Background: Since the outbreak of the COVID-19 pandemic, a growing number of evidence suggests that COVID-19 presents sex-dependent differences in clinical course and outcomes. Nevertheless, there is still an unmet need to stratify the risk for poor outcome at the beginning of hospitalization. Since individual C₂HEST components are similar COVID-19 mortality risk factors, we evaluated sex-related predictive value of the score. Material and Methods: A total of 2183 medical records of consecutive patients hospitalized due to confirmed SARS-CoV-2 infections were analyzed. Subjects were assigned to one of two of the study arms (male vs. female) and afterward allocated to different stratum based on the C₂HEST score result. The measured outcomes included: in-hospital-mortality, three-month- and six-month-all-cause-mortality and in-hospital non-fatal adverse clinical events. Results: The C₂HEST score predicted the mortality with better sensitivity in female population regarding the short- and mid-term. Among secondary outcomes, C₂HEST-score revealed predictive value in both genders for pneumonia, myocardial injury, myocardial infarction, acute heart failure, cardiogenic shock, and acute kidney injury. Additionally in the male cohort, the C₂HEST value predicted acute liver dysfunction and all-cause bleeding, whereas in the female arm-stroke/TIA and SIRS. Conclusion: In the present study, we demonstrated the better C₂HEST-score predictive value for mortality in women and illustrated sex-dependent differences predicting non-fatal secondary outcomes.

Interferons (IFNs) produced by airway epithelial cells are crucial in defending against pathogens. Fluctuations in IFN-λ levels may influence coronavirus disease 19 (COVID-19) severity. However, conflicting data have been reported regarding serum IFN-λ concentrations in COVID-19 patients. To address this, we evaluated serum IFN-λ levels over time in moderate and severe COVID-19 patients and their association with cytokine production and clinical parameters using the enzyme-linked immunosorbent assay (ELISA) and the Bio-Plex Pro Human Cytokine 17-plex Assay. Results from testing 51 COVID-19 patients showed that 68% lacked detectable serum IFN-λ. Among non-IFN-λ secretors, severe COVID-19 predominated. In contrast, IFN-λ secretors displayed stable IFN-λ levels in moderate cases, while severe cases showed a decline over time, which persisted even after recovery. A negative correlation was observed between IFN-λ levels and inflammatory markers. This, combined with an increase in tumor necrosis factor alpha (TNF-α) and clinical improvement, suggests a regulatory role for IFN-λ in promoting faster recovery. Despite this, survival rates were similar between the groups, indicating that while IFN-λ influences the course of the disease, it does not directly affect overall survival. In conclusion, IFN-λ is vital, but not unique, for the antiviral response and COVID-19 recovery. Simultaneously, serum IFN-λ deficiency signifies severe COVID-19.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces strong innate immune responses and sustained inflammation, which may promote immune exhaustion via PD-1-PD-L1/PD-L2 and LAG-3-MHC pathways. The longitudinal dynamics and prognostic significance of soluble immune checkpoint molecules in moderate to severe COVID-19 remain unclear. Therefore, we assessed whether markers of immune exhaustion are associated with disease severity and recovery. Material and Methods: We analyzed 51 hospitalized patients (36 males and 15 females) with moderate to severe COVID-19 on day 1 of hospitalization, day 8, and on days 40-50. Laboratory tests, including complete blood count (CBC), C-reactive protein, fibrinogen, D-dimers, and ferritin concentration in sera, were routinely performed in the hospital diagnostic unit using applicable diagnostic automated methods. Soluble exhaustion markers, including sPD-L1, sPD-L2, and sLAG-3, were assessed by ELISA. Results: sPD-L2 and sLAG-3 levels were elevated at the time of admission. sPD-L2 and sLAG-3 levels decreased in the course of the disease. LAG-3 concentrations had decreased by day 8 and remained lower on days 40-50. PD-L2 levels decreased only in the recovery phase. Decreases of sPD-L2 and sLAG-3 were associated with clinical improvement and declining inflammatory parameters. Conclusions: High serum levels of sPD-L2 and sLAG-3 characterize the early phase of COVID-19, may be associated with active infection with SARS-CoV-2, and may reflect disease activity. Declining levels of markers of immune exhaustion have potential prognostic value for recovery from COVID-19.

Introduction: Various risk factors have been attributed to coronavirus disease 19 (COVID-19) severity. Omalizumab as an immunoglobulin E blocker that enhances anti-viral immunity might be a potential cytokine storm trigger. Aim: Our goal was to investigate if the treatment with omalizumab due to severe asthma is a risk factor of severe COVID-19 pneumonia and if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger asthma exacerbation. Case study: We report the case of a 65-year-old patient with severe allergic asthma receiving treatment with omalizumab for last 8 months with good results, who in December 2020 was infected with SARS-CoV-2. The patient was not vaccinated against COVID-19 (no vaccine was available at that time), and had comorbidities. Results and discussion: COVID-19 course of presented patient was asymptomatic and resolved quickly without the need for hospitalization or asthma exacerbation. There was a slightly worse score on the asthma control questionnaire after COVID-19 resolution (2.1 point vs. 1.5 points) and a threefold increase in eosinophil counts (660 cell/µL vs. 230 cell/µL). However, no wheezing or deterioration in pulmonary function tests were found. A computed tomography of the chest revealed only minor densities of pulmonary parenchyma and thickened walls of bronchi. Conclusions: Omalizumab used in the treatment of severe allergic asthma proved to be safe and beneficial for the course of COVID-19 in the case reported. Simultaneously, SARS-CoV-2 was not a factor for asthma exacerbation.