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1. Risk of COVID-19 after natural infection or vaccinationResearch in context

Author

Anne-Marie Rick, Matthew B. Laurens, Ying Huang, Chenchen Yu, Thomas C.S. Martin, Carina A. Rodriguez, Christina A. Rostad, Rebone M. Maboa, Lindsey R. Baden, Hana M. El Sahly, Beatriz Grinsztejn, Glenda E. Gray, Cynthia L. Gay, Peter B. Gilbert, Holly E. Janes, James G. Kublin, Yunda Huang, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M. Dunkle, Kathleen M. Neuzil, Lawrence Corey, Paul A. Goepfert, Stephen R. Walsh, Dean Follmann, Karen L. Kotloff, Atoya Adams, Eric Miller, Bruce G. Rankin, Steven Shinn, Marshall Nash, Sinikka L. Green, Colleen Jacobsen, Jayasree Krishnankutty, Sikhongi Phungwayo, Richard M. Glover, II, Stacy Slechta, Troy Holdeman, Robyn Hartvickson, Amber Grant, Terry L. Poling, Terry D. Klein, Thomas C. Klein, Tracy R. Klein, William B. Smith, Richard L. Gibson, Jennifer Winbigler, Elizabeth Parker, Priyantha N. Wijewardane, Eric Bravo, Jeffrey Thessing, Michelle Maxwell, Amanda Horn, Catherine Mary Healy, Christine Akamine, Laurence Chu, R. Michelle Chouteau, Michael J. Cotugno, George H. Bauer, Jr., Greg Hachigian, Masaru Oshita, Michael Cancilla, Kristen Kiersey, William Seger, Mohammed Antwi, Allison Green, Anthony Kim, Michael Desjardins, Jennifer A. Johnson, Amy Sherman, Judith Borger, Nafisa Saleem, Joel Solis, Martha Carmen Medina, Westly Keating, Edgar Garcia, Cynthia Bueno, Nathan Segall, Douglas S. Denham, Thomas Weiss, Ayoade Avworo, Parke Hedges, Cynthia Becher Strout, Rica Santiago, Yvonne Davis, Patty Howenstine, Alison Bondell, Kristin Marks, Tina Wang, Timothy Wilkin, Mary Vogler, Carrie Johnston, Michele P. Andrasik, Jessica G. Andriesen, Gail Broder, Niles Eaton, Huub G. Gelderblom, Rachael McClennen, Nelson Michael, Merlin Robb, Carrie Sopher, Vicki E. Miller, Fredric Santiago, Blanca Gomez, Insiya Valika, Amy Starr, Valeria D. Cantos, Sheetal Kandiah, Carlos del Rio, Nadine Rouphael, Srilatha Edupuganti, Evan J. Anderson, Andres Camacho-Gonzalez, Satoshi Kamidani, Meghan Teherani, David J. Diemert, Elissa Malkin, Marc Siegel, Afsoon Roberts, Gary Simon, Bindu Balani, Carolene Stephenson, Steven Sperber, Cristina Cicogna, Marcus J. Zervos, Paul Kilgore, Mayur Ramesh, Erica Herc, Kate Zenlea, Abram Burgher, Ann M. Milliken, Joseph D. Davis, Brendan Levy, Sandra Kelman, Matthew W. Doust, Denise Sample, Sandra Erickson, Shane G. Christensen, Christopher Matich, James Longe, John Witbeck, James T. Peterson, Alexander Clark, Gerald Kelty, Issac Pena-Renteria, Michael J. Koren, Darlene Bartilucci, Alpa Patel, Carolyn Tran, Christina Kennelly, Robert Brownlee, Jacob Coleman, Hala Webster, Carlos A. Fierro, Natalia Leistner, Amy Thompson, Celia Gonzalez, Lisa A. Jackson, Janice Suyehira, Milton Haber, Maria M. Regalado, Veronica Procasky, Alisha Lutat, Carl P. Griffin, Ripley R. Hollister, Jeremy Brown, Melody Ronk, Wayne L. Harper, Lisa Cohen, Lynn Eckert, Matthew Hong, Rambod Rouhbakhsh, Elizabeth Danford, John Johnson, Richard Calderone, Shishir K. Khetan, Oyebisi Olanrewaju, Nan Zhai, Kimberly Nieves, Allison O'Brien, Paul S. Bradley, Amanda Lilienthal, Jim Callis, Adam B. Brosz, Andrea Clement, Whitney West, Luke Friesen, Paul Cramer, Frank S. Eder, Ryan Little, Victoria Engler, Heather Rattenbury-Shaw, David J. Ensz, Allie Oplinger, Brandon J. Essink, Jay Meyer, Frederick Raiser, III, Kimberly Mueller, Keith W. Vrbicky, Charles Harper, Chelsie Nutsch, Wendell Lewis, III, Cathy Laflan, Jordan L. Whatley, Nicole Harrell, Amie Shannon, Crystal Rowell, Christopher Dedon, Mamodikoe Makhene, Gregory M. Gottschlich, Kate Harden, Melissa Gottschlich, Mary Smith, Richard Powell, Murray A. Kimmel, Simmy Pinto, Timothy P. Vachris, Mark Hutchens, Stephen Daniels, Margaret Wells, Mimi Van Der Leden, Peta-Gay Jackson-Booth, Mira Baron, Pamela Kane, Shannen Seversen, Mara Kryvicky, Julia Lord, Jamshid Saleh, Matthew Miles, Rafael Lupercio, John W. McGettigan, Jr., Walter Patton, Riemke Brakema, Karin Choquette, Jonlyn McGettigan, Judith L. Kirstein, Marcia Bernard, Mary Beth Manning, Joan Rothenberg, Toby Briskin, Denise Roadman, Sharita Tedder-Edwards, Howard I. Schwartz, Surisday Mederos, Shobha Swaminathan, Amesika Nyaku, Tilly Varughese, Michelle DallaPiazza, Sharon E. Frey, Irene Graham, Getahun Abate, Daniel Hoft, Leland N. Allen, III, Leslie A. Edwards, William S. Davis, Jr., Jessica M. Mena, Mark E. Kutner, Jorge Caso, Maria Hernandez Moran, Marianela Carvajal, Janet Mendez, Larkin T. Wadsworth, III, Michael R. Adams, Leslie Iverson, Joseph L. Newberg, Laura Pearlman, Paul J. Nugent, Michele D. Reynolds, Jennifer Bashour, Robert Schmidt, Neil P. Sheth, Kenneth Steil, Ramy J. Toma, William Kirby, Pink Folmar, Samantha Williams, Paul Pickrell, Stefanie Mott, Carol Ann Linebarger, Hussain Malbari, David Pampe, Veronica G. Fragoso, Lisa Holloway, Cecilia McKeown-Bragas, Teresa Becker, Barton G. Williams, William H. Jones, Jesse L. Clark, Steven Shoptaw, Michele Vertucci, Will Hernandez, Stephen A. Spector, Amaran Moodley, Jill Blumenthal, Lisa Stangl, Karen Deutsch, Kathleen M. Mullane, David Pitrak, Cheryl Nuss, Judy Pi, Carl Fichtenbaum, Margaret Powers-Fletcher, Michelle Saemann, Sharon Kohrs, Thomas B. Campbell, Andrew Lauria, Jose C. Mancilla, Hillary Dunlevy, Richard M. Novak, Andrea Wendrow, Scott Borgetti, Ben Ladner, Lisa Chrisley, Cheryl Young, Susanne Doblecki-Lewis, Maria L. Alcaide, Jose Gonzales-Zamora, Stephen Morris, David Wohl, Joseph Eron, Jr., Ian Frank, Debora Dunbar, David Metzger, Florence Momplaisir, Judith Martin, Alejandro Hoberman, Timothy Shope, Gysella Muniz, Richard Rupp, Amber Stanford, Megan Berman, Laura Porterfield, Michael Lewis, Elham Ghadishah, Joseph Yusin, Mai Pham, Clarence B. Creech, II, Shannon Walker, Stephanie Rolsma, Robert Samuels, Isaac Thomsen, Spyros A. Kalams, Greg Wilson, Gregg H. Lucksinger, Kevin Parks, Ryan Israelsen, Jaleh Ostovar, Kary Kelly, Jeffrey S. Overcash, Hanh Chu, Kia Lee, Luis I. De La Cruz, Steve Clemons, Elizabeth Everette, Suzanna Studdard, Gowdhami Mohan, Stefanie Tyson, Alyssa-Kay Peay, Danyel Johnson, Gregory J. Feldman, May-Yin Suen, Jacqueline Muenzner, Joseph Boscia, Farhan Siddiqui, John Sanders, James Peacock, Julio Nasim, Michael L. Levin, Julie Hussey, Marcy Kulic, Mark M. McKenzie, Teresa Deese, Erica Osmundsen, Christy Sweet, Valentine M. Ebuh, Elwaleed Elnagar, Georgette Ebuh, Genevieve Iwuala, Laurie J. Han-Conrad, Todd Simmons, Denis Tarakjian, Jeremy Ackermann, Mark S. Adams, José O. Alemán, Mohamed