Valerie, Bolstad, Michael, Boyle, Katherine L., Cabrera, Payton, deVilla, Arnaldo, Ellis, Joshua C., Grafals, Ana, Hayes, Sharon, Higgins, Conor, Kurt, Lisa, Kurtzman, Nicholas, Redman, Kimberly, Rosseto, Elinita, Scaffidi, Douglas, Filbin, Michael R., Hibbert, Kathryn A., Parry, Blair, Margolin, Justin, Hillis, Brooklynn, Hamer, Rhonda, Brait, Kelsey, Beakes, Caroline, McKaig, Brenna, Kugener, Eleonore, Jones, Alan E., Galbraith, James, Nandi, Utsav, Peacock, Rebekah, Hendey, Gregory, Kangelaris, Kirsten, Ashktorab, Kimia, Gropper, Rachel, Agrawal, Anika, Yee, Kimberley J., Jauregui, Alejandra E., Zhuo, Hanjing, Almasri, Eyad, Fayed, Mohamed, Hubel, Kinsley A., Hughes, Alyssa R., Garcia, Rebekah L., Lim, George W., Chang, Steven Y., Lin, Michael Y., Vargas, Julia, Sihota, Hena, Beutler, Rebecca, Agarwal, Trisha, Wilson, Jennifer G., Vojnik, Rosemary, Perez, Cynthia, McDowell, Jordan H., Roque, Jonasel, Wang, Henry, Huebinger, Ryan M., Patel, Bela, Vidales, Elizabeth, Albertson, Timothy, Hardy, Erin, Harper, Richart, Moss, Marc A., Baduashvili, Amiran, Chauhan, Lakshmi, Douin, David J., Martinez, Flora, Finck, Lani L., Bastman, Jill, Howell, Michelle, Higgins, Carrie, McKeehan, Jeffrey, Finigan, Jay, Stubenrauch, Peter, Janssen, William J., Griesmer, Christine, VerBurg, Olivia, Hyzy, Robert C., Park, Pauline K., Nelson, Kristine, McSparron, Jake I., Co, Ivan N., Wang, Bonnie R., Jimenez, Jose, Olbrich, Norman, McDonough, Kelli, Jia, Shijing, Hanna, Sinan, Gong, Michelle N., Richardson, Lynne D., Nair, Rahul, Lopez, Brenda, Amosu, Omowunmi, Offor, Obiageli, Tzehaie, Hiwet, Nkemdirim, William, Boujid, Sabah, Mosier, Jarrod M., Hypes, Cameron, Campbell, Elizabeth Salvagio, Bixby, Billie, Gilson, Boris, Lopez, Anitza, Bime, Christian, Parthasarathy, Sairam, Cano, Ariana M., Hite, R. Duncan, Terndrup, Thomas E., Wiedemann, Herbert P., Hudock, Kristin, Tanzeem, Hammad, More, Harshada, Martinkovic, Jamie, Sellers, Susan, Houston, Judy, Burns, Mary, Kiran, Simra, Roads, Tammy, Kennedy, Sarah, Duggal, Abhijit, Thiruchelvam, Nirosshan, Ashok, Kiran, King, Alexander H., Mehkri, Omar, Dugar, Siddharth, Sahoo, Debasis, Yealy, Donald M., Angus, Derek C., Weissman, Alexandra J., Vita, Tina M., Berryman, Emily, Hough, Catherine L., Khan, Akram, Krol, Olivia F., Mills, Emmanuel, Kinjal, Mistry, Briceno, Genesis, Reddy, Raju, Hubel, Kinsley, Jouzestani, Milad K., McDougal, Madeline, Deshmukh, Rupali, Johnston, Nicholas J., Robinson, Bryce H., Gundel, Staphanie J., Katsandres, Sarah C., Chen, Peter, Torbati, Sam S., Parimon, Tanyalak, Caudill, Antonina, Mattison, Brittany, Jackman, Susan E., Chen, Po-En, Bayoumi, Emad, Ojukwu, Cristabelle, Fine, Devin, Weissberg, Gwendolyn, Isip, Katherine, Choi-Kuaea, Yunhee, Mehdikhani, Shaunt, Dar, Tahir B., Fleury Augustin, Nsole Biteghe, Tran, Dana, Dukov, Jennifer Emilow, Matusov, Yuri, Choe, June, Hindoyan, Niree A., Wynter, Timothy, Pascual, Ethan, Clapham, Gregg J., Herrera, Lisa, Caudill, Antonia, O’Mahony, D. Shane, Nyatsatsang, Sonam T., Wilson, David M., Wallick, Julie A., Duven, Alexandria M., Fletcher, Dakota D., Miller, Chadwick, Files, D. Clark, Gibbs, Kevin W., Flores, Lori S., LaRose, Mary E., Landreth, Leigha D., Palacios, D. Rafael, Parks, Lisa, Hicks, Madeline, Goodwin, Andrew J., Kilb, Edward F., Lematty, Caitlan T., Patti, Kerilyn, Grady, Abigail, Rasberry, April, Morris, Peter E., Sturgill, Jamie L., Cassity, Evan P., Dhar, Sanjay, Montgomery-Yates, Ashley A., Pasha, Sarah N., Mayer, Kirby P., Pharm.D., Brittany Bissel, Trott, Terren, Rehman, Shahnaz, de Wit, Marjolein, Mason, Jessica, Bledsoe, Joseph, Knowlton, Kirk U., Brown, Samuel, Lanspa, Michael, Leither, Lindsey, Pelton, Ithan, Armbruster, Brent P., Montgomery, Quinn, Kumar, Naresh, Fergus, Melissa, Imel, Karah, Palmer, Ghazal, Webb, Brandon, Klippel, Carolyn, Jensen, Hannah, Duckworth, Sarah, Gray, Andrew, Burke, Tyler, Knox, Dan, Lumpkin, Jenna, Aston, Valerie T., Applegate, Darrin, Serezlic, Erna, Brown, Katie, Merril, Mardee, Harris, Estelle S., Middleton, Elizabeth A., Barrios, Macy A.G., Greer, Jorden, Schmidt, Amber D., Webb, Melissa K., Paine, Roert, Callahan, Sean J., Waddoups, Lindsey J., Yamane, Misty B., Self, Wesley H., Rice, Todd W., Casey, Jonathan D., Johnson, Jakea, Gray, Christopher, Hays, Margaret, Roth, Megan, Menon, Vidya, Kasubhai, Moiz, Pillai, Anjana, Daniel, Jean, Sittler, Daniel, Kanna, Balavenkatesh, Jilani, Nargis, Amaro, Francisco, Santana, Jessica, Lyakovestsky, Aleksandr, Madhoun, Issa, Desroches, Louis Marie, Amadon, Nicole, Bahr, Alaa, Ezzat, Imaan, Guerrero, Maryanne, Padilla, Joane, Fullmer, Jessie, Singh, Inderpreet, Ali Shah, Syed Hamad, Narang, Rajeev, Mock, Polly, Shadle, Melissa, Hernandez, Brenda, Welch, Kevin, Payne, Andrea, Ertl, Gabriela, Canario, Daniel, Barrientos, Isabel, Goss, Danielle, DeVries, Mattie, Folowosele, Ibidolapo, Garner, Dorothy, Gomez, Mariana, Price, Justin, Bansal, Ekta, Wong, Jim, Faulhaber, Jason, Fazili, Tasaduq, Yeary, Brian, Ndolo, Ruth, Bryant, Christina, Smigeil, Bridgette, Robinson, Philip, Najjar, Rana, Jones, Patrice, Nguyen, Julie, Chin, Christina, Taha, Hassan, Najm, Salah, Smith, Christopher, Moore, Jason, Nassar, Talal, Gallinger, Nick, Christian, Amy, Mauer, D’Amber, Phipps, Ashley, Waters, Michael, Zepeda, Karla, Coslet, Jordan, Landazuri, Rosalynn, Pineda, Jacob, Uribe, Nicole, Garcia, Jose Ruiz, Barbabosa, Cecilia, Sandler, Kaitlyn, Overcash, J. Scott, Marquez, Adrienna, Chu, Hanh, Lee, Kia, Quillin, Kimberly, Garcia, Andrea, Lew, Pauline, Rogers, Ralph, Shehadeh, Fadi, Mylona, Evangelia K., Kaczynski, Matthew, Tran, Quynh-Lam, Benitez, Gregorio, Mishra, Biswajit, Felix, Lewis Oscar, Vafea, Maria Tsikala, Atalla, Eleftheria, Davies, Robin, Hedili, Salma, Monkeberg, Maria Andrea, Tabler, Sandra, Harrington, Britt, Meegada, Sreenath, Koripalli, Venkata Sandeep, Muddana, Prithvi, Jain, Lakshay, Undavalli, Chaitanya, Kavya, Parasa, Ibiwoye, Mofoluwaso, Akilo, Hameed, Lovette, Bryce D., Wylie, Jamie-Crystal, Smith, Diana M., Poon, Kenneth, Eckardt, Paula, Heysu, Rubio-Gomez, Sundararaman, Nithya, Alaby, Doris, Sareli, Candice, Sánchez, Adriana, Popielski, Laura, Kambo, Amy, Viens, Kimberley, Turner, Melissa, Vjecha, Michael J., Weintrob, Amy, Brar, Indira, Markowitz, Norman, Pastor, Erika, Corpuz, Roweena, Alangaden, George, McKinnon, John, Ramesh, Mayur, Herc, Erica, Yared, Nicholas, Lanfranco, Odaliz Abreu, Rivers, Emanuel, Swiderek, Jennifer, Gupta, Ariella Hodari, Pabla, Pardeep, Eliya, Sonia, Jazrawi, Jehan, Delor, Jeremy, Desai, Mona, Cook, Aaron, Jaehne, Anja Kathrina, Gill, Jasreen Kaur, Renaud, Sheri, Sarveswaran, Siva, Gardner, Edward, Scott, James, Bianchini, Monica, Melvin, Casey, Kim, Gina, Wyles, David, Kamis, Kevin, Miller, Rachel, Douglas, Ivor, Haukoos, Jason, Hicks, Carrie, Lazarte, Susana, Marines-Price, Rubria, Osuji, Alice, Agbor Agbor, Barbine Tchamba, Petersen, Tianna, Kamel, Dena, Hansen, Laura, Garcia, Angie, Cha, Christine, Mozaffari, Azadeh, Hernandez, Rosa, Cutrell, James, Kim, Mina, DellaValle, Natalie, Gonzales, Sonia, Somboonwit, Charurut, Oxner, Asa, Guerra, Lucy, Hayes, Michael, Nguyen, Thi, Tran, Thanh, Pinto, Avenette, Hatlen, Timothy, Anderson, Betty, Zepeda-Gutierrez, Ana, Martin, Dannae, Temblador, Cindi, Cuenca, Avon, Tanoviceanu, Roxanne, Prieto, Martha, Guerrero, Mario, Daar, Eric, Correa, Ramiro, Hartnell, Gabe, Wortmann, Glenn, Doshi, Saumil, Moriarty, Theresa, Gonzales, Melissa, Garman, Kristin, Baker, Jason V., Frosch, Anne, Goldsmith, Rachael, Driver, Brian, Frank, Christine, Leviton, Tzivia, Prekker, Matthew, Jibrell, Hodan, Lo, Melanie, Klaphake, Jonathan, Mackedanz, Shari, Ngo, Linh, Garcia-Myers, Kelly, Kunisaki, Ken M., Wendt, Chris, Melzer, Anne, Wetherbee, Erin, Drekonja, Dimitri, Pragman, Alexa, Hamel, Aimee, Thielen, Abbie, Hassler, Miranda, Walquist, Mary, Augenbraun, Michael, George, Jensen, Demeo, Lynette, Mishko, Motria, Thomas, Lorraine, Tatem, Luis, Dehovitz, Jack, Abassi, Mahsa, Leuck, Anne-Marie, Rao, Via, Pullen, Matthew, Luke, Darlette, LaBar, Derek, Christiansen, Theresa, Howard, Diondra, Biswas, Kousick, Harrington, Cristin, Garcia, Amanda, Bremer, Tammy, Burke, Tara, Koker, Brittany, Davis-Karim, Anne, Pittman, David, Vasudeva, Shikha S., Johnstone, Jaylynn R., Agnetti, Kate, Davis, Ruby, Trautner, Barbara, Hines-Munson, Casey, Van, John, Dillon, Laura, Wang, Yiqun, Nagy-Agren, Stephanie, Vasudeva, Shikha, Ochalek, Tracy, Caldwell, Erin, Humerickhouse, Edward, Boone, David, McGraw, William, Looney, David J., Mehta, Sanjay R., Johns, Scott Thompson, St. John, Melissa, Raceles, Jacqueline, Sear, Emily, Funk, Stephen, Cesarini, Rosa, Fang, Michelle, Nicalo, Keith, Drake, Wonder, Jones, Beatrice, Holtman, Teresa, Nguyen, Hien H., Maniar, Archana, Johnson, Eric A., Nguyen, Lam, Tran, Michelle T., Barrett, Thomas W., Johnston, Tera, Huggins, John T., Beiko, Tatsiana Y., Hughes, Heather Y., McManigle, William C., Tanner, Nichole T., Washburn, Ronald G., Ardelt, Magdalena, Tuohy, Patricia A., Mixson, Jennifer L., Hinton, Charles G., Thornley, Nicola, Allen, Heather, Elam, Shannon, Boatman, Barry, Baber, Brittany J., Ryant, Rudell, Roller, Brentin, Nguyen, Chinh, Mikail, Amani Morgan, Research, Marivic Hansen, Lichtenberger, Paola, Baracco, Gio, Ramos, Carol, Bjork, Lauren, Sueiro, Melyssa, Tien, Phyllis, Freasier, Heather, Buck, Theresa, Nekach, Hafida, Holodniy, Mark, Chary, Aarthi, Lu, Kan, Peters, Theresa, Lopez, Jessica, Tan, Susanna Yu, Lee, Robert H., Asghar, Aliya, Karyn Isip, Tasadduq Karim, Le, Katherine, Nguyen, Thao, Wong, Shinn, Raben, Dorthe, Murray, Daniel D., Jensen, Tomas O., Peters, Lars, Aagaard, Bitten, Nielsen, Charlotte B., Krapp, Katharina, Nykjær, Bente