15/09/2023

It is estimated that over 5-10% of individuals who have survived COVID-19 experience a post-viral syndrome known as post-COVID-19 condition (PCC), post-acute COVID-19 sequelae (PACS), or "Long COVID”. PCC encompasses a range of persistent, incapacitating symptoms and medical issues that frequently result in physical, social, and psychological impairment, significantly affecting the quality of life for patients. Up to date it remains uncertain whether PCC represents a singular entity or a diverse syndrome with shared underlying pathophysiological factors. 

As stated by this study authors: “Uncertainties around the pathophysiology of this syndrome, the lack of effective treatments, and the absence of validated biomarkers, force PCC to be identified and managed using clinical definitions that are useful but imprecise”. Few prospective observational studies have been conducted to study the implications and evolution  of PCC, and none of them have still clarify the long-term clinical implications of this syndrome, in particular the rate of recovery, which remains unknown. 

The US RECOVER study, a large cross-sectional study, introduced an operational definition for PCC through a symptom score grading system. Additionally, researchers categorized subjetcs into four distinct clusters based on their predominant symptoms, specifically related to changes in smell/taste, post-exertional malaise, cognitive difficulties, and a combination of palpitations and gastrointestinal symptoms. Notably, there was a substancial overlap and a gradual accumulation of symptoms across the four clusters.

In this context, the Spanish team aimed at characterized the clinical presentation and 2-year evolution of PCC, specially focusing on trying to establish the factors associated with its  onset and recovery. This observational prospective cohort study included 548 participants  from the Long COVID Unit of the Department of Infectious Diseases at the Hospital Germans Trias i Pujol in Badalona, known for being the most important monographic Long COVID Unit in Spain. As an inclusion criteria, all participants must have previously been exposed to SARS-CoV-2. 341 participants were diagnosed with PCC and 207) without it, following the WHO criteria. After recruitment, information such as demogragraphic data, comorbidities present at acute COVID-19 onset, and the characteristics of the acute COVID-19 episode were collected. The participants were them visited at moths 3, 6, 12, 18 and 24, where assessment of symptoms was carried out through questionaries. 

The authors stated “In our study, we found that preexisting medical conditions, including several comorbidities, socioeconomic factors like the educational level, as well as specific symptoms during acute COVID-19 presentation, predicted both the development of and recovery from the PCC”. Indeed, after the statistical analysis (unsupervised clustering analysis), in the model with the best fit, male subjects with tertiary education were found to have a lower likelihood of developing PCC. Conversely, a history of headaches or the presence of symptoms like tachycardia, fatigue, neurocognitive and neurosensitive complaints, as well as dyspnea at the time of COVID-19 diagnosis, were predictive factors for the development of "Long COVID". Consistent with the findings of the RECOVER study, the cluster analysis uncovered the existence of three distinct symptom clusters, in which predominant persistent symptoms displayed an accumulating pattern. 

The findings of the Spanish prospective observational study, together with the available evidence, contribute to clarify the possible common structure of PCC, despite the heterogeneous presentation at the individual level. “Although the PCC has a heterogeneous presentation at the individual level, the pattern of the observed subphenotypes likely reflects the additive severity of a single, multisystemic, multifaceted post-viral disease rather than different pathogenically-independent subsyndromes”, as stated by the study authors. 

Notably, only 7.6% of the particiants recovered from the PCC during the 2-year follow-up period. Most of the subjects who recovered belonged to the first cluster of symptoms, composed of individuals presenting predominantly with fatigue rather than other more complex symptoms. Regrettably, the limited chances of recovering from PCC within the initial two years emphasize that, as long as SARS-CoV-2 transmissions persist and few individuals achieve a cure, the number of subjects with PCC will continue to rise.  

Reference:

[1] Mateu L, Tebe C, Loste C et al. Determinants of the onset and prognosis of the post-COVID19 condition: a 2-year prospective observational cohort study. The Lancet Regional Health - Europe. 2023:100724. doi: https://doi.org/10.1016/j.lanepe.2023.100724 

Autor: Eduardo Martin Ruiz