Secondary infections and long-term outcomes among hospitalized elderly and non-elderly patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treated with baricitinib: a comparative study from the national centre of Hungary.

Baricitinib is considered a first-line treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adult patients with an associated cytokine storm syndrome (CSS). Our objective was to compare rates of secondary infections and long-term outcomes of elderly and non-elderly patients who received baricitinib for COVID-19. We conducted a single-centre observational study between November 2020 and September 2023, focusing on hospitalized adult SARS-CoV-2 patients with CSS, categorized as elderly (≥ 65 years) and non-elderly (< 65 years). Enrolment, severity stratification, and diagnosis of infectious complications followed predefined criteria. Outcomes of all-cause mortality and rates of non-severe and severe secondary infections were assessed at 1-year post-treatment initiation. Kaplan-Meier analysis was performed for survival analysis. In total, 490 patients were enrolled (median age 65 ± 23 (21-100) years (years, median ± IQR, min-max); 49.18% elderly; 59.59% male). Elderly patients were admitted to the hospital significantly earlier (7 ± 5 days vs. 8 ± 4 days; p = 0.02), experienced a higher occurrence of severe COVID-19 (121/241, 50.21% vs. 98/249, 39.36%; p = 0.02), and required the use of non-invasive ventilation at baseline (167/225, 74.22% vs. 153/236, 64.83%; p = 0.03). At 1 year, all-cause mortality was significantly higher in the elderly subgroup (111/241, 46.06% vs. 29/249, 11.65%; p < 0.01). At 90 days and 1 year, rates of any severe secondary infection were also more prevalent among the elderly (56/241, 23.24% vs. 37/249 14.86%; p = 0.02 and 58/241, 24.07% vs. 39/249, 15.66%; p = 0.02). In conclusion, elderly SARS-CoV-2-infected patients experience a more severe clinical course, higher secondary infection rates, and increased risk for long-term mortality, regardless of immunomodulatory therapy.

Clinical and Microbiological Outcomes and Follow-Up of Secondary Bacterial and Fungal Infections among Critically Ill COVID-19 Adult Patients Treated with and without Immunomodulation: A Prospective Cohort Study.

BACKGROUND: Nearly 10% of COVID-19 cases will require admission to the intensive care unit (ICU). Our aim was to assess the clinical and microbiological outcomes of secondary infections among critically ill COVID-19 adult patients treated with/without immunomodulation. METHODS: A prospective observational cohort study was performed between 2020 and 2022 at a single ICU. The diagnosis and severity classification were established by the ECDC and WHO criteria, respectively. Eligible patients were included consecutively at admission, and followed for +30 days post-inclusion. Bloodstream-infections (BSIs), ventilator-associated bacterial pneumonia (VAP), and COVID-19-associated invasive pulmonary aspergillosis (CAPA) were defined according to international guidelines. Patient stratification was performed by immunomodulatory therapy administration (dexamethasone, tocilizumab, baricitinib/ruxolitinib). The primary outcome was any microbiologically confirmed major infectious complication, secondary outcomes were invasive mechanical ventilation (IMV) requirement and all-cause mortality. RESULTS: Altogether, 379 adults were included. At baseline, 249/379 (65.7%) required IMV and 196/379 (51.7%) had a cytokine storm. At +30 days post-inclusion, the rate of any microbiologically confirmed major infectious complication was 151/379 (39.8%), IMV requirement and all-cause mortality were 303/379 (79.9%) and 203/379 (53.6%), respectively. There were no statistically significant outcome differences after stratification. BSI, VAP, and CAPA episodes were mostly caused by Enterococcus faecalis (27/124, 22.1%), Pseudomonas aeruginosa (26/91, 28.6%), and Aspergillus fumigatus (20/20, 100%), respectively. Concerning the primary outcome, Kaplan-Meier analysis showed similar probability distributions between the treatment subgroups (118/299, 39.5% vs. 33/80, 41.3%, log-rank p = 0.22), and immunomodulation was not retained as its independent predictor in multivariate logistic regression. CONCLUSIONS: Secondary infections among critically ill COVID-19 adult patients represent a relevant burden, probably irrespective of immunomodulatory treatment.

Outcomes of high-risk adult outpatients treated with early remdesivir therapy during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron era: experiences from the national centre of Hungary.

