Sequelae of Sars-CoV-2 Infections

Overview

By the end of 2019 a new coronavirus, named SARS-CoV-2, was discovered in patients with pneumonia in Wuhan, China. In the following weeks and months the virus spread globally, having a tremendous impact on global health and economy. To date, no vaccine or therapy is available. Severe courses of the infection not only affect the lungs, but also other organs like the heart, kidney, or liver. The lack of preexisting immunity might at least partially explain the affection of extra pulmonary organs not yet seen in infections due to other respiratory viruses. In this observational investigation the study group will follow up on patients that have been hospitalized due to a SARS-CoV-2 infection, and monitor sequelae in various organs, with an emphasis on the pulmo-cardiovascular system. Our that in some patients, organ damage will persist and require long-term medical care.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 requires hospitalization in a significant amount of patients. The hospitalization rate and disease severity increases in the elderly and patients with comorbidities such as diabetes, arterial hypertension, lung pathologies and obesity (Garg et al.). Patients with severe infections have pneumonia, requiring prolonged invasive ventilation. Sequelae of longer periods of mechanical ventilation and reduction of quality of life after acute respiratory distress syndrome (ARDS) are described (Herridge et al., 2 references). Besides, SARS-CoV-2 can induce - without preexisting immunity - strong inflammatory reactions, which can affect various organs. COVID-19 specific complications like thromboembolic events, neurologic events, myocardial involvement, or liver damage are reported during the acute stage of the infection. The lung is affected even during less severe infections, and ground glass opacities can result in consolidations (Shi et al.). These changes were reported to persist after discharge (Mo et al.). Acute kidney failure occurs in critically ill patients in 20-40% (Richardson et al.), and 40% of patients admitted to the hospital had proteinuria (Cheng et al.). Myocardial damage is reported, and some patients even presented initially with chest tightness and palpitations before having fever or cough (Zheng et al.). Moreover, patients with COVID-19 have a higher risk of thromboembolic events (Klok et al., Llitjos et al). Typically these patients have a prolonged activated partial thromboplastin time (aPTT), and often antiphospholipid antibodies (Bowles et al.). The long-term consequences of the strong inflammatory response affecting various organs are currently unknown. We hypothesize that some patients will have transient or persistent sequelae requiring medical care. The study group will therefore clinically examine patients that were hospitalized due to COVID-19, and monitor pulmonary, and other organ functions for at least one year after symptom onset. The study group will thereby perform lung and cardial examinations, monitor nephrologic parameters and perform radiology. Pneumologic tests will include a lung function test, a spiroergometry, a 6-minute walking test, and a grip-force test. Cardiac examination will include an echocardiography, and an electrocardiogram. In case of of severe pneumonia, or deterioration in lung function, computer tomography of the lungs will be performed. Blood (and urine) tests will include kidney parameters, inflammatory markers, liver values, and coagulation tests. Additional examinations will be done on an individual basis if clinically indicated, e.g. lung biopsies in case of suspected interstitial fibrosis. Additionally patient samples, which were taken for diagnostic purposes (serum, PBMCs, biopsies) will be stored in the biobank of the German center for lung research (DZL). Clinical evaluation and testing will start 2 months after symptom onset and the last visit is scheduled 10 months later. Depending on the results and the needs of the individual patient additional testing will be conducted.