Long COVID Clinical Phenotypes up to 6 Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms
Michael Gottlieb, Erica S. Spatz, Huihui Yu, Lauren E. Wisk, Joann G. Elmore, Nicole L. Gentile, Mandy J. Hill, Ryan Huebinger, Ahamed H. Idris, Efrat R. Kean, Katherine Koo, Shuxia Li, Samuel McDonald, Juan Carlos C. Montoy, Graham Nichol, Kelli N. O’Laughlin, Ian D. Plumb, Kristin L. Rising, Michelle Santangelo, Sharon Saydah, Ralph C. Wang, Arjun K. Venkatesh, Kari A. Stephens, Robert A Weinstein, INSPIRE Group, Robert A Weinstein, Michael Gottlieb, Michelle Santangelo, Katherine Koo, Antonia Derden, Michael Gottlieb, Kristyn Gatling, Diego Cordero, Geoffrey Yang, Marshall Kaadan, Minna Hassaballa, Ryan Jerger, Zohaib Ahmed, Michael Choi, Arjun K. Venkatesh, Erica S. Spatz, Zhenqiu Lin, Shuxia Li, Huihui Yu, Mengni Liu, Arjun K. Venkatesh, Erica S. Spatz, Andrew Ulrich, Jeremiah Kinsman, Jocelyn Dorney, Senyte Pierce, Xavier Puente, Graham Nichol, Kari A. Stephens, Jill Anderson, Dana Morse, Karen Adams, Zenoura Maat, Tracy Stober, Kelli N. O’Laughlin, Nikki Gentile, Rachel E Geyer, Michael Willis, Luis Ruiz, Kerry Malone, Jasmine Park, Kristin L. Rising, Efrat Kean, Morgan Kelly, Kevin Schaeffer, Paavali Hannikainen, Lindsey Shughart, Hailey Shughart, Nicole Renzi, Grace Amadio, Dylan Grau, Phillip B. Watts, David Cheng, Jessica Miao, Carly Shutty, Alex Charlton, Mandy J. Hill, Summer Chavez, Arun Kane, Peter Nikonowicz, Ahamed H. Idris, Samuel McDonald, David Gallegos, Riley Martin, Joann G. Elmore, Lauren E. Wisk, Michelle L’Hommedieu, Chris Chandler, Megan Eguchi, Kate Diaz Roldan, Nicole Villegas, Raul Moreno, Robertz Rodrigue, Ralph C. Wang, Juan Carlos C. Montoy
Abstract
Abstract Background The prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection. Methods This was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms. Results Among 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months. Conclusions We identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized. Clinical Trials Registration. NCT04610515.