The chronification of post-COVID condition associated with neurocognitive symptoms, functional impairment and increased healthcare utilization

Abstract

Post-COVID condition is prevalent in 10-35% of cases in outpatient settings, however a stratification of the duration and severity of symptoms is still lacking, adding to the complexity and heterogeneity of the definition of post-COVID condition and its oucomes. In addition, the potential impacts of a longer duration of disease are not yet clear, along with which risk factors are associated with a chronification of symptoms beyond the initial 12 weeks. In this study, follow-up was conducted at 7 and 15 months after testing at the outpatient SARS-CoV-2 testing center of the Geneva University Hospitals. The chronification of symptoms was defined as the continuous presence of symptoms at each evaluation timepoint (7 and 15 months). Adjusted estimates of healthcare utilization, treatment, functional impairment and quality of life were calculated. Logistic regression models were used to evaluate the associations between the chronification of symptoms and predictors. Overall 1383 participants were included, with a mean age of 44.3 years, standard deviation (SD) 13.4 years, 61.4% were women and 54.5% did not have any comorbidities. Out of SARS-CoV-2 positive participants (n = 767), 37.0% still had symptoms 7 months after their test of which 47.9% had a resolution of symptoms at the second follow-up (15 months after the infection), and 52.1% had persistent symptoms and were considered to have a chronification of their post-COVID condition. Individuals with a chronification of symptoms had an increased utilization of healthcare resources, more recourse to treatment, more functional impairment, and a poorer quality of life. Having several symptoms at testing and difficulty concentrating at 7 months were associated with a chronification of symptoms. COVID-19 patients develop post-COVID condition to varying degrees and duration. Individuals with a chronification of symptoms experience a long-term impact on their health status, functional capacity and quality of life, requiring a special attention, more involved care and early on identification considering the associated predictors.

Figure 1

Flowchart with 1383 participants included out of 2923 who had a follow-up at 7 and 15 months. Out of the 1383 participants, 767 were SARS-CoV-2 positive and 616 were SARS-CoV-2 negative.

Figure 2

Adjusted frequency estimates of utilization of healthcare resources since test date, stratified by SARS-CoV-2 infection and duration of symptoms, including infected individuals without post-COVID condition, with post-COVID condition without a chronification of symptoms and with a chronification of symptoms (n = 1383). Healthcare utilization was defined as the presence of any of the visits to the primary care physician, the emergency room or other specialists since the test date. Chronification of symptoms was defined as the continuous persistence of symptoms, present at 7 and 15 months of follow-up. Symptoms defining the persistence of symptoms were any new symptom onset after SARS-CoV-2 infection including: fatigue, insomnia, headache, dyspnea, chest pain, palpitations, dizziness, difficulty concentrating, paresthesia, loss or change in smell, loss or change in taste, generalized pain, myalgia, arthralgia, fever, cough, digestive symptoms (nausea, vomiting, diarrhea, constipation, abdominal pain), and hair loss. Estimates were adjusted for age, sex, physical activity, smoking status, vaccination status, hospitalization, self-rated health prior to testing, symptoms at testing and the following comorbidities: obesity or overweight, hypertension, diabetes, respiratory disease, cardiovascular disease, headache disorders, cognitive disorders, sleep disorders, depression, anxiety, hypothyroidism, rheumatologic disease, anemia, chronic pain or fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome.

Figure 3

Associations between predictors and chronification of symptoms in SARS-CoV-2 positive individuals with post-COVID condition (n = 284). Individuals who had symptoms at 7 months and no symptoms at 15 months were considered to have post-COVID condition without chronification. Individuals with symptoms at 7 months and 15 months were considered to have post-COVID condition with chronification. Symptoms defining the presence of symptoms were any new symptom onset after SARS-CoV-2 infection including: fatigue, insomnia, headache, dyspnea, chest pain, palpitations, dizziness, difficulty concentrating, paresthesia, loss or change in smell, loss or change in taste, generalized pain, myalgia, arthralgia, fever, cough, digestive symptoms (nausea, vomiting, diarrhea, constipation, abdominal pain), and hair loss. Odds ratios were adjusted for age, sex, profession, civil status (single, married, widowed/separated or divorced), symptoms at time of testing, number of symptoms at 7 months, nature of symptom at 7 months (fatigue, difficulty concentrating, headache, dizziness, loss or change in smell, loss or change in taste, insomnia, myalgia, arthralgia, dyspnea), vaccination status, hospitalization, and pre-existing comorbidities (cognitive disorders, headaches, depression, anxiety.