Age-Related Changes in the Clinical Picture of Long COVID

Mindy J Fain^{1

2}, Benjamin D Horne^{3

4}, Leora I Horwitz^{5

6}, Tanayott Thaweethai^{7

8}, Meredith Greene^{9

10}, Mady Hornig^{11

12}, Ariela R Orkaby¹³, Clifford Rosen¹⁴, Christine S Ritchie¹⁵, Hassan Ashktorab¹⁶, Nina Blachman¹⁷, Hassan Brim¹⁸, Sarah Emerson¹⁹, Nathan Erdmann²⁰, Kristine M Erlandson²¹, Gabriel de Erausquin²², Tamara Fong²³, Linda N Geng²⁴, Howard S Gordon^{25

26}, Jacqueline Rutter Gully²⁷, Jennifer Hadlock^{28

29}, Jenny Han³⁰, Weixing Huang⁷, Prasanna Jagannathan³¹, J Daniel Kelly^{32

33}, Jonathan D Klein^{34

35}, Jerry A Krishnan³⁵, Emily B Levitan³⁶, Grace A McComsey³⁷, Dylan McDonald³⁸, Aoyjai P Montgomery³⁹, Lisa O'Brien⁴⁰, Ighovwerha Ofotokun⁴¹, Thomas F Patterson⁴², Michael J Peluso⁴³, Priscilla Pemu⁴⁴, Alice Perlowski⁴⁵, Eric M Reiman^{46

47}, Martine Sanon⁴⁸, Sudha Seshadri⁴⁹, Judd Shellito⁵⁰, Zaki A Sherif⁵¹, Cecilia Shikuma⁵², Nora G Singer^{37

53}, Upinder Singh⁵⁴, Joel D Trinity^{55

56

57}, Juan Wisnivesky⁴⁸, Margot Gage Witvliet⁵⁸, Andrea Foulkes^{7

8}, Janko Ž Nikolich^{1

59

60}; RECOVER consortium

Affiliations

¹ Arizona Center on Aging, University of Arizona College of Medicine-Tucson, Tucson, Arizona, USA.
² Division of General Internal Medicine, Geriatrics and Palliative Medicine, Department of Medicine, University of Arizona College of Medicine-Tucson, Tucson, Arizona, USA.
³ Intermountain Heart Institute, Intermountain Health, Salt Lake City, Utah, USA.
⁴ Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁵ Center for Healthcare Innovation and Delivery Science, NYU Langone Health, New York, New York, USA.
⁶ Departments of Medicine and of Population Health, NYU Grossman School of Medicine, New York, New York, USA.
⁷ Massachusetts General Hospital Biostatistics, Harvard University, Boston, Massachusetts, USA.
⁸ Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
⁹ Indiana University Center for Aging Research at the Regenstrief Institute, Indianapolis, Indiana, USA.
¹⁰ Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹¹ The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA.
¹² RECOVER Patient Representative, New York, New York, USA.
¹³ New England Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System; Division of Aging, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁴ MaineHealth Institute for Research, Scarborough, Maine, USA.
¹⁵ Center for Aging and Serious Illness, Division of Palliative Care and Geriatric Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹⁶ Department of Medicine and Cancer Center, Howard University College of Medicine, Washington, DC, USA.
¹⁷ Division of Geriatrics and Palliative Care, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA.
¹⁸ Department of Pathology and Cancer Center, Department of Biochemistry & Molecular Biology, Howard University College of Medicine, Washington, DC, USA.
¹⁹ Providence Medical Research Center, Spokane, Washington, DC, USA.
²⁰ Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²¹ University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
²² Biggs Institute of Alzheimer's & Neurodegenerative Disorders, Long School of Medicine, University of Texas Health Sciences Center, San Antonio, Texas, USA.
²³ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
²⁴ Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
²⁵ Medical Service, Jesse Brown VA Medical Center, Chicago, Illinois, USA.
²⁶ Department of Medicine, University of Illinois College of Medicine, Chicago, Illinois, USA.
²⁷ RECOVER Patient Advocate & Caregiver, Dysautonomia International, East Moriches, New York, USA.
²⁸ Institute for Systems Biology, Seattle, Washington, DC, USA.
²⁹ Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, Washington, DC, USA.
³⁰ Pulmonary Allergy, Critical Care and Sleep Medicine Emory University School of Medicine, Atlanta, Georgia, USA.
³¹ Division of Infectious Diseases, Departments of Internal Medicine and Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
³² Department of Medicine, VA Medical Center, University of California, San Francisco, California, USA.
³³ Department of Epidemiology and Biostatistics, UCSF, San Francisco, California, USA.
³⁴ Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
³⁵ ILLInet, University of Illinois Chicago, Chicago, Illinois, USA.
³⁶ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
³⁷ Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
³⁸ Department of Allergy and Infectious Disease, School of Medicine, University of Washington, Seattle, Washington, DC, USA.
³⁹ Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴⁰ RECOVER Patient Representative, Utah Covid-19 Long Haulers, Salt Lake City, Utah, USA.
⁴¹ Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
⁴² Division of Infectious Diseases, Department of Medicine, University of Texas Health Sciences Center, San Antonio, Texas, USA.
⁴³ Division of Infectious Diseases, Department of Medicine, UCSF School of Medicine, San Francisco, California, USA.
⁴⁴ Morehouse School of Medicine, Atlanta, Georgia, USA.
⁴⁵ RECOVER Patient Representative, Blooming Magnolia, Los Angeles, California, USA.
⁴⁶ Banner Alzheimer's Institute and Banner Research, Phoenix, Arizona, USA.
⁴⁷ Arizona Alzheimer's Consortium, Phoenix, Arizona, USA.
⁴⁸ Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, New York, USA.
⁴⁹ Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, Texas, USA.
⁵⁰ Department of Microbiology, Immunology and Parasitology, School of Medicine, LSU Health Sciences Center, New Orleans, Louisiana, USA.
⁵¹ Department of Biochemistry & Molecular Biology, Howard University College of Medicine, Washington, DC, USA.
⁵² Department of Medicine, Burns School of Medicine, University of Hawaii, Manoa, Hawaii, USA.
⁵³ The Metro Health System, Cleveland, Ohio, USA.
⁵⁴ Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, Stanford University, Stanford, California, USA.
⁵⁵ Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA.
⁵⁶ Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah, USA.
⁵⁷ Geriatric Research, Education, and Clinical Center, Salt Lake City Veteran Affairs Health Care System, Salt Lake City, Utah, USA.
⁵⁸ RECOVER Patient Representative, Department of Sociology, Lamar University, Beaumont, Texas, USA.
⁵⁹ Department of Immunobiology, University of Arizona College of Medicine-Tucson, Tucson, Arizona, USA.
⁶⁰ Aegis Consortium for Pandemic-Free Future, University of Arizona Health Sciences, Tucson, Arizona, USA.