Rosdahl, Olsson, Christina, Kanne, Katja Lisa, Grevsen, Anne Louise, Joensen, Zillah Maria, Bruun, Tina, Bojesen, Ane, Woldbye, Frederik, Normand, Nick E., Esman, Frederik V.L., Benfield, Thomas, Clausen, Clara Lundetoft, Hovmand, Nichlas, Israelsen, Simone Bastrup, Iversen, Katrine, Leding, Caecilie, Pedersen, Karen Brorup, Thorlacius-Ussing, Louise, Tinggaard, Michaela, Tingsgard, Sandra, Krohn-Dehli, Louise, Pedersen, Dorthe, Villadsen, Signe, Staehr Jensen, Jens-Ulrik, Overgaard, Rikke, Rastoder, Ema, Heerfordt, Christian, Hedsund, Caroline, Ronn, Christian Phillip, Kamstrup, Peter Thobias, Hogsberg, Dorthe Sandbaek, Bergsoe, Christina, Søborg, Christian, Hissabu, Nuria M.S., Arp, Bodil C., Ostergaard, Lars, Staerke, Nina Breinholt, Yehdego, Yordanos, Sondergaard, Ane, Johansen, Isik S., Pedersen, Andreas Arnholdt, Knudtzen, Fredrikke C., Larsen, Lykke, Hertz, Mathias A., Fabricius, Thilde, Holden, Inge K., Lindvig, Susan O., Helleberg, Marie, Gerstoft, Jan, Kirk, Ole, Jensen, Tomas Ostergaard, Madsen, Birgitte Lindegaard, Pedersen, Thomas Ingemann, Harboe, Zitta Barrella, Roge, Birgit Thorup, Hansen, Thomas Michael, Glesner, Matilde Kanstrup, Lofberg, Sandra Valborg, Nielsen, Ariella Denize, Leicht von Huth, Sebastian, Nielsen, Henrik, Thisted, Rikke Krog, Petersen, Kristine Toft, Juhl, Maria Ruwald, Podlekareva, Daria, Johnsen, Stine, Andreassen, Helle Frost, Pedersen, Lars, Clara Ellinor Lindnér, Cecilia Ebba, Wiese, Lothar, Knudsen, Lene Surland, Skrøder Nytofte, Nikolaj Julian, Havmøller, Signe Ravn, Expósito, Maria, Badillo, José, Martínez, Ana, Abad, Elena, Chamorro, Ana, Figuerola, Ariadna, Mateu, Lourdes, España, Sergio, Lucero, Maria Constanza, Santos, José Ramón, Lladós, Gemma, Lopez, Cristina, Carabias, Lydia, Molina-Morant, Daniel, Loste, Cora, Bracke, Carmen, Siles, Adrian, Fernández-Cruz, Eduardo, Di Natale, Marisa, Padure, Sergiu, Gomez, Jimena, Ausin, Cristina, Cervilla, Eva, Balastegui, Héctor, Sainz, Carmen Rodríguez, Lopez, Paco, Carbone, Javier, Escobar, Mariam, Balerdi, Leire, Legarda, Almudena, Roldan, Montserrat, Letona, Laura, Muñoz, José, Camprubí, Daniel, Arribas, Jose R., Sánchez, Rocio Montejano, Díaz-Pollán, Beatriz, Stewart, Stefan Mark, Garcia, Irene, Borobia, Alberto, Mora-Rillo, Marta, Estrada, Vicente, Cabello, Noemi, Nuñez-Orantos, M.J., Sagastagoitia, I., Homen, J.R., Orviz, E., Montalvá, Adrián Sánchez, Espinosa-Pereiro, Juan, Bosch-Nicolau, Pau, Salvador, Fernando, Burgos, Joaquin, Morales-Rull, Jose Luis, Moreno Pena, Anna Maria, Acosta, Cristina, Solé-Felip, Cristina, Horcajada, Juan P., Sendra, Elena, Castañeda, Silvia, López-Montesinos, Inmaculada, Gómez-Junyent, Joan, Gonzáles, Carlota Gudiol, Cuervo, Guilermo, Pujol, Miquel, Carratalà, Jordi, Videla, Sebastià, Günthard, Huldrych, Braun, Dominique L., West, Emily, M’Rabeth-Bensalah, Khadija, Eichinger, Mareile L., Grüttner-Durmaz, Manuela, Grube, Christina, Zink, Veronika, pharmacist, Goes pharmacist, Josefine, Fätkenheuer, Gerd, Malin, Jakob J., Tsertsvadze, Tengiz, Abutidze, Akaki, Chkhartishvili, Nikoloz, Metchurtchlishvili, Revaz, Endeladze, Marina, Paciorek, Marcin, Bursa, Dominik, Krogulec, Dominika, Pulik, Piotr, Ignatowska, Anna, Horban, Andrzej, Bakowska, Elzbieta, Kowaska, Justyna, Bednarska, Agnieszka, Jurek, Natalia, Skrzat-Klapaczynska, Agata, Bienkowski, Carlo, Hackiewicz, Malgorzata, Makowiecki, Michal, Platowski, Antoni, Fishchuk, Roman, Kobrynska, Olena, Levandovska, Khrystyna, Kirieieva, Ivanna, Kuziuk, Mykhailo, Naucler, Pontus, Perlhamre, Emma, Mazouch, Lotta, Kelleher, Anthony, Polizzotto, Mark, Carey, Catherine, Chang, Christina C., Hough, Sally, Virachit, Sophie, Davidson, Sarah, Bice, Daniel J., Ognenovska, Katherine, Cabrera, Gesalit, Flynn, Ruth, Young, Barnaby E., Chia, Po Ying, Lee, Tau Hong, Lin, Ray J., Lye, David C., Ong, Sean W.X., Puah, Ser Hon, Yeo, Tsin Wen, Diong, Shiau Hui, Ongko, Juwinda, Yeo, He Ping, Eriobu, Nnakelu, Kwaghe, Vivian, Zaiyad, Habib, Idoko, Godwin, Uche, Blessing, Selvamuthu, Poongulali, Kumarasamy, Nagalingeswaran, Beulah, Faith Ester, Govindarajan, Narayan, Mariyappan, Kowsalya, Losso, Marcelo H., Abela, Cecilia, Moretto, Renzo, Belloc, Carlos G., Ludueña, Jael, Amar, Josefina, Toibaro, Javier, Macias, Laura Moreno, Fernandez, Lucia, Frare, Pablo S., Chaio, Sebastian R., Pachioli, Valeria, Timpano, Stella M., Sanchez, Marisa del Lujan, de Paz Sierra, Mariana, Stanek, Vanina, Belloso, Waldo, Cilenti, Flavia L., Valentini, Ricardo N., Stryjewski, Martin E., Locatelli, Nicolas, Soler Riera, Maria C., Salgado, Clara, Baeck, Ines M., Di Castelnuovo, Valentina, Zarza, Stella M., Hudson, Fleur, Parmar, Mahesh K.B., Goodman, Anna L., Dphil, Badrock, Jonathan, Gregory, Adam, Goodall, Katharine, Harris, Nicola, Wyncoll, James, Bhagani, S., Rodger, A., Luntiel, A., Patterson, C., Morales, J., Witele, E., Preston, A.-M., Nandani, A., Price, D.A., Hanrath, Aiden, Nell, Jeremy, Patel, Bijal, Hays, Carole, Jones, Geraldine, Davidson, Jade, Bawa, T., Mathews, M., Mazzella, A., Bisnauthsing, K., Aguilar-Jimenez, L., Borchini, F., Hammett, S., Touloumi, Giota, Pantazis, Nikos, Gioukari, Vicky, Souliou, Tania, Antoniadou, A., Protopapas, K., Kavatha, D., Grigoropoulou, S., Oikonomopoulo, C., Moschopoulos, C., Koulouris, N.G., Tzimopoulos, K., Koromilias, A., Argyraki, K., Lourida, P., Bakakos, P., Kalomenidis, I., Vlachakos, V., Barmparessou, Z., Balis, E., Zakynthinos, S., Sigala, I., Gianniou, N., Dima, E., Magkouta, S., Synolaki, E., Konstanta, S., Vlachou, M., Stathopoulou, P., Panagopoulos, P., Petrakis, V., Papazoglou, D., Tompaidou, E., Isaakidou, E., Poulakou, G., Rapti, V., Leontis, K., Nitsotolis, T., Athanasiou, K., Syrigos, K., Kyriakoulis, K., Trontzas, I., Arfara-Melanini, M., Kolonis, V., Kityo, Cissy, Mugerwa, Henry, Kiweewa, Francis, Kimuli, Ivan, Lukaakome, Joseph, Nsereko, Christoher, Lubega, Gloria, Kibirige, Moses, Nakahima, William, Wangi, Deus, Aguti, Evelyne, Generous, Lilian, Massa, Rosemary, Nalaki, Margaret, Magala, Felix, Nabaggala, Phiona Kaweesi, Kidega, Robert, Faith, Oryem Daizy, Florence, Apio, Emmanuel, Ocung, Beacham, Mugoonyi Paul, Geoffrey, Amone, Nakiboneka, Dridah, Apiyo, Paska, Kirenga, Bruce, Atukunda, Angella, Muttamba, Winters, Remmy, Kyeyume, Segawa, Ivan, Pheona, Nsubuga, Kigere, David, Mbabazi, Queen Lailah, Boersalino, Ledra, Nyakoolo, Grace, Fred, Aniongo, Alupo, Alice, Ebong, Doryn, Monday, Edson, Nalubwama, Ritah Norah, Kainja, Milton, Ambrose, Munu, Kwehayo, Vanon, Nalubega, Mary Grace, Ongoli, Augustine, Obbo, Stephen, Sebudde, Nicholus, Alaba, Jeniffer, Magombe, Geoffrey, Tino, Harriet, Obonya, Emmanuel, Lutaakome, Joseph, Kitonsa, Jonathan, Onyango, Martin, Naboth, Tukamwesiga, Naluyinda, Hadijah, Nanyunja, Regina, Irene, Muttiibwa, Jane, Biira, Wimfred, Kyobejja, Leonard, Ssemazzi, Deus, Tkiinomuhisha, Babra, Namasaba, Taire, Paul, Nabankema, Evelyn, Ogavu, Joseph, Mugerwa, Oscar, Okoth, Ivan, Mwebaze, Raymond, Mugabi, Timothy, Makhoba, Anthony, Arikiriza, Phiona, Theresa, Nabuuma, Nakayima, Hope, Frank, Kisuule, Ramgi, Patrícia, Pereira, Kássia, Osinusi, Anu, Cao, Huyen, Klekotka, Paul, Price, Karen, Nirula, Ajay, Osei, Suzette, Tipple, Craig, Wills, Angela, Peppercorn, Amanda, Watson, Helen, Gupta, Rajesh, Alexander, Elizabeth, Mogalian, Erik, Lin, Leo, Ding, Xiao, Margolis, David, Yan, Li, Girardet, Jean-Luc, Ma, Ji, Hong, Zhi, Zhu, Quing, Seegobin, Seth, Gibbs, Michael, Latchman, Mickel, Hasior, Katarzyna, Bouquet, Jerome, Wei, Jianxin, Streicher, Katie, Schmelzer, Albert, Brooks, Dennis, Butcher, Jonny, Tonev, Dimitar, Arbetter, Douglas, Damstetter, Philippe, Legenne, Philippe, Stumpp, Michael, Goncalves, Susana, Ramanathan, Krishnan, Chandra, Richa, Baseler, Beth, Teitelbaum, Marc, Schechner, Adam, Holley, H. Preston, Jankelevich, Shirley, Becker, Nancy, Dolney, Suzanne, Hissey, Debbie, Simpson, Shelly, Kim, Mi Ha, Beeler, Joy, Harmon, Liam, Asomah, Mabel, Jato, Yvonne, Stottlemyer, April, Tang, Olivia, Vanderpuye, Sharon, Yeon, Lindsey, Buehn, Molly, Eccard-Koons, Vanessa, Frary, Sadie, MacDonald, Leah, Cash, Jennifer, Hoopengardner, Lisa, Linton, Jessica, Schaffhauser, Marylu, Nelson, Michaela, Spinelli-Nadzam, Mary, Proffitt, Calvin, Lee, Christopher, Engel, Theresa, Fontaine, Laura, Osborne, C.K., Hohn, Matt, Galcik, Michael, Thompson, DeeDee, Kopka, Stacey, Shelley, Denise M., Mendez, Gregg, Brown, Shawn, Albert, Sara, Balde, Abby, Baracz, Michelle, Bielica, Mona, Billouin-Frazier, Shere, Choudary, Jay, Dixon, Mary, Eyler, Carolyn, Frye, Leanne, Gertz, Jensen, Giebeig, Lisa, Gulati, Neelam, Hankinson, Liz, Hogarty, Debi, Huber, Lynda, Krauss, Gary, Lake, Eileen, Manandhar, Meryan, Rudzinski, Erin, Sandrus, Jen, Suders, Connie, Natarajan, Ven, Rupert, Adam W., Baseler, Michael, Lynam, Danielle, Imamichi, Tom, Laverdure, Sylvain, McCormack, Ashley, Paudel, Sharada, Cook, Kyndal, Haupt, Kendra, Khan, Ayub, Hazen, Allison, Badralmaa, Yunden, Smith, Kenneth, Patel, Bhakti, Kubernac, Amanda, Kubernac, Robert, Hoover, Marie L., Solomon, Courtney, Rashid, Marium, Murphy, Joseph, Brown, Craig, DuChateau, Nadine, Ellis, Sadie, Flosi, Adam, Fox, Lisa, Johnson, Les, Nelson, Rich, Stojanovic, Jelena, Treagus, Amy, Wenner, Christine, Williams, Richard, Jensen, Tomas O, Murray, Thomas A, Grandits, Greg A, Jain, Mamta K, Shaw-Saliba, Kathryn, Matthay, Michael A, Baker, Jason V, Dewar, Robin L, Goodman, Anna L, Hatlen, Timothy J, Highbarger, Helene C, Lallemand, Perrine, Leshnower, Bradley G, Looney, David, Moschopoulos, Charalampos D, Murray, Daniel D, Mylonakis, Eleftherios, Rehman, M Tauseef, Rupert, Adam, Stevens, Randy, Turville, Stuart, Wick, Katherine, Lundgren, Jens, and Ko, Emily R

