Short-term exposure to ambient air pollution and COVID-19 severity during SARS-CoV-2 Delta and Omicron waves: A multicenter study.

Air pollution may affect the clinical course of respiratory diseases, including COVID-19. This study aimed to evaluate the relationship between exposure of adult patients to mean 24 h levels of particulate matter sized <10 µm (PM10 ) and <2.5 µm (PM2.5 ) and benzo(a)pyrene (B(a)P) during a week before their hospitalization due to SARS-CoV-2 infection and symptomatology, hyperinflammation, coagulopathy, the clinical course of disease, and outcome. The analyses were conducted during two pandemic waves: (i) dominated by highly pathogenic Delta variant (n = 1440) and (ii) clinically less-severe Omicron (n = 785), while the analyzed associations were adjusted for patient's age, BMI, gender, and comorbidities. The exposure to mean 24 h B(a)P exceeding the limits was associated with increased odds of fever and fatigue as early COVID-19 symptoms, hyperinflammation due to serum C-reactive protein >200 mg/L and interleukin-6 >100 pg/mL, coagulopathy due to  d-dimer >2 mg/L and fatal outcome. Elevated PM10 and PM2. 5 levels were associated with higher odds of respiratory symptoms, procalcitonin >0.25 ng/mL and interleukin >100 pg/mL, lower oxygen saturation, need for oxygen support, and death. The significant relationships between exposure to air pollutants and the course and outcomes of COVID-19 were observed during both pandemic waves. Short-term exposure to elevated PM and B(a)P levels can be associated with a worse clinical course of COVID-19 in patients requiring hospitalization and, ultimately, contribute to the health burden caused by SARS-CoV-2 variants of higher and lower clinical significance.

Transmitted HIV drug resistance in antiretroviral-treatment-naive patients from Poland differs by transmission category and subtype.

OBJECTIVES: The surveillance of HIV-transmitted drug resistance mutations (t-DRMs), including temporal trends across subtypes and exposure groups, remains a priority in the current management of the epidemic worldwide. METHODS: A cross-sectional analysis of 833 treatment-naive patients from 9 of 17 Polish HIV treatment centres. Partial pol sequences were used to analyse drug resistance with a general time reversible (GTR)-based maximum likelihood algorithm used for cluster/pair identification. Mutation frequencies and temporal trends were investigated. RESULTS: t-DRMs were observed in 9% of cases (5.8% for NRTI, 1.2% NNRTI and 2.0% PI mutations) and were more common among heterosexually infected (HET) individuals (13.4%) compared with MSM (8.3%, P = 0.03) or injection drug users (IDUs; 2.9%, P = 0.001) and in MSM compared with IDUs (P = 0.046). t-DRMs were more frequent in cases infected with the non-B variant (21.6%) compared with subtype B (6.6%, P < 0.001). With subtype B a higher mutation frequency was found in MSM compared with non-MSM cases (8.3% versus 1.8% for IDU + HET, P = 0.038), while non-B variants were associated with heterosexual exposure (30.4% for HET versus 4.8% for MSM, P = 0.019; versus 0 for IDU, P = 0.016). Trends in t-DRM frequencies were stable over time except for a decrease in NNRTI t-DRMs among MSM (P = 0.0662) and an NRTI t-DRM decrease in HET individuals (P = 0.077). With subtype B a higher frequency of sequence pairs/clusters in MSM (50.4%) was found compared with HET (P < 0.001) and IDUs (P = 0.015). CONCLUSIONS: Despite stable trends over time, patterns of t-DRMs differed notably between transmission categories and subtypes: subtype B was associated with MSM transmission and clustering while in non-B clades t-DRMs were more common and were associated with heterosexual infections.

Syphilitic hepatitis.

Syphilis is a sexually transmitted multisystemic disease known as "the great imitator" due to its variable presentations. Despite being preventable and curable, it still constitutes a major health problem. Hepatic manifestation of syphilis is usually mild cholestatic liver injury but in very rare cases can become fulminant. Moreover, syphilitic hepatitis, known for several decades, is considered rare but is probably under-diagnosed. Given the significant morbidity associated with a missed diagnosis, syphilitic hepatitis should be taken into account as an element of differential diagnosis in patients with unexplained elevation of liver enzymes.

Incidence of tuberculosis and mycobacteriosis among HIV-infected patients--clinical and epidemiological analysis of patients from north-eastern Poland.

