key: cord-0930565-d715fucg
authors: nan
title: Cardiopulmonary sequelae of COVID-19
date: 2022-04-11
journal: Memo
DOI: 10.1007/s12254-022-00802-z
sha: d0e110d4d3870170b0dc7569c96ebcb053f155da
doc_id: 930565
cord_uid: d715fucg

nan

In this interview, conducted in February 2022, Anna Fenzl, PhD from Springer Nature discusses cardiopulmonary sequelae of COVID-19 with Ivan Tancevski, MD from the Department of Internal Medicine II of the Medical University of Innsbruck.

The broad clinical spectrum from asymptomatic to fatal courses and variable duration of the coronavirus disease 2019 (COVID-19) [1] , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is challenging healthcare systems worldwide [2, 3] , causing high mortality, especially in the elderly and individuals with pre-existing risk conditions [4] [5] [6] [7] . Are there any clinical factors that can be linked to acute COVID-19 severity and protracted recovery? I. Tancevski: There are some clinical conditions that predispose for a severe course of COVID-19 inclu-Since the beginning of the pandemic, research has also focused on novel biomarkers associated with SARS-CoV-2 infection, which could potentially be useful in predicting the severity and prognosis of COVID-19 infection. Which circulating biomarkers have been identified and proposed for future clinical use in COVID-19? I. Tancevski: Following SARS-CoV-2 infection, a rapid systemic immune response is mounted, characterized by increased serum concentrations of chemokines and proinflammatory cytokines. In a prospective study with a 3-month cardiopulmonary follow-up analysis of patients with confirmed COVID-19, including critical cases, elevations in inflammatory markers such as interleukin-6, C-reactive protein, procalcitonin as well as biomarkers associated with COVID-19 disease severity including Ddimer, N-terminal pro B-type natriuretic peptide (NT-proBNP) and serum ferritin, were still present in a small portion of the study cohort. Moreover, most patients reported high rate of persisting dyspnea, two-thirds had residual radiological changes (prominently including the presence of ground-glass opacities combined with reticulation) and one-third of study participants displayed impaired lung function 8 . In the opinion paper of the ESC working group on Cellular Biology of the Heart, growth differentiation factor 15 (GDF-15), NT-proBNP and highsensitivity cardiac troponin (cTn) were postulated to have the strongest association with soluble angiotensinconverting enzyme 2 (ACE2) and the risk of death and cardiovascular complications [4] .

Of note, in our CovILD study, the most frequently observed COVID-19-related cardiac complications include high rates of diastolic dysfunction in moderate-to-severely ill COVID-19 patients, similar to what has been observed after SARS or MERS. Since these patients may be prone to develop arrhythmias or heart failure, an increasing number of studies is aiming at identifying potential cardiopulmonary damage after acute COVID-19 infection.

Moreover, there are several research groups trying to predict the severity and prognosis of COVID-19 infections by evaluating clinical diagnostic parameters and plasma proteomes [12] , and companies are in the process of developing clinical assays according to FDA or EMA standards to finally implement those findings into clinical practice. A significant number of patients who have recovered from acute COVID-19 infection are reporting lasting symptoms resulting in impairment of everyday activities beyond the initial acute period [13] . How should mild-tomoderate and severe COVID-19 survivors be evaluated after hospital discharge? Are there any algorithms that can be used? I. Tancevski: Many algorithms including the NICE and RAPID criteria, recommended by WHO, CDC and the national health care systems, have been established. Common to all of them is a stepwise assessment of patients, starting with a visit at the general practitioner who further refers patients to specialists (including cardiologist, pulmonologist, neurologist, psychiatrist) if necessary.

For those with severe acute COVID-19, including patients who had severe pneumonia, required ICU care, are elderly or have multiple comorbidities, a clinical assessment for respiratory, thromboembolic and psychiatric sequelae, as well as potential rehabilitation needs is recommended at 4-6 weeks after discharge from the hospital. In mild-to-moderate COVID-19 patients a routine clinical assessment, electrocardiogram and chest X-ray are recommended after 12 weeks [13] .

As more and more information about patient recovery is collected, lingering or recurring clinical manifestations as well as cardiopulmonary recovery, that can take several months to years, comes into focus, resulting in the introduction of the term "long COVID" and "post-acute sequelae of SARS-CoV-2" (PASC) [10, [14] [15] [16] [17] . How are "long COVID" and "PASC" defined and which emerging challenges does it pose to the healthcare system? I. Tancevski: COVID-19 is a novel disease with a variety of different symptoms and although its classification is still in a dynamic stage, "long COVID" and "PASC" are defined as persistent symptoms and/or delayed or longterm complications of SARS-CoV-2 infection persisting for 4-12 weeks and more than 12 weeks, respectively, from the onset of symptoms that cannot be explained by any other underlying disease.

The most common symptoms comprise fatigue, decline in quality of life, myalgia, dyspnea, cough, breathlessness on exercise, cognitive disturbances (brain fog), headaches, palpitations, chest pain, hypercoagulability, psychological or psychiatric abnormalities [13, 18] . Thus, in the outpatient setting an interdisciplinary cooperation is needed for comprehensive care of patients who suffered from COVID-19.