Published
2024
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7. Generalisable long COVID subtypes: findings from the NIH N3C and RECOVER programmes

Author

Spratt, Heidi, Visweswaran, Shyam, Flack, Joseph Eugene, IV, Yoo, Yun Jae, Gabriel, Davera, Alexander, G. Caleb, Mehta, Hemalkumar B., Liu, Feifan, Miller, Robert T., Wong, Rachel, Hill, Elaine L., Thorpe, Lorna E., Divers, Jasmin, Reese, Justin T., Blau, Hannah, Casiraghi, Elena, Bergquist, Timothy, Loomba, Johanna J., Callahan, Tiffany J., Laraway, Bryan, Antonescu, Corneliu, Coleman, Ben, Gargano, Michael, Wilkins, Kenneth J., Cappelletti, Luca, Fontana, Tommaso, Ammar, Nariman, Antony, Blessy, Murali, T.M., Caufield, J. Harry, Karlebach, Guy, McMurry, Julie A., Williams, Andrew, Moffitt, Richard, Banerjee, Jineta, Solomonides, Anthony E., Davis, Hannah, Kostka, Kristin, Valentini, Giorgio, Sahner, David, Chute, Christopher G., Madlock-Brown, Charisse, Haendel, Melissa A., and Robinson, Peter N.

Published
2023
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9. Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial

Author

Ginde, Adit A., Paredes, Roger, Murray, Thomas A., Engen, Nicole, Grandits, Greg, Vekstein, Andrew, Ivey, Noel, Mourad, Ahmad, Sandkovsky, Uriel, Gottlieb, Robert L., Berhe, Mezgebe, Jain, Mamta K., Marines-Price, Rubria, Agbor Agbor, Barbine Tchamba, Mateu, Lourdes, España-Cueto, Sergio, Lladós, Gemma, Mylonakis, Eleftherios, Rogers, Ralph, Shehadeh, Fadi, Filbin, Michael R., Hibbert, Kathryn A., Kim, Kami, Tran, Thanh, Morris, Peter E., Cassity, Evan P., Trautner, Barbara, Pandit, Lavannya M., Knowlton, Kirk U., Leither, Lindsay, Matthay, Michael A., Rogers, Angela J., Drake, Wonder, Jones, Beatrice, Poulakou, Garyfallia, Syrigos, Konstantinos N., Fernández-Cruz, Eduardo, Natale, Marisa Di, Almasri, Eyad, Balerdi-Sarasola, Leire, Bhagani, Sanjay R., Boyle, Katherine L., Casey, Jonathan D., Chen, Peter, Douin, David J., Files, D. Clark, Günthard, Huldrych F., Hite, R. Duncan, Hyzy, Robert C., Khan, Akram, Kibirige, Moses, Kidega, Robert, Kiweewa, Francis, Jensen, Jens-Ulrik, Leshnower, Bradley G., Lutaakome, Joseph K., Manian, Prasad, Menon, Vidya, Morales-Rull, Jose Luis, O'Mahony, D. Shane, Overcash, J. Scott, Ramachandruni, Srikant, Steingrub, Jay S., Taha, Hassan S., Waters, Michael, Young, Barnaby E., Phillips, Andrew N., Murray, Daniel D., Jensen, Tomas O., Padilla, Maria L., Sahner, David, Shaw-Saliba, Katy, Dewar, Robin L., Teitelbaum, Marc, Natarajan, Ven, Rehman, M. Tauseef, Pett, Sarah, Hudson, Fleur, Touloumi, Giota, Brown, Samuel M., Self, Wesley H., Chang, Christina C., Sánchez, Adriana, Weintrob, Amy C., Hatlen, Timothy, Grund, Birgit, Sharma, Shweta, Reilly, Cavan S., Garbes, Pedro, Esser, Mark T., Templeton, Alison, Babiker, Abdel G., Davey, Victoria J., Gelijns, Annetine C., Higgs, Elizabeth S., Kan, Virginia, Matthews, Gail, Thompson, B. Taylor, Neaton, James D., Lane, H. Clifford, and Lundgren, Jens D.