S. Al-Ibrahim, David R. Andes, Jeb Andrews, Roberto C. Arduino, Martín Bäcker, Diana Badillo, Emma Bainbridge, Teresa A. Batteiger, Jose A. Bazan, Roger J. Bedimo, Jorge A. Benitez, Annette R. Bennett, David I. Bernstein, Kristin Bialobok, Rebecca Boas, Judith Brady, Cynthia Brown, Catherine A. Bunce, Robert S. Call, Wesley Campbell, Ellie Carmody, Christopher Carpenter, Steven E. Carsons, Marvin Castellon, Mario Castro, Hannah Catan, Jennifer Chang, Mouna G. Chebib, Corey M. Chen, Margaret Cheng, Brian D.W. Chow, Annie Ciambruschini, Joseph P. Connor, James H. Conway, Maureen Cooney, Marcel Curlin, Claudia De La Matta Rodriguez, Jon F. Dedon, Emily Degan, Michelle Dickey, Craig Dietz, Jennifer L. Dong, Brenda Dorcely, Michael P. Dube, Carmel B. Dyer, Benjamin Eckhardt, Edward Ellerbeck, Evan C. Ewers, Amy Falk, Brittany Feijoo, Uriel R. Felsen, Tom Fiel, David Fitz-Patrick, Charles M. Fogarty, Stacy Ford, Lina M. Forero, Elizabeth Formentini, Doris Franco-Vitteri, Robert W. Frenck, Jr., Elie Gharib, Suzanne Gharib, Rola G. Rucker, James N. Goldenberg, Luis H. González, Brett Gray, Rusty Greene, Robert M. Grossberg, Juan V. Guanira-Carranza, Alfredo Gilberto Guerreros Benavides, Clint C. Guillory, Shauna H. Gunaratne, David Halpert, Holli Hamilton, William R. Hartman, Sheryl L. Henderson, Ramin Herati, Laura Hernandez Guarin, Robin Hilder, Ken Ho, Leila Hojat, Sybil G. Hosek, Jeffrey M. Jacobson, Melanie Jay, Diane H. Johnson, Kathleen S. Jones, Edward C. Jones-López, Jessica E. Justman, Scott Kahney, Lois Katz, Melinda Katz, Daniel Kaul, Michael C. Keefer, Ashley Kennedy, Jennifer Knishinsky, Laura Kogelman, Susan L. Koletar, Angelica Kottkamp, Maryrose Laguio-Vila, Raphael J. Landovitz, Jessica L. Lee, Albert Liu, Eneyda Giuvanela Llerena Zegarra, Anna S. Lok, James Lovell, Ronald Lubelchek, John Lucaj, Gary Luckasen, Annie Luetkemeyer, Njira Lucia Lugogo, Janine Maenza, Carlos Malvestutto, Monica Mauri, Ryan C. Maves, Kenneth H. Mayer, Michael J. McCartney, Margaret E. McCort, M. Juliana McElrath, Meredith McNairy, Fernando L. Merino, Eric A. Meyerowitz, Carol L. Mitchell, Cynthia L. Monaco, Sauda Muhammad, Sigridh Muñoz-Gómez, Sonal Munsiff, Paul Nee, Nicole L. Nollen, Asif Noor, Claudio Nuñez Lagos, Jason F. Okulicz, Patrick A. Oliver, Jessica Ortega, Steven Palmer, Lalitha Parameswaran, Purvi Parikh, Susan Parker, Reza Parungao, Juana R. Pavie, Rebecca P. Madan, Henry Peralta, Jennifer Petts, Kristen K. Pierce, E. Javier Pretell Alva, Lawrence J. Purpura, Vanessa Raabe, Sergio E. Recuenco, Tamara Richards, Sharon A. Riddler, Barbara Rizzardi, Rachel Rokser, Charlotte-Paige Rolle, Adam Rosen, Jeffrey Rosen, Lena R. Freese, María E. Santolaya, Linda M. Schipani, Adam Schwartz, Tiffany Schwasinger-Schmidt, Hyman Scott, Beverly E. Sha, Shivanjali Shankaran, Adrienne E. Shapiro, Stephan C. Sharp, Bo Shopsin, Matthew D. Sims, Stephanie Skipper, Derek M. Smith, Michael J. Smith, M. Mahdee Sobhanie, Brit Sovic, Stephanie Sterling, Robert Striker, Karla Beatriz Tafur Bances, Kawsar R. Talaat, Edward M. Tavel, Jr., Hong V. Tieu, Christian Tomaszewski, Ryan Tomlinson, Juan P. Torres, Julian A. Torres, John J. Treanor, Sade Tukuru, Robert J. Ulrich, Gregory C. Utz, Veronica Viar, Roberto A. Viau Colindres, Edward E. Walsh, Mary C. Walsh, Emmanuel B. Walter, Jessica L. Weidler, Yi H. Wu, Kinara S. Yang, Juan Luis Yrivarren Giorza, Arthur L. Zemanek, Kevin Zhang, Barry S. Zingman, Richard Gorman, Carmen A. Paez, Edith Swann, Simbarashe G. Takuva, Alex Greninger, Pavitra Roychoudhury, Robert W. Coombs, Keith R. Jerome, Flora Castellino, Xiaomi Tong, Corrina Pavetto, Teletha Gipson, Tina Tong, Marina Lee, James Zhou, Michael Fay, Kelly McQuarrie, Chimeremma Nnadi, Obiageli Sogbetun, Nina Ahmad, Ian De Proost, Cyrus Hoseyni, Paul Coplan, Najat Khan, Peter Ronco, Dawn Furey, Jodi Meck, Johan Vingerhoets, Boerries Brandenburg, Jerome Custers, Jenny Hendriks, Jarek Juraszek, Anne Marit de Groot, Griet Van Roey, Dirk Heerwegh, Ilse Van Dromme, Jorge F. Méndez Galván, Monica B. Carrascal, Adriana Sordo Duran, Laura Ruy Sanchez Guerrero, Martha Cecilia Gómora Madrid, Alejandro Quintín Barrat Hernández, Sharzhaad Molina Guizar, Denisse Alejandra González Estrada, Silvano Omar Martínez Pérez, Zindy Yazmín Zárate Hinojosa, Guillermo Miguel Ruiz-Palacios, Aurelio Cruz-Valdez, Janeth Pacheco-Flores, Anyela Lara, Secia Díaz-Miralrio, María José Reyes Fentanes, Jocelyn Zuleica Olmos Vega, Daniela Pineda Méndez, Karina Cano Martínez, Winniberg Stephany Alvarez León, Vida Veronica Ruiz Herrera, Eduardo Gabriel Vázquez Saldaña, Laura Julia Camacho Choza, Karen Sofia Vega Orozco, Sandra Janeth Ortega Domínguez, Jorge A. Chacón, Juan J. Rivera, Erika A. Cutz, Maricruz E. Ortegón, María I. Rivera, David Browder, Cortney Burch, Terri Moye, Paul Bondy, Lesley Browder, Rickey D. Manning, James W. Hurst, Rodney E. Sturgeon, Paul H. Wakefield, John A. Kirby, James Andersen, Szheckera Fearon, Rosa Negron, Amy Medina, John M. Hill, Vivek Rajasekhar, Hayes Williams, LaShondra Cade, Rhodna Fouts, Connie Moya, Corey G. Anderson, Naomi Devine, James Ramsey, Ashley Perez, David Tatelbaum, Michael Jacobs, Kathleen Menasche, Vincent Mirkil, Peter J. Winkle, Amina Z. Haggag, Michelle Haynes, Marysol Villegas, Sabina Raja, Robert Riesenberg, Stanford Plavin, Mark Lerman, Leana Woodside, Maria Johnson, C. Mary Healy, Jennifer A. Whitaker, Wendy A. Keitel, Robert L. Atmar, Gary Horwith, Robin Mason, Lisa Johnson, Tambra Dora, Deborah Murray, Logan Ledbetter, Beverly Ewing, Kathryn E. Stephenson, Chen S. Tan, Rebecca Zash, Jessica L. Ansel, Kate Jaegle, Caitlin J. Guiney, Jeffrey A. Henderson, Marcia O'Leary, Kendra Enright, Jill Kessler, Pete Ducheneaux, Asha Inniss, Donald M. Brandon, William B. Davis, Daniel T. Lawler, Yaa D. Oppong, Ryan P. Starr, Scott N. Syndergaard, Rozeli Shelly, Mashrur Islam Majumder, Danny Sugimoto, Jeffrey Dugas, Sr., Dolores Rijos, Sandra Shelton, Stephan Hong, Howard Schwartz, Nelia Sanchez-Crespo, Jennifer Schwartz, Terry Piedra, Barbara Corral, Carmen Medina, Michael E. Dever, Mitul Shah, Michael Delgado, Tameika Scott, Lisa S. Usdan, Lora J. McGill, Valerie K. Arnold, Carolyn Scatamacchia, Codi M. Anthony, Rajan Merchant, Anelgine C. Yoon, Janet Hill, Lucy Ng-Price, Teri Thompson-Seim, Ronald Ackerman, Jamie Ackerman, Florida Aristy, Nzeera Ketter, Jon Finley, Mildred Stull, Monica Murray, Zainab Rizvi, Sonia Guerrero, Yogesh K. Paliwal, Amit Paliwal, Sarah Gordon, Bryan Gordon, Cynthia Montano-Pereira, Christopher Galloway, Candice Montros, Lily Aleman, Samira