Petr Jakubec

Rationale: Persistent respiratory symptoms following Coronavirus Disease 2019 (COVID-19) are associated with residual radiological changes in lung parenchyma, with a risk of development into lung fibrosis, and with impaired pulmonary function. Previous studies hinted at the possible efficacy of corticosteroids (CS) in facilitating the resolution of post-COVID residual changes in the lungs, but the available data is limited. Aim: To evaluate the effects of CS treatment in post-COVID respiratory syndrome patients. Patients and methods: Post-COVID patients were recruited into a prospective single-center observational study and scheduled for an initial (V1) and follow-up visit (V2) at the Department of Respiratory Medicine and Tuberculosis, University Hospital Olomouc, comprising of pulmonary function testing, chest x-ray, and complex clinical examination. The decision to administer CS or maintain watchful waiting (WW) was in line with Czech national guidelines. Results: The study involved 2729 COVID-19 survivors (45.7% male; mean age: 54.6). From 2026 patients with complete V1 data, 131 patients were indicated for CS therapy. These patients showed significantly worse radiological and functional impairment at V1. Mean initial dose was 27.6 mg (SD ± 10,64), and the mean duration of CS therapy was 13.3 weeks (SD ± 10,06). Following therapy, significantly better improvement of static lung volumes and transfer factor for carbon monoxide (DLCO), and significantly better rates of good or complete radiological and subjective improvement were observed in the CS group compared to controls with available follow-up data (n = 894). Conclusion: Better improvement of pulmonary function, radiological findings and subjective symptoms were observed in patients CS compared to watchful waiting. Our findings suggest that glucocorticoid therapy could benefit selected patients with persistent dyspnea, significant radiological changes, and decreased DLCO.

Introduction: Severe respiratory failure is one of the most serious complications of coronavirus disease 2019 (COVID-19). In a small proportion of patients, mechanical ventilation fails to provide adequate oxygenation and extracorporeal membrane oxygenation (ECMO) is needed. The surviving individuals need long-term follow-up as it is not clear what their prognosis is. Aim: To provide a complex clinical picture of patients during follow-up exceeding one year after the ECMO therapy due to severe COVID-19. Methods: All subjects involved in the study required ECMO in the acute stage of COVID-19. The survivors were followed-up for over one year at a specialized respiratory medical center. Results: Of the 41 patients indicated for ECMO, 17 patients (64.7% males) survived. The average age of survivors was 47.8 years, and the average BMI was 34.7 kg·m⁻². The duration of ECMO support was 9.4 days. A mild decrease in vital capacity (VC) and transfer factor (DLCO) was observed on the initial follow-up visit (82.1% and 60%, respectively). VC improved by 6.2% and by an additional 7.5% after 6 months and 1 year, respectively. DLCO improved by 21.1% after 6 months and remained stable after 1 year. Post-intensive care consequences included psychological problems and neurological impairment in 29% of patients; 64.7% of the survivors got vaccinated against SARS-CoV-2 within 12 months of hospitalization and 17.6% experienced reinfection with a mild course. Conclusion: The COVID-19 pandemic has significantly increased the need for ECMO. Patients’ quality of life after ECMO is temporarily significantly reduced but most patients do not experience permanent disability.

Analysing complex datasets while maintaining the interpretability and explainability of outcomes for clinicians and patients is challenging, not only in viral infections. These datasets often include a variety of heterogeneous clinical, demographic, laboratory, and personal data, and it is not a single factor but a combination of multiple factors that contribute to patient characterisation and host response. Therefore, multivariate approaches are needed to analyse these complex patient datasets, which are impossible to analyse with univariate comparisons (e.g., one immune cell subset versus one clinical factor). Using a SARS-CoV-2 infection as an example, we employed a patient similarity network (PSN) approach to assess the relationship between host immune factors and the clinical course of infection and performed visualisation and data interpretation. A PSN analysis of ~85 immunological (cellular and humoral) and ~70 clinical factors in 250 recruited patients with coronavirus disease (COVID-19) who were sampled four to eight weeks after a PCR-confirmed SARS-CoV-2 infection identified a minimal immune signature, as well as clinical and laboratory factors strongly associated with disease severity. Our study demonstrates the benefits of implementing multivariate network approaches to identify relevant factors and visualise their relationships in a SARS-CoV-2 infection, but the model is generally applicable to any complex dataset.