Published
2022
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11. List of Contributors

Author

Allen, Chris, primary, Anthony, Jack M., additional, Baylor, Norman W., additional, Beeler, John F., additional, Boclair, Dave, additional, Boni, Arthur A., additional, Bradley, Craig C., additional, Busenitz, Lowell W., additional, Byrne, Mark, additional, Calcaterra, Robert J., additional, Conner, John, additional, Elman, Gerry J., additional, Ferguson, Steven M., additional, Ferré, François, additional, Freedman, Toby, additional, Garfield, Susan, additional, Greenwood, The Honorable James C., additional, Gutterson, Neal, additional, Haworth, Philip, additional, Javitt, Gail H., additional, Kaundinya, Uma S., additional, Kirsch, Donald R., additional, Kostov, Konstantin S., additional, Kureczka, Joan E., additional, Langer, Lynn Johnson, additional, Lopez, Maria, additional, Marks, Lara V., additional, Marquet, Magda, additional, Mills, Gayle M., additional, Minshall, Bill, additional, Peterson, Jay, additional, Prusti, Rabi, additional, Sahner, David, additional, Sammut, Stephen M., additional, Shah, Alaap B., additional, Shimasaki, Craig, additional, Spellmeyer, David C., additional, Termeer, Henri A., additional, Tillman, Donna-Bea, additional, Todorova, Gergana, additional, Walker, Tom D., additional, Wanerman, Robert E., additional, Weingart, Laurie R., additional, White, Gladys B., additional, Wuchterl, Don, additional, Zhang, Jay Z., additional, and Zhang, Jimmy Zhimin, additional

Published
2020
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13. Paxlovid (nirmatrelvir/ritonavir) effectiveness against hospitalization and death in N3C: A target trial emulation study

Author

Hansen, Kristen, Makkar, Steve R., Sahner, David, Fessel, Josh, Hotaling, Nathan, and Sidky, Hythem

Subjects
Article
Abstract

IMPORTANCE: COVID-19 has placed a monumental burden on the health care system globally. Although no longer a public health emergency, there is still a pressing need for effective treatments to prevent hospitalization and death. Paxlovid (nirmatrelvir/ritonavir) is a promising and potentially effective antiviral that has received emergency use authorization by the U.S. FDA. OBJECTIVE: Determine real world effectiveness of Paxlovid nationwide and investigate disparities between treated and untreated eligible patients. DESIGN/SETTING/PARTICIPANTS: Population-based cohort study emulating a target trial, using inverse probability weighted models to balance treated and untreated groups on baseline confounders. Participants were patients with a SARS-CoV-2 positive test or diagnosis (index) date between December 2021 and February 2023 selected from the National COVID Cohort Collaborative (N3C) database who were eligible for Paxlovid treatment. Namely, adults with at least one risk factor for severe COVID-19 illness, no contraindicated medical conditions, not using one or more strictly contraindicated medications, and not hospitalized within three days of index. From this cohort we identified patients who were treated with Paxlovid within 5 days of positive test or diagnosis (n = 98,060) and patients who either did not receive Paxlovid or were treated outside the 5-day window (n = 913,079 never treated; n = 1,771 treated after 5 days). EXPOSURES: Treatment with Paxlovid within 5 days of positive COVID-19 test or diagnosis. MAIN OUTCOMES AND MEASURES: Hospitalization and death in the 28 days following COVID-19 index date. RESULTS: A total of 1,012,910 COVID-19 positive patients at risk for severe COVID-19 were included, 9.7% of whom were treated with Paxlovid. Uptake varied widely by geographic region and timing, with top adoption areas near 50% and bottom near 0%. Adoption increased rapidly after EUA, reaching steady state by 6/2022. Participants who were treated with Paxlovid had a 26% (RR, 0.742; 95% CI, 0.689-0.812) reduction in hospitalization risk and 73% (RR, 0.269, 95% CI, 0.179-0.370) reduction in mortality risk in the 28 days following COVID-19 index date. CONCLUSIONS/RELEVANCE: Paxlovid is effective in preventing hospitalization and death in at-risk COVID-19 patients. These results were robust to a large number of sensitivity considerations. DISCLOSURE: The authors report no disclosures KEY POINTS: Question: Is treatment with Paxlovid (nirmatrelvir/ritonavir) associated with a reduction in 28-day hospitalization and mortality in patients at risk for severe COVID-19? Findings: In this multi-institute retrospective cohort study of 1,012,910 patients, Paxlovid treatment within 5 days after COVID-19 diagnosis reduced 28-day hospitalization and mortality by 26% and 73% respectively, compared to no treatment with Paxlovid within 5 days. Paxlovid uptake was low overall (9.7%) and highly variable. Meaning: In Paxlovid-eligible patients, treatment was associated with decreased risk of hospitalization and death. Results align with prior randomized trials and observational studies, thus supporting the real-world effectiveness of Paxlovid.

Published
2023

15. Pre-existing autoimmunity is associated with increased severity of COVID-19: A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C)

Author

Hotaling, Nathan, the N3C consortium, Mathé, Ewy A, Yadaw, Arjun S, Afzali, Behdad, Sahner, David K, Pfaff, Emily R, and Sidky, Hythem

Abstract

Identifying individuals with a higher risk of developing severe COVID-19 outcomes will inform targeted or more intensive clinical monitoring and management. To date, there is mixed evidence regarding the impact of pre-existing autoimmune disease (AID) diagnosis and/or immunosuppressant (IS) exposure on developing severe COVID-19 outcomes.A retrospective cohort of adults diagnosed with COVID-19 was created in the National COVID Cohort Collaborative enclave. Two outcomes, life-threatening disease, and hospitalization were evaluated by using logistic regression models with and without adjustment for demographics and comorbidities.Of the 2,453,799 adults diagnosed with COVID-19, 191,520 (7.81%) had a pre-existing AID diagnosis and 278,095 (11.33%) had a pre-existing IS exposure. Logistic regression models adjusted for demographics and comorbidities demonstrated that individuals with a pre-existing AID (OR = 1.13, 95% CI 1.09 - 1.17; P< 0.001), IS (OR= 1.27, 95% CI 1.24 - 1.30; P< 0.001), or both (OR = 1.35, 95% CI 1.29 - 1.40; P< 0.001) were more likely to have a life-threatening COVID-19 disease. These results were consistent when evaluating hospitalization. A sensitivity analysis evaluating specific IS revealed that TNF inhibitors were protective against life-threatening disease (OR = 0.80, 95% CI 0.66- 0.96; P=0.017) and hospitalization (OR = 0.80, 95% CI 0.73 - 0.89; P< 0.001).Patients with pre-existing AID, exposure to IS, or both are more likely to have a life-threatening disease or hospitalization. These patients may thus require tailored monitoring and preventative measures to minimize negative consequences of COVID-19.

Published
2023
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16. Generalisable long COVID subtypes: findings from the NIH N3C and RECOVER programmes

Author

Reese, Justin T., primary, Blau, Hannah, additional, Casiraghi, Elena, additional, Bergquist, Timothy, additional, Loomba, Johanna J., additional, Callahan, Tiffany J., additional, Laraway, Bryan, additional, Antonescu, Corneliu, additional, Coleman, Ben, additional, Gargano, Michael, additional, Wilkins, Kenneth J., additional, Cappelletti, Luca, additional, Fontana, Tommaso, additional, Ammar, Nariman, additional, Antony, Blessy, additional, Murali, T.M., additional, Caufield, J. Harry, additional, Karlebach, Guy, additional, McMurry, Julie A., additional, Williams, Andrew, additional, Moffitt, Richard, additional, Banerjee, Jineta, additional, Solomonides, Anthony E., additional, Davis, Hannah, additional, Kostka, Kristin, additional, Valentini, Giorgio, additional, Sahner, David, additional, Chute, Christopher G., additional, Madlock-Brown, Charisse, additional, Haendel, Melissa A., additional, Robinson, Peter N., additional, Spratt, Heidi, additional, Visweswaran, Shyam, additional, Flack, Joseph Eugene, additional, Yoo, Yun Jae, additional, Gabriel, Davera, additional, Alexander, G. Caleb, additional, Mehta, Hemalkumar B., additional, Liu, Feifan, additional, Miller, Robert T., additional, Wong, Rachel, additional, Hill, Elaine L., additional, Thorpe, Lorna E., additional, and Divers, Jasmin, additional

Published
2023
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18. Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial

