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Study finds long-COVID symptoms fluctuate over time, difficult treatment approaches

In a study posted to The Lancet, researchers followed up individuals with long COVID (LC), which involves persistent symptoms beyond 4 weeks of a suspected or confirmed coronavirus disease 2019 (COVID-19) infection, throughout a longitudinal study. They found that greater than half of those patients switched between different levels of clinical severities in the course of the study period.

Study: Long Covid Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation

*Necessary notice: Preprints with The Lancet / SSRN publishes preliminary scientific reports that aren’t peer-reviewed and, subsequently, shouldn’t be considered conclusive, guide clinical practice/health-related behavior, or treated as established information.


Researchers estimate that 1.9 million people within the UK and greater than 200 million people worldwide have LC, nevertheless it remains to be not well understood. LC is believed to affect 10 organ systems and is related to 200 symptoms, including breathlessness, pain, fatigue, dizziness, sleep problems, anxiety, depression, allergic reactions, skin rashes, and post-traumatic stress. Cognitive problems or ‘brain fog’ are essentially the most well-known symptom of LC.

In UK-based clinical studies, patients were asked to record their symptoms on the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) in order that clinicians could understand how patients experience this condition. They rating their overall health (OH), functional disability (FD), and symptom severity (SS).

A study on hospitalized LC patients found that they experienced impairment of various severities and reported experiencing, on average, nine symptoms persistently even five months after they were discharged. One other cross-sectional assessment found that some patients who weren’t hospitalized also experienced severe cases of LC. Nevertheless, whether the severity of LC fluctuated over time and if there have been correlations between the three domains of the C19-YRS.

Concerning the study

In the current longitudinal study, researchers aimed to explore fluctuations in clinical severity between two assessments and describe the linear relationship between OH, FD, and SS. The study included participants diagnosed with LC but didn’t require a positive test result, as tests weren’t widely available at the start of the pandemic. Participants were receiving treatment for LC from recognized LC services and showed symptoms that one other diagnosis couldn’t explain. As well as, all participants were registered on the identical medical platform and asked to finish modified C19-YRS forms every three months.

The modified C19-YRS form contained 17 items to measure LC symptoms and their impact on overall health and day by day activities. Along with the OH, FD, and SS domains, participants also listed some other symptoms they’d experienced the previous week. Researchers analyzed this data using Spearman correlations, heat maps, cluster evaluation, and polychoric factor evaluation and assessed intra-patient agreement using Kendall’s kappa and tau.

Key findings

The primary round of assessments was accomplished by 759 patients, of whom 69.4% were females. Nevertheless, 47% or 356 individuals accomplished the second round, of whom 68% were females. On average, participants took the second assessment 16.2 days after the primary. Most patients were Caucasian (74%) and were 46.8 years old on average.

Barely over half had never smoked. Greater than half were on sick leave, had reduced their working hours, or made changes to their employment due to LC. The median participant had experienced symptoms for nearly a 12 months in the course of the first assessment.

Researchers observed three distinct varieties of clinical severity of their study population, of whom two showed ‘mild’ and ‘severe’ dysfunction and symptomatology, and a 3rd were classified as ‘moderate.’ The moderate group had, on average, high scores for symptoms like fatigue and post-exertional malaise (PEM) but low scores for smell and cough and moderate scores for other symptoms.

The intra-patient agreement evaluation found that 41% of participants showed several types of clusters of FD and SS when it comes to severity. Slightly below half of the patients fell in the identical category of SS and FD within the second assessment as they’d in the primary, indicating that many participants experienced a change within the severity of their symptoms. However, although OH remained stable for many patients, roughly one-third experienced OH changes between assessments. The polychoric factor evaluation showed that a single underlying factor explained 41-45% of the variance within the SS subscale and 60-62% of the variance within the FD subscale.


This study’s findings show how symptoms experienced by greater than half of LC patients can fluctuate over time, which has significant implications for healthcare interventions and self-management. The co-existence of various severity types for many symptoms indicates common underlying mechanisms for LC, including immune activation, immune dysregulation, endothelial damage, viral persistence, and dysautonomia.

Classifying LC conditions as mild, moderate, and severe can improve patient interventions. The authors recommend monitoring mild cases through primary care services and providing specialist look after moderate and severe cases. Such interventions should consider the dynamic and fluctuating nature of LC symptoms.

“Long COVID must be assessed and evaluated in the sunshine of the fluctuant nature of the condition and never necessarily assumed at all times to have the identical type or severity of the symptoms.”

Despite these significant findings, the authors acknowledge certain limitations concerning their study population. The predominantly Caucasian female patient sample highlights the potential for inequalities within the healthcare system. Other challenges included the incontrovertible fact that greater than half of the participants didn’t complete their second assessment and the inherent subjectivity of self-reported data. Further study can yield invaluable insights into LC and the way it might be managed effectively.

*Necessary notice: Preprints with The Lancet / SSRN publishes preliminary scientific reports that aren’t peer-reviewed and, subsequently, shouldn’t be considered conclusive, guide clinical practice/health-related behavior, or treated as established information.

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