Shairi, Wesley Van Ever, George H. Freeman, Esther L. Harmon, Marshall A. Cross, Kacie Sales, Catherine Q. Gular, Matthew Hepburn, Nathan Alderson, Shana Harshell, Siham Mahgoub, Celia Maxwell, Thomas Mellman, Karl M. Thompson, Glenn Wortman, Jeff Kingsley, April Pixler, LaKondria Curry, Sarah Afework, Austin Swanson, Jeffry Jacqmein, Maggie Bowers, Dawn Robison, Victoria Mosteller, Janet Garvey, Mary Easley, Rebecca J. Kurnat, Raymond Cornelison, Shanda Gower, William Schnitz, Destiny S. Heinzig-Cartwright, Derek Lewis, Fred E. Newton, Aeiress Duhart, Breanz Watkins, Brandy Ball, Jill York, Shelby Pickle, David B. Musante, William P. Silver, Linda R. Belhorn, Nicholas A. Viens, David Dellaero, Priti Patel, Kendra Lisec, Beth Safirstein, Luz Zapata, Lazaro Gonzalez, Evelyn Quevedo, Farah Irani, Joseph Grillo, Amy Potts, Julie White, Patrick Flume, Gary Headden, Brandie Taylor, Ashley Warden, Amy Chamberlain, Robert Jeanfreau, Susan Jeanfreau, Paul G. Matherne, Amy Caldwell, Jessica Stahl, Mandy Vowell, Lauren Newhouse, Vladimir Berthaud, Zudi-Mwak Takizala, Genevieve Beninati, Kimberly Snell, Sherrie Baker, James Walker, Tavane Harrison, Meagan Miller, Janet Otto, Roni Gray, Christine Wilson, Tiffany Nemecek, Hannah Harrington, Sally Eppenbach, Wendell Lewis, Tana Bourgeois, Lyndsea Folsom, Gregory Holt, Mehdi Mirsaeidi, Rafael Calderon, Paola Lichtenberger, Jalima Quintero, Becky Martinez, Lilly Immergluck, Erica Johnson, Austin Chan, Norberto Fas, LaTeshia Thomas-Seaton, Saadia Khizer, Jonathan Staben, Tatiana Beresnev, Maryam Jahromi, Mary A. Marovich, Julia Hutter, Martha Nason, Julie Ledgerwood, John Mascola, Mark Leibowitz, Fernanda Morales, Mike Delgado, Rosario Sanchez, Norma Vega, Germán Áñez, Gary Albert, Erin Coston, Chinar Desai, Haoua Dunbar, Mark Eickhoff, Jenina Garcia, Margaret Kautz, Angela Lee, Maggie Lewis, Alice McGarry, Irene McKnight, Joy Nelson, Patrick Newingham, Patty Price-Abbott, Patty Reed, Diana Vegas, Bethanie Wilkinson, Katherine Smith, Wayne Woo, Iksung Cho, Gregory M. Glenn, Filip Dubovsky, David L. Fried, Lynne A. Haughey, Ariana C. Stanton, Lisa Stevens Rameaka, David Rosenberg, Lee Tomatsu, Viviana Gonzalez, Millie Manalo, Bernard Grunstra, Donald Quinn, Phillip Claybrook, Shelby Olds, Amy Dye, Kevin D. Cannon, Mesha M. Chadwick, Bailey Jordan, Morgan Hussey, Hannah Nevarez, Colleen F. Kelley, Michael Chung, Caitlin Moran, Paulina Rebolledo, Christina Bacher, Elizabeth Barranco-Santana, Jessica Rodriguez, Rafael Mendoza, Karen Ruperto, Odette Olivieri, Enrique Ocaña, Paul E. Wylie, Renea Henderson, Natasa Jenson, Fan Yang, Amy Kelley, Kenneth Finkelstein, David Beckmann, Tanya Hutchins, Sebastian Garcia Escallon, Kristen Johnson, Teresa S. Sligh, Parul Desai, Vincent Huynh, Carlos Lopez, Erika Mendoza, Jeffrey Adelglass, Jerome G. Naifeh, Kristine J. Kucera, Waseem Chughtai, Shireen H. Jaffer, Matthew G. Davis, Jennifer Foley, Michelle L. Burgett, Tammi L. Shlotzhauer, Sarah M. Ingalsbe-Geno, Daniel Duncanson, Kelly Kush, Lori Nesbitt, Cora Sonnier, Jennifer McCarter, Michael B. Butcher, James Fry, Donna Percy, Karen Freudemann, Bruce C. Gebhardt, Padma N. Mangu, Debra B. Schroeck, Rajesh K. Davit, Gayle D. Hennekes, Benjamin J. Luft, Melissa Carr, Sharon Nachman, Alison Pellecchia, Candace Smith, Bruno Valenti, Maria I. Bermudez, Noris Peraita, Ernesto Delgado, Alicia Arrazcaeta, Natalie Ramirez, Carmen Amador, Horacio Marafioti, Lyly Dang, Lauren Clement, Jennifer Berry, Mohammed Allaw, Georgettea Geuss, Chelsea Miles, Zachary Bittner, Melody Werne, Cornell Calinescu, Shannon Rodman, Joshua Rindt, Erin Cooksey, Kristina Harrison, Deanna Cooper, Manisha Horton, Amanda Philyaw, William Jennings, Hilario Alvarado, Michele Baka, Malina Regalado, Linda Murray, Sherif Naguib, Justin Singletary, Sha-Wanda Richmond, Sarah Omodele, Emily Oppenheim, Reuben Martinez, Victoria Andriulis, Leonard Singer, Jeanne Blevins, Meagan Thomas, Christine Hull, Isabel Pereira, Gina Rivero, Tracy Okonya, Frances Downing, Paulina Miller, Margaret Rhee, Katherine Stapleton, Jeffrey Klein, Rosamond Hong, Suzanne Swan, Tami Wahlin, Elizabeth Bennett, Amy Salzl, Sharine Phan, Jewel J. White, Amanda Occhino, Ruth Paiano, Morgan McLaughlin, Elisa Swieboda, Veronica Garcia-Fragoso, Maria G. Becerra, Toni White, Christine B. Turley, Andrew McWilliams, Tiffany Esinhart, Natasha Montoya, Shamika Huskey, Leena Paul, Karen Tashima, Jennie Johnson, Marguerite Neill, Martha Sanchez, Natasha Rybak, Maria Mileno, Stuart H. Cohen, Monica Ruiz, Dean M. Boswell, Elizabeth E. Robison, Trina L. Reynolds, Sonja Neumeister, Carmen D. Zorrilla, Juana Rivera, Jessica Ibarra, Iris García, Dianca Sierra, Wanda Ramon, Suzanne Fiorillo, Rebecca Pitotti, Victoria R. Anderson, Jose Castillo Mancilla, Nga Le, Patricia L. Winokur, Dilek Ince, Theresa Hegmann, Jeffrey Meier, Jack Stapleton, Laura Stulken, Monica McArthur, Andrea Berry, Milagritos Tapia, Elizabeth Hammershaimb, Toni Robinson, Rosa MacBryde, Susan Kline, Joanne L. Billings, Winston Cavert, Les B. Forgosh, Timothy W. Schacker, Tyler D. Bold, Dima Dandachi, Taylor Nelson, Andres Bran, Grant Geiger, S. Hasan Naqvi, Diana F. Florescu, Richard Starlin, David Kline, Andrea Zimmer, Anum Abbas, Natasha Wilson, Joseph J. Eron, Michael Sciaudone, A. Lina Rosengren, John S. Kizer, Sarah E. Rutstein, Elizabeth Bruce, Claudia Espinosa, Lisa J. Sanders, Kami Kim, Denise Casey, Barbara S. Taylor, Thomas Patterson, Ruth S. Pinilla, Delia Bullock, Philip Ponce, Jan Patterson, R. Scott McClelland, Dakotah C. Lane, Anna Wald, Frank James, Elizabeth Duke, Kirsten Hauge, Jessica Heimonen, Erin A. Goecker, Youyi Fong, Carol Kauffman, Kathleen Linder, Kimberly Nofz, Andrew McConnell, Robert J. Buynak, Angella Webb, Taryn Petty, Stephanie Andree, Erica Sanchez, Nolan Mackey, Clarisse Baudelaire, Sarah Dzigiel, Adrienna Marquez, Kim Quillin, Michelle King, Vanessa Abad, Jennifer Knowles, Michael Waters, Karla Zepeda, Jordan Coslet, Dalia Tovar, Marian E. Shaw, Mark A. Turner, Cory J. Huffine, Esther S. Huffine, Julie A. Ake, Elizabeth Secord, Eric McGrath, Phillip Levy, Brittany Stewart, Charnell Cromer, Ayanna Walters, Grant Ellsworth, Caroline Greene, Sarah Galloway, Shashi Kapadia, Elliot DeHaan, Clint Wilson, Jason Milligan, Danielle Raley, Joseph Bocchini, Bruce McClenathan, Mary Hussain, Evelyn Lomasney, Evelyn Hall, Sherry Lamberth, Christy Schmeck, Vickie Leathers, Deborah A. Theodore, Angela R. Branche, Daniel S. Graciaa, Timothy J. Hatlen, Jacqueline Miller, Jerald Sadoff, Ann R. Falsey, and Magdalena E. Sobieszczyk