Author

Holland, Thomas L., primary, Ginde, Adit A., additional, Paredes, Roger, additional, Murray, Thomas A., additional, Engen, Nicole, additional, Grandits, Greg, additional, Vekstein, Andrew, additional, Ivey, Noel, additional, Mourad, Ahmad, additional, Sandkovsky, Uriel, additional, Gottlieb, Robert L., additional, Berhe, Mezgebe, additional, Jain, Mamta K., additional, Marines-Price, Rubria, additional, Agbor Agbor, Barbine Tchamba, additional, Mateu, Lourdes, additional, España-Cueto, Sergio, additional, Lladós, Gemma, additional, Mylonakis, Eleftherios, additional, Rogers, Ralph, additional, Shehadeh, Fadi, additional, Filbin, Michael R., additional, Hibbert, Kathryn A., additional, Kim, Kami, additional, Tran, Thanh, additional, Morris, Peter E., additional, Cassity, Evan P., additional, Trautner, Barbara, additional, Pandit, Lavannya M., additional, Knowlton, Kirk U., additional, Leither, Lindsay, additional, Matthay, Michael A., additional, Rogers, Angela J., additional, Drake, Wonder, additional, Jones, Beatrice, additional, Poulakou, Garyfallia, additional, Syrigos, Konstantinos N., additional, Fernández-Cruz, Eduardo, additional, Di Natale, Marisa, additional, Almasri, Eyad, additional, Balerdi-Sarasola, Leire, additional, Bhagani, Sanjay R., additional, Boyle, Katherine L., additional, Casey, Jonathan D., additional, Chen, Peter, additional, Douin, David J., additional, Files, D. Clark, additional, Günthard, Huldrych F., additional, Hite, R. Duncan, additional, Hyzy, Robert C., additional, Khan, Akram, additional, Kibirige, Moses, additional, Kidega, Robert, additional, Kimuli, Ivan, additional, Kiweewa, Francis, additional, Jensen, Jens-Ulrik, additional, Leshnower, Bradley G., additional, Lutaakome, Joseph K., additional, Manian, Prasad, additional, Menon, Vidya, additional, Morales-Rull, Jose Luis, additional, O'Mahony, D. Shane, additional, Overcash, J. Scott, additional, Ramachandruni, Srikant, additional, Steingrub, Jay S., additional, Taha, Hassan S., additional, Waters, Michael, additional, Young, Barnaby E., additional, Phillips, Andrew N., additional, Murray, Daniel D., additional, Jensen, Tomas O., additional, Padilla, Maria L., additional, Sahner, David, additional, Shaw-Saliba, Katy, additional, Dewar, Robin L., additional, Teitelbaum, Marc, additional, Natarajan, Ven, additional, Rehman, M. Tauseef, additional, Pett, Sarah, additional, Hudson, Fleur, additional, Touloumi, Giota, additional, Brown, Samuel M., additional, Self, Wesley H., additional, Chang, Christina C., additional, Sánchez, Adriana, additional, Weintrob, Amy C., additional, Hatlen, Timothy, additional, Grund, Birgit, additional, Sharma, Shweta, additional, Reilly, Cavan S., additional, Garbes, Pedro, additional, Esser, Mark T., additional, Templeton, Alison, additional, Babiker, Abdel G., additional, Davey, Victoria J., additional, Gelijns, Annetine C., additional, Higgs, Elizabeth S., additional, Kan, Virginia, additional, Matthews, Gail, additional, Thompson, B. Taylor, additional, Neaton, James D., additional, Lane, H. Clifford, additional, and Lundgren, Jens D., additional

Published
2022
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19. Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes

Author

Chan, Lauren E., primary, Casiraghi, Elena, additional, Laraway, Bryan, additional, Coleman, Ben, additional, Blau, Hannah, additional, Zaman, Adnin, additional, Harris, Nomi, additional, Wilkins, Kenneth, additional, Gargano, Michael, additional, Valentini, Giorgio, additional, Sahner, David, additional, Haendel, Melissa, additional, Robinson, Peter N., additional, Bramante, Carolyn, additional, and Reese, Justin, additional

Published
2022
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20. LETTERS TO THE EDITOR

Author

MATTHIAS, JOHN, BLAKE, JONATHAN, OVITT, GEORGE, GOTTLIEB-MILLER, JOSHUA, SMOCK, FREDERICK, WEBB, IGOR, DICKMAN, MICHAEL, SAHNER, DAVID, and THOMPSON, RICHARD

Published
2010

21. A Randomized, Partially Blinded Phase 2 Trial of Antiretroviral Therapy, HIV-Specific Immunizations, and Interleukin-2 Cycles to Promote Efficient Control of Viral Replication (ACTG A5024)

Author

The Adult AIDS Clinical Trials Group A5024 Protocol Team, Kilby, J. Michael, Bucy, R. Pat, Mildvan, Donna, Fischl, Margaret, Santana-Bagur, Jorge, Lennox, Jeff, Pilcher, Chris, Zolopa, Andrew, Lawrence, Jody, Pollard, Richard B., Habib, Raphaelle El, Sahner, David, Fox, Lawrence, Aga, Evgenia, Bosch, Ronald J., and Mitsuyasu, Ronald

Published
2006

23. Tixagevimab/Cilgavimab for Treatment of Hospitalised COVID-19 Patients: A Randomised, Double-Blind, Phase 3 Trial

Author

Holland, Thomas L., primary, Ginde, Adit A., additional, Paredes, Roger, additional, Murray, Thomas A., additional, Engen, Nicole, additional, Grandits, Greg, additional, Vekstein, Andrew, additional, Ivey, Noel, additional, Mourad, Ahmad, additional, Sandkovsky, Uriel, additional, Gottlieb, Robert L., additional, Berhe, Mezgebe, additional, Jain, Mamta, additional, Marines-Price, Rubria, additional, Tchamba Agbor Agbor, Barbine, additional, Mateu, Lourdes, additional, Espana-Cueto, Sergio, additional, Llados, Gemma, additional, Mylonakis, Eleftherios, additional, Rogers, Ralph, additional, Shehadeh, Fadi, additional, Filbin, Michael R., additional, Hibbert, Kathryn A., additional, Kim, Kami, additional, Tran, Thanh, additional, Morris, Peter E., additional, Cassity, Evan P., additional, Trautner, Barbara, additional, Pandit, Lavannya M., additional, Knowlton, Kirk U., additional, Leither, Lindsay, additional, Matthay, Michael A., additional, Rogers, Angela J., additional, Drake, Wonder, additional, Jones, Beatrice, additional, Poulakou, Garyfallia, additional, Syrigos, Konstantinos N., additional, Fernandez-Cruz, Eduardo, additional, Di Natale, Marisa, additional, Almasri, Eyad, additional, Balerdi-Sarasola, Leire, additional, Bhagani, Sanjay R., additional, Boyle, Katherine L., additional, Casey, Jonathan D., additional, Chen, Peter, additional, Douin, David J., additional, Files, D. Clark, additional, Günthard, Huldrych F., additional, Hite, R. Duncan, additional, Hyzy, Robert C., additional, Khan, Akram, additional, Kibirige, Moses, additional, Kidega, Robert, additional, Kimuli, Ivan, additional, Kiweewa, Francis, additional, Jensen, Jens Ulrik Stæhr, additional, Leshnower, Bradley G., additional, Lutaakome, Joseph K., additional, Manian, Prasad, additional, Menon, Vidya, additional, Morales-Rull, Jose Luis, additional, O&apos;Mahony, Darragh, additional, Overcash, J. Scott, additional, Ramachandruni, Srikant, additional, Steingrub, Jay S., additional, Taha, Hassan S., additional, Waters, Michael, additional, Young, Barnaby E., additional, Phillips, Andrew N., additional, Murray, Daniel D., additional, Jensen, Tomas O., additional, Padilla, Maria L., additional, Sahner, David, additional, Shaw-Saliba, Katy, additional, Dewar, Robin L., additional, Teitelbaum, Marc, additional, Natarajan, Ven, additional, Rehman, M. Tauseef, additional, Pett, Sarah, additional, Hudson, Fleur, additional, Touloumi, Giota, additional, Brown, Samuel M., additional, Self, Wesley H., additional, Chang, Christina C., additional, Sanchez, Adriana, additional, Weintrob, Amy C., additional, Hatlen, Timothy, additional, Grund, Birgit, additional, Sharma, Shweta, additional, Reilly, Cavan S., additional, Garbes, Pedro, additional, Esser, Mark T., additional, Templeton, Alison, additional, Babiker, Abdel G., additional, Davey, Victoria J., additional, Gelijns, Annetine C., additional, Higgs, Elizabeth S., additional, Kan, Virginia, additional, Matthews, Gail, additional, Thompson, B. Taylor, additional, Neaton, James D., additional, Lane, H. Clifford, additional, and Lundgren, Jens, additional

Published
2022
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27. A randomized, partially blinded phase 2 trial of antiretroviral therapy, HIV-specific immunizations, and interleukin-2 cycles to promote efficient control of viral replication (ACTG A5024)

Author

Kilby, J. Michael, Bucy, R. Pat, Mildvan, Donna, Fischl, Margaret, Santana-Bagur, Jorge, Lennox, Jeff, Pilcher, Chris, Zolopa, Andrew, Lawrence, Jody, Pollard, Richard B., Habib, Raphaelle El, Sahner, David, Fox, Lawrence, Aga, Evgenia, Bosch, Ronald J., and Mitsuyasu, Ronald

Subjects
Antiviral agents -- Research, Interleukin-2 -- Research, HIV infection -- Care and treatment, Health
Published
2006

30. Interleukin‐2 Increases CD4+Lymphocyte Numbers but Does Not Enhance Responses to Immunization: Results of A5046s

Author

Valdez, Hernan, primary, Mitsuyasu, Ronald, additional, Landay, Alan, additional, Sevin, Anne D., additional, Chan, Ellen S., additional, Spritzler, John, additional, Kalams, Spyros A., additional, Pollard, Richard B., additional, Fahey, John, additional, Fox, Lawrence, additional, Namkung, Ann, additional, Estep, Scharla, additional, Moss, Ronald, additional, Sahner, David, additional, and Lederman, Michael M., additional

Published
2003
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31. Predictors of CD4 count change over 8 months of follow up in HIV-1-infected patients with a CD4 count >= 300 cells/mu L who were assigned to 7.5 MIU interleukin-2

