Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
Authors: Thaweethai Tanayott , Jolley Sarah E. , Karlson Elizabeth W. , Levitan Emily B. , Levy Bruce , McComsey Grace A. , McCorkell Lisa , Nadkarni Girish N. , Parthasarathy Sairam , Singh Upinder , Walker Tiffany A. , Selvaggi Caitlin A. , Shinnick Daniel J. , Schulte Carolin C. M. , Atchley-Challenner Rachel , Horwitz Leora I. , Foulkes Andrea S. ,   RECOVER Consortium Authors,   RECOVER Consortium, Aberg Judith A. , Adolphi Natalie L. , Ahirwar Shreya , Ahmed Shifa , Ahuja Neera , Aikawa Masanori , Akerlundh Almary , Akintonwa Teresa T. , Al-Jadiri Aseel , Alekhina Natalya , Algren Heather A. , Alshawabkeh Akram N. , Ammar Nariman , Anand Adit , Anderson Brett R. , Aponte-Soto Lisa , Aschner Judy L. , Atha Mary M. , Atz Andrew M. , Aupperle Robin L. , Ayache Mirna , Azziz-Baumgartner Eduardo , Bailey L. C. , Baker Fiona C. , Balaraman Venkataraman , Bandy Jennifer A. , Banerjee Dithi , Barch Deanna M. , Bardes James M. , Barlocker Jackson , Barr R. G. , Baskin-Sommers Arielle , Basu Sanjib , Battaglia Tracy A. , Baucom Leah , Beamon Carmen J. , Beaty Casey L. , Beckmann Noam D. , Berry Jasmine A. , Bhadelia Nahid , Bhargava Daksh , Bhuiyan Sultana , Bian Jiang , Bime Christian , Bjork James M. , Black Lora J. , Blish Catherine A. , Block Jason P. , Bogie Amanda , Bolliger Dawn , Bonaventura William , Bose-Brill Seuli , Bower Mary B. , Boyd Andrew D. , Boyineni Jerusha , Bradfute Steven B. , Bramante Carolyn T. , Brannock M. D. , Bremner J. D. , Brosnahan Shari B. , Buchbinder Natalie C. , Bueler Elliott , Buhimschi Irina A. , Bukulmez Hulya , Bunnell H. T. , Buse John B. , Calhoun Elizabeth A. , Cao Tingyi , Carrithers Michael D. , Carton Thomas W. , Case Abigail , Casey B.J. , Casimero Faye Victoria C. , Castro Lauren , Cato Teresa , Ceger Patricia , Cerullo Connie L. , Chang Linda , Chang Arunee A. , Chebrolu Praneeth , Chen Yong , Chen Li Qing , Chen Benjamin K. , Chestek David , Chew Robert F. , Chisolm Deena J. , Chow Dominic C. , Chrisant Maryanne R. , Christakis Dimitri A. , Chute Christopher G. , Cicek Mine S. , Clark Cheryl R. , Clark Duncan B. , Clarke Geoffrey D. , Clouser Katharine N. , Connors Thomas J. , Cook Judith A. , Coombs Krista , Cordon-Cardo Carlos , Costello Julie L. , Cottrell Lesley , Cowan Kelly , Cowell Lindsay G. , Cranford Savannah , Cronin Jamie , Cummins Mollie R. , Curry Hannah L. , D'Sa Viren , Dabney Sean G. , Daniel Casey L. , Dapretto Mirella , Darbar Dawood , Darden Paul M. , Dasgupta Raktima , Dasgupta Soham , Davis Blakley Felicia , Dea Katherine , Deakyne Davies Sara J. , Decker Lauren A. , DeFronzo Ralph A. , Dehority Walter , Deitchman Amelia N. , del Alcazar James , Del Boccio Phoebe , del Rio Carlos , Del Rios Marina , DeLisa Julie A. , Deoni Sean C. , Diaz Maya Z. , Dickinson John D. , Dionne Audrey , Diviak Kathleen R. , Donohue Sarah E. , Downey Michael J. , Dozor Allen J. , Dreyer Benard P. , Dummer Kirsten B. , Durstenfeld Matthew S. , Dworkin Mark S. , Edmonds Sherrie L. , Elias Matthew D. , Elifritz Jamie , Ellingworth Evan , Elliott Amy J. , Ellison Angela M. , Enger Mike L. , Espinosa Joaquin