Subjects
COVID-19, Natural infection, Hybrid immunity, Vaccination, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Published
2023
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2. Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence

Author

Cheryl N. Miller, Keri N. Althoff, David J. Schlueter, Hoda Anton-Culver, Qingxia Chen, Shawn Garbett, Francis Ratsimbazafy, Isaac Thomsen, Elizabeth W. Karlson, Mine Cicek, Ligia A. Pinto, Bradley A. Malin, Lucila Ohno-Machado, Carolyn Williams, David Goldstein, Aymone Kouame, Andrea Ramirez, Kelly A. Gebo, and Sheri D. Schully

Subjects
SARS-CoV-2, IgG antibodies, spike protein, nucleocapsid protein, low prevalence, Microbiology, QR1-502
Abstract

ABSTRACT Accurate, highly specific immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to evaluate seroprevalence. This study investigated the concordance of results across four immunoassays targeting different antigens for sera collected at the beginning of the SARS-CoV-2 pandemic in the United States. Specimens from All of Us participants contributed between January and March 2020 were tested using the Abbott Architect SARS-CoV-2 IgG (immunoglobulin G) assay (Abbott) and the EuroImmun SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) (EI). Participants with discordant results, participants with concordant positive results, and a subset of concordant negative results by Abbott and EI were also tested using the Roche Elecsys anti-SARS-CoV-2 (IgG) test (Roche) and the Ortho-Clinical Diagnostics Vitros anti-SARS-CoV-2 IgG test (Ortho). The agreement and 95% confidence intervals were estimated for paired assay combinations. SARS-CoV-2 antibody concentrations were quantified for specimens with at least two positive results across four immunoassays. Among the 24,079 participants, the percent agreement for the Abbott and EI assays was 98.8% (95% confidence interval, 98.7%, 99%). Of the 490 participants who were also tested by Ortho and Roche, the probability-weighted percentage of agreement (95% confidence interval) between Ortho and Roche was 98.4% (97.9%, 98.9%), that between EI and Ortho was 98.5% (92.9%, 99.9%), that between Abbott and Roche was 98.9% (90.3%, 100.0%), that between EI and Roche was 98.9% (98.6%, 100.0%), and that between Abbott and Ortho was 98.4% (91.2%, 100.0%). Among the 32 participants who were positive by at least 2 immunoassays, 21 had quantifiable anti-SARS-CoV-2 antibody concentrations by research assays. The results across immunoassays revealed concordance during a period of low prevalence. However, the frequency of false positivity during a period of low prevalence supports the use of two sequentially performed tests for unvaccinated individuals who are seropositive by the first test. IMPORTANCE What is the agreement of commercial SARS-CoV-2 immunoglobulin G (IgG) assays during a time of low coronavirus disease 2019 (COVID-19) prevalence and no vaccine availability? Serological tests produced concordant results in a time of low SARS-CoV-2 prevalence and no vaccine availability, driven largely by the proportion of samples that were negative by two immunoassays. The CDC recommends two sequential tests for positivity for future pandemic preparedness. In a subset analysis, quantified antinucleocapsid and antispike SARS-CoV-2 IgG antibodies do not suggest the need to specify the antigen targets of the sequential assays in the CDC’s recommendation because false positivity varied as much between assays targeting the same antigen as it did between assays targeting different antigens.

Published
2022
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3. Passive Immunity Trial for Our Nation (PassITON): study protocol for a randomized placebo-control clinical trial evaluating COVID-19 convalescent plasma in hospitalized adults

Author

Wesley H. Self, Thomas G. Stewart, Allison P. Wheeler, Wissam El Atrouni, Amanda J. Bistran-Hall, Jonathan D. Casey, Vince D. Cataldo, James D. Chappell, Claudia S. Cohn, Jessica B. Collins, Mark R. Denison, Marjolein de Wit, Sheri L. Dixon, Abhijit Duggal, Terri L. Edwards, Magali J. Fontaine, Adit A. Ginde, Michelle S. Harkins, Thelma Harrington, Estelle S. Harris, Daanish Hoda, Tina S. Ipe, Stuti J. Jaiswal, Nicholas J. Johnson, Alan E. Jones, Maryrose Laguio-Vila, Christopher J. Lindsell, Jason Mallada, Manoj J. Mammen, Ryan A. Metcalf, Elizabeth A. Middleton, Simon Mucha, Hollis R. O’Neal, Sonal R. Pannu, Jill M. Pulley, Xian Qiao, Jay S. Raval, Jillian P. Rhoads, Harry Schrager, Carl Shanholtz, Nathan I. Shapiro, Stephen J. Schrantz, Isaac Thomsen, Krista K. Vermillion, Gordon R. Bernard, Todd W. Rice, and For the Passive Immunity Trial for Our Nation (PassITON) Investigators

Subjects
COVID-19, SARS-CoV-2: convalescent plasma, Passive immunity, Neutralizing antibodies, Clinical trials, Randomized controlled trial, Medicine (General), R5-920
Abstract

Abstract Background Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear. Methods The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the USA to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200–399 mL) of COVID-19 convalescent plasma that has demonstrated neutralizing function using a SARS-CoV-2 chimeric virus neutralization assay. Study treatments are administered in a blinded fashion and patients are followed for 28 days. The primary outcome is clinical status 14 days after study treatment as measured on a 7-category ordinal scale assessing mortality, respiratory support, and return to normal activities of daily living. Key secondary outcomes include mortality and oxygen-free days. The trial is projected to enroll 1000 patients and is designed to detect an odds ratio ≤ 0.73 for the primary outcome. Discussion This trial will provide the most robust data available to date on the efficacy of COVID-19 convalescent plasma for the treatment of adults hospitalized with acute moderate to severe COVID-19. These data will be useful to guide the treatment of COVID-19 patients in the current pandemic and for informing decisions about whether developing a standardized infrastructure for collecting and disseminating convalescent plasma to prepare for future viral pandemics is indicated. Trial registration ClinicalTrials.gov NCT04362176 . Registered on 24 April 2020.

