In a study posted to The Lancet, researchers followed up individuals with long COVID (LC), which involves persistent symptoms beyond four weeks of a suspected or confirmed coronavirus disease 2019 (COVID-19) infection, throughout a longitudinal study. They found that more than half of these patients switched between different levels of clinical severities during the study period.
Study: Long Covid Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation
*Important notice: Preprints with The Lancet / SSRN publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Background
Researchers estimate that 1.9 million people in the UK and more than 200 million people worldwide have LC, but it is still not well understood. LC is thought to affect 10 organ systems and is associated with 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 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) so that clinicians could understand how patients experience this condition. They score their overall health (OH), functional disability (FD), and symptom severity (SS).
A study on hospitalized LC patients found that they experienced impairment of varying severities and reported experiencing, on average, nine symptoms persistently even five months after they were discharged. Another cross-sectional assessment found that some patients who were not hospitalized also experienced severe cases of LC. However, whether the severity of LC fluctuated over time and if there were correlations between the three domains of the C19-YRS.
About the study
In the present 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 did not require a positive test result, as tests were not widely available at the beginning of the pandemic. Participants were receiving treatment for LC from recognized LC services and showed symptoms that another diagnosis could not explain. In addition, all participants were registered on the same medical platform and asked to complete 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 daily activities. In addition to the OH, FD, and SS domains, participants also listed any other symptoms they had experienced the previous week. Researchers analyzed this data using Spearman correlations, heat maps, cluster analysis, and polychoric factor analysis and assessed intra-patient agreement using Kendall's kappa and tau.
Key findings
The first round of assessments was completed by 759 patients, of whom 69.4% were females. However, 47% or 356 individuals completed the second round, of whom 68% were females. On average, participants took the second assessment 16.2 days after the first. Most patients were Caucasian (74%) and were 46.8 years old on average.
Slightly over half had never smoked. More than half were on sick leave, had reduced their working hours, or made changes to their employment because of LC. The median participant had experienced symptoms for nearly a year during the first assessment.
Researchers observed three distinct types of clinical severity in their study population, of whom two showed 'mild' and 'severe' dysfunction and symptomatology, and a third 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 analysis found that 41% of participants showed different types of clusters of FD and SS in terms of severity. Slightly under half of the patients fell in the same category of SS and FD in the second assessment as they had in the first, indicating that many participants experienced a change in the severity of their symptoms. On the other hand, although OH remained stable for most patients, approximately one-third experienced OH changes between assessments. The polychoric factor analysis showed that a single underlying factor explained 41-45% of the variance in the SS subscale and 60-62% of the variance in the FD subscale.
Conclusions
This study's findings show how symptoms experienced by more than half of LC patients can fluctuate over time, which has significant implications for healthcare interventions and self-management. The co-existence of different severity types for most 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 care for moderate and severe cases. Such interventions should consider the dynamic and fluctuating nature of LC symptoms.
"Long COVID should be assessed and evaluated in the light of the fluctuant nature of the condition and not necessarily assumed always to have the same 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 possibility of inequalities in the healthcare system. Other challenges included the fact that more than half of the participants did not complete their second assessment and the inherent subjectivity of self-reported data. Further study can yield valuable insights into LC and how it can be managed effectively.
*Important notice: Preprints with The Lancet / SSRN publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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