The global scale of this pandemic and the resulting large number of people whose healthcare needs will continue to increase, poses a global economic, social, political and medical challenge. However, centers for the treatment of patients with long COVID, spanning multiple medical specialties, are now being established.

The reported symptoms after the acute phase of the infection, are wide-ranging and may involve nearly all organ systems [13, 19, 20] . Thus, to provide integrated multispecialty care in the outpatient setting, a comprehensive understanding of patient care needs beyond the acute phase is urgently needed. Are there any strategies for prediction, monitoring and treatment of post-acute sequelae of COVID-19 yet? I. Tancevski: Our research group recently published an open-source risk modeling app called "CovILD pulmonary recovery assessment tool" providing a screening tool for the identification of subjects at risk of protracted lung (long-term radiological lung abnormalities and lung function impairment) and symptom recovery that is based on easily accessible clinical, demographic and biochemical variables during early COVID-19 convalescence. The app (https://im2-ibk.shinyapps.io/Cov-ILD/) is available for scientific purposes at the moment, and may well become implemented into national assessment algorithms soon [10] .

Moreover, multiple studies have assessed the prevalence of post-acute COVID-19 syndrome, showing that it is alarmingly common. For example, a meta-analysis recently published by Ceban F. et al. who analyzed 81 long-COVID studies published up to last June, reported that 32 % of patients were experiencing fatigue and 22 % reported cognitive impairment months after acute illness [21] .

Greater severity of acute illness, and pre-existing comorbidities are among the most common reported factors in literature associated with a higher incidence of PACS, including persistent diffusion impairment and radiographic pulmonary abnormalities (such as pulmonary fibrosis).

Given that there are no evidence-based treatment options for PASC due to the variety of symptoms, clinical guidelines including the Austrian consensus report on "long COVID" focus on symptom management [18] .

After moderate COVID-19, about one-third of patients still present with severe impairment of the diffusing capacity of the lungs and fibrotic lung damage according to literature 22. Thus, do anti-fibrotic therapies play a role in the prevention of pulmonary fibrosis and other respiratory complications after COVID-19? I. Tancevski: It is well known that almost all immediate and/or short term lung abnormalities (including interstitial lung disease (ILD)) respond well to corticosteroids. Based on treatment recommendations for cryptogenic organizing pneumonia, pneumologists may recommend treatment with corticosteroids for at least 3 months if ILD with inflammatory signatures develops. If a patient does not respond to corticosteroid monotherapy, we and others would suggest to add anti-fibrotic drugs such as nintedanib or pirfenidone. Of note, the NICE guideline recommend nintedanib for the treatment of rapid progressing ILD independent from COVID-19.

Although, up to date, we haven't observed many cases of post-COVID ILD in Tyrol., there is a phylogenetic relationship between SARS-CoV-1 and SARS-CoV-2, a similar clinical course in severe cases and overlapping CT patterns in the acute setting that may point towards potential persistent pulmonary and radiological functional changes as well as the development of progressive ILD in survivors, either due to viral or ventilator-induced alveolar damage. Hence, we continue to systematically investigate the development of ILD in patients with severe SARS-CoV-2 (NCT04416100).

A significant proportion of patients with SARS-CoV-2 (approximately 6 % to 10 %) develop COVID-19-associated acute respiratory distress syndrome (ARDS), thus extracorporeal membrane oxygenation (ECMO) may be initiated. In severe cases, ECMO was already used as a bridge to lung transplantation [23, 24] . The lung allocation score (LAS) to allocate donor lungs is used by both, the eurotransplant and the US. What are important considerations for evaluating patients with COVID-19 for lung transplantation? And how should the LAS be set for patients with COVID-19 associated ARDS? I. Tancevski: It has to be said that lung transplantation for COVID-19 associated lung failure is rare both in Europe as well as in the US, and still limited information about the long-term outcome exists. Although lung transplantation is a well-established treatment for several chronic end-stage lung diseases, it was barely considered for the treatment of ARDS prior to the COVID-19 pandemic [25] .

In Tyrol, lung transplantation was successfully performed in patients with severe COVID-19 associated ARDS. The patients were selected under high scrutiny, with multiple intense multi-disciplinary meetings necessary to evaluate the clinical characteristics of potential candidates at different time points to further exclude possible spontaneous lung recovery while following the general guidelines for lung transplantation.

In my opinion, the most important finding from different ARDS studies is that those patients are likely be needing lung transplantation after several years. Thus, with an ongoing pandemic and millions of cases, there may be the need for important adaptions in the LAS to further deal with ARDS or post-COVID-19-ILD in patients whose health status deteriorates requiring lung transplantation.

Overall, there has been a plethora of research and discussions resulting in improved patient treatment since the beginning of the COVID-19 pandemic, and based on these achievements many guidelines are likely to change in the near future.

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

SnapShot: COVID-19

An interactive web-based dashboard to track COVID-19 in real time

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