INTRODUCTION: According to WHO data, among patients infected with HIV, tuberculosis occurs in about 30% of patients and causes approximately 25% of deaths due to AIDS worldwide. The incidence rate of tuberculosis in the Polish population was 22.2/100,000 in 2011, while the average in European Union countries in 2011 was 14/100,000. Since 1985 to 30 April 2013 HIV infection in Poland was confirmed in 16,588 patients, while the number of reported tuberculosis cases in HIV-infected individuals in 2011 was 26. The aim of this study was to assess the prevalence and clinical course of tuberculosis and mycobacterial disease in HIV-infected patients treated in the Department of Infectious Diseases and Hepatology in Bialystok. MATERIAL AND METHODS: We analysed documentation of 577 HIV-infected patients, their demographic data, epidemiological status, degree of immunosuppression (T CD4 and CD8 numbers) and stage of HIV infection. RESULTS: Complete follow-up was possible in 389 patients, of whom 265 (68%) were male. Tuberculosis (TB) was diagnosed in 41 patients (10.5%) and mycobacteriosis in 4 patients (1.03%). In 19 patients (42%) HIV and TB or mycobacteriosis were diagnosed simultaneously. The median CD4 T lymphocyte count was lower in patients with a simultaneous diagnosis of HIV and tuberculosis or mycobacteriosis compared to the group in whom TB/mycobacteriosis was diagnosed later. The number of CD4 T-cells less than 50 cells/µL was found in 63.2% (12/19) of patients when HIV and TB or mycobacteriosis were diagnosed simultaneously and in 38.5% (10/26) of patients who were diagnosed with TB or mycobacteriosis later than the HIV infection (p = 0.14). The median HIV viral load in patients in whom HIV infection and tuberculosis or mycobacteriosis were diagnosed at the same time was higher than in other patients and this difference was statistically significant. Pulmonary tuberculosis was the most common form of clinical disease and accounted for 60% of all cases. Among the analysed cases with HIV and tuberculosis or mycobacteriosis coinfection, tuberculosis or mycobacteriosis was the cause of death in 8 patients, and 9 died of other causes. CONCLUSION: In our material of 389 HIV-infected patients, tuberculosis was diagnosed in 41 (10.5%) and mycobacterial diseases in 4 (1.03%). In 42% of co-infected patients (HIV+TB or mycobacteriosis) the diagnosis of both diseases was made at the same time. In these patients, a deep deficit of cellular immunity (CD4 < 50 cells/µL) was observed more frequently than in patients diagnosed with TB or mycobacteriosis in the later course of HIV. HIV RNA viral load was significantly higher in the group diagnosed simultaneously than in the remaining patients with HIV and TB or mycobacteriosis coinfection.

Rotational Thromboelastometry (ROTEM®) in Relation to Inflammatory Biomarkers and Clinical Outcome in COVID-19 Patients.

Background: The pathogenesis of hypercoagulability in COVID-19 patients is complex and not fully understood. Rotational thromboelastometry (ROTEM®) is a viscoelastic method that allows the definition of a patient's hemostatic profile. This study aimed to assess the relationship between ROTEM® parameters, the profile of inflammatory cytokines, and clinical outcomes in COVID-19 patients. Methods: A total of 63 participants (n = 29 symptomatic non-ICU COVID-19 patients, and n = 34 healthy controls) were prospectively included in the study. We assessed the relationship between the parameters of three ROTEM® tests (NATEM®, EXTEM®, and FIBTEM®) and levels of CRP, interleukin-8, interleukin-1ß, interleukin-6, interleukin-10, tumor necrosis factor, interleukin 12p70, and clinical outcomes. Results: ROTEM® indicated hypercoagulability in COVID-19 patients in all the tests performed. The levels of all inflammatory cytokines were significantly higher in COVID-19 patients. NATEM more frequently detected hypercoagulability in COVID-19 patients compared to EXTEM. The strongest correlations with inflammatory biomarkers and CT severity score were with FIBTEM parameters. The elevated maximum clot elasticity (MCE) in FIBTEM was the strongest predictor of poor outcomes. Conclusions: Increased FIBTEM MCE may be associated with greater severity of COVID-19. Non-activated ROTEM (NATEM test) seems to be more valuable for detecting hypercoagulability in COVID-19 patients compared to the tissue factor activated test (EXTEM).

