Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection
Abstract Background Fatigue is a common sequela of SARS-CoV-2 infection, with many COVID-19 patients subsequently developing chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME). Long-term associations between COVID-19, new-onset CFS/ME, and other independent predictors such as vaccinatio...
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BMC
2025-07-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06625-w |
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| author | Roham Hadidchi Bhakti Patel Japji Madan Alex Liu Sonya Henry Tim Q. Duong |
| author_facet | Roham Hadidchi Bhakti Patel Japji Madan Alex Liu Sonya Henry Tim Q. Duong |
| author_sort | Roham Hadidchi |
| collection | DOAJ |
| description | Abstract Background Fatigue is a common sequela of SARS-CoV-2 infection, with many COVID-19 patients subsequently developing chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME). Long-term associations between COVID-19, new-onset CFS/ME, and other independent predictors such as vaccination for SARS-CoV-2, re-infection, and blood biomarkers at time of infection remain unclear. This study investigated the incidence and independent predictors of developing new-onset CFS/ME up to 4 years post SARS-CoV-2 infection in comparison to COVID− controls. Methods This retrospective analysis conducted within the Montefiore Health System from February 1, 2020, to January 12, 2024 included adults without a prior diagnosis of fatigue or CFS/ME who were hospitalized for COVID-19 (n = 10,667), not hospitalized for COVID-19 (n = 25,409), and non-COVID-19 controls (n = 111,301). The observation time was between 30 days and 4 years post index date. The outcome was new-onset CFS/ME. Multivariate adjusted hazard ratios (HR) with 95% confidence intervals were calculated, assessing risk posed by SARS-CoV-2 infection, re-infection, and vaccination. Whether abnormal levels of aspartate aminotransferase, creatinine, D-dimer, lactate dehydrogenase, ferritin, hemoglobin, platelets, neutrophil/lymphocyte ratio, and temperature during hospitalization were associated with future CFS/ME risk was examined. Results Compared to COVID− controls, the risk of developing new-onset CFS/ME was higher among both COVID-19 hospitalized (adjusted HR = 1.46 [1.07, 1.99]) and non-hospitalized patients (1.56 [1.25, 1.93]). Females (1.54 [1.27, 1.89]), patients with liver disease (1.61 [1.29, 2.00]), autoimmune disorders (1.57 [1.18, 2.08]), and anxiety disorders (1.35 [1.04, 1.74]) were more likely to develop CFS/ME (p < 0.05). Re-infection with SARS-CoV-2 was not associated with increased risk of incident CFS/ME. COVID-19 vaccination status during the initial phase of the rollout (prior to 2022) was associated with an increased risk of new-onset CFS/ME (p < 0.05). None of the blood biomarkers during acute COVID-19 were associated with new-onset CFS/ME risk (p > 0.05). Conclusion SARS-CoV-2 infection is associated with an increased risk of new-onset CFS/ME, independent of hospitalization status. Females, and individuals with autoimmune and anxiety disorders were more susceptible. These findings highlight the need for ongoing surveillance and management of fatigue-related symptoms in COVID-19 survivors. |
| format | Article |
| id | doaj-art-e2e13d724ef9403285374bfb7c8ca9f6 |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj-art-e2e13d724ef9403285374bfb7c8ca9f62025-08-20T03:06:04ZengBMCJournal of Translational Medicine1479-58762025-07-0123111010.1186/s12967-025-06625-wElevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infectionRoham Hadidchi0Bhakti Patel1Japji Madan2Alex Liu3Sonya Henry4Tim Q. Duong5Department of Radiology, Montefiore Health System and Albert Einstein College of MedicineDepartment of Radiology, Montefiore Health System and Albert Einstein College of MedicineDepartment of Radiology, Montefiore Health System and Albert Einstein College of MedicineDepartment of Radiology, Montefiore Health System and Albert Einstein College of MedicineDepartment of Radiology, Montefiore Health System and Albert Einstein College of MedicineDepartment of Radiology, Montefiore Health System and Albert Einstein College of MedicineAbstract Background Fatigue is a common sequela of SARS-CoV-2 infection, with many COVID-19 patients subsequently developing chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME). Long-term associations between COVID-19, new-onset CFS/ME, and other independent predictors such as vaccination for SARS-CoV-2, re-infection, and blood biomarkers at time of infection remain unclear. This study investigated the incidence and independent predictors of developing new-onset CFS/ME up to 4 years post SARS-CoV-2 infection in comparison to COVID− controls. Methods This retrospective analysis conducted within the Montefiore Health System from February 1, 2020, to January 12, 2024 included adults without a prior diagnosis of fatigue or CFS/ME who were hospitalized for COVID-19 (n = 10,667), not hospitalized for COVID-19 (n = 25,409), and non-COVID-19 controls (n = 111,301). The observation time was between 30 days and 4 years post index date. The outcome was new-onset CFS/ME. Multivariate adjusted hazard ratios (HR) with 95% confidence intervals were calculated, assessing risk posed by SARS-CoV-2 infection, re-infection, and vaccination. Whether abnormal levels of aspartate aminotransferase, creatinine, D-dimer, lactate dehydrogenase, ferritin, hemoglobin, platelets, neutrophil/lymphocyte ratio, and temperature during hospitalization were associated with future CFS/ME risk was examined. Results Compared to COVID− controls, the risk of developing new-onset CFS/ME was higher among both COVID-19 hospitalized (adjusted HR = 1.46 [1.07, 1.99]) and non-hospitalized patients (1.56 [1.25, 1.93]). Females (1.54 [1.27, 1.89]), patients with liver disease (1.61 [1.29, 2.00]), autoimmune disorders (1.57 [1.18, 2.08]), and anxiety disorders (1.35 [1.04, 1.74]) were more likely to develop CFS/ME (p < 0.05). Re-infection with SARS-CoV-2 was not associated with increased risk of incident CFS/ME. COVID-19 vaccination status during the initial phase of the rollout (prior to 2022) was associated with an increased risk of new-onset CFS/ME (p < 0.05). None of the blood biomarkers during acute COVID-19 were associated with new-onset CFS/ME risk (p > 0.05). Conclusion SARS-CoV-2 infection is associated with an increased risk of new-onset CFS/ME, independent of hospitalization status. Females, and individuals with autoimmune and anxiety disorders were more susceptible. These findings highlight the need for ongoing surveillance and management of fatigue-related symptoms in COVID-19 survivors.https://doi.org/10.1186/s12967-025-06625-wChronic fatigue syndromeMyalgic encephalomyelitisPost-acute sequelaeCOVID-19Long-COVIDRisk factors |
| spellingShingle | Roham Hadidchi Bhakti Patel Japji Madan Alex Liu Sonya Henry Tim Q. Duong Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection Journal of Translational Medicine Chronic fatigue syndrome Myalgic encephalomyelitis Post-acute sequelae COVID-19 Long-COVID Risk factors |
| title | Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection |
| title_full | Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection |
| title_fullStr | Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection |
| title_full_unstemmed | Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection |
| title_short | Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection |
| title_sort | elevated risk of new onset chronic fatigue syndrome myalgic encephalomyelitis up to four years after sars cov 2 infection |
| topic | Chronic fatigue syndrome Myalgic encephalomyelitis Post-acute sequelae COVID-19 Long-COVID Risk factors |
| url | https://doi.org/10.1186/s12967-025-06625-w |
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