Emerging evidence suggests that remdesivir might improve clinical outcome of high-risk outpatients with coronavirus disease 2019 (COVID-19). Our aim was to evaluate characteristics and outcomes of nonhospitalised adults diagnosed with COVID-19 and treated with early remdesivir therapy during the omicron wave. A single-centre prospective cohort study was performed among adult patients between February and June 2022, during the circulation of phylogenetic assignment of named global outbreak (PANGO) subvariants BA.2, BA.4, and BA.5 in Hungary. Patients were enrolled based on pre-defined criteria. Clinical characteristics (demography, comorbidities, vaccination status, imaging, treatment, and disease course) and outcomes (COVID-19 related hospitalisation, oxygen supplementation, intensive care support, and all-cause death) were assessed at 28 days post-treatment. A subgroup analysis of patients with and without active haematological malignancies was also carried out. Altogether, 127 patients were enrolled: 51.2% (65/127) were female with a median age of 59 (IQR: 22, range: 21‒92) years, and 48.8% (62/127) had active haematological malignancy. At 28 days post-treatment, 7.1% (9/127) of patients required COVID-19-related hospitalisation, 2.4% (3/127) required oxygen supplementation, 1.6% (2/127) required intensive care, and 0.8% (1/127) died due to a non-COVID-19-related secondary infection at the intensive care unit, all with haematological malignancies. Early remdesivir treatment might be a feasible strategy among high-risk outpatients with COVID-19 during the omicron wave.

Baricitinib vs tocilizumab treatment for hospitalized adult patients with severe COVID-19 and associated cytokine storm: a prospective, investigational, real-world study.

OBJECTIVES: Our aim was to compare outcomes of hospitalized adults with severe COVID-19 and cytokine storm treated with tocilizumab or baricitinib. METHODS: A prospective, investigational, real-world study was performed from April 2020 to April 2021 at our center. COVID-19 severity was classified by World Health Organization criteria, and cytokine storm was documented along predefined criteria. Eligible patients were enrolled at diagnosis if they fulfilled a priori inclusion criteria and received standard-of-care plus tocilizumab or baricitinib for >48 hours. Patients were followed per protocol for 28 days post-diagnosis. The primary outcome was all-cause mortality; secondary outcomes were invasive mechanical ventilation and major infectious complications. RESULTS: Of 463 patients, 102/463 (22.1%) received tocilizumab, and 361/463 (77.9%) baricitinib. Baseline characteristics were balanced. At 28 days, there was no difference in all-cause mortality (22/102, 21.6% vs 64/361, 17.7%; P-value = 0.38). Requirement for invasive mechanical ventilation was more frequent after tocilizumab (52/102, 50.9% vs 96/361, 26.6%; P <0.01), rate of major infectious complications was similar (32/102, 31.4% vs 96/361, 26.6%; P-value = 0.34). In logistic regression, the immunomodulatory drug was not retained as a predictor of all-cause mortality. Kaplan-Meier analysis revealed statistically similar survival distributions. CONCLUSION: All-cause mortality was similar between adults treated with baricitinib or tocilizumab for severe COVID-19 with cytokine storm.

COVID­19-associated liver enzyme elevation is probably multifactorial / A COVID-19-hez kapcsolódó májenzim-emelkedés valószínuleg multifaktoriális eredetu

Elevation of serum hepatic enzymes are common during the course of COVID­19. There are three possible mechanisms behind this phenomenon: 1) direct and indirect cytotoxic effects of SARS-CoV-2, 2) pharmacological side effects of COVID­19 drugs (e.g., remdesivir, favipiravir, tocilizumab, baricitinib, systemic corticosteroids, etc.) and 3) the progression of chronic hepatic diseases. Both the differential diagnosis and the clinical decision-making may pose difficulty for the the astute clinician, as an inappropriate treatment may result in COVID­19 progression or liver function deterioration. This review aims to provide basic guidance on the clinical decision-making for physicians managing patients with COVID­19.

Favipiravir treatment does not influence disease progression among adult patients hospitalized with moderate-to-severe COVID-19: a prospective, sequential cohort study from Hungary.