Published
2021
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4. Standardized two-step testing of antibody activity in COVID-19 convalescent plasma

Author

Pavlo Gilchuk, Isaac Thomsen, Sandra Yoder, Eric Brady, James D. Chappell, Laura J. Stevens, Mark R. Denison, Rachel E. Sutton, Rita E. Chen, Laura A. VanBlargan, Naveenchandra Suryadevara, Seth J. Zost, Jonathan Schmitz, Jill M. Pulley, Michael S. Diamond, Jillian P. Rhoads, Gordon R. Bernard, Wesley H. Self, Todd W. Rice, Allison P. Wheeler, James E. Crowe, Jr., and Robert H. Carnahan

Subjects
Immunology, Virology, Science
Abstract

Summary: The COVID-19 pandemic revealed an urgent need for rapid profiling of neutralizing antibody responses and development of antibody therapeutics. The current Food and Drug Administration-approved serological tests do not measure antibody-mediated viral neutralization, and there is a need for standardized quantitative neutralization assays. We report a high-throughput two-step profiling approach for identifying neutralizing convalescent plasma. Screening and downselection for serum antibody binding to the receptor-binding domain are followed by quantitative neutralization testing using a chimeric vesicular stomatitis virus expressing spike protein of SARS-CoV-2 in a real-time cell analysis assay. This approach enables a predictive screening process for identifying plasma units that neutralize SARS-CoV-2. To calibrate antibody neutralizing activity in serum from convalescent plasma donors, we introduce a neutralizing antibody standard reagent composed of two human antibodies that neutralize SARS-CoV strains, including SARS-CoV-2 variants of concern. Our results provide a framework for establishing a standardized assessment of antibody-based interventions against COVID-19.

Published
2022
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5. Performance Analysis of the National Early Warning Score and Modified Early Warning Score in the Adaptive COVID-19 Treatment Trial Cohort

Author

Christopher J. Colombo, MD, MA, FACP, FCCM, Rhonda E. Colombo, MD, MHS, FACP, FIDSA, Ryan C. Maves, MD, FCCM, FCCP, FIDSA, Angela R. Branche, MD, Stuart H. Cohen, MD, Marie-Carmelle Elie, MD, Sarah L. George, MD, Hannah J. Jang, PhD, RN, CNL, PHN, Andre C. Kalil, MD, MPH, David A. Lindholm, MD, FACP, Richard A. Mularski, MD, MSHS, MCR, ATSF, FCCP, FACP, Justin R. Ortiz, MD, MS, FACP, FCCP, Victor Tapson, MD, C. Jason Liang, PhD, On behalf of the ACTT-1 Study Group, Aneesh K. Mehta, Nadine G. Rouphael, Jessica J. Traenkner, Valeria D Cantos, Ghina Alaaeddine, Barry S. Zingman, Robert Grossberg, Paul F. Riska, Elizabeth Hohmann, Mariam Torres-Soto, Nikolaus Jilg, Helen Y. Chu, Anna Wald, Margaret Green, Annie Luetkemeyer, Pierre-Cedric B. Crouch, Hannah Jang, Susan Kline, Joanne Billings, Brooke Noren, Diego Lopez de Castilla, Jason W. Van Winkle, Francis X. Riedo, Robert W. Finberg, Jennifer P. Wang, Mireya Wessolossky, Kerry Dierberg, Benjamin Eckhardt, Henry J Neumann, Victor Tapson, Jonathan Grein, Fayyaz Sutterwala, Lanny Hsieh, Alpesh N. Amin, Thomas F. Patterson, Heta Javeri, Trung Vu, Roger Paredes, Lourdes Mateu, Daniel A. Sweeney, Constance A. Benson, Farhana Ali, William R. Short, Pablo Tebas, Jessie Torgersen, Giota Touloumi, Vicky Gioukari, David Chien Lye, Sean WX Ong, Norio Ohmagari, Ayako Mikami, Gerd Fätkenheuer, Jakob J. Malin, Philipp Koehler, Andre C. Kalil, LuAnn Larson, Angela Hewlett, Mark G. Kortepeter, C. Buddy Creech, Isaac Thomsen, Todd W. Rice, Babafemi Taiwo, Karen Krueger, Stuart H. Cohen, George R. Thompson, 3rd, Cameron Wolfe, Emmanuel B. Walter, Maria Frank, Heather Young, Ann R. Falsey, Angela R. Branche, Paul Goepfert, Nathaniel Erdmann, Otto O. Yang, Jenny Ahn, Anna Goodman, Blair Merrick, Richard M. Novak, Andrea Wendrow, Henry Arguinchona, Christa Arguinchona, Sarah L. George, Janice Tennant, Robert L. Atmar, Hana M. El Sahly, Jennifer Whitaker, D. Ashley Price, Christopher J. A. Duncan, Simeon Metallidis, Theofilos Chrysanthidis, F. McLellan, Myoung-don Oh, Wan Beom Park, Eu Suk Kim, Jongtak Jung, Justin R. Ortiz, Karen L. Kotloff, Brian Angus, Jack David Germain Seymour, Noreen A. Hynes, Lauren M. Sauer, Neera Ahuja, Kari Nadeau, Patrick E. H. Jackson, Taison D. Bell, Anastasia Antoniadou, Konstantinos Protopapas, Richard T Davey, Jocelyn D. Voell, Jose Muñoz, Montserrat Roldan, Ioannis Kalomenidis, Spyros G. Zakynthinos, Catharine I. Paules, Fiona McGill, Jane Minton, Nikolaos Koulouris, Zafeiria Barmparessou, Edwin Swiatlo, Kyle Widmer, Nikhil Huprikar, Anuradha Ganesan, Guillermo M. Ruiz-Palacios, Alfredo Ponce de León, Sandra Rajme, Justino Regalado Pineda, José Arturo Martinez-Orozco, Mark Holodniy, Aarthi Chary, Timo Wolf, Christoph Stephan, Jan-Christian Wasmuth, Christoph Boesecke, Martin Llewelyn, Barbara Philips, Christopher J. Colombo, Rhonda E. Colombo, David A. Lindholm, Katrin Mende, Tida Lee, Tahaniyat Lalani, Ryan C. Maves, Gregory C. Utz, Jens Lundgren, Marie Helleberg, Jan Gerstoft, Thomas Benfield, Tomas Jensen, Birgitte Lindegaard, Lothar Weise, Lene Knudsen, Isik Johansen, Lone W Madsen, Lars Østergaard, Nina Stærke, Henrik Nielsen, Timothy H. Burgess, Michelle Green, Mat Makowski, Jennifer L. Ferreira, Michael R. Wierzbicki, Tyler Bonnett, Nikki Gettinger, Theresa Engel, Jing Wang, John H. Beigel, Kay M. Tomashek, Seema Nayak, Lori E. Dodd, Walla Dempsey, Effie Nomicos, Marina Lee, Peter Wolff, Rhonda PikaartTautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Dean Follmann, and H. Clifford Lane

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. We sought to validate prognostic scores in coronavirus disease 2019 including National Early Warning Score, Modified Early Warning Score, and age-based modifications, and define their performance characteristics. DESIGN:. We analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected daily during the trial, Modified Early Warning Score was calculated, and age applied to both scores. We assessed prognostic value for the end points of recovery, mechanical ventilation, and death for score at enrollment, average, and slope of score over the first 48 hours. SETTING:. A multisite international inpatient trial. PATIENTS:. A total of 1,062 adult nonpregnant inpatients with severe coronavirus disease 2019 pneumonia. INTERVENTIONS:. Adaptive COVID-19 Treatment Trial 1 randomized participants to receive remdesivir or placebo. The prognostic value of predictive scores was evaluated in both groups separately to assess for differential performance in the setting of remdesivir treatment. MEASUREMENTS AND MAIN RESULTS:. For mortality, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.60–0.68), and improved with addition of age (c-index, 0.66–0.74). For recovery, baseline National Early Warning Score and Modified Early Warning Score demonstrated somewhat better prognostic ability (c-index, 0.65–0.69); however, National Early Warning Score+age and Modified Early Warning Score+age further improved performance (c-index, 0.68–0.71). For deterioration, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.59–0.69) and improved with addition of age (c-index, 0.63–0.70). All prognostic performance improvements due to addition of age were significant (p < 0.05). CONCLUSIONS:. In the Adaptive COVID-19 Treatment Trial 1 cohort, National Early Warning Score and Modified Early Warning Score demonstrated moderate prognostic performance in patients with severe coronavirus disease 2019, with improvement in predictive ability for National Early Warning Score+age and Modified Early Warning Score+age. Area under receiver operating curve for National Early Warning Score and Modified Early Warning Score improved in patients receiving remdesivir versus placebo early in the pandemic for recovery and mortality. Although these scores are simple and readily obtainable in myriad settings, in our data set, they were insufficiently predictive to completely replace clinical judgment in coronavirus disease 2019 and may serve best as an adjunct to triage, disposition, and resourcing decisions.