Thrombospondin-2 as a potential noninvasive biomarker of hepatocyte injury but not liver fibrosis in children with MAFLD: A preliminary study.

Aim of the study: Metabolic-associated fatty liver disease (MAFLD) requires close monitoring due to its increased incidence and progression to fibrosis, cirrhosis and even hepatocellular carcinoma. The search for non-invasive markers to diagnose liver fibrosis is ongoing. The aim of our study was to evaluate the serum levels of growth differentiation factor-15 (GDF-15), thrombospondin-2 (TSP2), pentraxin 3 (PTX3) and angiopoietin-like protein 8 (ANGPTL8) in children with MAFLD. Material and methods: Fifty-six overweight/obese children with suspected liver disease were included in this prospective study. MAFLD was diagnosed according to the latest consensus. Vibration-controlled transient elastography (TE) was performed to detect clinically significant liver fibrosis. Serum concentrations of GDF-15, TSP2, PTX3 and ANGPTL8 were measured by enzyme-linked immunosorbent assay (ELISA). Results: Liver steatosis was diagnosed in abdominal ultrasound in 31 (55.36%) overweight/obese patients who were classified as the MAFLD group. Aspartate aminotransferase (AST)/platelet ratio (APRI) and liver stiffness measurement (LSM) values and TSP2 concentrations showed significantly higher values in patients in MAFLD than in the non-MAFLD group. TSP2 was significantly positively correlated with alanine transaminase (ALT), AST, γ-glutamyltransferase (GGT) and APRI in the study group. The receiver operating characteristics (ROC) analysis showed that the area under the curve (AUC) of LSM, APRI and serum TSP2 was significant for predicting MAFLD in obese children. In the multivariable regression model, LSM was the only significant parameter associated with the diagnosis of MAFLD in children. Conclusions: TSP2 may be a potential biomarker of hepatocyte injury in pediatric patients with MAFLD. None of the examined biomarkers were found to be effective non-invasive markers of liver fibrosis in children.

Variability in the Clinical Course of COVID-19 in a Retrospective Analysis of a Large Real-World Database.

The COVID-19 pandemic proceeds in waves, with variable characteristics of the clinical picture resulting from the evolution of the SARS-CoV-2 virus. This study aimed to compare the epidemiological characteristics, symptomatology, and outcomes of the disease in patients hospitalized for COVID-19 during periods of different variants dominance. Comparing the periods of dominance of variants preceding the Delta variant, the Delta period was characterized by a higher share of hospitalized females, less frequent comorbidities among patients, and a different age distribution. The lowest need for oxygen therapy and mechanical ventilation was observed under Omicron dominance. The triad of classic COVID-19 symptoms, cough, fever, dyspnoea, and fatigue, were most prevalent during the Delta period, and significantly less common under the Omicron dominance. During the Omicron period, nearly twice as many patients as in the previous periods could be discharged from the hospital within 7 days; the overall 28-day mortality was significantly lower compared to that of the Delta period. It also did not differ between periods that were dominated by the BA.1 and BA.2 subvariants. The study indicates that the Omicron SARS-CoV-2 variant that dominated between January and June 2022 caused a disease which resembled the common cold, and was caused by seasonal alpha and beta-coronaviruses with a low pathogenicity for humans. However, one should note that this effect may not only have been related to biological features of the Omicron lineage, but may additionally have been driven by the increased levels of immunization through natural infections and vaccinations, for which we could not account for due to a lack of sufficient data.

Differences between the course of SARS-CoV-2 infections in the periods of the Delta and Omicron variant dominance in Poland.

INTRODUCTION: Up to now, COVID­19 caused more than 6 million deaths worldwide. So far, 5 variants of concerns have been identified, with Delta and Omicron being the subject of our analysis. OBJECTIVES: We aimed to compare baseline characteristics and outcomes of patients hospitalized during the Delta and Omicron predominance in Poland. PATIENTS AND METHODS: The study population consisted of 2225 patients divided into 2 groups depending on the variant with which they were infected during the corresponding period of the pandemic. RESULTS: During the Delta wave, the median age of patients was significantly lower (65 vs 73 years; P <0.001), and the cohort was significantly less burdened with comorbidities than during the Omicron surge. The Omicron­infected patients presented significantly less often in an unstable symptomatic state with SpO2 equal to or below 90% on admission (49.9% for Delta vs 29.9% for Omicron; P <0.001). Regardless of the pandemic period, the 2 most common early symptoms of COVID­19 were fever and cough. In­hospital treatment consisted of antiviral drugs, more frequently used in the Omicron wave, and immunomodulatory drugs, more frequently used during the Delta wave. The risk of mechanical ventilation was significantly lower in the patients infected with the Omicron variant (7.2% for Delta vs 3.1% for Omicron; P <0.001). For the age group above 80 years old, the risk of death was significantly higher during the Delta wave than during the Omicron wave. The risk of death was significantly lower in the patients treated with antiviral drugs regardless of the pandemic wave. CONCLUSIONS: The Delta variant is associated with a more severe clinical course of the disease and a higher risk of death than the Omicron variant.

