Post‑COVID‑19 Syndrome in Outpatients: a Cohort Study

Abstract

Background: After mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed.

Objectives: To characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors.

Participants: Outpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative).

Design: Monocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics.

Main measures: Data of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey.

Key results: The study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16), and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms.

Conclusions: More than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.

Keywords: Post-COVID-19 syndrome; Post-acute COVID-19 syndrome; obesity.

Fig. 1

Study flow-chart

Fig. 2

Proportions of patients with long-term symptoms at the time of the phone survey. (A) Comparison between COVID-positive (positive SARS-CoV-2 RT-PCR) and COVID-negative (negative SARS-CoV-2 RT-PCR); (B) comparison between COVID-positive surveyed during three different period: period 1— > 3 to 5 months after SARS-CoV-2 diagnosis; period 2— > 5 to 7 months after SARS-CoV-2 diagnosis; period 3— > 7 to 10 months after SARS-CoV-2 diagnosis. Data are shown as proportions (%) with 95% confidence intervals

Fig. 3

Factors associated with the presence of selected long-term symptoms (fatigue, smell or taste disorder, dyspnea, and memory impairment) during the phone survey in COVID-positive patients. Selected symptoms are those associated with COVID status. Multivariable analysis adjusted for age, gender, smoking, overweight/obesity, diabetes, asthma, hypertension, cancer, cardiovascular disease, chronic inflammatory disease, period of the phone survey. Adjusted odds ratio for age indicates the risk of fatigue, smell/taste disorder, dyspnea, or memory impairment per 5-year age increase. aOR: adjusted odds ratio; CI: confidence interval. *p < 0.05