PMID: 40888500
DOI: 10.1111/jgs.70043

Age-Related Changes in the Clinical Picture of Long COVID

Mindy J Fain et al. J Am Geriatr Soc. 2025.

. 2025 Sep 1.

doi: 10.1111/jgs.70043. Online ahead of print.

Authors

Affiliations

¹ Arizona Center on Aging, University of Arizona College of Medicine-Tucson, Tucson, Arizona, USA.
² Division of General Internal Medicine, Geriatrics and Palliative Medicine, Department of Medicine, University of Arizona College of Medicine-Tucson, Tucson, Arizona, USA.
³ Intermountain Heart Institute, Intermountain Health, Salt Lake City, Utah, USA.
⁴ Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁵ Center for Healthcare Innovation and Delivery Science, NYU Langone Health, New York, New York, USA.
⁶ Departments of Medicine and of Population Health, NYU Grossman School of Medicine, New York, New York, USA.
⁷ Massachusetts General Hospital Biostatistics, Harvard University, Boston, Massachusetts, USA.
⁸ Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
⁹ Indiana University Center for Aging Research at the Regenstrief Institute, Indianapolis, Indiana, USA.
¹⁰ Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹¹ The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA.
¹² RECOVER Patient Representative, New York, New York, USA.
¹³ New England Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System; Division of Aging, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁴ MaineHealth Institute for Research, Scarborough, Maine, USA.
¹⁵ Center for Aging and Serious Illness, Division of Palliative Care and Geriatric Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹⁶ Department of Medicine and Cancer Center, Howard University College of Medicine, Washington, DC, USA.
¹⁷ Division of Geriatrics and Palliative Care, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA.
¹⁸ Department of Pathology and Cancer Center, Department of Biochemistry & Molecular Biology, Howard University College of Medicine, Washington, DC, USA.
¹⁹ Providence Medical Research Center, Spokane, Washington, DC, USA.
²⁰ Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²¹ University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
²² Biggs Institute of Alzheimer's & Neurodegenerative Disorders, Long School of Medicine, University of Texas Health Sciences Center, San Antonio, Texas, USA.
²³ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
²⁴ Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
²⁵ Medical Service, Jesse Brown VA Medical Center, Chicago, Illinois, USA.
²⁶ Department of Medicine, University of Illinois College of Medicine, Chicago, Illinois, USA.
²⁷ RECOVER Patient Advocate & Caregiver, Dysautonomia International, East Moriches, New York, USA.
²⁸ Institute for Systems Biology, Seattle, Washington, DC, USA.
²⁹ Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, Washington, DC, USA.
³⁰ Pulmonary Allergy, Critical Care and Sleep Medicine Emory University School of Medicine, Atlanta, Georgia, USA.
³¹ Division of Infectious Diseases, Departments of Internal Medicine and Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
³² Department of Medicine, VA Medical Center, University of California, San Francisco, California, USA.
³³ Department of Epidemiology and Biostatistics, UCSF, San Francisco, California, USA.
³⁴ Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
³⁵ ILLInet, University of Illinois Chicago, Chicago, Illinois, USA.
³⁶ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
³⁷ Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
³⁸ Department of Allergy and Infectious Disease, School of Medicine, University of Washington, Seattle, Washington, DC, USA.
³⁹ Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴⁰ RECOVER Patient Representative, Utah Covid-19 Long Haulers, Salt Lake City, Utah, USA.
⁴¹ Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
⁴² Division of Infectious Diseases, Department of Medicine, University of Texas Health Sciences Center, San Antonio, Texas, USA.
⁴³ Division of Infectious Diseases, Department of Medicine, UCSF School of Medicine, San Francisco, California, USA.
⁴⁴ Morehouse School of Medicine, Atlanta, Georgia, USA.
⁴⁵ RECOVER Patient Representative, Blooming Magnolia, Los Angeles, California, USA.
⁴⁶ Banner Alzheimer's Institute and Banner Research, Phoenix, Arizona, USA.
⁴⁷ Arizona Alzheimer's Consortium, Phoenix, Arizona, USA.
⁴⁸ Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, New York, USA.
⁴⁹ Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, Texas, USA.
⁵⁰ Department of Microbiology, Immunology and Parasitology, School of Medicine, LSU Health Sciences Center, New Orleans, Louisiana, USA.
⁵¹ Department of Biochemistry & Molecular Biology, Howard University College of Medicine, Washington, DC, USA.
⁵² Department of Medicine, Burns School of Medicine, University of Hawaii, Manoa, Hawaii, USA.
⁵³ The Metro Health System, Cleveland, Ohio, USA.
⁵⁴ Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, Stanford University, Stanford, California, USA.
⁵⁵ Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA.
⁵⁶ Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah, USA.
⁵⁷ Geriatric Research, Education, and Clinical Center, Salt Lake City Veteran Affairs Health Care System, Salt Lake City, Utah, USA.
⁵⁸ RECOVER Patient Representative, Department of Sociology, Lamar University, Beaumont, Texas, USA.
⁵⁹ Department of Immunobiology, University of Arizona College of Medicine-Tucson, Tucson, Arizona, USA.
⁶⁰ Aegis Consortium for Pandemic-Free Future, University of Arizona Health Sciences, Tucson, Arizona, USA.