Published
2021
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6. A high-throughput liquid bead array assay confirms strong correlation between SARS-CoV-2 antibody level and COVID-19 severity

Author

Monique Bennett, Sandra Yoder, Eric Brady, Jill M. Pulley, Jillian P. Rhoads, Thomas G. Stewart, Gordon R. Bernard, C. Buddy Creech, Allison P. Wheeler, and Isaac Thomsen

Subjects
Biological Sciences, Microbiology, Virology, Viral Microbiology, Science
Abstract

Summary: A detailed understanding of the adaptive host response to SARS-CoV-2 infection in humans is urgently needed. We developed a sensitive, high-throughput, and efficient assay using liquid bead array technology. We observed advantages over traditional ELISA for the detection and quantification of binding IgG against the receptor binding domain (RBD) of SARS-CoV-2. To determine whether COVID-19 symptom severity correlates with SARS-CoV-2 IgG, we measured anti-RBD IgG levels from 67 subjects recovered from PCR-confirmed COVID-19. We found that COVID-19 symptom severity strongly correlated with RBD IgG level (p < 0.001). These findings have substantial implications for public policy surrounding assessments of antibody responses and possible immunity, as not all cases of COVID-19 can be assumed to generate a protective antibody response, and mild disease in particular is capable of generating very low-level anti-RBD IgG levels. These findings also have important implications for the selection of donors for convalescent plasma to be used therapeutically.

Published
2021
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7. Molecular epidemiology and expression of capsular polysaccharides in Staphylococcus aureus clinical isolates in the United States.

Author

Naglaa Mohamed, Yekaterina Timofeyeva, Dorota Jamrozy, Eduardo Rojas, Li Hao, Natalie C Silmon de Monerri, Julio Hawkins, Guy Singh, Bing Cai, Paul Liberator, Shite Sebastian, Robert G K Donald, Ingrid L Scully, C Hal Jones, C Buddy Creech, Isaac Thomsen, Julian Parkhill, Sharon J Peacock, Kathrin U Jansen, Matthew T G Holden, and Annaliesa S Anderson

Subjects
Medicine, Science
Abstract

Staphylococcus aureus capsular polysaccharides (CP) are important virulence factors under evaluation as vaccine antigens. Clinical S. aureus isolates have the biosynthetic capability to express either CP5 or CP8 and an understanding of the relationship between CP genotype/phenotype and S. aureus epidemiology is valuable. Using whole genome sequencing, the clonal relatedness and CP genotype were evaluated for disease-associated S. aureus isolates selected from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T) to represent different geographic regions in the United States (US) during 2004 and 2009-10. Thirteen prominent clonal complexes (CC) were identified, with CC5, 8, 30 and 45 representing >80% of disease isolates. CC5 and CC8 isolates were CP type 5 and, CC30 and CC45 isolates were CP type 8. Representative isolates from prevalent CC were susceptible to in vitro opsonophagocytic killing elicited by anti-CP antibodies, demonstrating that susceptibility to opsonic killing is not linked to the genetic lineage. However, as not all S. aureus isolates may express CP, isolates representing the diversity of disease isolates were assessed for CP production. While approximately 35% of isolates (primarily CC8) did not express CP in vitro, CP expression could be clearly demonstrated in vivo for 77% of a subset of these isolates (n = 20) despite the presence of mutations within the capsule operon. CP expression in vivo was also confirmed indirectly by measuring an increase in CP specific antibodies in mice infected with CP5 or CP8 isolates. Detection of antigen expression in vivo in relevant disease states is important to support the inclusion of these antigens in vaccines. Our findings confirm the validity of CP as vaccine targets and the potential of CP-based vaccines to contribute to S. aureus disease prevention.

Published
2019
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8. Next-generation phenotyping: introducing phecodeX for enhanced discovery research in medical phenomics.

Author

Megan M. Shuey, William W. Stead, Ida Aka, April L. Barnado, Lisa Bastarache, Elly Brokamp, Meredith Campbell, Robert J. Carroll, Jeffrey A. Goldstein, Adam Lewis, Beth A. Malow, Jonathan D. Mosley, Travis Osterman, Dolly A Padovani-Claudio, Andrea Ramirez, Dan M. Roden, Bryce A Schuler, Edward Siew, Jennifer Sucre, Isaac Thomsen, Rory J. Tinker, Sara Van Driest, Colin Walsh, Jeremy L. Warner, Quinn Stanton Wells, and Lee E. Wheless

Published
2023
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9. Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19

Author

Wesley H. Self, Allison P. Wheeler, Thomas G. Stewart, Harry Schrager, Jason Mallada, Christopher B. Thomas, Vince D. Cataldo, Hollis R. O’Neal, Nathan I. Shapiro, Conor Higgins, Adit A. Ginde, Lakshmi Chauhan, Nicholas J. Johnson, Daniel J. Henning, Stuti J. Jaiswal, Manoj J. Mammen, Estelle S. Harris, Sonal R. Pannu, Maryrose Laguio-Vila, Wissam El Atrouni, Marjolein de Wit, Daanish Hoda, Claudia S. Cohn, Carla McWilliams, Carl Shanholtz, Alan E. Jones, Jay S. Raval, Simon Mucha, Tina S. Ipe, Xian Qiao, Stephen J. Schrantz, Aarthi Shenoy, Richard D. Fremont, Eric J. Brady, Robert H. Carnahan, James D. Chappell, James E. Crowe, Mark R. Denison, Pavlo Gilchuk, Laura J. Stevens, Rachel E. Sutton, Isaac Thomsen, Sandra M. Yoder, Amanda J. Bistran-Hall, Jonathan D. Casey, Christopher J. Lindsell, Li Wang, Jill M. Pulley, Jillian P. Rhoads, Gordon R. Bernard, and Todd W. Rice

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2022
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11. Contributors

