Analysis of Deaths among HIV-Infected Patients Hospitalized in 2009-2018 in Main Centre of Infectious Disease in Region of Lower Silesia in Poland, Detailing Lesions in the Central Nervous System.

Background and Objectives: Patients living with HIV (PLWH), especially those diagnosed too late or not receiving treatment with antiretroviral drugs in the stage of advanced immunodeficiency AIDS for various reasons, develop additional opportunistic infections or AIDS-defining diseases that may contribute directly to the death of these patients. Material and Methods: In this work, we focused on disorders of the central nervous system (CNS) by retrospectively analyzing the symptoms, clinical and autopsy diagnoses of patients diagnosed with HIV infection who died in the provincial specialist hospital in the Lower Silesia region in Poland. Results: The autopsy was performed in 27.4% cases. The cause of death was determined to be HIV-related/AIDS-associated in 78% patients. The most common AIDS-defining CNS diseases in our cohort were toxoplasmosis and cryptococcosis. Conslusions: The presented results of the most common causes of changes in the central nervous system among deceased HIV-infected patients are comparable to the results of studies by other scientists cited in the publication.

Simple demographic characteristics and laboratory findings on admission may predict in-hospital mortality in patients with SARS-CoV-2 infection: development and validation of the covid-19 score.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a major health burden worldwide due to high mortality rates and hospital bed shortages. SARS-CoV-2 infection is associated with several laboratory abnormalities. We aimed to develop and validate a risk score based on simple demographic and laboratory data that could be used on admission in patients with SARS-CoV-2 infection to predict in-hospital mortality. METHODS: Three cohorts of patients from different hospitals were studied consecutively (developing, validation, and prospective cohorts). The following demographic and laboratory data were obtained from medical records: sex, age, hemoglobin, mean corpuscular volume (MCV), platelets, leukocytes, sodium, potassium, creatinine, and C-reactive protein (CRP). For each variable, classification and regression tree analysis were used to establish the cut-off point(s) associated with in-hospital mortality outcome based on data from developing cohort and before they were used for analysis in the validation and prospective cohort. The covid-19 score was calculated as a sum of cut-off points associated with mortality outcome. RESULTS: The developing, validation, and prospective cohorts included 129, 239, and 497 patients, respectively (median age, 71, 67, and 70 years, respectively). The following cut of points associated with in-hospital mortality: age > 56 years, male sex, hemoglobin < 10.55 g/dL, MCV > 92.9 fL, leukocyte count > 9.635 or < 2.64 103/µL, platelet count, < 81.49 or > 315.5 103/µL, CRP > 51.14 mg/dL, creatinine > 1.115 mg/dL, sodium < 134.7 or > 145.4 mEq/L, and potassium < 3.65 or > 6.255 mEq/L. The AUC of the covid-19 score for predicting in-hospital mortality was 0.89 (0.84-0.95), 0.850 (0.75-0.88), and 0.773 (0.731-0.816) in the developing, validation, and prospective cohorts, respectively (P < 0.001The mortality of the prospective cohort stratified on the basis of the covid-19 score was as follows: 0-2 points,4.2%; 3 points, 15%; 4 points, 29%; 5 points, 38.2%; 6 and more points, 60%. CONCLUSION: The covid-19 score based on simple demographic and laboratory parameters may become an easy-to-use, widely accessible, and objective tool for predicting mortality in hospitalized patients with SARS-CoV-2 infection.

Is an 8-week regimen of glecaprevir/pibrentasvir sufficient for all hepatitis C virus infected patients in the real-world experience?

BACKGROUND AND AIMS: The revolution of the antiviral treatment of hepatitis C virus (HCV) infection resulting in higher effectiveness came with the introduction of direct-acting antivirals with pangenotypic regimens as a final touch. Among them, the combination of glecaprevir (GLE) and pibrentasvir (PIB) provides the opportunity for shortening therapy to 8 weeks in the majority of patients. Because of still insufficient evaluation of this regimen in the real-world experience, our study aimed to assess the efficacy and safety of 8-week GLE/PIB in chronic hepatitis C patients depending on liver fibrosis and genotype (GT). METHODS: The analysis included patients who received GLE/PIB for 8 weeks selected from the EpiTer-2 database, large retrospective national real-world study evaluating antiviral treatment in 12 584 individuals in 22 Polish hepatology centers. RESULTS: A total of 1034 patients with female predominance (52%) were enrolled in the analysis. The majority of them were treatment naïve (94%), presented liver fibrosis (F) of F0-F3 (92%), with the most common GT1b, followed by GT3. The overall sustained virologic response after exclusion of nonvirologic failures was achieved in 95.8% and 98%, respectively (P = 0.19). In multivariate logistic regression HCV GT-3 (beta = 0.07, P = 0.02) and HIV infection (beta = -0.14, P < 0.001) were independent predictors of nonresponse. CONCLUSIONS: We demonstrated high effectiveness of 8-week GLE/PIB treatment in a non-GT3 population irrespective of liver fibrosis stage. Comparable efficacy was achieved in non-cirrhotic patients regardless of the genotype, including GT3 HCV.

