Determine the paths of post-COVID-19 situation development


A recent study published in International Journal of Infectious Diseases Analyze the evolution of the post-coronavirus disease 2019 (COVID-19) situation up to two years after its emergence.

Study: Trajectories of post-COVID-19 case progression, up to two years after onset of symptoms.  Image credit: AriyaJ /

Stady: Trajectories of post-COVID-19 case progression, up to two years after symptom onset. Image credit: AriyaJ /


Most individuals with SARS-CoV-2 infection recover from the disease. However, some report symptoms beyond 4-12 weeks after infection, a condition called prolonged COVID or post-COVID-19 condition.

The most common symptoms are fatigue, shortness of breath, altered sense of taste and smell, cognitive disturbances, and chest pain.

Most longitudinal studies have described the prevalence of symptomatic patients at specific time points after infection without identifying or defining distinct subgroups of patients.

Only a few studies have evaluated the heterogeneity of this condition, focusing on the presence of clusters of symptoms. Specifically, grouping was based on similarities in symptoms and patients’ clinical presentation rather than on evolution over time.

about studying

In this study, the researchers evaluated whether distinct evolutionary trajectories of the post-COVID-19 condition could be identified.

They obtained data from an electronic cohort of more than 50,000 French patients with chronic diseases, who were followed by self-reported outcomes or trial measurements. A long COVID group was created under this e-group in December 2020.

The team included all adults in the group who had suspected or confirmed COVID-19 and at least one of the 53 symptoms within three months of the onset of the disease for at least two months.

Individuals lacking a history of symptom onset were excluded. Participants were instructed to complete periodic questionnaires, and they reported a history of symptom onset.

Patients were considered to be in remission if they reported no symptoms in three consecutive questionnaires. The primary outcome was the COVID-19 Symptom Tool long score, which assessed 53 symptoms.

Latent layer mixed modeling was used to identify pathways in the development of symptoms over time. The robustness of the model was examined using the numerical sampling method.

the findings

The study included 2,197 long-term COVID patients, mostly female (79%), with an average age of 46. Most participants (90%) were enrolled before June 7, 2021, when SARS-CoV-2 Alpha was the dominant variant in France .

Patients were followed for an average of 291 days. Overall, 10,799 measurements were obtained. Seventy-seven patients reported reinfection; 141 patients were considered to be in remission.

The researchers observed three pathways — 1) persistently high symptoms, 2) a rapid decrease in symptoms, and 3) a slowly declining symptom. Ninety-four patients had high scores at onset of symptoms with little or no change in symptoms.

Those patients with severe persistent symptoms often reported bradycardia, tachycardia, palpitations, tachycardia, paresthesia, sweating, heat or cold intolerance, phonophobia, and photophobia within the first year of symptom onset. .

Daily relapses were reported by half of these patients, which were persistent 18 months after onset. Less than weekly relapses were reported by 4% and 10% of these subjects at symptom onset and 18 months after onset, respectively.

There were 104 patients with moderate onset symptoms who showed a reduction in symptoms. These people were more likely to report back pain, lower back pain, neck pain, and diarrhea in the first year of onset. Less than weekly relapses increased to 75% after 18 months.

Most participants (90.8%) with a low score showed slow improvement in symptoms over time. Fewer weekly relapses were reported in 11% and 30% of these patients at symptom onset and 18 months later, respectively. Results were similar for the subgroup of patients with laboratory-confirmed COVID-19.

Older individuals, current smokers, people with systemic disease, and those without functional disease were more likely to have very persistent symptoms than those with slowly declining symptoms.

Current smokers and those without a functional disease were more likely to have rapidly declining symptoms than those with slowly declining symptoms. Older patients and participants with systemic disease were less likely to have rapid symptom reduction.


Taken together, the researchers identified three pathways for post-COVID-19 condition development. Most patients (about 91%) showed a much slower improvement in symptoms over time.

Most subjects were recruited when a wild-type strain and an alpha variant were prevalent. Although few individuals were infected during an Omicron wave, no severe persistent symptoms developed.

Further studies should explore the association of these pathways with biological and clinical markers.


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