M. , Esquenazi-Karonika Shari , Evans Michael D. , Evans Danielle N. , Facelli Julio C. , Fang Camila S. , Faustino E. Vincent S. , Fayad Lara Maria E. , Feldman Candace H. , Fiks Alexander G. , Fineman Rebecca , Finn Aloke V. , Fischer Melinda S. , Fitzgerald Megan L. , Flaherman Valerie J. , Flotte Thomas J. , Forsha Daniel , Fortune Meghan R. , Foxe John J. , Franks Nicole , Freedman Michael B. , Freeland Catherine E. , Friedman Naomi P. , Fry Greta , Gage Witvliet Margot , Gallagher Emily J. , Gallagher Richard , Garavan Hugh , Gaur Sunanda M. , Gee Dylan G. , Gennaro Maria Laura , Gerald Lynn B. , Ghosh Saikat B. , Giacino Joseph T. , Girvin Andrew T. , Godfrey Stephanie L. , Goldberg Mark P. , Goodman Steven N. , Gordon Howard S. , Gouripeddi Ramkiran , Graham Paige , Granger Joey P. , Gray Kevin M. , Greimes Tina , Gross Rachel S. , Guthe Nicholas , Gutter Evan , Haasnoot Stephanie , Hadley Emily C. , Haendel Melissa A. , Hafner Stephanie , Halabi Katia C. , Hanley Patrick C. , Harahsheh Ashraf S. , Harkins Michelle S. , Hartwig Kimberly L. , Hasbani Keren , Hasek Sharon , Hauser Kristine S. , Heath Andrew C. , Hebson Camden L. , Heitzeg Mary M. , Hendrickson Monica , Henrich Timothy J. , Hernandez-Romieu Alfonso C. , Hester Christina M. , Higginbotham Miranda , Hill Sophia , Hirabayashi Kathryn , Ho On , Hobart-Porter Laura , Hoffman M. C. , Holtcamp Maryann , Hong Travis K. , Horne Benjamin D. , Horowitz Carol R. , Hsia Daniel S. , Hsu Harvey , Hsue Priscilla Y. , Huentelman Matthew , Huerta Bryan E. , Huling Jared D. , Hummel Kathy , Iacono William G. , Ibanez Alejandra L. , Ibeawuchi Carmel , Irby Katherine , Ismail Nahed , Jacobus Joanna , Jacoby Vanessa L. , Jason Leonard A. , Javia Vidhi , Jennette Kyle J. , Jernigan Terry L. , Jiang Sihang , Jing Naimin , Johnny Jace D. , Johnson Nadia , Johnson Brandi , Johnson Brandon , Jone Pei-Ni , Judd Suzanne E. , Juskowich Joy J. , Kabagambe Edmond K. , Kaelber David C. , Kanjilal Diane G. , Kansal Mayank M. , Kasmarcak Tyler J. , Kaufman Daniel , Kawakami Rika , Kellogg Dean L. , Kent Denise A. , Kewlani Deepshikha , Khullar Dhruv , Kim Keri S. , Kim Arthur Y. , Kinser Patricia A. , Kleinman Lawrence C. , Klerman Elizabeth B. , Kluko Matthew J. , Knight Stacey , Kobayashi Misaki , Kopp Karla J. , Koropsak Michael , Kosut Jessica S. , Kraig Ellen , Krausert Amanda , Krieger Ana C. , Krishna Hema , Krishnamoorthy Aparna , Krishnan Sankaran S. , Lahs James P. , Laird Angela R. , Laleau Victoria , Lamendola-Essel Michelle F. , Landeo-Gutierrez Jeremy , Lang Sean M. , Larson Christine L. , Lash James P. , Lasky-Su Jessica , Laynor Gregory , Lee Simon , Lee Grace M. , Lee F. E. , Lee Matthew A. , Leese Peter J. , Lefebvre R. C. , Levreault Angelica J. , Lewis Kennedy C. , Li Lu , Lim Peter Paul C. , Lin Janet Y. , Lisdahl Krista M. , Litvack Matthew B. , Liu Xiaokang , Lloyd Jennifer , Logue Jennifer K. , Loomba Johanna J. , Lorman Vitaly , Lu Yiwen , Ludwig Katelyn R. , Lutz Allison M. , Mack Jeri , Mahmoud Abeer M. , Maier Cheryl L. , Malakooti Shahdi K. , Malchenko Sergey , Mallett Gail L. , Maranga Gabrielle , Martel Megan W. , Martin-Herz Susanne P. , Martinez-Lage