PMID: 40888500
DOI: 10.1111/jgs.70043

Abstract

Background: This study evaluated the impact of aging on the frequency and prevalent symptoms of Long COVID, also termed post-acute sequelae of SARS-CoV-2, using a previously developed Long COVID research index (LCRI) of 41 self-reported symptoms in which those with 12 or more points were classified as likely to have Long COVID.

Methods: We analyzed community-dwelling participants ≥ 60 years old (2662 with prior infection, 461 controls) compared to participants 18-59 years (7549 infected, 728 controls) in the Researching COVID to Enhance Recovery adult (RECOVER-Adult) cohort ≥ 135 days post-onset.

Results: Compared to the Age 18-39 group, the adjusted odds of LCRI ≥ 12 were higher for the Age 40-49 group (odds ratio [OR] = 1.40, 95% confidence intervals [CI] = 1.21-1.61, p < 0.001) and 50-59 group (OR = 1.31, CI = 1.14-1.51, p < 0.001), similar for the Age 60-69 group (OR = 1.09, CI = 0.93-1.27, p = 0.299), and lower for the ≥ 70 group (OR = 0.68, CI = 0.54-0.85, p < 0.001). Participants ≥ 70 years had smaller adjusted differences between infected and uninfected symptom prevalence rates than those aged 18-39 for the following symptoms: hearing loss, fatigue, pain (including joint, back, chest pain and headache), post-exertional malaise, sleep disturbance, hair loss, palpitations, and sexual desire/capacity, making these symptoms less discriminating for Long COVID in older adults than in younger. Symptom clustering, as described in Thaweethai et al. (JAMA 2023) also exhibited age-related shifts: clusters 1 (anosmia and ageusia) and 2 (gastrointestinal, chronic cough and palpitations, without anosmia, ageusia or brain fog) were more likely, and clusters 3 (brain fog, but no loss of smell or taste) and 4 (a mix of symptoms) less likely to be found in older adults (relative risk ratios for clusters 3-4 ranging from 0.10-0.34, p < 0.001 vs. 18-39 year-olds).

Conclusions: Within the limits of this observational study, we conclude that in community-dwelling older adults, aging alters the prevalence and pattern of reported Long COVID.

Keywords: Long COVID; age prevalence; epidemiology; older adults; patient‐reported outcomes.

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References

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Age-Related Changes in the Clinical Picture of Long COVID

Affiliations

Age-Related Changes in the Clinical Picture of Long COVID

Authors

Affiliations

Abstract

References

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous