In a study published in The Lancet, researchers followed people with long COVID (LC), which includes persistent symptoms beyond four weeks of suspected or confirmed coronavirus 2019 (COVID-19) infection, throughout a longitudinal study. They found that more than half of these patients switched between different levels of clinical severity during the study period.
Study: Clinical subtypes of long-term Covid severity based on symptoms and functional disability: A longitudinal assessment
*Important note: Preprints with The Lancet / SSRN publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered definitive, guide clinical practice/health-related behavior or be treated as established information.
Record
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 shortness of breath, pain, fatigue, dizziness, sleep problems, anxiety, depression, allergic reactions, skin rashes and post-traumatic stress. Cognitive problems or “brain fog” is the most well-known symptom of LC.
In UK-based clinical studies, patients were asked to record their symptoms on the Yorkshire COVID-19 Recovery Scale (C19-YRS) so that clinicians could understand how patients were experiencing this condition. They rate their overall health (OH), functional disability (FD) and symptom severity (SS).
A study of hospitalized LC patients found that they experienced impairment of varying severity and reported experiencing, on average, nine symptoms persisting even five months after discharge. Another cross-sectional review found that some patients who were not hospitalized also experienced severe LC events. However, whether the severity of LC varied over time and whether there were correlations between the three domains of the C19-YRS.
About the study
In the present longitudinal study, the researchers aimed to investigate variations in clinical severity between two assessments and to describe the linear relationship between OH, FD, and SS. The study included participants who had been diagnosed with LC but did not require a positive test result, as tests were not widely available at the start of the pandemic. Participants were receiving treatment for LC from recognized LC services and experienced symptoms that could not be explained by another diagnosis. In addition, all participants were enrolled in the same medical platform and were 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 in the previous week. The researchers analyzed these data using Spearman correlations, heat maps, cluster analysis, and multivariate factor analysis, and assessed agreement between patients using kappa and Kendall’s tau.
Important findings
The first round of assessments was completed by 759 patients, of whom 69.4% were women. However, 47% or 356 people completed the second round, of which 68% were women. On average, participants took the second assessment 16.2 days after the first. Most patients were Caucasian (74%) and had a mean age of 46.8 years.
Just over half had never smoked. More than half were on sick leave, had reduced work hours, or made changes in their employment due to LC. The median participant had experienced symptoms for almost a year at the time of the first assessment.
The researchers observed three different types of clinical severity in their study population, of which two exhibited “mild” and “severe” dysfunction and symptomatology, and the third was classified as “moderate.” The moderate group had, on average, high scores for symptoms such as fatigue and post-exercise malaise (PEM) but low scores for smell and cough and moderate scores for other symptoms.
Within-patient concordance analysis found that 41% of participants exhibited different types of FD and SS clusters in terms of severity. Just under half of the patients were in the same SS and FD category at the second assessment as at 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. Multivariate factor analysis indicated 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
The findings of this study show how the symptoms experienced by more than half of LC patients can fluctuate over time, which has important implications for health care interventions and self-management. The coexistence of different types of severity for most symptoms suggests common underlying mechanisms for LC, including immune activation, immune dysregulation, endothelial damage, viral persistence, and dysautonomia.
Classifying LC conditions as mild, moderate, and severe may 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 take into account the dynamic and fluctuating nature of LC symptoms.
“Long-term COVID should be assessed and evaluated in light of the fluctuating nature of the condition and not necessarily assumed to always have the same type or severity of symptoms.”
Despite these important findings, the authors acknowledge some limitations regarding their study population. The predominantly Caucasian sample of female patients highlights the potential for disparities in the health care 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 may provide valuable insights into LC and how it can be effectively managed.
*Important note: Preprints with The Lancet / SSRN publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered definitive, guide clinical practice/health-related behavior or be treated as established information.
