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

Thomas Sonnweber, Sabina Sahanic, Alex Pizzini, Anna Luger, Christoph Schwabl, Bettina Sonnweber, Katharina Kurz, Sabine Koppelstätter, David Haschka, Verena Petzer, Anna Boehm, Magdalena Aichner, Piotr Tymoszuk, Daniela Lener, Markus Theurl, Almut Lorsbach-Köhler, Amra Tancevski, Anna Schapfl, Marc Schaber, Richard Hilbe, Manfred Nairz, Bernhard Puchner, Doris Hüttenberger, Christoph Tschurtschenthaler, Malte Aßhoff, Andreas Peer, Frank Hartig, Romuald Bellmann, Michael Joannidis, Can Gollmann-Tepeköylü, Johannes Holfeld, Gudrun Feuchtner, Alexander Egger, Gregor Hoermann, Andrea Schroll, Gernot Fritsche, Sophie Wildner, Rosa Bellmann-Weiler, Rudolf Kirchmair, Raimund Helbok, Helmut Prosch, Dietmar Rieder, Zlatko Trajanoski, Florian Kronenberg, Ewald Wöll, Günter Weiss, Gerlig Widmann, Judith Löffler-Ragg, Ivan Tancevski, Thomas Sonnweber, Sabina Sahanic, Alex Pizzini, Anna Luger, Christoph Schwabl, Bettina Sonnweber, Katharina Kurz, Sabine Koppelstätter, David Haschka, Verena Petzer, Anna Boehm, Magdalena Aichner, Piotr Tymoszuk, Daniela Lener, Markus Theurl, Almut Lorsbach-Köhler, Amra Tancevski, Anna Schapfl, Marc Schaber, Richard Hilbe, Manfred Nairz, Bernhard Puchner, Doris Hüttenberger, Christoph Tschurtschenthaler, Malte Aßhoff, Andreas Peer, Frank Hartig, Romuald Bellmann, Michael Joannidis, Can Gollmann-Tepeköylü, Johannes Holfeld, Gudrun Feuchtner, Alexander Egger, Gregor Hoermann, Andrea Schroll, Gernot Fritsche, Sophie Wildner, Rosa Bellmann-Weiler, Rudolf Kirchmair, Raimund Helbok, Helmut Prosch, Dietmar Rieder, Zlatko Trajanoski, Florian Kronenberg, Ewald Wöll, Günter Weiss, Gerlig Widmann, Judith Löffler-Ragg, Ivan Tancevski

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.

Conflict of interest statement

Conflict of interest: T. Sonnweber has nothing to disclose. Conflict of interest: S. Sahanic has nothing to disclose. Conflict of interest: A. Pizzini has nothing to disclose. Conflict of interest: A. Luger has nothing to disclose. Conflict of interest: C. Schwabl has nothing to disclose. Conflict of interest: B. Sonnweber has nothing to disclose. Conflict of interest: K. Kurz has nothing to disclose. Conflict of interest: S. Koppelstätter has nothing to disclose. Conflict of interest: D. Haschka has nothing to disclose. Conflict of interest: V. Petzer has nothing to disclose. Conflict of interest: A. Boehm has nothing to disclose. Conflict of interest: M. Aichner has nothing to disclose. Conflict of interest: P. Tymoszuk has nothing to disclose. Conflict of interest: D. Lener has nothing to disclose. Conflict of interest: M. Theurl has nothing to disclose. Conflict of interest: A. Lorsbach-Köhler has nothing to disclose. Conflict of interest: A. Tancevski has nothing to disclose. Conflict of interest: A. Schapfl has nothing to disclose. Conflict of interest: M. Schaber has nothing to disclose. Conflict of interest: R. Hilbe has nothing to disclose. Conflict of interest: M. Nairz has nothing to disclose. Conflict of interest: B. Puchner has nothing to disclose. Conflict of interest: D. Hüttenberger has nothing to disclose. Conflict of interest: C. Tschurtschenthaler has nothing to disclose. Conflict of interest: M. Aßhoff has nothing to disclose. Conflict of interest: A. Peer has nothing to disclose. Conflict of interest: F. Hartig has nothing to disclose. Conflict of interest: R. Bellmann has nothing to disclose. Conflict of interest: M. Joannidis has nothing to disclose. Conflict of interest: C. Gollmann-Tepeköylü has nothing to disclose. Conflict of interest: J. Holfeld has nothing to disclose. Conflict of interest: G. Feuchtner has nothing to disclose. Conflict of interest: A. Egger has nothing to disclose. Conflict of interest: G. Hoermann has nothing to disclose. Conflict of interest: A. Schroll has nothing to disclose. Conflict of interest: G. Fritsche has nothing to disclose. Conflict of interest: S. Wildner has nothing to disclose. Conflict of interest: R. Bellmann-Weiler has nothing to disclose. Conflict of interest: R. Kirchmair has nothing to disclose. Conflict of interest: R. Helbok has nothing to disclose. Conflict of interest: H. Prosch has nothing to disclose. Conflict of interest: D. Rieder has nothing to disclose. Conflict of interest: Z. Trajanoski has nothing to disclose. Conflict of interest: F. Kronenberg has nothing to disclose. Conflict of interest: E. Wöll has nothing to disclose. Conflict of interest: G. Weiss has nothing to disclose. Conflict of interest: G. Widmann has nothing to disclose. Conflict of interest: J. Löffler-Ragg has nothing to disclose. Conflict of interest: I. Tancevski reports an Investigator Initiated Study (IIS) grant from Boehringer Ingelheim (IIS 1199-0424).

Copyright ©ERS 2021.

Figures

FIGURE 1
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 (pacute=145, nfollow-up=135.
FIGURE 2
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. nacute=23, nV1=145, nV2=135.
FIGURE 3
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
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
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 pse.

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