Author

Fox, Zoe, Antunes, Francisco, Davey, Rick, Gazzard, Brian, Klimas, Nancy, Labriola, Ann, Losso, Marcelo, Neaton, James D., Phillips, Andrew N., Ruxrungtham, Kiat, Staszewski, Schlomo, Weiss, Laurence, Lundgren, Jens D., Abrams, Donald I., Cooper, David A., Darbyshire, Janet H., Duncan, William R., Emery, Sean, Lane, H. Clifford, Lehrman, Sandra, Aguilar, Liliana, Betina Angel, Eleonora, Aquilia, Silvia, Belloso, Waldo, Benetucci, Jorge, Bittar, Victor, Cahn, Pedro, Casiro, Arnaldo, Contarelli, Jorge, Corral, Jorge, Daciuk, Lucia, David, Daniel, Ferrari, Ines, Fridman, Diego, Galache, Viviana, Guaragna, Graciela, Ivalo, Silvina, Laplume, Hector, Lanusse, Isabel, Lasala, Maria B., Lattes, Roberta, Lasovsky, Jaime, Lopardo, Gustavo, Lourtau, Leonardo, Lupo, Sergio, Maranzana, Aldo, Marson, Cristina, Massera, Lucila, Del Lujan Sanchez, Marisa, Somenzini, Carla, Tocci, Mariel, Algar, Sally, Anderson, Jonathan, Baker, David, Blavius, Kathy, Bloch, Mark, Boyle, Michael, Bradford, David, Britton, Phillip, Carrall, Leah, Carr, Andrew, Chuah, John, Curry, Michael, D Arcy-Evans, Clive, Dobson, Pauline, Doong, Nicholas, Egan, Cari, Ferguson, Wendy, Finlayson, Robert, French, Martyn, Frater, Anthony, Gold, Julian, Habel, Philip, Haig, Kay, Holland, Rohan, Hyland, Natalie, Hoy, Jennifer, Hudson, Jeff, James, Robyn, Leung, Jenny, Lowe, Kaye, Macrae, Karen, Mcmurchie, Marilyn, Medland, Nicholas, Miller, Samantha, Murray, Jo, Newman, Rosie, Orth, David, Patching, Julie, Primrose, Ruth, Ree, Hugo, Richardson, Robyn, Rogers, Gary, Roney, Janine, Roth, Norman, Sarangapany, Jeganathan, Shaw, David, Silberberg, Carol, Skett, Jenny, Williams, Leah, Soo, Tuck Meng, Sowden, David, Street, Alan, Vale, Robyn, Villella, Claudio, Walker, Alan, Watson, Ashley, Wendt, Ngaire, Wood, Helen, Youds, David, Aichelburg, Alexander, Rieger, Armin, Vetter, Norbert, Clumeck, Nathan, Wit, Stephane, Kabeya, Kabamba, O Doherty, Elizabeth, Amorim, Cristiane Sales, Basso, Caritas Relva, Lewi, David Salamao, Pereira, Luiz Carlos, Da Silva, Mariliza, Lobato Souza, Tamara Newman, Angel, Jonathan, Bouchard, Pierrette-Rolande, Clark, Fran, Cohen, Jeff, Dambreville, Mimose, Ellis, Michele, Fiset, Stephan, Foster, Andrea, Fraser, Christopher, Gagnon, Susan, Gilmour, Janet, Guenette, Richard, Haldane, Heather, Hawley-Foss, Nanci, Hyndman, Susan, Johnston, Lynn, Jubinville, Nathalie, Juneau, Francoise, Kelleher, Lynn, Lapointe, Lyne, Latendre-Paquette, Judy, Lindemulder, Adeline, Mashinter, Laura, Lefebvre, Eric, Mcfarland, Nancy, Morisseau, Chantal, O Neill, Robert, Piche, Alain, Ralph, Edward, Rouleau, Danielle, Routy, Jean-Pierre, Sandre, Roger, Schmidt, Shelley, Shafran, Stephen, Smaill, Fiona, Stromberg, Dale, Trepanier, Jean-Marc, Trottier, Sylvie, Veal, Susanne, Walmsley, Sharon, Weiss, Karl, Williams, Kurt, Young, Mavis, Zaleschuk, Barbara, Zarowny, Don, Baadegaard, Bente, Black, Finn, Boedker, Kirsten, Gerstoft, Jan, Jensen, Lene, Mathiesen, Lars, Nielsen, Henrik, Pedersen, Court, Petersen, Dorthe, Aboulker, Jean-Pierre, Baakili, Adyb, Bengrait, Nafissa, Bensalem, Maryse, Berthe, Huguette, Bloche, Martin, Bazin, Claude, Boue, Francois, Bouvet, Elisabeth, Brancon, Christiane, Capitant, Catherine, Ceppi, Carole, Cheneau, Christine, Coutellier, Anne, Chennebault, Jean Marie, Coquet, Fabienne, Truchis, Pierre, Delavalle, Anne-Marie, Frixon-Marin, Veronique, Gastaut, Jean-Albert, Delfraissy, Francois, Eliaszeicz, Muriel, Gallais, Herve, Gataut, Jean-Albert, Gilquin, Jacques, Gonzalez-Canali, Gustavo, Gaudebout, Chrisiane, Goujard, Cecile, Hoen, Bruno, Honore, Patricia, Jarousse, Bernard, Lang, Jean-Marie, Lefebvre, Benedict, Levy, Yves, Loison, Jocelyne, Maignan, Aline, Meynard, Jean-Luc, Michon, Christophe, Mole, Martin, Marsal, Laurence, Matheron, Sophie, Mortier, Emmanuel, Oksenhendler, Eric, Poirier, Sandrine, Picard-Dahan, Catherine, Ravaux, Isabelle, Raffi, Francois, Raguin, Gilles, Reynes, Jacque, Rozenbaum, Willy, Salmon, Dominique, Simon, Anne, Spiridon, Gabriella, Viard, Jean-Paul, Vidal, Michele, Zucman, David, Bergmann, Frank, Brockmeyer, Norbert, Faetkenheuer, Gerd, Fenske, Stefan, Gey, Daniela, Goebel, Frank-Detlef, Goetsch, Martina, Hartmann, Martin, Klinker, Hartwig, Kremer, Gisela, Mantzsch, Kathleen, Mauss, Stefan, Rockstroh, Juergen, Rotty, Jessica, Rund, Ellen, Schneider, Katrin, Schuermann, Dirk, Staszweski, Schlomo, Tilmann, Klaus, Vogel, Martin, Bentwich, Zvi, Drora, Goldstain, Kedem, Eynat, Lang, Ruth, Levi, Itzic, Maayan, Shlomo, Magen, Eli, Mamorsky, Merav, Pilpul, Anat, Pollack, Shimon, Sthoeger, Zev, Vered, Hadas, Yust, Israel, Lyons, Fiona, Mulcahy, Fiona, Rochford, Annette, Auiti, Fernando, Angarano, Gioacchino, Bertelli, Davide, Bini, Teresa, Bruno, Raffaele, Cadeo, Gian Pietro, Carosi, Giampietro, D Arminio Monforte, Antonella, Del Giacco, Sergio, Di Pietro, Massimo, Esposito, Roberto, Filice, Gaetano, Gavazzeni, Gabriella, Guaraldi, Giovanni, Indiveri, Francesco, Lazzarin, Adriano, Mazzotta, Francesco, Minolli, Lorenzo, Montroni, Maria, Moroni, Mauro, Nozza, Silvia, Pastor, Guiseppe, Poli, Guido, Raise, Enzo, Romagnani, Sergio, Rusconi, Vega, Sacchi, Paolo, Suter, Fredy, Tambussi, Giuseppe, Tirelli, Umberto, Fraser, Helen, Iwamoto, Aikichi, Kikuchi, Yoshida, Mori, Masahiko, Nakamura, Tetsuya, Odawara, Takashi, Oka, Shinichi, Shirasaka, Takuma, Takano, Misao, To, Junichiro, Ueta, Chisato, El Filali, Kamal, Erradey, Ikbale, Himmich, Hakima, Blok, W., Borleffs, J., Bravenboer, B., Bronveld, W., Claessen, F., Duurvoort, Maurice, Ferwerda, J., Frissen, P., Hulshoff, Nicolette, Juttman, Job, Kauffmann, R., Koopmans, P., Kroon, F., Lowe, Selwyn, Leemhuis, M., Meenhorst, P., Boer, Lieselotte Posthuma, Reiss, Peter, Reinders-Folmer, S., Richter, C., Santegoets, Rick, Schoemaker, Marijke, Schrey, G., Sprenger, Herman, Ten Veen, Jacob, Tessalaar, Judith, Ende, M., Vall, H., Eeden, Arne, Leeuwen, Remko, Vermeulen, Joost, Ten Kate, Reinier W., Boxtel, Renee, Eden, Arne, Ven, Bernadette, Meulen, Piet, Ten Napei, C., Vriesendrop, R., Bruun, Johann, Bakowska, Elzbieta, Beniowski, Marek, Boron-Kaczmarska, Anna, Gasiorowski, Jacek, Gxadysz, Andrzej, Horban, Andrzej, Knysz, Brygida, Mularska, Elzbieta, Pynka, Magdelena, Szymczak, Aleksandra, Aldir, Isabel, Doroana, Manuela, Duque, Luis, Mansinho, Kamal, Pinto, Inez, Valadas, Emilia, Vera, Jose, Foo, Estelle, Panchalingham, Anushia, Lim, Poh Lian, Paton, Nick, Peperstraete, Bernard, Quek, Angela, Alcazar-Caballero, Rosario, Arrizabalaga, Julio, Bouza, Emilio, Cepeda, Concepcion, Barron, Xabier, Cervero Jimenez, Miguel, Clotet, Bonaventura, Cortes, Luis, Domingo, Pere, Fernandez, Pompeyo, Fernandez-Cruz, Eduardo, Fuster, Montserrat, Gatell, Jose, Gijon, Paloma, Gil, Ignacio, Gonzales-Lahoz, Juan, Gonzalez, Alicia, Hernandez, Manuel, Iribarren, Jose, Jimenez, Miguel, Knobel, Hernando, Leon, Agathe, Carlos Lopez, Juan, Lozano, Angeles, Lopez, Paco, Moreno, Jose, Munoz, Rosa, Padilla, Belen, Parras, Angeles, Pastor, Antoni, Pedreira, Jose, Pristo, Julio, Pena, Jose, Roca, Victor, Rubio, Rafael, Sanchez Rivera, Jose, Sanz, Jesus, Tamargo, Lara, Torres, Rafael, Pehrson, Pehr O., Sandstrom, Eric, Bernasconi, Enos, Gurtner, Vanina, Magenta, Lorenzo, Ampunpong, Uangarun, Bowonwatnuwong, Chureeratana, Chanchai, Patimoaporn, Chetchotisakd, Ploenchan, Chuenyam, Thesinee, Duncombe, Chris, Horsakulthai, Mannassinee, Kantipong, Pacharee, Liddy, John, Phanuphak, Praphan, Pongsurachet, Vithaya, Seekaew, Samroeng, Sonjai, Areerat, Subsri, Nuramon, Suwanagool, Surapol, Techasathit, Wichai, Wankoon, Jaturaporn, Adebiyi, Aderonke, Aldam, Diana, Alexander, Ian, Angus, Brian, Barber, Tristan, Bonnington, Sue, Care, Chris, Carroll, Anne, Cornforth, David, Donaldson, Oscar, Druiff, Laurance, Easterbrook, Philippa, Edwards, Beverley, Ellis, Chris, Fisher, Martin, Fox, Ray, Harrison, Allan, Herman, Sandra, Heald, Lisa, Higgs, Christopher, Jendrulek, Isabelle, Johnson, Margaret, Judges, Lucy, Karim, Fatimah, Kinghorn, George, Laurenti, Julie, Lee, Christine, Leen, Clifford, Legg, Ken, Maw, Raymond, Macconachie, Alisdair, Mckernan, Sinead, Mclean, Lorna, Mcmillan, Andrew, Mguni, Sifiso, Morris, Sheila, Mulchay, Fiona, Mullan, Dee, Mullaney, Scott, Murphy, Maurice, Nunn, Andrew, Ong, Edmund, Owen, Maxine, Palfreeman, Adrian, Perry, Nicky, Peters, Barry, Pozniak, Anton, Ronan, Agnes, Skinner, Cecilia, Stroud, Carol, Takawira, Martin, Tamm, Norbert, Thomas, Rachel, Yee, Thynn Thynn, Vanthuyne, An, Wansborough-Jones, Mark, Weber, Jonathan, White, David, Wilkins, Ed, Wiselka, Martin, Williams, Ian, Waugh, Mike, Wotherspoon, Joyce, Youle, Mike, Doyle, Margaret, Goodwin, Edward, Luskin-Hawk, Roberta, Sullivan, James, Verheggen, Rita, Abrams, Donald, Baxter, John, Besch, C. Lynn, Child, Carroll, Cohn, David, Cooper, Pam, El-Sadr, Wafaa, Farrough, Martha, Fisher, Evelyn, Fuentes, Luis, Gordin, Fred, Graeber, Carol, Kelly, Mary Ellen, Kostman, Jay, Lattanzi, Kelly, Macarthur, Rodger, Makohon, Linda, Markowitz, Norman P., Martinez, Norma, Mastro-Polak, Diane, Mitchell, Vinnie, Mushatt, David, Patterson, Kathryn, Perez, George, Rosmarin, Corey, Rouff, Jack R., Saldanha, Jennifer, Sampson, James, Sawyer, Robert, Standridge, Barbara, Sweeton, Bentley, Tedaldi, Ellen, Thompson, Melanie, Valencia, Patricia, Verlinghieri, Gwen, Walker, Janice, Watson, Vicky, Williams, Bruce, Armstrong, Adam, Banks, Susan, Blazes, David, Barile, Anthony, Coelho, Linda, Dennis, Marilyn, Flaks, Hannah, Gilcrest, Joyce, Gittens, Kathleen, Hopper, Shelia, Humphries, M. J., Spooner, Katherine, Tamminga, Cindy L., Vita, Jean, Wegner, Scott A., Wortmann, Glenn, Bisby, Nicole, Blake, William, Brown, Sheldon, Chilliade, Phillippe, Cole, Teresa, Elliot, Katherine, Geisler, Christiane, Goetz, Matthew, Gomez-Perez, Elizabeth, Helman, Jami, Nahass, Ronald, Leflore, Dirk, Marston, Barbara, Obregon, Maria, Petrolati, Jennifer, Pitrak, David L., Roland, Robert, Rosa, Carol, Rossman, Barbara, Schlueter Wirtz, Susan, Schuck, Suzanne, Scretchings, Tiffany, Simon, Gary, Smith, Mack, Summers, Kimberley, Werhane, Mary Jo, Arduino, Roberto, Bell, Brian, Breaux, Katherine, Cuervo, Hilda, Hale, Carl, Lewis, Stanley, Mall, Mark, Mora, Fransisco, Diez, Martine M., Okhuysen, Pablo, Rodriguez-Barradas, Maria, Schrader, Shannon R., Healy, Lynn, Kaszubski, Chris, Kolber, Michael, Tanner, Tom, Armstrong, Joann, Dahlke, Jennifer, Johnson, Leonard, Kaminski, Patricia, Rhame, Frank, Shoden, Cheryl, Temesgen, Zelalem, Urbanich, Marcy, Valenti, Sharon, Zervos, Marcus, Barrick, Bill, Chaitt, Doreen, Hahn, Barbara, Lane, Cliff, Martell, Dennis, Mcnay, Laura, Metcalf, Julia, Powers, April, Tavel, Jorge A., Loveless, Karen, Peterson, Sue, Sweek, Suzanne, Albrecht, Helmut, Antoine, Nicole, Pell, Paula, Gatell, Jose Maria, Hoy, Jenny, Lifson, Alan, Pederson, Court, Borup, Liselotte, Dragsted, Ulrik Bak, Greve, Anne Fau, Jensen, Karoline, Jens Lundgren, Mollerup, David, Pearson, Mary, Phillips, Andrew, Aboulhab, Jamila, Babiker, Abdel, Cordwell, Brooke, Darbyshire, Janet, Hack, Lisa, Hooker, Malcolm, Moraes, Yolanda, Newberry, Douglas, Nuwagaba-Biribonwoha, Harriet, Hooff, Fionna, Denning, Eileen, Holland Klemme, Leslie, Carey, Cate, Chan, Fonnie, Cooper, David, Courtney-Rodgers, David, Drummond, Fraser, Jacoby, Simone, Law, Matthew, Stewart, Morgan, Pett, Sarah, Alloo, Zarina, Bebchuk, Judy, Bollenbeck, Patty, Duchene, Alain G., Fosdick, Lisa, Harrison, Merrie, Krum, Eric, Larson, Gregg, Meger, Sue, Neaton, James, Nelson, Ray, Quan, Siu-Fun L., Schultz, Terri, Telke, Susan, Thackeray, Lisa, Thompson, Greg, Wentworth, Deborah, Wyman, Nicole, Duncan, William, Ferguson, Elaine, Fox, Lawrence, Gettinger, Nikki, Herrera, Janet, Luzar, Mary Anne, Maeshiro, Mieko, Martinez, Ana, Oseekey, Karen, Baigent, Greg, Capra, William, Duliege, Anne-Marie, Fitzgerald, Linda, Kwakkelstein, Marthin, Maral, Jean, O Hara, Mary, Sahner, David, Weber, Claire, Adam-Perchec, Christine, Barron, Nigel, Bell, Mary Louise, Dolan, Sandra, Eckstrand, Julie, Hicks, Steven, Mcauley, George, Beck, Sharon, Brown, Shawn, and Rupert, Adam

