Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study
Al Ozonoff, Naresh Doni Jayavelu, Shanshan Liu, Esther Melamed, Carly E. Milliren, Jingjing Qi, Linda N. Geng, Grace A. McComsey, Charles B. Cairns, Lindsey R. Baden, Joanna Schaenman, Albert C. Shaw, Hady Samaha, Vicki Seyfert‐Margolis, Florian Krammer, Lindsey B. Rosen, Hanno Steen, Caitlin Syphurs, Ravi Dandekar, Casey P. Shannon, Rafick‐Pierre Sékaly, Lauren I. R. Ehrlich, David B. Corry, Farrah Kheradmand, Mark A. Atkinson, Scott C. Brakenridge, Nelson Iván Agudelo Higuita, Jordan P. Metcalf, Catherine L. Hough, William B. Messer, Bali Pulendran, Kari C. Nadeau, Mark M. Davis, Ana Fernández-Sesma, Viviana Simon, Harm van Bakel, Seunghee Kim‐Schulze, David A. Hafler, Ofer Levy, Monica Kraft, Chris Bime, Elias K. Haddad, Carolyn S. Calfee, David J. Erle, Charles Langelier, Walter L. Eckalbar, Steven E. Bosinger, IMPACC Network, Kerry McEnaney, Brenda Barton, Claudia Lentucci, Mehmet Saluvan, Ana C. Chang, Annmarie Hoch, Albert Marisa, Tanzia Shaheen, Alvin T. Kho, Sanya Thomas, Jing Chen, Maimouna D. Murphy, Mitchell Cooney, Arash Nemati Hayati, Robert W. Bryant, James Abraham, IMPACC Data Analysis Group, Scott Presnell, Tomasz Jancsyk, Cole Maguire, Brian Lee, Slim Fourati, Denise Esserman, Leying Guan, Jeremy P. Gygi, Shrikant Pawar, Anderson F. Brito, Gabriela K. Fragiadakis, Ravi K. Patel, Scott J. Tebbutt, James A. Overton, Randi Vita, Kerstin Westendorf, IMPACC Site Investigators, Rama Thyagarajan, Justin F. Rousseau, Dennis Wylie, Todd Triplett, Erna Milunka Kojic, R. Sharon Chinthrajah, Neera Ahuja, Angela J. Rogers, Maja Artandi, George A. Yendewa, Debra Powell, James N. Kim, Brent Simmons, I. Michael Goonewardene, Cecilia M. Smith, Mark G. Martens, Amy C Sherman, Stephen R. Walsh
Abstract
Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.