Data suggests that favipiravir (FVP) could be used against SARS-CoV-2. Our aim was to investigate the role of FVP in COVID-19 treatment. A prospective sequential cohort study was performed among adults hospitalized at our center between March and August 2020 with moderate-to-severe, PCR-confirmed COVID-19. For diagnosis and severity, ECDC and WHO definitions were utilized. Patients were screened for inclusion by a priori criteria and included in the FVP cohort if standard-of-care (SOC) + FVP or the non-FVP cohort if SOC ± other antivirals without FVP were administered for > 48 h from diagnosis. Treatment allocation was done per national guidelines, based on severity and drug availability. Primary endpoint was disease progression, a composite of 14-day all-cause death, need for mechanical ventilation, or immunomodulatory therapy. The impact of FVP exposure on disease progression was analyzed by binomial logistic regression. In all, 150 patients were included, 75 in each cohort. Disease progression (17/75, 22.7% vs. 10/75, 13.3%, p = 0.13), 14-day all-cause death (9/75, 12.0% vs. 10/75, 13.3%, p = 0.8), and need for mechanical ventilation (8/75, 10.7% vs. 4/75, 5.3%, p = 0.22) were similar, while immunomodulatory therapies were required more frequently among patients receiving FVP (10/75, 13.3% vs. 1/75, 1.3%, p < 0.01). The use of favipiravir was not retained as a protective factor against disease progression in multivatiate analysis. Time to antiviral therapy from PCR positivity, disease severity, need for oxygen supportation, and ICU admittance rates did not differ statistically between cohorts. In this study, favipiravir did not seem to positively affect disease progression.

Laboratory parameters predicting mortality of adult in-patients with COVID-19 associated cytokine release syndrome treated with high-dose tocilizumab.

Large randomized clinical trials in severe Coronavirus Disease 2019 (COVID-19) patients have proven efficacy of intravenous tocilizumab. Our aim was to describe the laboratory parameters predicting in-hospital mortality of patients with tocilizumab administration in COVID-19 associated cytokine release syndrome (CRS).We evaluated high-dose (8 mg/kg) intravenous tocilizumab administration in severe and critically ill COVID-19 adult patients fulfilling predefined strict CRS criteria. A single-centre, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between April 1 and December 31, 2020. The primary endpoint was 28-day all-cause mortality. The changes in laboratory parameters from baseline on day 7 and 14 after administration of tocilizumab were analysed.In total, 1801 patients were admitted to our centre during the study period. One hundred and six patients received tocilizumab, and among them 62 (58.5%) required intensive care unit admittance while 25 (23.6%) deceased. At day 7 after tocilizumab administration, inflammatory markers (CRP, IL-6, ferritin) and lactate dehydrogenase (LDH) values were significantly lower among survivors. Subsequently, at day 14, differences of IL-6 and LDH levels has become more pronounced between subgroups. Restoration of absolute lymphocyte count (ALC) by day 7 and 14 was insufficient among patients who died.In our cohort, administration of high-dose tocilizumab for COVID-19 patients with CRS demonstrated clinical and sustained biochemical parameter improvement in 76.4%. In this patient population high and increasing LDH, IL-6, and low ALC levels had a predictive role for mortality.

Changes in endogenous metal element concentrations in various aetiologies of chronic liver disease. / Az endogén fémionok koncentrációinak változása különbözo kórokú, idült májbetegségekben.

Our body contains physiologically many metal ions used for its metabolic processes and function. Metal ion changes can start pathological processes, however, the pathological processes may also lead to changes in metal ion concentration. In this study, the authors summarize the physiologically present metal ions' change in liver diseases with various aetiologies, the consequences are discussed as well as the connections with the progression. Further, the authors point out the element concentration changes as diagnostic or prognostic values for the liver diseases as well. Orv Hetil. 2020; 161(22): 917-923.

[Hepatitis C virus infection and hepatocarcinogenesis]. / Hepatitis C-vírus-fertozés és hepatocarcinogenesis.

Hepatitis C virus infection causes approximately 4 million new infections worldwide, and 399 000 deaths due to its complications, cirrhosis and hepatocellular carcinoma (HCC). Microenvironmental changes, chronic inflammation, oxidative stress, endoplasmic reticulum stress caused by HCV infection, via genetic and epigenetic changes can result in primary liver cancer during decades. The direct oncogenic property of HCV is wellknown. The transforming effect of four HCV proteins (core, NS3, NS4B, NS5A) has been proven. Effective antiviral therapy, sustained viral response decreases the HCV-related general and liver-related mortality. Interferon-based therapy reduces the risk of HCC development. Shorter therapy with direct acting antiviral agents (DAA) has higher efficacy, fewer side-effects. Publications have reported the unexpected effects of DAA. The authors review the articles focusing on the occurrence of HCC in connection with DAA therapies. There is a need for prospective, multicentric studies with longer follow-up to examine the risk of HCC formation. After antiviral therapy, HCC surveillance is of high importance which means abdominal ultrasound every 3-6-12 months in sustained viral response patients as well. Orv Hetil. 2019; 160(22): 846-853.