32. Minerali.

Author

SAHNER, DAVID

Subjects
MINERALI (Poem), SAHNER, David
Published
2017

33. POEISIS.

Author

Sahner, David

Subjects
POEISIS (Poem), SAHNER, David
Published
2019

34. Epicurus Counsels the Moderns.

Author

Sahner, David

Abstract

Presents the poem "Epicurus Counsels the Moderns," by David Sahner. First Line: Listen; Last line: No more than this.

Published
2006

35. In Two Centuries.

Author

Sahner, David

Subjects
IN Two Centuries (Poem), SAHNER, David
Abstract

Presents the poem "In Two Centuries," by David Sahner. First Line: Will; Last Line: That fill the horizons of these days.

Published
2008

36. You.

Author

Sahner, David

Subjects
YOU (Poem), SAHNER, David
Abstract

Presents the poem "You," by David Sahner. First Line: Acacia bleeding into the night. Last Line: Is You.

Published
2006

37. Influence of Prior SARS-CoV-2 Infection on COVID-19 Severity: Evidence from the National COVID Cohort Collaborative.

Author

Hendrix N, Sidky H, and Sahner DK

Abstract

Background: A large share of SARS-CoV-2 infections now occur among previously infected individuals. In this study, we sought to determine whether prior infection modifies disease severity relative to no prior infection., Methods: We used data from first and second COVID-19 episodes in the National COVID Cohort Collaborative, a nationwide collection of de-identified electronic health records. We used nested logistic regressions of monthly cohorts weighted on the inverse probability of prior infection to assess risk of hospitalization, death, and increased severity in the first versus second infection cohorts., Results: We included a total of 2,058,274 individuals in the analysis, 147,592 of whom had two recorded infections. The impact of prior infection differed meaningfully between months. Prior infection was largely protective prior to March 2022, with odds ratios (ORs) as low as 0.66 (95% confidence interval: 0.51 to 0.86) in November 2021 for hospitalization. and as low as 0.23 (0.06 to 0.86) in June 2021 for death. However, prior infection was associated with an increased risk of hospitalization and death, mostly after March 2022 when the ORs were as high as 1.87 (1.26 to 2.80) and 2.99 (1.65 to 5.41) in April 2022, respectively. The overall OR for more severe disease was 1.06 (1.03 to 1.10) among previously infected individuals., Conclusion: In the pandemic's first two years, previously infected patients generally had less severe disease than people without prior infection. During the Omicron era, however, previously infected patients had the same or worse severity of disease as patients without prior infection.

Published
2024
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38. Paxlovid (nirmatrelvir/ritonavir) effectiveness against hospitalization and death in N3C: A target trial emulation study.

