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

In a recent study published in 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 such as cognitive deficits and fatigue and attempted to identify the risk factors that could 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: p.ill.i / ShutterstockStudy: Predictors of non-recovery from fatigue and cognitive deficits after COVID-19: a prospective, longitudinal, population-based study. Image Credit: p.ill.i / Shutterstock

Background

Although worldwide vaccination efforts have successfully limited the transmission and severity of SARS-CoV-2 infections and lowered the morbidity and mortality associated with 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 the most common symptoms.

Approximately 26% of the long-COVID patients suffer from cognitive deficits, while fatigue impacts 19% of the patients, with both symptoms significantly affecting their overall quality of life and preventing the resumption of everyday activities such as work and exercise.

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

About the study

In the present study, the researchers used data from the German National Pandemic Cohort Network to evaluate the trajectories of the two 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 both symptoms in most patients.

The scientists also aimed to identify the risk factors that could indicate non-recovery from cognitive deficits or fatigue following COVID-19, which could 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 reaction (PCR) test.

Baseline assessments were conducted six months after the first SARS-CoV-2 infection, and those 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 an online questionnaire about fatigue, and those with symptoms that indicated post-COVID syndrome or long-COVID were invited for on-site appointments to undergo cognitive assessments. Matched controls were selected 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 of the primary 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 assess 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.

Results

The results showed that while cognitive deficits and fatigue were the two most prevalent long-COVID symptoms, these symptoms showed improvements over two years in close to half the patients recovering from post-COVID syndrome. Furthermore, depressive symptoms and headaches were risk factors that predicted non-recovery from fatigue in the long term, while male sex, old age, and school education levels below 12 years were predictors of non-recovery from cognitive deficits.

Compared to the pre-COVID-19 pandemic levels of fatigue, which were around 9%, clinically relevant fatigue was reported by 21% of the participants, indicating a significant health burden due to fatigue in the post-pandemic period. However, the fatigue scores were seen to improve significantly after the follow-up period of 18 months to two years.

Psychological distress before the SARS-CoV-2 infection was thought to be linked to the persistence of fatigue since depressive symptoms were found to be one of the significant 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.

Conclusions

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

The findings suggested that while both symptoms showed improvements over a span of two years in approximately 50% of the patients, specific risk factors such as depressive symptoms and headache predicted non-recovery from fatigue in the long term. Old age and male sex were two of the risk factors 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, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00035-X/fulltext
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

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