Age-Related Changes in the Clinical Picture of Long COVID, 2025, Fain, Hornig et al

[Wyva]

Spoiler: authors

Mindy J. Fain, Benjamin D. Horne, Leora I. Horwitz, Tanayott Thaweethai, Meredith Greene, Mady Hornig, Ariela R. Orkaby, Clifford Rosen, Christine S. Ritchie, Hassan Ashktorab, Nina Blachman, Hassan Brim, Sarah Emerson, Nathan Erdmann, Kristine M. Erlandson, Gabriel de Erausquin, Tamara Fong, Linda N. Geng, Howard S. Gordon, Jacqueline Rutter Gully, Jennifer Hadlock, Jenny Han, Weixing Huang, Prasanna Jagannathan, J. Daniel Kelly, Jonathan D. Klein, Jerry A. Krishnan, Emily B. Levitan, Grace A. McComsey, Dylan McDonald, Aoyjai P. Montgomery, Lisa O'Brien, Ighovwerha Ofotokun, Thomas F. Patterson, Michael J. Peluso, Priscilla Pemu, Alice Perlowski, Eric M. Reiman, Martine Sanon, Sudha Seshadri, Judd Shellito, Zaki A. Sherif, Cecilia Shikuma, Nora G. Singer, Upinder Singh, Joel D. Trinity, Juan Wisnivesky, Margot Gage Witvliet, Andrea Foulkes, Janko Ž. Nikolich, on behalf of the RECOVER consortium

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.

Paywall: https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.70043

 

[Wyva]

Paper suggested by @Yann04

 

[Yann04]

I thought this severity stratification by age group was interesting. (1 is mild illness 4 is severe illness).

 

[Utsikt]

I thought this severity stratification by age group was interesting. (1 is mild illness 4 is severe illness).

Huh. So less severe illness the older they are. I wonder why that is. Maybe the more severe simply die sooner of various causes, so survivorship bias causes the appearance of better outcomes at older ages?

 

[Yann04]

Huh. So less severe illness the older they are. I wonder why that is. Maybe the more severe simply die sooner of various causes, so survivorship bias causes the appearance of better outcomes at older ages?

Maybe but this is long covid so there’s not that much time.

 

[Mij]

The older more severe died earlier from Covid infection?

 

[SNT Gatchaman]

The paper discusses the possible explanations —

There are several potential explanations for our finding that Long COVID is less prevalent in older adults. First, older people who survive (or have less severe) acute COVID-19 may genuinely be at lower biologic risk. This may be a function of the competing risk of death; that is, the sicker people with acute COVID-19 died, leaving a healthier group that survived, who may also be at lower risk not only of severe acute COVID-19 but also Long COVID.

Second, the reduction in innate immune response with aging may be protective if Long COVID is primarily an immune-mediated phenomenon. Younger people have been shown to be at high risk of health effects past the acute stage of infection with other pathogens. For example, Epstein–Barr virus has been closely linked in some younger individuals to the development of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS; peak incidence ages 10–19 and 30–39 years). That predisposition could be linked to immune system changes with aging, which could influence the prevalence and presentation of Long COVID in older adults in several ways.

Age-related reduced immunity to SARS- CoV-2 could lead to prolonged persistence of the virus and/or its components, potentially facilitating and/or extending their stimulation of direct or indirect (via stimulation of host defense mechanisms) pathogenesis. On the other hand, reduced immunity and inflammation could potentially mitigate those immunopathogenic processes that depend on exuberant immune and/or inflammatory host responses. Our results are consistent with the latter scenario.

Further, it is possible that older people have an altogether different form of Long COVID that is not captured by our symptom survey or by the LCRI [Long Covid Research Index].

It is also possible that older adults under-report symptoms, leading to misclassification. For example, a participant might consider symptoms to be a normal part of the aging process rather than a consequence of SARS- CoV-2 infection, or symptoms of age-related chronic conditions and/or medications. This suggests that the questionnaire may not have been attuned to older adults. Additionally, some older adults may have unrecognized cognitive impairment, potentially making the survey responses less reliable.

 

[Evergreen]

Is it just me or is the title and framing off? They didn't look at "age-related changes", they looked at "age-related differences". They didn't look at the "impact of aging", they looked at the impact of "age".

To look at the impact of aging they'd have to follow people over time and see what happened. Ditto for changes.