Retrospective Analysis of the Effectiveness of Remdesivir in COVID-19 Treatment during Periods Dominated by Delta and Omicron SARS-CoV-2 Variants in Clinical Settings.

Continuous evaluation of real-world treatment effectiveness of COVID-19 medicines is required due to the ongoing evolution of SARS-CoV-2 and the possible emergence of resistance. Therefore, this study aimed to analyze, in a retrospective manner, the outcomes in patients hospitalized with COVID-19 during the pandemic waves dominated by Delta and Omicron variants and treated with remdesivir (RDV) (n = 762) in comparison to a demographically and clinically matched group not treated with any antivirals (n = 1060). A logistic regression analysis revealed that RDV treatment was associated with a significantly lower risk of death during both Delta wave (OR = 0.42, 95%CI: 0.29-0.60; p < 0.0001) and Omicron-dominated period (OR = 0.56, 95%CI: 0.35-0.92; p = 0.02). Moreover, RDV-treated groups were characterized by a lower percentage of patients requiring mechanical ventilation, but the difference was not statistically significant. This study is the first real-world evidence that RDV remains effective during the dominance of more pathogenic SARS-CoV-2 variants and those that cause a milder course of the disease, and continues to be an essential element of COVID-19 therapy.

Change in the Clinical Picture of Hospitalized Patients with COVID-19 between the Early and Late Period of Dominance of the Omicron SARS-CoV-2 Variant.

This study aimed to compare the clinical picture of COVID-19 in the initial and later period of Omicron dominance and to identify populations still at risk. A retrospective comparison of the clinical data of 965 patients hospitalized during the early period of Omicron's dominance (EO, January-June 2022) with 897 patients from a later period (LO, July 2022-April 2023) from the SARSTer database was performed. Patients hospitalized during LO, compared to EO, were older, had a better clinical condition on admission, had a lower need for oxygen and mechanical ventilation, had less frequent lung involvement in imaging, and showed much faster clinical improvement. Moreover, the overall mortality during EO was 14%, higher than that in LO-9%. Despite the milder course of the disease, mortality exceeding 15% was similar in both groups among patients with lung involvement. The accumulation of risk factors such as an age of 60+, comorbidities, lung involvement, and oxygen saturation <90% resulted in a constant need for oxygen in 98% of patients, an 8% risk of mechanical ventilation, and a 30% mortality rate in the LO period. Multiple logistic regression revealed lower odds of death during the LO phase. Despite the milder course of infections caused by the currently dominant subvariants, COVID-19 prophylaxis is necessary in people over 60 years of age, especially those with comorbidities, and in the case of pneumonia and respiratory failure.

Real-world experience with molnupiravir during the period of SARS-CoV-2 Omicron variant dominance.

BACKGROUND: The real-world effectiveness of molnupiravir (MOL) during the dominance of Omicron SARS-CoV-2 lineage is urgently needed since the available data relate to the period of circulation of other viral variants. Therefore, this study assessed the efficacy of MOL in patients hospitalized for COVID-19 in a real-world clinical practice during the wave of Omicron infections. METHODS: Among 11,822 patients hospitalized after 1 March 2020 and included in the SARSTer national database, 590 were treated between 1 January and 30 April 2022, a period of dominance of the Omicron SARS-CoV-2 variant. MOL was administered to 203 patients, whereas 387 did not receive any antiviral regimen. Both groups were similar in terms of sex, BMI and age allowing for direct comparisons. RESULTS: Patients who did not receive antiviral therapy significantly more often required the use of Dexamethasone and Baricitinib. Treatment with MOL resulted in a statistically significant reduction in mortality during the 28-day follow-up (9.9 vs. 16.3%), which was particularly evident in the population of patients over 80 years of age treated in the first 5 days of the disease (14.6 vs. 35.2%). MOL therapy did not affect the frequency of the need for mechanical ventilation, but patients treated with MOL required oxygen supplementation less frequently than those without antivirals (31.7 vs. 49.2%). The time of hospitalization did not differ between groups. CONCLUSIONS: The use of molnupiravir in patients hospitalized for COVID-19 during the dominance of Omicron variant reduced mortality. This effect is particularly evident in patients over 80 years of age.

