Study population characteristics
The study population was composed of 51.5% of women, mean age was 41.6 years (± 12.6), and mean BMI was 25.1kg/m2 [16.7,55.1]. Thirty-two percent of the participants took at least one regular treatment and 6.3% had at least 2 comorbidities prior COVID-19 infection.
The most frequent treatments were anti-hypertensive (10.4%), antibiotics (10.4%), and anti-cholesterol (7.4%).
Total symptom score trajectories
Based on the lowest BIC and the highest entropy, the optimal number of total score trajectories was identified as 2 (see Supplementary table 1, additional file 1).
The total score trajectories were named according to their characteristics: T1, mild symptoms, fast resolution, and T2, elevated and persisting symptoms. The trajectories are presented in Fig. 1.
Total symptom score evolution in T1 “Mild symptoms, fast resolution”, and T2 “Elevated and persisting symptoms”, from baseline up to 24 months after (in days).
The grey areas show the 95% confidence intervals.
The number of participants in each trajectory was 376/555 (67.7%) in T1 and 179/555 (32.3%) in T2. Participants in the T2 “Elevated and persisting symptom” trajectory were more frequently female (61.5% vs 46.8%), had a higher BMI (26.3 vs 24.7), were older (44 vs 40.5 years), had more frequently more than 2 comorbidities (10.6% vs 4.3%), and took more frequently at least 1 chronic medication (44.7% vs 26.3%) than participants in the T1 “Mild symptoms, fast resolution” trajectory.
Participants characteristics in total study population and in each trajectory are summarized in table 1.
The main determinants of experiencing a T2 “Elevated and persisting symptoms” trajectory were older age, being a female, higher BMI, multi comorbidities, diabetes, hypertension, the number and type of chronic medications (for pain, diabetes in particular) (see Fig. 2).
When exploring symptom frequencies at each time point in the 2 trajectories we observed that fatigue, cough and fever were the most frequent symptoms at baseline in both trajectories. Symptom frequencies decreased in T1 from baseline until M24, at various speeds. In particular, fatigue decreased more slowly than couch or fever. In T2, fatigue, pain-related symptoms (chest pain, myalgia), shortness of breath, and conjunctivitis frequencies increased between baseline and M12 and remained elevated until M24. Cough frequency decreased between baseline and M12, and increased again between M15 and M24. Symptom frequencies in both trajectories are shown in Fig. 3.
Symptom frequencies are provided for each trajectory at baseline, M12, M15, and M24 (%).
Individual symptom trajectories
Individual symptom trajectories from baseline up to M24 were also identified and are summarized in Fig. 4. Briefly, some symptoms evolved following 2 trajectories, one trajectory remaining at a low level and the other one increasing over time (chest pain, conjunctivitis, shortness of breath, myalgia, rash and cough). Diarrhea and sore throat evolved following 3 trajectories, one being low, one increasing and one decreasing. Fever and fatigue had particular patterns of evolution. Fever followed 2 trajectories, one including participants with low level and the other one with fever decreasing in a fast way after baseline.
Fatigue was the most complex symptom in terms of individual trajectories as we identified 4 different trajectories: one with half of the participants experiencing low level of fatigue, but with a slight increase over time, the second trajectory with initial low level of fatigue but increasing and remaining at a high level until M24, the third one with initial high level of fatigue but decreasing rapidly over time, and the last one with fatigue being highly present from baseline until M24. Individual characteristics of participants in the 4 fatigue trajectories are provided in supplementary table 2 (see additional file 2).
Individual symptom trajectories were modelled for the 555 participants from baseline until month 24 (in days)
Sensitivity analysis
The trajectories obtained on 84 participants with complete data at each timepoint were similar to those obtained on the population of 555 participants described above (See supplementary Fig. 1, additional file 3).
We also described the quality of life of 138 participants who completed the month 24 questionnaire, in the total population and in the 2 trajectories. In brief, participants in the T2 “Elevated and persisting symptoms” trajectory had higher stress, fatigue and anxiety levels, and were more likely to experience poor sleep quality and poor respiratory quality of life than participants in the T1 “Mild symptoms, fast resolution” trajectory. They also less frequently recovered a similar life rhythm and professional activity as before SARS-CoV-2 infection, and they were more likely to experience a worsening of their relationships with their family or friends (see Table 2).
The percentage of participants above the cut-off in each of the PSS4, FSS9, GAD7, PSQI and VQ11 scales is summarized in Fig. 5 and shows a degradation of these 5 indicators in participants from the T2 “Elevated and persisting symptoms” trajectory.
Radar diagram showing the percentage of participants with high levels of fatigue, stress, anxiety and with poor sleep and respiratory quality of life in each trajectory using the specific cut-off score of each scale.
The viral load was measured in nasopharyngeal swabs from 172 participants, collected during the study inclusion visit taking place within 5 days after the initial confirmation of infection. Among them, 145 (84.3%) still had detectable levels of viral RNA, and 129 (75%) had a measurable viral load. Viral RNA levels were below LoQ cut-off for 16 participants preventing viral load calculation.
The median viral load at baseline was 1.2E6 [1.4E3,1.8E9] RNA copies/ml in the entire cohort, and was higher in T2 than in T1 (2.6E6 [1.5E3,1.8E9] and 9.3E5[1.4E3,1.3E9] RNA copies/ml respectively ; p = 0.139).