Maria , Maughan Christine , Mauntel-Medici Cammeo , May Heidi T. , Mayer Kenneth H. , Mazzotti Diego R. , McCallum Caitryn M. , McCrindle Brian W. , McCulloh Russell J. , McDonald Dylan , McInnis Stephanie , McMurry Julie A. , Mejias Asuncion , Melamed Jonathan , Menchaca Martha , Mendelsohn Alan L. , Miele Lucio , Miglis Mitchell G. , Milne Cris , Milner Joshua D. , Mitchell Roger A. , Mittleman Murray A. , Mohandas Sindhu , Monteiro Jonathan G. , Monzon Vanessa , Moreno David J. , Morgan Lerraughn M. , Morozyuk Dmitry , Morse Keith E. , Moyneur Erick , Mudumbi Praveen C. , Müller-Oehring Eva M. , Muramatsu Naoko , Musick Hugh , Nagavedu Kshema , Nahin Erica R. , Nambiar Anoop M. , Natelson Benjamin H. , Neale Michael C. , Ness-Cochinwala Manette , Newburger Jane W. , Newman Lisa T. , Nguyen Amber N. , Nichols Lauren , Nolan Sheila M. , Noland Seth , Novak Richard M. , O'Connor George T. , O'Keefe John J. , Ogbogu Princess U. , Oliveira Carlos R. , Oster Matthew E. , Padera Robert F. , Paik Henry H. , Pajor Nathan M. , Pan Huaqin Helen , Pant Deepti , Partridge Andrew , Patel Payal B. , Patel Saaya , Patel Khushboo , Paulus Martin P. , Payne Ronald M. , Pearman Ann , Peralta-Carcelen Myriam , Perez Nicolas L. , Pfaff Emily R. , Pillers De-Ann M. , Pitsch Chloe E. , Pliskin Neil H. , Portman Michael A. , Postelnicu Radu , Potter Jennifer S. , Prabhakar Bellur S. , Prahalad Priya , Prasad Bharati , Predki Barbara , Preiss Alexander J. , Prendergast Heather M. , Quinn Davin K. , Quintana Yuri , Rabideau Dustin J. , Radosta Jonathan M. , Radwell Jeffrey , Raissy Hengameh , Ramchandran Ramaswamy , Randall Isabelle , Rao Suchitra , Rapkiewicz Amy , Rasmussen Sonja A. , Razzaghi Hanieh , Rebello Candida J. , Rebolledo Paulina A. , Reddy Neha V. , Reddy Unma M. , Reedy Cara , Rehman Jalees , Reichard R. R. , Reid Kayleigh M. , Reusch Jane E. , Rhee Kyung E. , Rice Mary B. , Rizzo John-Ross R. , Roan Nadia R. , Robarts Polly , Roberts Timothy R. , Rochez Nitza , Rodgers Kathleen E. , Rogerson Colin M. , Romero Maria E. , Rosas Johana M. , Rosenzweig Erika B. , Rothman Russell L. , Rouphael Nadine G. , Russell Mark W. , Rutherfoord Melissa , Sabati Arash A. , Sader Samer B. , Salehi Marzieh , Salisbury Amy L. , Sampson Barbara A. , Sanil Yamuna , Sato Alice I. , Saydah Sharon H. , Schechter Michael S. , Schenck Edward J. , Schlepphorst Katherine I. , Schuchard Julia , Schuh Tina L. , Sculley Jennifer A. , Seifert Alan C. , Sekar Anisha K. , Selvarangan Rangaraj , Seshadri Sudha , Sesso Howard D. , Shah Dimpy P. , Shakti Divya , Shapiro Nancy L. , Sharma Suchetha , Sharma Kumar , Sharma Shubhi , Sharma Kavita , Shaw Gwendolyn , Shemesh Eyal , Shen Yishan , Shenkman Elizabeth , Shiau Stephanie , Siciliano Michelle , Simsir Aylin , Smith Veronica E. , Snowden Jessica N. , Solomon Isaac H. , Spikes Leslie A. , Squeglia Lindsay M. , Srivastava Shubhika , St. Jean Mary L. , Stapleford Kenneth A. , Stein Cheryl R. , Stevenson Michelle D. , Stewart de Ramirez Sarah A. , Stiles Lauren E. , Stock Aryeh , Stockwell Melissa S. , Stone James R. , Stratford Jeran , Stürmer Til , Subbian Vignesh , Sun Jun , Suthar Mehul S. , Sylvera