Author

Mark J. Abzug, Elisabeth E. Adderson, Aastha Agarwal, Allison L. Agwu, Lindsey Albenberg, Jonathan Albert, Kevin Alby, Grace M. Aldrovandi, Upton D. Allen, Gerardo Alvarez-Hernndez, Krow Ampofo, Evan J. Anderson, Grace D. Appiah, Monica I. Ardura, Stephen S. Arnon, Naomi E. Aronson, Ann M. Arvin, Shai Ashkenazi, Liat Ashkenazi-Hoffnung, Edwin J. Asturias, Kestutis Aukstuolis, Vahe Badalyan, Carol J. Baker, Karthik Balakrishnan, Elizabeth D. Barnett, Kirsten Bechtel, William E. Benitz, Rachel Berkovich, David M. Berman, Stephanie R. Bialek, Else M. Bijker, Matthew J. Bizzarro, Karen C. Bloch, Joseph A. Bocchini, Thomas G. Boyce, John S. Bradley, Denise F. Bratcher, Paula K. Braverman, Itzhak Brook, Kevin Edward Brown, Kristina P. Bryant, Andres F. Camacho-Gonzalez, Connie F. Caete-Gibas, Joseph B. Cantey, Paul Cantey, Cristina V. Cardemil, Mary T. Caserta, Luis A. Castagnini, Jessica R. Cataldi, Ellen Gould Chadwick, Rebecca J. Chancey, Cara C. Cherry, Silvia S. Chiang, Mary Choi, John C. Christenson, Susan E. Coffin, Amanda Cohn, Despina G. Contopoulos-Ioannidis, James H. Conway, Margaret M. Cortese, C. Buddy Creech, Jonathan D. Crews, Donna Curtis, Nigel Curtis, Lara A. Danziger-Isakov, Toni Darville, Gregory A. Dasch, Irini Daskalaki, H. Dele Davies, Fatimah S. Dawood, J. Christopher Day, M. Teresa de la Morena, Gregory P. DeMuri, Dickson D. Despommier, Daniel S. Dodson, Stephen J. Dolgner, Clinton Dunn, Jonathan Dyal, Kathryn M. Edwards, Morven S. Edwards, Dawn Z. Eichenfield, Lawrence F. Eichenfield, Dirk M. Elston, Beth Emerson, Leslie A. Enane, Moshe Ephros, Guliz Erdem, Marina E. Eremeeva, Douglas H. Esposito, Monica M. Farley, Anat R. Feingold, Kristina N. Feja, Adam Finn, Marc Fischer, Brian T. Fisher, Randall G. Fisher, Patricia Michele Flynn, Monique A. Foster, LeAnne M. Fox, Michael M. Frank, Douglas R. Fredrick, Robert W. Frenck, James Gaensbauer, Hayley A. Gans, Gregory M. Gauthier, Patrick Gavigan, Jeffrey S. Gerber, Yael Gernez, Francis Gigliotti, Mark A. Gilger, Carol A. Glaser, Jane M. Gould, James Graziano, Amanda M. Green, Michael Green, Daniel Griffin, Patricia M. Griffin, David C. Griffith, Piyush Gupta, Bruce J. Gutelius, Julie R. Gutman, Aron J. Hall, Rana F. Hamdy, Jin-Young Han, Lori K. Handy, Benjamin Hanisch, Marvin B. Harper, Aaron M. Harris, Christopher J. Harrison, David B. Haslam, Julia C. Haston, Sarah.J. Hawkes, Taylor Heald-Sargent, J. Owen Hendley, Adam L. Hersh, Joseph A. Hilinski, Susan L. Hills, David K. Hong, Peter J. Hotez, Katherine K. Hsu, Felicia Scaggs Huang, David A. Hunstad, W. Garrett Hunt, Loris Y. Hwang, Christelle M. Ilboudo, Preeti Jaggi, Sophonie Jean, Ravi Jhaveri, Kateina Jirk-Pomajbkov, Nadia A. Kadry, Mary L. Kamb, Ronak K. Kapadia, Ben Z. Katz, Sophie E. Katz, Ishminder Kaur, Gilbert J. Kersh, Muhammad Ali Khan, Ananta Khurana, David W. Kimberlin, Bruce Klein, Miwako Kobayashi, Larry K. Kociolek, Andrew Y. Koh, Karen L. Kotloff, Andrew T. Kroger, Matthew P. Kronman, Leah Lalor, Christine T. Lauren, Amy Leber, Eyal Leshem, David B. Lewis, Robyn A. Livingston, Eloisa Llata, Kevin Lloyd, Katrina Loh, Sarah S. Long, Benjamin A. Lopman, Yalda C. Lucero, Debra J. Lugo, Jorge Lujn-Zilbermann, Yvonne A. Maldonado, John J. Manaloor, Kalpana Manthiram, Stacey W. Martin, Roshni Mathew, Tony Mazzulli, Elizabeth J. McFarland, Kathleen A. McGann, Lucy A. McNamara, Debrah Meislich, H. Cody Meissner, Asuncion Mejias, Jussi Mertsola, Kevin Messacar, Mohammad Nael Mhaissen, Marian G. Michaels, Melissa B. Miller, Hilary Miller-Handley, Eric Mintz, Parvathi Mohan, Susan P. Montgomery, Jose G. Montoya, Anne C. Moorman, Pedro L. Moro, Anna-Barbara Moscicki, William J. Muller, Angela L. Myers, Simon Nadel, Jennifer Lynn Nayak, Michael Noel Neely, Karen P. Neil, Christina A. Nelson, Noele P. Nelson, Megin Nichols, William Nicholson, Amy Jo Nopper, Laura E. Norton, Theresa J. Ochoa, Liset Olarte, Timothy R. Onarecker, Walter A. Orenstein, Miguel ORyan, William R. Otto, Christopher P. Ouellette, Christopher D. Paddock, Debra L. Palazzi, Suresh Kumar Panuganti, Diane E. Pappas, Michal Paret, Daniel M. Pastula, Thomas F. Patterson, Brett W. Petersen, Mikael Petrosyan, Larry K. Pickering, Talia Pindyck, Swetha Pinninti, Laure F. Pittet, Paul J. Planet, Andrew J. Pollard, Klara M. Posfay-Barbe, Casper S. Poulsen, Susan M. Poutanen, Ann M. Powers, Nina Salinger Prasanphanich, Bobbi S. Pritt, Charles G. Prober, Neha Puar, Laura A.S. Quilter, Octavio Ramilo, Suchitra Rao, Adam J. Ratner, Sarah A. Rawstron, Jennifer S. Read, Ryan F. Relich, Megan E. Reller, Candice L. Robinson, Jos R. Romero, David A. Rosen, Shannon A. Ross, G. Ingrid J.G. Rours, Peter C. Rowe, Anne H. Rowley, Lorry G. Rubin, Edward T. Ryan, Alexandra Sacharok, Thomas J. Sandora, Sarah G.H. Sapp, Kabir Sardana, Jason B. Sauberan, Joshua K. Schaffzin, Sarah Schillie, Jennifer E. Schuster, Kevin L. Schwartz, Bethany K. Sederdahl, Jose Serpa-Alvarez, Kara N. Shah, Samir S. Shah, Nader Shaikh, Andi L. Shane, Eugene D. Shapiro, Jana Shaw, Avinash K. Shetty, Timothy R. Shope, Linda M. Dairiki Shortliffe, Stanford T. Shulman, Gail F. Shust, George Kelly Siberry, Jane D. Siegel, Robert David Siegel, Kari A. Simonsen, Upinder Singh, Christiana Smith, Lauren L. Smith, Eunkyung Song, Emily Souder, Paul Spearman, Joseph W. St. Geme, Mary Allen Staat, J. Erin Staples, Jeffrey R. Starke, Victoria A. Statler, William J. Steinbach, Christen Rune Stensvold, Erin K. Stokes, Bradley P. Stoner, Gregory A. Storch, Anne Straily, Kathleen E. Sullivan, Douglas S. Swanson, Robert R. Tanz, Gillian Taormina, Jacqueline E. Tate, Jeanette Taveras, Marc Tebruegge, Eyasu H. Teshale, George R. Thompson, Robert Thompson-Stone, Isaac Thomsen, Richard B. Thomson, Emily A. Thorell, Vivian Tien, Nicole H. Tobin, Philip Toltzis, James Treat, Stephanie B. Troy, Russell B. Van Dvke, Louise Elaine Vaz, Vini Vijayan, Jennifer Vodzak, Thor A. Wagner, Ellen R. Wald, Rebecca Wallihan, Huanyu Wang, Zoon Wangu, Matthew Washam, Valerie Waters, Joshua R. Watson, Jill E. Weatherhead, Geoffrey A. Weinberg, Mark K. Weng, Nathan P. Wiederhold, Harold C. Wiesenfeld, Cydni Williams, John V. Williams, Rodney E. Willoughby, Robert R. Wittler, James B. Wood, Charles Reece Woods, Kimberly A. Workowski, Terry W. Wright, Hsi-Yang Wu, Huan Xu, Pablo Yagupsky, Jumi Yi, Jonathan Yoder, Edward J. Young, Andrea L. Zaenglein, Petra Zimmermann, and Wenjing Zong

Published
2023
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12. 1319. Evolution of Invasive and Colonizing Pediatric Staphylococcus aureus Isolates

Author

Margaret Free, Nicole Soper, Shristi Shrestha, Jean-Philippe Cartailler, and Isaac Thomsen

Subjects
Infectious Diseases, Oncology
Abstract

Background Staphylococcus aureus is the most common invasive bacterial pathogen in children. The constant evolution of S. aureus is a barrier to the development of successful interventions. A detailed understanding of the current molecular epidemiology of actively circulating, invasive S. aureus strains and a comparison to both colonization strains and historical invasive strains to determine which virulence factors and genetic lineages are preserved over time are important unmet needs in this field. Methods We compared four groups of S. aureus isolates: 45 invasive strains obtained during the epidemic methicillin-resistance S. aureus (MRSA) peak (2010-2012); 74 invasive contemporary strains (2015-2021); 61 colonizing strains from 2004; and 30 colonizing strains from 2021. Genetic relatedness (via clonal complex typing) and virulence factor presence were determined via whole genome sequencing. Results Among invasive isolates, the prevalence of clonal complex 8 (CC8) decreased significantly over time from 87% to 46% among typeable strains (p< 0.05, Fig.1). Similarly, the presence of Panton-Valentine leucocidin (PVL) decreased from 71% to 40% (p< 0.01). 56% of invasive isolates from 2010-2012 were MRSA, vs 37% from 2015-2021 (p= 0.05, Fig. 2). In contrast to PVL, the presence of leukocidins LukED and LukAB remained stably prevalent over time at 84% and 100% (Fig. 3). Colonization isolates overall remained diverse, with no dominant clonal complex (Fig. 1). Figure 1Figure 2Figure 3 Conclusion Invasive S. aureus molecular epidemiology has changed significantly over the past decade. The former dominance of CC8 and PVL-positive MRSA strains has shifted to a more diverse, predominantly MSSA group of contemporary strains. Other virulence factors (LukED, LukAB) have remained prevalent among invasive strains regardless of genetic lineage. Targets of intervention should be those that are preserved throughout the evolution of this major human pathogen. Disclosures All Authors: No reported disclosures.