The association of airborne particulate matter and benzo[a]pyrene with the clinical course of COVID-19 in patients hospitalized in Poland.

Air pollution can adversely affect the immune response and increase the severity of the viral disease. The present study aimed to explore the relationship between symptomatology, clinical course, and inflammation markers of adult patients with coronavirus disease 2019 (COVID-19) hospitalized in Poland (n = 4432) and air pollution levels, i.e., mean 24 h and max 24 h level of benzo(a)pyrene (B(a)P) and particulate matter <10 µm (PM10) and <2.5 µm (PM2.5) during a week before their hospitalization. Exposures to PM2.5 and B(a)P exceeding the limits were associated with higher odds of early respiratory symptoms of COVID-19 and hyperinflammatory state: interleukin-6 > 100 pg/mL, procalcitonin >0.25 ng/mL, and white blood cells count >11 × 103/mL. Except for the mean 24 h PM10 level, the exceedance of other air pollution parameters was associated with increased odds for oxygen saturation <90%. Exposure to elevated PM2.5 and B(a)P levels increased the odds of oxygen therapy and death. This study evidences that worse air quality is related to increased severity of COVID-19 and worse outcome in hospitalized patients. Mitigating air pollution shall be an integral part of measures undertaken to decrease the disease burden during a pandemic of viral respiratory illness.

The Course of COVID-19 in Patients with Systemic Autoimmune Rheumatic Diseases.

Patients with systemic autoimmune rheumatic disease (SARD) have increased susceptibility to viral infections, including SARS-CoV-2. The aim of this study was to analyse the SARD patient population with COVID-19 (coronavirus disease 2019) in terms of baseline characteristics, severity, course and outcomes of the disease compared with the non-SARD group, and to identify factors associated with prognosis, including remdesivir therapy efficacy. Retrospective study comprised 8220 COVID-19 cases from the SARSTer database, including 185 with SARD. Length of hospitalisation, duration of oxygen therapy, mortality and the need for HFNO (high-flow nasal oxygen) and/or NIV (noninvasive ventilation) were significantly higher in the SARD versus non-SARD group. There was no difference in clinical features on admission to hospital. Patients with SARD were older and more likely to have cardiovascular, pulmonary and chronic kidney diseases. Age, the presence of cardiovascular disease, more severe conditions on admission and higher inflammatory marker values were found to be risk factors for death in the SARD group. In patients with SARD treated with remdesivir, there was a trend towards improved mortality but without statistical significance. Length of hospitalisation, 28-day mortality and the need for HFNO and/or NIV were higher in the SARD group. These patients often had other chronic diseases and were older.

Remdesivir Decreases Mortality in COVID-19 Patients with Active Malignancy.

Data on the use of remdesivir, the first antiviral agent against SARS-CoV-2, are limited in oncologic patients. We aimed to analyze contributing factors for mortality in patients with malignancies in the real-world CSOVID-19 study. In total, 222 patients with active oncological disorders were selected from a nationwide COVID-19 study of 4890 subjects. The main endpoint of the current study was the 28-day in-hospital mortality. Approximately half of the patients were male, and the majority had multimorbidity (69.8%), with a median age of 70 years. Baseline SpO2 < 85% was observed in 25%. Overall, 59 (26.6%) patients died before day 28 of hospitalization: 29% due to hematological, and 20% due to other forms of cancers. The only factor increasing the odds of death in the multivariable model was eGFR < 60 mL/min/m2 (4.621, p = 0.02), whereas SpO2 decreased the odds of death at baseline (0.479 per 5%, p = 0.002) and the use of remdesivir (0.425, p = 0.03). This study shows that patients with COVID-19 and malignancy benefit from early remdesivir therapy, resulting in a decrease in early mortality by 80%. The prognosis was worsened by low glomerular filtration rate and low peripheral oxygen saturation at baseline underlying the role of kidney protection and early hospitalization.