Ashley , Systrom David M. , Szmuszkovicz Jacqueline , Talavera-Barber Maria M. , Tantisira Kelan G. , Tartt Nancy , Terlinde Tracy , Teufel Ronald J. , Thacker Deepika , Thakrar Mansi , Thibodeau Stephen N. , Thomas Gelise L. , Thomason Moriah E. , Tong Jiayi , Torres Robert , Traenkner Jessica , Tragus Robin , Trinity Joel D. , Tronieri Jena S. , Troxel Andrea B. , Truong Jennifer , Truong Dongngan T. , Tsevat Joel , Udosen Mmekom M. , Unterberger Kristen , Utz Paul J. , Vaccarino Viola , Vallejos Brittany B. , Vanden Hoek Terry L. , Vangeepuram Nita , Varma Jay K. , Vernon Suzanne D. , Vidal Crystal M. , Vivensi Sara , Vohra Adam S. , Wagner Laura K. , Wang Fei , Warburton David , Warner Megan R. , Watkins Rebecca L. , Watson Sara E. , Webb Ryan , Weeks Ryan M. , Weiner Mark G. , Werzberger Alan , West Shelby C. , Weyer Jordan C. , Wheeler Jennifer L. , Wilkins Kenneth J. , Williams Natasha J. , Williams Charles T. , Wimberly Erika S. , Winter Terra J. , Woller Scott C. , Wong Rachel , Wood Jeremy P. , Wood John C. , Wood Marion J. J. , Wu Qiong , Xia Yinglin , Xu Jie , Yang Samuel , Yin H. S. , Yin Hsiang S. , Yoo Yun Jae , Young Chloe E. , Young Natalie M. , Zang Chengxi , Zempsky William T. , Zhang Bingyu , Zhang Yongkang , Zhang Dazheng , Zimmerman Emily , Andrefsky John , Marrazzo Jeanne M , Dixon Jennifer , Gale Lisa , Maholovich Phoebe , Sudhindra Praveen , Thompson Tiffany , Sheehan Elyce , Parada Alisha , Knowlton Kiirk , Anderson Jeffrey L. , McIntyre Marjorie , McCandless Sean , Montoya Sarah , Davis Debra , Spanier Eric , Wodushek Thomas , Sokol Ron , Maldonado Yvonne , Jacobson Karen , Jia Xiaolin "Kathleen" , Scott Jake , Quintero Orlando , Haddad Francois , Valantine Hannah , Zamanian Roham , Pathak Divya , Boyce Jeanette , Facco Francesca , Hankle Sarah , Vargo John A. , Campbell Donna , Armstrong Donna , Mann Madison , Burrell Nicole , Bartholomew Anna , Grobman William A. , Cackovic Barbara , Klopfenstein Baylee , Weigand Samantha , Snow E. Kaye , Fennig Kathleen , Esplin M. Sean , Lamb Denise , Nelsen Amanda , Phipers Jocelyn , Fischer Lauren , Docter Olivia , Brown Jeanette , DeMartino Angelica , Allard Donna , Miller Emily , Bousleiman Sabine Z. , Loffredo Megan M. , Vanneman Ashley , Beche Imene , Chan-Akeley Rosalyn , Pacheco Luis D. , DeVolder Jennfier D. , Salazar Ashley , Thibodeaux Lisa , Cornwell Jennifer , Nounes Amelia A. , Sweet Eugenia , Pierse Abigail , Desantis Brittany , Gill-Jones Parmjit , Hackney David N. , Chauhan Suneet P. , Ortiz Felecia , Treadway Jenifer , Rugerio Juanita , Clark Kelly , Leatherland Molly , Timlin Sally , Grinnan Chelsea , Ferrara Jennifer , Kominiarek Michelle , Jones Dequana , Reynolds Trista , Kearns Katherine M , Saffian Eleanor , Karasti Mariana , Pizzi Chrsitinia , Filipczak Anna , Long Emily , Mitchell Megan , Barrett Katia J. , Mullowney Celia , Macones George A. , Alba George A. , Alicic Radica , Altman Natasha , Anglin Khamal , Argueta Urania , Ashktorab Hassan , Baslet Gaston , Bassett Ingrid V. , Bateman Lucinda , Bedi Brahmchetna , Bhattacharyya Shamik , Bind Marie-Abele , Blomkalns Andra L. , Bonilla Hector , Brim Hassan , Bush Patricia