Lusutrombopag for the Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Invasive Procedures (L-PLUS 2).

Thrombocytopenia may be associated with increased bleeding risk impacting timing and outcome of invasive procedures in patients with chronic liver disease (CLD). Lusutrombopag, a small-molecule, thrombopoietin (TPO) receptor agonist, was evaluated as a treatment to raise platelet counts (PCs) in patients with thrombocytopenia and CLD undergoing invasive procedures. L-PLUS 2 was a global, phase 3, randomized, double-blind, placebo-controlled study. Adults with CLD and baseline PCs < 50 × 109 /L were randomized to receive once-daily lusutrombopag 3 mg or placebo ≤ 7 days before an invasive procedure scheduled 2-7 days after the last dose. The primary endpoint was avoidance of preprocedure platelet transfusion and avoidance of rescue therapy for bleeding. A key secondary endpoint was number of days PCs were ≥ 50 × 109 /L throughout the study. Safety analysis was performed on patients who received at least one dose of study drug. This study occurred between June 15, 2015, and April 19, 2017, with a total of 215 randomized patients (lusutrombopag, 108; placebo, 107); 64.8% (70/108) of patients in the lusutrombopag group versus 29.0% (31/107) in the placebo group met the primary endpoint (P < 0.0001; difference of proportion 95% confidence interval [CI], 36.7 [24.9, 48.5]). The median duration of PCs ≥ 50 × 109 /L was 19.2 days with lusutrombopag (without platelet transfusion) compared with 0.0 in the placebo group (with platelet transfusion) (P = 0.0001). Most adverse events were mild or moderate in severity, and rates were similar in the lusutrombopag and placebo groups (47.7% and 48.6%, respectively). Conclusion: Lusutrombopag was superior to placebo for reducing the need for platelet transfusions and achieved durable PC response in patients with thrombocytopenia and CLD undergoing invasive procedures, with a safety profile similar to placebo.

Real-world experience with Grazoprevir/Elbasvir in the treatment of previously "difficult to treat" patients infected with hepatitis C virus genotype 1 and 4.

BACKGROUND AND AIM: Grazoprevir/elbasvir (GZR/EBR) was approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 and 4 infected patients with or without compensated liver cirrhosis. The aim of this study was to assess GZR/EBR regimen in the real-world experience, particularly in previously "difficult-to-treat" patients with chronic kidney diseases, human immunodeficiency virus-coinfected, cirrhotics, and treatment-experienced. METHODS: The analysis included patients treated with GZR/EBR selected from 10 152 individuals from the EpiTer-2 database, large national real-world study evaluating antiviral treatment in 22 Polish hepatology centers between 2015 and 2018. Data were completed retrospectively and submitted online. RESULTS: A total of 1615 patients who started GZR/EBR therapy in 2017 and 2018 with a female predominance (54%) and median age of 54 years were analyzed. The majority were infected with GT1b (89%) and treatment naïve (81%). Liver cirrhosis was diagnosed in 19%, and 70% of patients had comorbidities, of which chronic renal disease was present in 7% and HIV-coinfection in 4%. Overall, a sustained virologic response (SVR) was achieved by 95% according to intent-to-treat (ITT) and 98% after exclusion of lost to follow up (modified ITT). No differences were found in cure rate between all included patients and subpopulations previously considered as difficult-to-treat. Majority of patients completed the treatment course as scheduled, adverse events were mostly mild and did not lead to therapy discontinuation. CONCLUSIONS: GZR/EBR treatment carried-out in patients infected with HCV genotype 1 and 4 demonstrated good tolerability and an excellent SVR rate with no effectiveness reduction in so called difficult-to-treat populations.

Differences in the courses of meningococcal and pneumococcal cerebrospinal meningitis.

Neisseria meningitidis and Streptococcus pneumoniae are the most common pathogens causing cerebrospinal meningitis (CSM) in adults. The mortality rate and the number of complications remain high. In our study, retrospective evaluations were conducted on data concerning 98 adult patients with bacterial cerebrospinal meningitis caused by Neisseria meningitidis (n = 42) and Streptococcus pneumoniae (n = 56), hospitalised at the Regional Specialistic Hospital in Wroclaw (Poland) within the period 1998-2018. Compared to the group infected with S. pneumoniae, patients infected with N. meningitidis were younger and were less often affected by an additional disease burden; they presented more frequently with haemorrhagic rashes. Compared to the S. pneumoniae group, in patients with meningococcal CSM, cytosis in cerebrospinal fluid measuring < 1,000 cells/ mL was less frequent; intravascular coagulation syndrome appeared more frequently; the hospitalisation time was shorter and the rate of mortality was lower. Meningococcal meningitis occurs more frequently among young people with no history of disease. It is characterised by the rapid development of symptoms, which results in earlier diagnosis and more favourable prognosis compared to cases of S. pneumoniae. Irrespective of the pathogen, advanced age and a level of cytosis in cerebrospinal fluid of < 1,000 cells /µl indicate an unfavourable prognosis.

