Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial

Abstract

Background: After the 2002/2003 severe acute respiratory syndrome outbreak, 30% of survivors exhibited persisting structural pulmonary abnormalities. The long-term pulmonary sequelae of coronavirus disease 2019 (COVID-19) are yet unknown, and comprehensive clinical follow-up data are lacking.

Methods: In this prospective, multicentre, observational study, we systematically evaluated the cardiopulmonary damage in subjects recovering from COVID-19 at 60 and 100 days after confirmed diagnosis. We conducted a detailed questionnaire, clinical examination, laboratory testing, lung function analysis, echocardiography and thoracic low-dose computed tomography (CT).

Results: Data from 145 COVID-19 patients were evaluated, and 41% of all subjects exhibited persistent symptoms 100 days after COVID-19 onset, with dyspnoea being most frequent (36%). Accordingly, patients still displayed an impaired lung function, with a reduced diffusing capacity in 21% of the cohort being the most prominent finding. Cardiac impairment, including a reduced left ventricular function or signs of pulmonary hypertension, was only present in a minority of subjects. CT scans unveiled persisting lung pathologies in 63% of patients, mainly consisting of bilateral ground-glass opacities and/or reticulation in the lower lung lobes, without radiological signs of pulmonary fibrosis. Sequential follow-up evaluations at 60 and 100 days after COVID-19 onset demonstrated a vast improvement of symptoms and CT abnormalities over time.

Conclusion: A relevant percentage of post-COVID-19 patients presented with persisting symptoms and lung function impairment along with radiological pulmonary abnormalities >100 days after the diagnosis of COVID-19. However, our results indicate a significant improvement in symptoms and cardiopulmonary status over time.

Trial registration: ClinicalTrials.gov NCT04416100.

FIGURE 1

Symptom burden in the Development of Interstitial Lung Disease (ILD) in Patients with SARS-CoV-2 infection (CovILD) study cohort during acute coronavirus disease 2019 (COVID-19) and at follow-up. a) Using a standardised questionnaire, performance status and overall burden of symptoms were assessed for the time-point of disease onset, 60 days (V1), and 100 days (V2) after diagnosis of COVID-19. b) Symptom burden was assessed using a standardised questionnaire at COVID-19 onset and at 100 days post-COVID-19 diagnosis. All symptoms significantly improved over time (p<0.001 for all read-outs). n_acute=145, n_follow-up=135.

FIGURE 2

Chest computed tomography (CT) lung analysis at coronavirus disease 2019 (COVID-19) onset and follow-up. a) The pattern of pathological findings assessed with CT at 60 (V1) and 100 days (V2) after diagnosis of COVID-19. b) Automated analysis of lung opacities assessed on CT scans from the acute disease phase, 60 days and 100 days after COVID-19 diagnosis employing Syngo.via CT Pneumonia Analysis software (Siemens Healthineers, Erlangen, Germany). c) CT severity scoring by radiologists at COVID-19 onset, 60 days and 100 days after COVID-19 diagnosis. The severity score was calculated via CT evaluation by three independent radiologists who qualitatively graded lung impairment for each lobe separately (grade 0–5, with 0 for no involvement and 5 for massive involvement). A total score was achieved by summation of grades for all five lobes (maximum 25 points). Data are presented as mean±se. n_acute=23, n_V1=145, n_V2=135.

FIGURE 3

Representative computed tomography scans of coronavirus disease 2019 patients with a) minimal, b) moderate and c) severe radiological findings at first follow-up. Percentage of opacity/high opacity a) 0.07/0.00; b) 10.29/0.69; c) 56.87/5.92.

FIGURE 4

Representative sequential computed tomography (CT) scans of a 56-year-old male coronavirus disease 2019 (COVID-19) patient during acute disease and follow-up. Pulmonary three-dimensional modelling assessed with CT is shown a) during acute COVID-19, b) at 60 days follow-up and c) at 100 days follow-up. Pulmonary opacities, mainly reflecting ground-glass opacities and/or consolidation, were quantified with Syngo.via CT Pneumonia Analysis software (Siemens Healthineers, Erlangen, Germany). Areas with increased opacity are marked in red, whereas normal lung areas are indicated in green.

FIGURE 5

Changes in pulmonary impairment according to computed tomography (CT) analysis in patients of different acute coronavirus disease 2019 (COVID-19) disease severities. Time-dependent changes of CT severity score in patients with mild to critical COVID-19. Disease severity was graded by the need for acute medical treatment, as follows. Mild: outpatient care; moderate: hospitalisation without respiratory support; severe: hospitalisation with the need for oxygen supply; critical: patients treated at the intensive care unit with the need for noninvasive or invasive ventilation. Except for patients with mild COVID-19, who demonstrated only minor pulmonary CT abnormalities, all other patient groups demonstrated a significant improvement of lung abnormalities in CT scans (p=0.042 to p<0.001 for time-dependent changes). CT severity scoring ranges from 0 to 25 and was applied as detailed in the methods section. Visit 1 (V1) and visit 2 (V2) were performed 60 and 100 days after the diagnosis of COVID-19, respectively. Data are presented as mean±se.