Published
2022
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13. Response

Author

Wesley H. Self, Allison P. Wheeler, James D. Chappell, Isaac Thomsen, Jill M. Pulley, Jillian P. Rhoads, Gordon R. Bernard, and Todd W. Rice

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2022

14. Humoral and cellular immune responses to the SARS‐CoV‐2 BNT162b2 vaccine among a cohort of solid organ transplant recipients and healthy controls

Author

Ahmad Yanis, Zaid Haddadin, Andrew J. Spieker, Danya Waqfi, Danielle A. Rankin, Rana Talj, Lora Thomas, Kelly A. Birdwell, Lauren Ezzell, Marcia Blair, Joan Eason, Rebekkah Varjabedian, Christian M. Warren, Cynthia H. Nochowicz, Eric C. Olson, Joshua D. Simmons, Sandra Yoder, Madeline Guy, Isaac Thomsen, James D. Chappell, Spyros A. Kalams, and Natasha B. Halasa

Subjects
Immunity, Cellular, Vaccines, Synthetic, Transplantation, COVID-19 Vaccines, Infectious Diseases, SARS-CoV-2, COVID-19, Humans, Organ Transplantation, mRNA Vaccines, Antibodies, Viral, BNT162 Vaccine, Transplant Recipients
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased morbidity and mortality in solid organ transplant (SOT) recipients. Despite exclusion from SARS-CoV-2 vaccine clinical trials, these individuals were identified as high-risk and prioritized for vaccination in public health guidelines.We prospectively evaluated humoral and cellular immune responses to two doses of the SARS-CoV-2 mRNA vaccine, BNT162b2, in 56 SOT recipients and 26 healthy controls (HCs). Blood specimens collected from participants prior to each dose and following the second dose were tested for SARS-CoV-2-specific antibodies, as well as CD4+ and CD8+ T-cell responses.SOT recipients demonstrated lower mean anti-SARS-CoV-2 antibody levels compared to HCs after each dose, and only 21.6% achieved an antibody response after the second dose within the range of HC responses. Similarly, the percentage of responsive CD4+ and CD8+ T cells in SOT recipients was lower than in HCs. While most HCs showed notable humoral and cellular responses, responses were less concordant in SOT recipients, with some showing evidence of either humoral or cellular response, but not both.Humoral and cellular immune responses to the BNT162b2 vaccine are markedly reduced in SOT recipients as compared to HCs, suggesting that SOT recipients may benefit from more tailored regimens such as higher dose and/or additional vaccinations.

Published
2021
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15. Standardized two-step testing of antibody activity in COVID-19 convalescent plasma

Author

Pavlo Gilchuk, Isaac Thomsen, Sandra Yoder, Eric Brady, James D. Chappell, Laura J. Stevens, Mark R. Denison, Rachel E. Sutton, Rita E. Chen, Laura A. VanBlargan, Naveenchandra Suryadevara, Seth J. Zost, Jonathan Schmitz, Jill M. Pulley, Michael S. Diamond, Jillian P. Rhoads, Gordon R. Bernard, Wesley H. Self, Todd W. Rice, Allison P. Wheeler, James E. Crowe, and Robert H. Carnahan

Subjects
Multidisciplinary, Science, Virology, Immunology, Article
Abstract

The COVID-19 pandemic revealed an urgent need for rapid profiling of neutralizing antibody responses and development of antibody therapeutics. The current Food and Drug Administration-approved serological tests do not measure antibody-mediated viral neutralization, and there is a need for standardized quantitative neutralization assays. We report a high-throughput two-step profiling approach for identifying neutralizing convalescent plasma. Screening and downselection for serum antibody binding to the receptor-binding domain are followed by quantitative neutralization testing using a chimeric vesicular stomatitis virus expressing spike protein of SARS-CoV-2 in a real-time cell analysis assay. This approach enables a predictive screening process for identifying plasma units that neutralize SARS-CoV-2. To calibrate antibody neutralizing activity in serum from convalescent plasma donors, we introduce a neutralizing antibody standard reagent composed of two human antibodies that neutralize SARS-CoV strains, including SARS-CoV-2 variants of concern. Our results provide a framework for establishing a standardized assessment of antibody-based interventions against COVID-19., Graphical abstract, Immunology; Virology

Published
2021

16. Methicillin-Resistant Staphylococcus aureus in a Trauma Population: Does Decolonization Prevent Infection?

Author

Robert A. Maxwell, Chasen A. Croft, C. Buddy Creech, Isaac Thomsen, Nicole Soper, Laura E. Brown, Vicente A. Mejia, Benjamin W. Dart, and Donald E. Barker

Subjects
0301 basic medicine, 03 medical and health sciences, 0302 clinical medicine, 030106 microbiology, 030212 general & internal medicine, General Medicine
Abstract

The purpose of this study was to determine if a decolonization regimen reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infections and if colonization isolates are genetically related to subsequent infectious strains. Trauma patients admitted to the intensive care unit with positive MRSA nasal swabs were randomized to either daily chlorhexidine gluconate (CHG) baths and mupirocin (MUP) ointment to the nares or soap and water baths and placebo ointment for five days. Nasal swabs performed at the end of treatment and invasive MRSA infections during the remaining hospitalization were compared with the original nasal isolate via polymerase chain reaction for genetic relatedness as well as CHG and MUP resistance genes. Six hundred and seventy-eight intensive care unit admissions were screened, and 92 (13.6%) had positive (+) MRSA nasal swabs over a 22-month period ending in 3/2014. After the five day treatment period, there were 13 (59.1%) +MRSA second nasal swabs for CHG + MUP and 9 (90%) for soap and water baths and placebo, P = 0.114. No isolates tested positive for the MUP or CHG resistance genes mupA and qacA/B but 7 of 20 (35%) contained smr. There were seven (31.8%) MRSA infections in the CHG group and six (60%) for soap, P = 0.244. All 13 patients with MRSA infections had the same MRSA isolate present in the original nasal swab. There was no difference in all-cause Gram-negative or positive infections for CHG versus soap, 12 (54.5%) versus 7 (70%), P = 0.467. CHG + MUP are ineffective in eradicating MRSA from the anterior nares but may reduce the incidence of infection. Subsequent invasive MRSA infections are typically caused by the endogenous colonization strain.

Published
2017
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17. Methicillin-Resistant Staphylococcus aureus in a Trauma Population: Does Decolonization Prevent Infection?

Author

Robert A, Maxwell, Chasen A, Croft, C Buddy, Creech, Isaac, Thomsen, Nicole, Soper, Laura E, Brown, Vicente A, Mejia, Benjamin W, Dart, and Donald E, Barker

Subjects
Adult, Male, Methicillin-Resistant Staphylococcus aureus, Cross Infection, Chlorhexidine, Baths, Microbial Sensitivity Tests, Middle Aged, Staphylococcal Infections, Polymerase Chain Reaction, Intensive Care Units, Mupirocin, Treatment Outcome, Bacterial Proteins, Trauma Centers, Drug Resistance, Bacterial, Anti-Infective Agents, Local, Humans, Female, Prospective Studies, Nasal Cavity, Aged
Abstract

The purpose of this study was to determine if a decolonization regimen reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infections and if colonization isolates are genetically related to subsequent infectious strains. Trauma patients admitted to the intensive care unit with positive MRSA nasal swabs were randomized to either daily chlorhexidine gluconate (CHG) baths and mupirocin (MUP) ointment to the nares or soap and water baths and placebo ointment for five days. Nasal swabs performed at the end of treatment and invasive MRSA infections during the remaining hospitalization were compared with the original nasal isolate via polymerase chain reaction for genetic relatedness as well as CHG and MUP resistance genes. Six hundred and seventy-eight intensive care unit admissions were screened, and 92 (13.6%) had positive (+) MRSA nasal swabs over a 22-month period ending in 3/2014. After the five day treatment period, there were 13 (59.1%) +MRSA second nasal swabs for CHG + MUP and 9 (90%) for soap and water baths and placebo, P = 0.114. No isolates tested positive for the MUP or CHG resistance genes mupA and qacA/B but 7 of 20 (35%) contained smr. There were seven (31.8%) MRSA infections in the CHG group and six (60%) for soap, P = 0.244. All 13 patients with MRSA infections had the same MRSA isolate present in the original nasal swab. There was no difference in all-cause Gram-negative or positive infections for CHG versus soap, 12 (54.5%) versus 7 (70%), P = 0.467. CHG + MUP are ineffective in eradicating MRSA from the anterior nares but may reduce the incidence of infection. Subsequent invasive MRSA infections are typically caused by the endogenous colonization strain.

Published
2018

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