About half of adults with likely long COVID 12 months following their initial COVID-19 infection may experience sustained symptom improvement by 36 months, but just one-quarter may have complete resolution of symptoms.
Investigators analyzed data from the RECOVER-Adult cohort, a prospective observational study conducted at 83 sites across the United States. The primary analysis included 1,019 adults who met criteria for likely long COVID 12 months following their first infection, defined by a Long COVID Research Index (LCRI) score of at least 11. Participants completed symptom assessments at 3-month intervals. Additional analyses included 1,283 participants with likely long COVID at 18 months and 1,488 at 24 months following infection.
The primary outcome was time to sustained improvement, defined as an LCRI score below 11 at 2 consecutive visits. Secondary outcomes included a reduction of at least 50% in LCRI score accompanied by self-reported quality of life rated as good or better, and an LCRI score of 0. The investigators estimated cumulative probabilities of improvement and examined differences by age, sex, infection period, and symptom subtype, adjusting for demographic and clinical characteristics.
Among participants with likely long COVID at 12 months, the estimated cumulative probability of sustained improvement was 36% by 24 months and 50% by 36 months. The median time to meet the primary outcome was 36 months.
Using the secondary definition of improvement, 41% of participants achieved at least a 50% reduction in symptom score accompanied by good or better quality of life by 24 months, increasing to 56% by 36 months. Complete resolution of symptoms occurred in an estimated 15% by 24 months and 27% by 36 months.
After adjustment, the estimated probability of meeting the primary outcome by 36 months was 60% among participants with predominantly smell or taste disturbances vs. 19% among those with multisystem symptoms. Corresponding probabilities were 55% among participants with chronic cough–predominant symptoms, 49% among those with brain fog–predominant symptoms, and 44% among those with palpitations-predominant symptoms.
Age and COVI-19 infection period wereassociated with differences in improvement. The adjusted probability of meeting the primary outcome by 36 months was 51% among participants aged 18 to 45 years vs. 40% among those aged 46 to 64 years and 44% among those aged 65 years or older.
Participants initially infected during the Omicron period had a higher adjusted probability of improvement compared with those infected during the pre-Omicron period (48% vs. 36%). Improvement probabilities were similar between female and male participants.
Additional analyses of participants who continued to meet criteria for likely long COVID at 18 or 24 months showed similar patterns of improvement. However, estimated improvement probabilities were slightly lower in the 24-month cohort. The investigators cautioned that the cohorts included overlapping but nonidentical populations and could not be directly compared.
The study had several limitations. Participants were selected based on meeting criteria for likely long COVID at specific time points, limiting the generalizability of findings to all patients with a history of COVID-19 infection. The symptom-based classification could not establish whether all reported symptoms were attributable to infection. The observational design prevented causal conclusions about factors associated with improvement, and treatments received during follow-up were not evaluated. Missing follow-up assessments also required statistical imputation. The primary outcome indicated improvement below the threshold for likely long COVID rather than complete symptom resolution.
“These findings underscore both the potential for natural recovery and the urgent need for placebo-controlled therapeutic intervention trials,” wrote lead study author Harrison T. Reeder, PhD, of Massachusetts General Hospital, and colleagues.
Full disclosures of the study authors can be found in the study.
Source: Annals of Internal Medicine
