Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing.
Jerome Bouquet, Tony Li, Jennifer L Gardy, Xiaoying Kang, Staci Stevens, Jared Stevens, Mark VanNess, Christopher Snell, James Potts, Ruth R Miller, Muhammad Morshed, Mark McCabe, Shoshana Parker, Miguel Uyaguari, Patrick Tang, Theodore Steiner, Wee-Shian Chan, Astrid-Marie De Souza, Andre Mattman, David M Patrick, Charles Y Chiu
Author Information
Jerome Bouquet: Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America.
Tony Li: Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America.
Jennifer L Gardy: Communicable Disease Prevention and Control Services, Vancouver, Canada.
Xiaoying Kang: School of Population and Public Health, University of British Columbia, Vancouver, Canada. ORCID
Staci Stevens: Workwell Foundation, Ripon, California, United States of America.
Jared Stevens: Workwell Foundation, Ripon, California, United States of America.
Mark VanNess: Workwell Foundation, Ripon, California, United States of America. ORCID
Christopher Snell: Workwell Foundation, Ripon, California, United States of America.
James Potts: Department of Pediatrics, Division of Cardiology, University of British Columbia, Vancouver, Canada. ORCID
Ruth R Miller: School of Population and Public Health, University of British Columbia, Vancouver, Canada.
Muhammad Morshed: British Columbia Centre for Disease Control Public Health Laboratory, Vancouver, Canada.
Mark McCabe: Communicable Disease Prevention and Control Services, Vancouver, Canada.
Shoshana Parker: Centre for Health Evaluation Outcome Sciences, Vancouver, Canada.
Miguel Uyaguari: British Columbia Centre for Disease Control Public Health Laboratory, Vancouver, Canada.
Patrick Tang: Department of Pathology, Sidra Medical and Research Center, Doha, Qatar.
Theodore Steiner: Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, Canada.
Wee-Shian Chan: Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, Canada.
Astrid-Marie De Souza: Division of Cardiology, British Columbia's Children's Hospital, Vancouver, Canada.
Andre Mattman: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
David M Patrick: Communicable Disease Prevention and Control Services, Vancouver, Canada.
Charles Y Chiu: Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America. ORCID
Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes. ME/CFS patients (n = 14) and matched sedentary controls (n = 11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing reduced oxygen consumption ([Formula: see text]) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points. None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P = 0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes.