Inflammatory and thrombotic parameters associated with the COVID-19 course in Poland (SARSTer study).

PURPOSE: The aim of the study was to assess the coagulation and inflammatory markers connected with severe course of COVID-19 and no clinical improvement. MATERIAL AND METHODS: The study population included 2590 adult patients, diagnosed with COVID-19, selected from the SARSTer national database - an ongoing project led by the Polish Association of Epidemiologists and Infectiologists and supported by the Medical Research Agency. Clinical and laboratory parameters, such as C-reactive protein (CRP), white blood cells (WBCs), neutrophil and lymphocyte count, procalcitonin, ferritin, interleukin-6 (IL-6), D-dimer concentration and platelet (PLT) count were analyzed before and after treatment (remdesivir, tocilizumab, dexamethasone, anticoagulants). RESULTS: Significant differences between patients with mild and severe course of the disease were observed in all examined parameters before treatment (p â€‹< â€‹0.05). After treatment only ferritin concentration did not differ significantly. In patients with pulmonary embolism, CRP concentration, neutrophil count, D-dimer and IL-6 concentration were significantly higher than in patients without embolism (p â€‹< â€‹0.05). The significant differences between the groups with and without fatal outcome were observed within all analyzed parameters. Significant differences in all examined parameters before treatment were observed between patients with and without clinical improvement (p â€‹< â€‹0.05). Multivariate logistic regression showed that no clinical improvement was associated with: IL-6>100 â€‹pg/ml (OR-2.14), D-dimer concentration over 1000 â€‹ng/ml (OR-1.62) and PLT count below 150,000/µl (OR-1.57). CONCLUSIONS: Severe course of the disease is associated with lower PLT and lymphocyte count, higher D-dimer, CRP, neutrophil count and IL-6 concentration. The best predictors of no clinical improvement in COVID-19 are: IL-6>100 â€‹pg/ml, D-dimer>1000 â€‹ng/ml and PLT<150,000/µl.

The Role of Th17 Response in COVID-19.

COVID-19 is an acute infectious disease of the respiratory system caused by infection with the SARS-CoV-2 virus (Severe Acute Respiratory Syndrome Coronavirus 2). Transmission of SARS-CoV-2 infections occurs through droplets and contaminated objects. A rapid and well-coordinated immune system response is the first line of defense in a viral infection. However, a disturbed and over-activated immune response may be counterproductive, causing damage to the body. Severely ill patients hospitalised with COVID-19 exhibit increased levels of many cytokines, including Interleukin (IL)-1ß, IL-2, IL-6, IL-7, IL-8, IL-10, IL-17, granulocyte colony stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF). Increasing evidence suggests that Th17 cells play an important role in the pathogenesis of COVID-19, not only by activating cytokine cascade but also by inducing Th2 responses, inhibiting Th1 differentiation and suppressing Treg cells. This review focuses on a Th17 pathway in the course of the immune response in COVID-19, and explores plausible targets for therapeutic intervention.

Effectiveness of Tocilizumab with and without Dexamethasone in Patients with Severe COVID-19: A Retrospective Study.

PURPOSE: The pathogenesis of coronavirus disease 2019 (COVID-19) is complicated, and in addition to antiviral therapy and combating coagulopathy, treatment should also include inhibition of the proinflammatory cytokines overproduction. The purpose of this study is to compare the effectiveness of tocilizumab (TCZ) and dexamethasone (DEX) administered alone or in combination in patients with severe COVID-19. PATIENTS AND METHODS: Patients were selected from the SARSTer database, containing 3330 individuals with COVID-19 treated between 1 March 2020 and 10 March 2021. The current study included adult patients with baseline oxygen saturation (SpO2) ≤90%, requiring regular or non-invasive high-flow oxygen supplementation. RESULTS: Among included 460 patients, 59 were treated with TCZ, 125 with TCZ and DEX, 169 with DEX, and 107 did not receive TCZ nor DEX. The groups were balanced regarding demographics, coexisting diseases, baseline SpO2, and comedications with remdesivir or low-molecular-weight heparin. The death rate of 6.8% was significantly lower in patients receiving TCZ alone than each arm (19.6%-23.1%), particularly in patients with interleukin-6 concentration exceeding 100pg/mL (5% vs 22.9%-51.7%, respectively). Analysis of clinical improvement demonstrated doubled, significantly higher rate after 21 and 28 days in patients treated with TCZ alone (60% and 75%, respectively) compared to DEX (27.6% and 37.9%, respectively). The need for mechanical ventilation was similar in all arms. CONCLUSION: In patients with severe course of COVID-19, particularly those developing cytokine storm, administration of TCZ provides a significantly better effect than DEX regarding survival, clinical improvement, and hospital discharge rate. The combination of TCZ and DEX does not improve therapy effectiveness in patients with severe COVID-19 compared to the administration of TCZ alone.

