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Long-COVID recovery insight: Fatigue and cognitive deficits improve over two years

In a recent study published within the journal EClinicalMedicine, a team of scientists from Germany assessed the long-term trajectories of sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections comparable to cognitive deficits and fatigue and attempted to discover the danger aspects that would predict non-recovery from these sequelae.

Study: Predictors of non-recovery from fatigue and cognitive deficits after COVID-19: a prospective, longitudinal, population-based study. Image Credit: poor health.i / Shutterstock


Although worldwide vaccination efforts have successfully limited the transmission and severity of SARS-CoV-2 infections and lowered the morbidity and mortality related to the coronavirus disease 2019 (COVID-19) pandemic, long coronavirus disease (long-COVID) has emerged as a serious consequential health concern. Over 60 million COVID-19 patients are believed to suffer from long-COVID, with cognitive impairments and fatigue being probably the most common symptoms.

Roughly 26% of the long-COVID patients suffer from cognitive deficits, while fatigue impacts 19% of the patients, with each symptoms significantly affecting their overall quality of life and stopping the resumption of on a regular basis activities comparable to work and exercise.

Moreover, while electronic health records of long-COVID patients indicate that cognitive deficits are observed throughout the primary two years following a SARS-CoV-2 infection, the longitudinal information on fatigue is sparse. The few existing studies are totally on older patients with preexisting comorbidities, and the outcomes are conflicting, making it difficult to extrapolate these findings to the final population.

Concerning the study

In the current study, the researchers used data from the German National Pandemic Cohort Network to judge the trajectories of the 2 most prevalent long-COVID symptoms — cognitive deficits and fatigue — over a period of 18 months in 3,000 patients. They hypothesized that long-term follow-up would indicate a recovery from each symptoms in most patients.

The scientists also aimed to discover the danger aspects that would indicate non-recovery from cognitive deficits or fatigue following COVID-19, which might be used to predict recovery rates and make informed decisions on treating these conditions. The longitudinal, prospective, multicenter, population-based study included participants above the age of 18 years who tested positive for SARS-CoV-2 through a polymerase chain response (PCR) test.

Baseline assessments were conducted six months after the primary SARS-CoV-2 infection, and people with reinfections were excluded from the study. Assessments for follow-up were conducted a minimum of 18 months after the SARS-CoV-2 infection.

All participants were required to fill out a web-based questionnaire about fatigue, and people with symptoms that indicated post-COVID syndrome or long-COVID were invited for on-site appointments to undergo cognitive assessments. Matched controls were chosen based on the PCR test date, with 30% of the baseline participants and their matched controls being invited for in-person follow-ups.

The FACIT-Fatigue or Functional Assessment of Chronic Illness Therapy-Fatigue scale, which assesses 13 symptoms related to fatigue on a five-point scale, was used to measure one in all the first measures. Scores below the cut-off indicated recovery from fatigue, while those above the cut-off indicated persistent fatigue. The scores were used to further characterize fatigue severity.

The Montreal Cognitive Assessment was used to evaluate cognitive performance, with scores between 0 and 30 indicating severe to no cognitive deficits. Educational levels were considered while assessing these scores to account for learning deficits.


The outcomes showed that while cognitive deficits and fatigue were the 2 most prevalent long-COVID symptoms, these symptoms showed improvements over two years in near half the patients recovering from post-COVID syndrome. Moreover, depressive symptoms and headaches were risk aspects that predicted non-recovery from fatigue in the long run, while male sex, old age, and faculty education levels below 12 years were predictors of non-recovery from cognitive deficits.

In comparison with the pre-COVID-19 pandemic levels of fatigue, which were around 9%, clinically relevant fatigue was reported by 21% of the participants, indicating a major health burden because of fatigue within the post-pandemic period. Nonetheless, the fatigue scores were seen to enhance significantly after the follow-up period of 18 months to 2 years.

Psychological distress before the SARS-CoV-2 infection was regarded as linked to the persistence of fatigue since depressive symptoms were found to be one in all the numerous predictors of non-recovery from fatigue. Depressive symptoms and headaches could potentially be targeted for accurate diagnosis and targeted treatment of fatigue in long-COVID patients.


To summarize, the study investigated the long-term trajectories of fatigue and cognitive impairment, the 2 most prevalent long-COVID symptoms, in a longitudinal cohort of long-COVID patients.

The findings suggested that while each symptoms showed improvements over a span of two years in roughly 50% of the patients, specific risk aspects comparable to depressive symptoms and headache predicted non-recovery from fatigue in the long run. Old age and male sex were two of the danger aspects indicating non-recovery from cognitive deficits in long-COVID patients.

Journal reference:

  • Hartung, T. J., Bahmer, T., ChaplinskayaSobol, I., Deckert, J., Endres, M., Franzpötter, K., Geritz, J., Haeusler, K. G., Hein, G., Heuschmann, P. U., Hopff, S. M., Horn, A., Keil, T., Krawczak, M., Krist, L., Lieb, W., Maetzler, C., Montellano, F. A., Morbach, C., & Neumann, C. (2024). Predictors of nonrecovery from fatigue and cognitive deficits after COVID-19: a prospective, longitudinal, population-based study. EClinicalMedicine, 69.  DOI: 10.1016/j.eclinm.2024.102456,
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