COVID-19 Patient-Reported Symptoms Using FLU-PRO Plus in a Cohort Study: Associations With Infecting Genotype, Vaccine History, and Return to Health

Stephanie A Richard; Nusrat J Epsi; David A Lindholm; Allison M W Malloy; Ryan C Maves; Catherine M Berjohn; Tahaniyat Lalani; Alfred G Smith; Rupal M Mody; Anuradha Ganesan; Nikhil Huprikar; Rhonda E Colombo; Christopher J Colombo; Cristian Madar; Milissa U Jones; Derek T Larson; Evan C Ewers; Samantha Bazan; Anthony C Fries; Carlos J Maldonado; Mark P Simons; Julia S Rozman; Liana Andronescu; Katrin Mende; David R Tribble; Brian K Agan; Timothy H Burgess; Simon D Pollett; John H Powers 3rd; EPICC COVID-19 Cohort Study Group

doi:10.1093/ofid/ofac275

COVID-19 Patient-Reported Symptoms Using FLU-PRO Plus in a Cohort Study: Associations With Infecting Genotype, Vaccine History, and Return to Health

Open Forum Infect Dis. 2022 Jun 7;9(7):ofac275. doi: 10.1093/ofid/ofac275. eCollection 2022 Jul.

Authors

Stephanie A Richard¹, Nusrat J Epsi¹, David A Lindholm², Allison M W Malloy³, Ryan C Maves¹, Catherine M Berjohn³, Tahaniyat Lalani¹, Alfred G Smith⁴, Rupal M Mody⁵, Anuradha Ganesan¹, Nikhil Huprikar³, Rhonda E Colombo¹, Christopher J Colombo³, Cristian Madar⁶, Milissa U Jones³, Derek T Larson⁷, Evan C Ewers⁸, Samantha Bazan⁹, Anthony C Fries¹⁰, Carlos J Maldonado¹¹, Mark P Simons¹, Julia S Rozman¹, Liana Andronescu¹, Katrin Mende¹, David R Tribble¹, Brian K Agan¹, Timothy H Burgess¹, Simon D Pollett¹, John H Powers 3rd¹²; EPICC COVID-19 Cohort Study Group

Collaborators

EPICC COVID-19 Cohort Study Group:
J Cowden, M Darling, S DeLeon, D Lindholm, A Markelz, K Mende, S Merritt, T Merritt, N Turner, T Wellington, R Carl, S Bazan, P K Love, N Dimascio-Johnson, E Ewers, K Gallagher, D Larson, A Rutt, P Blair, J Chenoweth, D Clark, S Chambers, C Colombo, R Colombo, C Conlon, K Everson, P Faestel, T Ferguson, L Gordon, S Grogan, S Lis, C Mount, D Musfeldt, D Odineal, M Perreault, W Robb-McGrath, R Sainato, C Schofield, C Skinner, M Stein, M Switzer, M Timlin, S Wood, S Banks, R Carpenter, L Kim, K Kronmann, T Lalani, T Lee, A Smith, R Smith, R Tant, T Warkentien, C Berjohn, S Cammarata, N Kirkland, D Libraty, R Maves, G Utz, S Chi, R Flanagan, M Jones, C Lucas, C Madar, K Miyasato, C Uyehara, B Agan, L Andronescu, A Austin, C Broder, T Burgess, C Byrne, K Chung, J Davies, C English, N Epsi, C Fox, M Fritschlanski, A Hadley, P Hickey, E Laing, C Lanteri, J Livezey, A Malloy, R Mohammed, C Morales, P Nwachukwu, C Olsen, E Parmelee, S Pollett, S Richard, J Rozman, J Rusiecki, E Samuels, M Sanchez, A Scher, M Simons, A Snow, K Telu, D Tribble, M Tso, L Ulomi, M Wayman, T Merritt, T Wellington, D Clark, S Chambers, P Faestel, C Mount, D Musfeldt, C Schofield, N Kirkland, C Madar, C Uyehara, C Broder, C Byrne, K Chung, C English, P Hickey, E Laing, C Lanteri, J Livezey, P Nwachukwu, E Parmelee, E Samuels, M Sanchez, A Scher, M Tso, M Wayman, T Chao, K Lanter, J Meyer, K Reynolds, C Starr, J Iskander, I Kamara, D Hostler, K Lago

Affiliations

¹ Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
² Brooke Army Medical Center, Fort Sam Houston, Texas, USA.
³ Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
⁴ Naval Medical Center Portsmouth, Portsmouth, Virginia, USA.
⁵ William Beaumont Army Medical Center, El Paso, Texas, USA.
⁶ Tripler Army Medical Center, Honolulu, Hawaii, USA.
⁷ Naval Medical Center San Diego, San Diego, California, USA.
⁸ Fort Belvoir Community Hospital, Fort Belvoir, Virginia, USA.
⁹ Carl R. Darnall Army Medical Center, Fort Hood, Texas, USA.
¹⁰ US Air Force School of Aerospace Medicine, Dayton, Ohio, USA.
¹¹ Womack Army Medical Center, Fort Bragg, North Carolina, USA.
¹² Clinical Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.

Abstract

Background: Patient-reported outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are an important measure of the full burden of coronavirus disease (COVID). Here, we examine how (1) infecting genotype and COVID-19 vaccination correlate with inFLUenza Patient-Reported Outcome (FLU-PRO) Plus score, including by symptom domains, and (2) FLU-PRO Plus scores predict return to usual activities and health.

Methods: The epidemiology, immunology, and clinical characteristics of pandemic infectious diseases (EPICC) study was implemented to describe the short- and long-term consequences of SARS-CoV-2 infection in a longitudinal, observational cohort. Multivariable linear regression models were run with FLU-PRO Plus scores as the outcome variable, and multivariable Cox proportional hazards models evaluated effects of FLU-PRO Plus scores on return to usual health or activities.

Results: Among the 764 participants included in this analysis, 63% were 18-44 years old, 40% were female, and 51% were White. Being fully vaccinated was associated with lower total scores (β = -0.39; 95% CI, -0.57 to -0.21). The Delta variant was associated with higher total scores (β = 0.25; 95% CI, 0.05 to 0.45). Participants with higher FLU-PRO Plus scores were less likely to report returning to usual health and activities (health: hazard ratio [HR], 0.46; 95% CI, 0.37 to 0.57; activities: HR, 0.56; 95% CI, 0.47 to 0.67). Fully vaccinated participants were more likely to report returning to usual activities (HR, 1.24; 95% CI, 1.04 to 1.48).

Conclusions: Full SARS-CoV-2 vaccination is associated with decreased severity of patient-reported symptoms across multiple domains, which in turn is likely to be associated with earlier return to usual activities. In addition, infection with the Delta variant was associated with higher FLU-PRO Plus scores than previous variants, even after controlling for vaccination status.

Keywords: COVID-19; SARS-CoV-2; patient-reported outcomes; symptoms; vaccine breakthrough.

Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2022.