Long COVID Clinical Phenotypes up to 6 Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms
Authors: Gottlieb Michael , Spatz Erica S , Yu Huihui , Wisk Lauren E , Elmore Joann G , Gentile Nicole L , Hill Mandy , Huebinger Ryan M , Idris Ahamed H , Kean Efrat R , Koo Katherine , Li Shu-Xia , McDonald Samuel , Montoy Juan Carlos C , Nichol Graham , O’Laughlin Kelli N , Plumb Ian D , Rising Kristin L , Santangelo Michelle , Saydah Sharon , Wang Ralph C , Venkatesh Arjun , Stephens Kari A , Weinstein Robert A ,   INSPIRE Group, Weinstein Robert A , Gottlieb Michael , Santangelo Michelle , Koo Katherine , Derden Antonia , Gottlieb Michael , Gatling Kristyn , Guzman Diego , Yang Geoffrey , Kaadan Marshall , Hassaballa Minna , Jerger Ryan , Ahmed Zohaib , Choi Michael , Venkatesh Arjun , Spatz Erica , Lin Zhenqiu , Li Shu-Xia , Yu Huihui , Liu Mengni , Venkatesh Arjun , Spatz Erica , Ulrich Andrew , Kinsman Jeremiah , Dorney Jocelyn , Pierce Senyte , Puente Xavier , Nichol Graham , Stephens Kari , Anderson Jill , Morse Dana , Adams Karen , Maat Zenoura , Stober Tracy , O’Laughlin Kelli N , Gentile Nikki , Geyer Rachel E , Willis Michael , Ruiz Luis , Malone Kerry , Park Jasmine , Rising Kristin , Kean Efrat , Kelly Morgan , Schaeffer Kevin , Hannikainen Paavali , Shughart Lindsey , Shughart Hailey , Renzi Nicole , Amadio Grace , Grau Dylan , Watts Phillip , Cheng David , Miao Jessica , Shutty Carly , Charlton Alex , Hill Mandy , Chavez Summer , Kane Arun , Nikonowicz Peter , Idris Ahamed H , McDonald Samuel , Gallegos David , Martin Riley , Elmore Joann , Wisk Lauren , L’Hommedieu Michelle , Chandler Chris , Eguchi Megan , Roldan Kate Diaz , Villegas Nicole , Moreno Raul , Rodrigue Robertz , Wang Ralph C , Montoy Juan Carlos , Kemball Robin , Chan Virginia , Chavez Cecilia Lara , Wong Angela , Arreguin Mireya 
Published: May 2023

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.