Author

Hansen K, Makkar SR, Sahner D, Fessel J, Hotaling N, and Sidky H

Abstract

Importance: COVID-19 has placed a monumental burden on the health care system globally. Although no longer a public health emergency, there is still a pressing need for effective treatments to prevent hospitalization and death. Paxlovid (nirmatrelvir/ritonavir) is a promising and potentially effective antiviral that has received emergency use authorization by the U.S. FDA., Objective: Determine real world effectiveness of Paxlovid nationwide and investigate disparities between treated and untreated eligible patients., Design/setting/participants: Population-based cohort study emulating a target trial, using inverse probability weighted models to balance treated and untreated groups on baseline confounders. Participants were patients with a SARS-CoV-2 positive test or diagnosis (index) date between December 2021 and February 2023 selected from the National COVID Cohort Collaborative (N3C) database who were eligible for Paxlovid treatment. Namely, adults with at least one risk factor for severe COVID-19 illness, no contraindicated medical conditions, not using one or more strictly contraindicated medications, and not hospitalized within three days of index. From this cohort we identified patients who were treated with Paxlovid within 5 days of positive test or diagnosis (n = 98,060) and patients who either did not receive Paxlovid or were treated outside the 5-day window (n = 913,079 never treated; n = 1,771 treated after 5 days)., Exposures: Treatment with Paxlovid within 5 days of positive COVID-19 test or diagnosis., Main Outcomes and Measures: Hospitalization and death in the 28 days following COVID-19 index date., Results: A total of 1,012,910 COVID-19 positive patients at risk for severe COVID-19 were included, 9.7% of whom were treated with Paxlovid. Uptake varied widely by geographic region and timing, with top adoption areas near 50% and bottom near 0%. Adoption increased rapidly after EUA, reaching steady state by 6/2022. Participants who were treated with Paxlovid had a 26% (RR, 0.742; 95% CI, 0.689-0.812) reduction in hospitalization risk and 73% (RR, 0.269, 95% CI, 0.179-0.370) reduction in mortality risk in the 28 days following COVID-19 index date., Conclusions/relevance: Paxlovid is effective in preventing hospitalization and death in at-risk COVID-19 patients. These results were robust to a large number of sensitivity considerations., Disclosure: The authors report no disclosures., Key Points: Question: Is treatment with Paxlovid (nirmatrelvir/ritonavir) associated with a reduction in 28-day hospitalization and mortality in patients at risk for severe COVID-19? Findings: In this multi-institute retrospective cohort study of 1,012,910 patients, Paxlovid treatment within 5 days after COVID-19 diagnosis reduced 28-day hospitalization and mortality by 26% and 73% respectively, compared to no treatment with Paxlovid within 5 days. Paxlovid uptake was low overall (9.7%) and highly variable. Meaning: In Paxlovid-eligible patients, treatment was associated with decreased risk of hospitalization and death. Results align with prior randomized trials and observational studies, thus supporting the real-world effectiveness of Paxlovid.

Published
2023
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39. Assessing the Effect of Selective Serotonin Reuptake Inhibitors in the Prevention of Post-Acute Sequelae of COVID-19.

Author

Sidky H, Sahner DK, Girvin AT, Hotaling N, Michael SG, and Gersing K

Abstract

Importance: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties and therefore may be postulated to be of benefit in patients with PASC, although clinical trial data are lacking., Objectives: The main objective was to evaluate whether SSRIs with agonist activity at the sigma-1 receptor lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. A secondary objective was to determine whether potential benefit could be traced to sigma-1 agonism by evaluating the risk of PASC among recipients of SSRIs that are not S1R agonists., Design: Retrospective study leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C), a large centralized multi-institutional de-identified EHR database. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code to more comprehensively identify patients likely to have the condition, since the ICD code has come into wide-spread use only recently., Setting: Population-based study at US medical centers., Participants: Adults (≥ 18 years of age) with a confirmed COVID-19 diagnosis date between October 1, 2021 and April 7, 2022 and at least one follow up visit 45 days post-diagnosis. Of the 17 933 patients identified, 2021 were exposed at baseline to a S1R agonist SSRI, 1328 to a non-S1R agonist SSRI, and 14 584 to neither., Exposures: Exposure at baseline (at or prior to COVID-19 diagnosis) to an SSRI with documented or presumed agonist activity at the S1R (fluvoxamine, fluoxetine, escitalopram, or citalopram), an SSRI without agonist activity at S1R (sertraline, an antagonist, or paroxetine, which does not appreciably bind to the S1R), or none of these agents., Main Outcome and Measurement: Development of PASC based on a previously validated XGBoost-trained algorithm. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed., Results: A 26% reduction in the RR of PASC (0.74 [95% CI, 0.63-0.88]; P = 5 × 10 -4 ) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 25% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.75 [95% CI, 0.62 - 0.90]; P = 0.003) compared to SSRI unexposed patients., Conclusions and Relevance: SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC. Future prospective studies are warranted., Competing Interests: Conflicting Interests The authors hereby declare no conflicting interests pertaining to the material in this manuscript.

Published
2023
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40. Pre-existing autoimmunity is associated with increased severity of COVID-19: A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C).

Author

Yadaw AS, Afzali B, Hotaling N, Sidky H, Pfaff ER, Sahner DK, and Mathé EA

Abstract

Importance: Identifying individuals with a higher risk of developing severe COVID-19 outcomes will inform targeted or more intensive clinical monitoring and management., Objective: To examine, using data from the National COVID Cohort Collaborative (N3C), whether patients with pre-existing autoimmune disease (AID) diagnosis and/or immunosuppressant (IS) exposure are at a higher risk of developing severe COVID-19 outcomes., Design Setting and Participants: A retrospective cohort of 2,453,799 individuals diagnosed with COVID-19 between January 1 st , 2020, and June 30 th , 2022, was created from the N3C data enclave, which comprises data of 15,231,849 patients from 75 USA data partners. Patients were stratified as those with/without a pre-existing diagnosis of AID and/or those with/without exposure to IS prior to COVID-19., Main Outcomes and Measures: Two outcomes of COVID-19 severity, derived from the World Health Organization severity score, were defined, namely life-threatening disease and hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression models with and without adjustment for demographics (age, BMI, gender, race, ethnicity, smoking status), and comorbidities (cardiovascular disease, dementia, pulmonary disease, liver disease, type 2 diabetes mellitus, kidney disease, cancer, and HIV infection)., Results: In total, 2,453,799 (16.11% of the N3C cohort) adults (age> 18 years) were diagnosed with COVID-19, of which 191,520 (7.81%) had a prior AID diagnosis, and 278,095 (11.33%) had a prior IS exposure. Logistic regression models adjusted for demographic factors and comorbidities demonstrated that individuals with a prior AID (OR = 1.13, 95% CI 1.09 - 1.17; p =2.43E-13), prior exposure to IS (OR= 1.27, 95% CI 1.24 - 1.30; p =3.66E-74), or both (OR= 1.35, 95% CI 1.29 - 1.40; p =7.50E-49) were more likely to have a life-threatening COVID-19 disease. These results were confirmed after adjusting for exposure to antivirals and vaccination in a cohort subset with COVID-19 diagnosis dates after December 2021 (AID OR = 1.18, 95% CI 1.02 - 1.36; p =2.46E-02; IS OR= 1.60, 95% CI 1.41 - 1.80; p =5.11E-14; AID+IS OR= 1.93, 95% CI 1.62 - 2.30; p =1.68E-13). These results were consistent when evaluating hospitalization as the outcome and also when stratifying by race and sex. Finally, a sensitivity analysis evaluating specific IS revealed that TNF inhibitors were protective against life-threatening disease (OR = 0.80, 95% CI 0.66-0.96; p =1.66E-2) and hospitalization (OR = 0.80, 95% CI 0.73 - 0.89; p =1.06E-05)., Conclusions and Relevance: Patients with pre-existing AID, exposure to IS, or both are more likely to have a life-threatening disease or hospitalization. These patients may thus require tailored monitoring and preventative measures to minimize negative consequences of COVID-19.

Published
2023
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41. Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes.

Author

Chan LE, Casiraghi E, Laraway B, Coleman B, Blau H, Zaman A, Harris N, Wilkins K, Gargano M, Valentini G, Sahner D, Haendel M, Robinson PN, Bramante C, and Reese J

Abstract

Background: With the continuing COVID-19 pandemic, identifying medications that improve COVID-19 outcomes is crucial. Studies suggest that use of metformin, an oral antihyperglycemic, is associated with reduced COVID-19 severity in individuals with diabetes compared to other antihyperglycemic medications. Some patients without diabetes, including those with polycystic ovary syndrome (PCOS) and prediabetes, are prescribed metformin for off-label use, which provides an opportunity to further investigate the effect of metformin on COVID-19., Participants: In this observational, retrospective analysis, we leveraged the harmonized electronic health record data from 53 hospitals to construct cohorts of COVID-19 positive, metformin users without diabetes and propensity-weighted control users of levothyroxine (a medication for hypothyroidism that is not known to affect COVID-19 outcome) who had either PCOS (n = 282) or prediabetes (n = 3136). The primary outcome of interest was COVID-19 severity, which was classified as: mild, mild ED (emergency department), moderate, severe, or mortality/hospice., Results: In the prediabetes cohort, metformin use was associated with a lower rate of COVID-19 with severity of mild ED or worse (OR: 0.630, 95% CI 0.450 - 0.882, p < 0.05) and a lower rate of COVID-19 with severity of moderate or worse (OR: 0.490, 95% CI 0.336 - 0.715, p < 0.001). In patients with PCOS, we found no significant association between metformin use and COVID-19 severity, although the number of patients was relatively small., Conclusions: Metformin was associated with less severe COVID-19 in patients with prediabetes, as seen in previous studies of patients with diabetes. This is an important finding, since prediabetes affects between 19 and 38% of the US population, and COVID-19 is an ongoing public health emergency. Further observational and prospective studies will clarify the relationship between metformin and COVID-19 severity in patients with prediabetes, and whether metformin usage may reduce COVID-19 severity.

Published
2022
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42. Generalizable Long COVID Subtypes: Findings from the NIH N3C and RECOVER Programs.

Author

Reese JT, Blau H, Bergquist T, Loomba JJ, Callahan T, Laraway B, Antonescu C, Casiraghi E, Coleman B, Gargano M, Wilkins KJ, Cappelletti L, Fontana T, Ammar N, Antony B, Murali TM, Karlebach G, McMurry JA, Williams A, Moffitt R, Banerjee J, Solomonides AE, Davis H, Kostka K, Valentini G, Sahner D, Chute CG, Madlock-Brown C, Haendel MA, and Robinson PN

Abstract

Accurate stratification of patients with post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies. However, the natural history of long COVID is incompletely understood and characterized by an extremely wide range of manifestations that are difficult to analyze computationally. In addition, the generalizability of machine learning classification of COVID-19 clinical outcomes has rarely been tested. We present a method for computationally modeling PASC phenotype data based on electronic healthcare records (EHRs) and for assessing pairwise phenotypic similarity between patients using semantic similarity. Our approach defines a nonlinear similarity function that maps from a feature space of phenotypic abnormalities to a matrix of pairwise patient similarity that can be clustered using unsupervised machine learning procedures. Using k-means clustering of this similarity matrix, we found six distinct clusters of PASC patients, each with distinct profiles of phenotypic abnormalities. There was a significant association of cluster membership with a range of pre-existing conditions and with measures of severity during acute COVID-19. Two of the clusters were associated with severe manifestations and displayed increased mortality. We assigned new patients from other healthcare centers to one of the six clusters on the basis of maximum semantic similarity to the original patients. We show that the identified clusters were generalizable across different hospital systems and that the increased mortality rate was consistently observed in two of the clusters. Semantic phenotypic clustering can provide a foundation for assigning patients to stratified subgroups for natural history or therapy studies on PASC.

Published
2022
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