Because of the invasiveness of examination methods as bronchoscopy for the diagnosis of lung cancer, there is currently no preventive screening for this disease. Thus, lung cancer is usually diagnosed in stage 3 or 4, when it is too late for successful treatment. However, if diagnosed early, it can be cured entirely. Therefore, it is necessary to find a suitable method to screen the high-risk populations and reveal lung cancer in the early stages. Since the mucous membranes of the respiratory tract are naturally moistened by fluids containing proteins, metabolites, chemoattractants and growth factors released by the highly active epithelium, the collection of the respiratory tract fluids can be used to diagnose malignant and benign respiratory tract diseases. The most commonly used method in this sense is bronchoalveolar lavage. However, the technique itself is not pleasant and can be accompanied by possible complications. Therefore, intensive research work is conducted to develop non-invasive methods for biomarker detection in exhaled breath, sputum, saliva or nasal secretion. We have studied an exhaled breath condensate (EBC) matrix, which is collected non-invasively and the patients are not suffering from its collection. Several studies have reported proteomic analysis of EBC while identifying low hundreds of proteins by mass spectrometry (MS). We have developed a potent gel-free MS-based approach for sample preparation and analysis. Together with a powerful search tool, we were able to identify a ten times higher number of proteins across a comparable group of individuals of about three hundred peoples’ samples. Our approach seems to be highly reproducible and applicable to various respiratory and systemic diseases. In our work focused on non-small lung cancer biomarkers compared to chronic obstructive pulmonary disease (COPD) and healthy controls, we have identified 7694 proteins and of them, 6525 proteins were quantified at least in one replicate across 296 individuals’ samples measured in triplicates. Combining univariate and multivariate statistical approaches and sensitivity analysis, we have suggested biomarkers that could distinguish lung cancer patients from COPD and healthy individuals. This research was supported by grants from the Czech Ministry of Education, Youth and Sports (EATRIS-CZ - LM2018133), European Regional Development Fund - Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868) and IGA_LF_2021_036 (Palacky University in Olomouc). Citation Format: Jana Vaclavkova, Jana Vrbkova, Pavla Kourilova, Dusan Holub, Juraj Kultan, Petr Jakubec, Ondrej Fischer, Frantisek Kopriva, Vendula Latalova, Tatiana Gvozdiakova, Marian Hajduch, Petr Dzubak. Proteomic signature in exhaled breath condensates for a non-invasive diagnostics of lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2797.

In the relatively short period of time since December 2019, hundreds of millions of people globally have been infected with SARS-CoV-2, irrespective of their age, gender or ethnicity. Over that time, numerous mutations of various degrees of virulence and pathogenicity have occurred. The course of COVID-19 infection, an acute disease caused by the virus, is rather varied, ranging from asymptomatic or symptoms of common viral respiratory diseases to critical, with multiorgan failure and high mortality in high-risk patients. The overall mortality of the disease is 1-2 %. Unlike other viral respiratory diseases, this infection is often associated with frequent and rather diverse clinical manifestations developing after the acute phase of the infection, that is, more than 28 days after its onset. These complications are observed in both individuals with mild illness treated at home and inpatients with severe to critical illness. They develop both early after acute infection and some time after recovering from the disease. This rather heterogeneous group of pathologies may affect various organs and organ systems, with respiratory tract involvement being the most common and one of the most serious complications. Severe respiratory post-COVID-19 complications often include respiratory tract infections, in particular pneumonia.

Coronavirus disease 2019 (COVID-19) is a threat to patients not only because of its acute course, but also because of various complications occurring in the following period, that is, more than 28 days after the onset of acute infection. The present study identified a total of 121 patients hospitalized 29 or more days after the first positive result of a PCR test for SARS-CoV-2, of whom 98 patients were included in the study. Patients were divided into two groups by the time interval between the positive COVID-19 test result and hospitalization date. The time intervals were week 5–11 in an ongoing-COVID group (57.1% of patients) and 12 or more weeks in a post-COVID-group (42.9%). The most frequent reason for hospitalization was respiratory tract infection (58.2%). Pneumonia accounted for 77.2% of these cases. Other reasons for hospitalization were interstitial lung disease (22.4%), pulmonary embolism (8.2%), and sarcoidosis (6.1%). The study group was further divided according to the causes of hospitalization into subgroups with infections and other causes. In the group with infectious diseases, there was a shorter time period between PCR positivity and hospitalization and there were significantly more frequent non-respiratory complications. In the entire sample, the in-hospital mortality was 5.1%.