A. , Castro Mario , Chan James , Charney Alexander W. , Chen Peter , Chibnik Lori B. , Chu Helen Y. , Clifton Rebecca G. , Costantine Maged M. , Cribbs Sushma K. , Davila Nieves Sylvia I. , Deeks Steven G. , Duven Alexandria , Emery Ivette F. , Erdmann Nathan , Erlandson Kristine M. , Ernst Kacey C. , Farah-Abraham Rachael , Farner Cheryl E. , Feuerriegel Elen M. , Fleurimont Judes , Fonseca Vivian , Franko Nicholas , Gainer Vivian , Gander Jennifer C. , Gardner Edward M. , Geng Linda N. , Gibson Kelly S. , Go Minjoung , Goldman Jason D. , Grebe Halle , Greenway Frank L. , Habli Mounira , Hafner John , Han Jenny E. , Hanson Keith A. , Heath James , Hernandez Carla , Hess Rachel , Hodder Sally L. , Hoffman Matthew K. , Hoover Susan E. , Huang Beatrice , Hughes Brenna L. , Jagannathan Prasanna , John Janice , Jordan Michael R. , Katz Stuart D. , Kaufman Elizabeth S. , Kelly John D. , Kelly Sara W. , Kemp Megan M. , Kirwan John P. , Klein Jonathan D. , Knox Kenneth S. , Krishnan Jerry A. , Kumar Andre , Laiyemo Adeyinka O. , Lambert Allison A. , Lanca Margaret , Lee-Iannotti Joyce K. , Logarbo Brian P. , Longo Michele T. , Luciano Carlos A. , Lutrick Karen , Maley Jason H. , Mallett Gail , Marathe Jai G. , Marconi Vincent , Marshall Gailen D. , Martin Christopher F. , Matusov Yuri , Mehari Alem , Mendez-Figueroa Hector , Mermelstein Robin , Metz Torri D. , Morse Richard , Mosier Jarrod , Mouchati Christian , Mullington Janet , Murphy Shawn N. , Neuman Robert B. , Nikolich Janko Z. , Ofotokun Ighovwerha , Ojemakinde Elizabeth , Palatnik Anna , Palomares Kristy , Parimon Tanyalak , Parry Samuel , Patterson Jan E. , Patterson Thomas F. , Patzer Rachel E. , Peluso Michael J. , Pemu Priscilla , Pettker Christian M. , Plunkett Beth A. , Pogreba-Brown Kristen , Poppas Athena , Quigley John G. , Reddy Uma , Reece Rebecca , Reeder Harrison , Reeves W. B. , Reiman Eric M. , Rischard Franz , Rosand Jonathan , Rouse Dwight J. , Ruff Adam , Saade George , Sandoval Grecio J. , Santana Jorge L. , Schlater Shannon M. , Sciurba Frank C. , Shepherd Fitzgerald , Sherif Zaki A. , Simhan Hyagriv , Singer Nora G. , Skupski Daniel W. , Sowles Amber , Sparks Jeffrey A. , Sukhera Fatima I. , Taylor Barbara S. , Teunis Larissa , Thomas Robert J. , Thorp John M. , Thuluvath Paul , Ticotsky Amberly , Tita Alan T. , Tuttle Katherine R. , Urdaneta Alfredo E. , Valdivieso Daisy , VanWagoner Timothy M. , Vasey Andrew , Verduzco-Gutierrez Monica , Wallace Zachary S. , Ward Honorine D. , Warren David E. , Weiner Steven J. , Welch Shelley , Whiteheart Sidney W. , Wiley Zanthia , Wisnivesky Juan P. , Yee Lynn M. , Zisis Sokratis 
Published: May 2023

Importance

SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.

Objective

To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.

Design, Setting, and Participants

Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.

Exposure

SARS-CoV-2 infection.

Main Outcomes and Measures

PASC and 44 participant-reported symptoms (with severity thresholds).

Results

A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.

Conclusions and Relevance

A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.