Five-Year Follow-Up of Cured HCV Patients under Real-World Interferon-Free Therapy.

(1) Background: Treatment of hepatitis C virus (HCV) infections with direct-acting antivirals (DAA) has demonstrated high efficacy and an excellent safety profile. The cured patients showed a sustained virological response and improved liver function, but also a continued risk of hepatocellular carcinoma (HCC) during the 2-3 years of follow-up after treatment; (2) Methods: A total of 192 patients out of 209 of the primary AMBER study were analyzed five years after treatment with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin. Results: We confirmed that HCV clearance after DAA treatment is stable regardless of baseline liver fibrosis. We found that sustained virologic response is associated with a gradual but significant reduction in liver stiffness over 5 years. Liver function improved during the first 2 years of follow-up and remained stable thereafter. The risk of death due to HCC as well as death due to HCV persists through 5 years of follow-up after successful DAA treatment. However, in non-cirrhotic patients, it appears to clear up 3 years after treatment; (3) Conclusions: Monitoring for more than 5 years after curing HCV infection is necessary to assess the long-term risk of possible development of HCC, especially in patients with cirrhosis of the liver.

Tocilizumab Improves the Prognosis of COVID-19 in Patients with High IL-6.

Despite direct viral effect, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore, tocilizumab (TOC), a monoclonal antibody against IL-6 receptors, was considered as a possible therapeutic option. Patients were selected from the SARSTer database, containing 2332 individuals with COVID-19. Current study included 825 adult patients with moderate to severe course. Analysis was performed in 170 patients treated with TOC and 655 with an alternative medication. The end-points of treatment effectiveness were death rate, need for mechanical ventilation, and clinical improvement. Patients treated with TOC were balanced compared to non-TOC regarding gender, age, BMI, and prevalence of coexisting conditions. Significant effect of TOC on death was demonstrated in patients with baseline IL-6 > 100 pg/mL (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.08-0.57). The best effectiveness of TOC was achieved in patients with a combination of baseline IL-6 > 100 pg/mL and either SpO2 ≤ 90% (HR: 0.07) or requiring oxygen supplementation (HR: 0.18). Tocilizumab administration in COVID-19 reduces mortality and speeds up clinical improvement in patients with a baseline concentration of IL-6 > 100 pg/mL, particularly if they need oxygen supplementation owing to the lower value of SpO2 ≤ 90%.

Demographic and Clinical Overview of Hospitalized COVID-19 Patients during the First 17 Months of the Pandemic in Poland.

Long-term analyses of demographical and clinical characteristics of COVID-19 patients can provide a better overview of the clinical course of the disease. They can also help understand whether changes in infection symptomatology, disease severity, and outcome occur over time. We aimed to analyze the demographics, early symptoms of infection, laboratory parameters, and clinical manifestation of COVID-19 patients hospitalized during the first 17 months of the pandemic in Poland (March 2020-June 2021). The patients' demographical and clinical data (n = 5199) were extracted from the national SARSTer database encompassing 30 medical centers in Poland and statistically assessed. Patients aged 50-64 were most commonly hospitalized due to COVID-19 regardless of the pandemic period. There was no shift in the age of admitted patients and patients who died throughout the studied period. Men had higher C-reactive protein and interleukin-6 levels and required oxygenation and mechanical ventilation more often. No gender difference in fatality rate was seen, although the age of males who died was significantly lower. A share of patients with baseline SpO2 < 91%, presenting respiratory, systemic and gastrointestinal symptoms was higher in the later phase of a pandemic than in the first three months. Cough, dyspnea and fever were more often presented in men, while women had a higher frequency of anosmia, diarrhea, nausea and vomiting. This study shows some shifts in SARS-CoV-2 pathogenicity between March 2020 and July 2021 in the Polish cohort of hospitalized patients and documents various gender-differences in this regard. The results represent a reference point for further analyses conducted under the dominance of different SARS-CoV-2 variants.