Prospective Cohort; Restrospective Cohort
Study population and setting
This ambidirectional cohort study included 1733 individuals (median age: 57 years, 48% female) with PCR-confirmed SARS-CoV-2 infection, who were discharged from Jin Yin-Tan Hospital in Wuhan, Hubei, China between January 7 and May 29, 2020 and had follow-up data collected between June 16 and September 3, 2020. Data on the acute phase (from symptom onset to hospital discharge) of infection were collected retrospectively from electronic medical records, including demographics, clinical characteristics, laboratory results, and treatment. Three groups of disease severity were considered: did not require supplemental oxygen (grade 3, n=439, 25%), required supplemental oxygen (grade 4, n=1172, 68%), required high flow nasal cannula, non-invasive mechanical ventilation, or invasive mechanical ventilation (grade 5/6 , n=122, 7%). Prospective follow-up data were collected in-person, including self-reported data on standardized questionnaires/surveys on previous and persistent symptoms, quality of life, and cardiovascular events as well as via a physical exam, laboratory tests, and a walking test. Additionally, 94 patients received SARS-CoV-2 antibody tests (neutralizing, IgM, IgA, IgG) and 390 patients were randomly selected to receive pulmonary function tests, ultrasonography of lower limb veins, or chest CT.
Summary of Main Findings
Follow-up visits occurred a median 186 days after symptom onset (IQR: 175-199) and 153 days after hospital discharge (IQR: 146-160). At the time of follow-up, 76% of patients reported at least one persistent symptom (most common was fatigue or muscle weakness, 63%), 27% reported pain or discomfort, 23% reported anxiety or depression, 23% performed worse than normal on the walking test, and 35% had eGFR <90 mL/min per 1.73 m2. Overall, follow-up data was relatively similar between severity groups 3 and 4, but severity group 5/6 seemed to have a bit more persistent symptoms and worse quality of life at follow-up. Among 349 participants with lung function tests, lung diffusion impairment was relatively common and increased with severity grade (22% grade 3, 29% grade 4, 56% grade 5/6). Of 353 with chest CT results, median CT scores were 3, 4, and 5 for grades 3, 4, and 5/6, respectively, and more than half of all patients had at least one abnormal CT pattern. Among 94 patients with antibody titres, seropositivity (96.2% vs. 58.5%) and median neutralizing antibody titer (19 vs. 10) decreased between acute phase and follow-up visit, but IgG antibodies remained constant.
This was a large, well-defined ambidirectional cohort study that presents data on several important questions that remain regarding long-term sequelae following hospitalization with COVID-19. For the most part, questionnaires were based on validated and standardized measures, including the British Medical Research Council dyspnoea scale (mMRC) and the EuroQol five-dimension five-level (EQ-5D-5L) questionnaire / EuroQol Visual Analogue Scale (EQ-VAS) to evaluate quality of life.
Of 2469 eligible participants, only 1733 were included in the study, which likely introduced selection bias; included participants may be different from those who were not included for a variety of reasons, such as being more motivated to participate because of unresolved symptoms. Notably, 33 patients died following hospital discharge and 25 patients were readmitted due to underlying disease complications. Results may not be applicable to those with mild disease who were not hospitalized. Pre-hospitalization data on symptoms, quality of life, and laboratory values were not available, so it is not possible to evaluate how different the prevalence of these factors are at follow-up vs. pre-infection. Additionally, factors such as baseline walking distance and data on pulmonary function were not available at the start of hospitalization, which limited ability to compare acute phase and follow-up data. Most findings presented were unadjusted and confounding is likely.
This is the largest known study evaluating long-term sequelae of moderate-severe COVID-19 cases in a well-defined cohort study.
This review was posted on: 25 January 2021