Home Monitoring and Molecular Phenotyping of Patients With Post-COVID With Focus on Lung Involvement
Post-acute COVID syndrome (PACS) /post-acute sequale of COVID-19 (PASC) / post-COVID is a novel clinical syndrome with unknown biological mechanisms, and to date no standard-of-care, routines for follow-up, or evidence-based treatments have been established. In this project, we will employ a systems medicine approach to identify pathways and networks of genes, proteins and metabolites that are critical in disease onset and progression, towards the goal of understanding specific mechanisms in the etiology of PASC. The objective of the project is to perform clinical and molecular characterization and sub-phenotyping of patients with PASC, (a.k.a. PACS, or post-COVID), into mechanistically relevant groups, with focus on sex differences in patients with lung involvement. Molecular pathways involved in disease etiology will be identified by correlating rigorous clinical phenotyping and longitudinal eHealth data (home-monitoring via App, home spirometer etc), with multi-molecular level omics profiling of samples collected from the lung, integrated with our systems medicine framework. Aim I involves longitudinal home-monitoring at baseline to investigate fluctuations in general wellbeing, and causes thereof, in PASC patients with lung involvement compared to healthy controls. In Aim II, a set of omics technologies will be employed to provide in-depth molecular characterization of samples from the lung, exhaled particles (PExA), blood and urine. In depth clinical characterizations including photon-counting CT will be performed. In Aim III, integrative statistical- and network modeling approaches will be utilized to: i) identify molecularly distinct sub-groups of obstructive lung diseases based on multi-molecular level network-integration, and ii) identify individual mediators and molecular pathways related to clinical phenotype including longitudinal home-monitoring data, prognosis, diagnosis, and disease etiology of the identified sub-groups.
• PASC group (n=50): Verified SARS-CoV-2 infections (PCR or serology prior to vaccination) during wave 1 and 2 (prior to 2021-02-28). Symptoms \>12 weeks after initial illness but with mild-to-moderate disease that did not require hospitalization during the initial infection, disabling persistent symptoms that at some point has affect work capacity 50%. Focus in this study will be placed on subject with some level of lung involvement, including but not limited to Air-trapping on HRCT images, ground glass alterations in radiology, airway obstruction, or shortness of breath as defined by CAT. Experience of dyspnea (mMRC\>3 within past 2 weeks) is a required inclusion criteria, with the addition of one of the following: lung obstruction (FEv1/FVC\>70 or Z-score \< -1.64), lung restriction (FEV1\<80% or FVC \< 80%, air-trapping, ground glass- or mosaic attenuation observed by HRCT.
• Health control group (n=50): Confirmed SARS-CoV-2 infection during wave 1 or 2. Fully recovered within 12 weeks of primary infection.