BackgroundAfter the 2002/2003 SARS 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.MethodsIn 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).ResultsData from 145 COVID-19 patients were evaluated, and 41% of all subjects exhibited persistent symptoms 100 days after COVID-19 onset, with dyspnea 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 both, symptoms and CT abnormalities over time.ConclusionA relevant percentage of post-COVID-19 patients presented with persisting symptoms and lung function impairment along with pulmonary abnormalities more than 100 days after the diagnosis of COVID-19. However, our results indicate a significant improvement in symptoms and cardiopulmonary status over time.

No abstract

Background Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology. Methods We herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing. Results We investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia. Discussion Alterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19. Trial registration ClinicalTrials.gov number: NCT04416100.

Background: The optimal procedures to prevent, identify, monitor and treat long-term pulmonary sequelae of COVID-19 are elusive. Here, we characterized the kinetics of respiratory and symptom recovery following COVID-19.Methods: We conducted a longitudinal, multi-center observational study in ambulatory and hospitalized COVID-19 patients recruited in early 2020 (n = 145). Pulmonary computed tomography (CT) and lung function (LF) readouts, symptom prevalence, clinical and laboratory parameters were collected during acute COVID-19 and at 60-, 100- and 180-days follow-up visits. Recovery kinetics and risk factors were investigated by logistic regression. Classification of clinical features and participants was accomplished by unsupervised and semi-supervised multi-parameter clustering and machine learning.Results: At the six-month follow-up, 49% of participants reported persistent symptoms. The frequency of structural lung CT abnormalities ranged from 18% in the mild outpatient cases to 76% in the ICU convalescents. Prevalence of impaired LF ranged from 14% in the mild outpatient cases to 50% in the ICU survivors. Incomplete radiological lung recovery was associated with increased anti-S1/S2 antibody titer, IL-6 and CRP levels at the early follow-up. We demonstrated that the risk of perturbed pulmonary recovery could be robustly estimated at early follow-up by clustering and machine learning classifiers employing solely non-CT and non-LF parameters.Conclusion: The severity of acute COVID-19 and protracted systemic inflammation is strongly linked to persistent structural and functional lung abnormality. Automated screening of multi-parameter health record data may assist at the prediction of incomplete pulmonary recovery and optimize COVID-19 follow-up management.Funding: The State of Tyrol (GZ 71934), Boehringer Ingelheim/Investigator initiated study (IIS 1199-0424).Trial Registration: ClinicalTrials.gov: NCT04416100