Hepatitis B core-related antigen monitoring during peginterferon alfa treatment for HBeAg-negative chronic hepatitis B.

Serum Hepatitis B core-related antigen (HBcrAg) level moderately correlates with cccDNA. We examined whether HBcrAg can add value in monitoring the effect of peginterferon (PEG-IFN) therapy for HBeAg-negative chronic hepatitis B (CHB) infection. Thus, serum HBcrAg level was measured in 133 HBeAg-negative, mainly Caucasian CHB patients, treated with 48 weeks of PEG-IFN alfa-2a. We assessed its association with response (ALT normalization & HBV DNA < 2000 IU/mL) at week 72. HBcrAg level strongly correlated with HBV DNA level (r = 0.8, P < 0.001) and weakly with qHBsAg and ALT (both r = 0.2, P = 0.01). At week 48, mean HBcrAg decline was -3.3 log U/mL. Baseline levels were comparable for patients with and without response at week 72 (5.0 vs 4.9 log U/mL, P = 0.59). HBcrAg decline at week 72 differed between patients with and without response (-2.4 vs -1.0 log U/mL, P = 0.001), but no cut-off could be determined. The pattern of decline in responders resembled that of HBV DNA, but HBcrAg decline was weaker (HBcrAg -2.5 log U/mL; HBV DNA: -4.0 log IU/mL, P < 0.001). For early identification of nonresponse, diagnostic accuracy of HBV DNA and qHBsAg decline at week 12 (AUC 0.742, CI-95% [0.0.629-0.855], P < 0.001) did not improve by adding HBcrAg decline (AUC 0.747, CI-95% [0.629-0.855] P < 0.001), nor by replacing HBV DNA decline by HBcrAg decline (AUC 0.754, CI-95% [0.641-0.867], P < 0.001). In conclusion, in Caucasian patients with HBeAg-negative CHB, decline of HBcrAg during PEG-IFN treatment was stronger in patients with treatment response. However, HBcrAg was not superior to HBV DNA and qHBsAg in predicting response during PEG-IFN treatment.

Long-term follow-up of patients treated with entecavir and peginterferon add-on therapy for HBeAg-positive chronic hepatitis B infection: ARES long-term follow-up.

Addition of peginterferon alpha (PEG-IFN add-on) to entecavir (ETV) treatment after a short lead-in phase results in more response than ETV monotherapy in HBeAg-positive chronic hepatitis B infection (CHB). This study is the first to assess long-term efficacy of this treatment strategy. Patients who received ETV ± 24 weeks of PEG-IFN add-on in a global trial (ARES study) and completed follow-up were eligible to participate in this observational LTFU study if they had at least one combined HBeAg and HBV DNA measurement beyond week 96 of the ARES study. The primary endpoint was combined response (HBeAg loss and HBV DNA <200 IU/mL) at LTFU. In total, 48 patients treated with PEG-IFN add-on and 48 patients treated with ETV monotherapy were included. The median follow-up duration was 226 (IQR 51) weeks, and 86/96 (90%) patients were initial non-responders. At LTFU, combined response was present in 13 (27%) vs 11 (23%) patients (P = 0.81), and 1 log10  HBsAg decline in 59% vs 28% (P = 0.02) for PEG-IFN add-on and ETV monotherapy, respectively. In 41 initial non-responders who continued ETV therapy, combined response at LTFU was present in 9 patients (PEG-IFN add-on: 5/22 [23%]; ETV monotherapy: 4/19 [21%]). Beyond week 96 of follow-up, rates of serological response became comparable between PEG-IFN add-on and ETV monotherapy. Although in this LTFU study initial non-responders were overrepresented in the add-on arm, PEG-IFN add-on possibly leads rather to accelerated HBeAg loss than to increased long-term HBeAg loss rates.

A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis.

The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of CC chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis (LF). A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score (NAS) ≥4, and LF (stages 1-3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis (SH) and no worsening of fibrosis; improvement in fibrosis by ≥1 stage and no worsening of SH. Biomarkers of inflammation and adverse events were assessed. Full study recruitment was achieved. The primary endpoint of NAS improvement in the intent-to-treat population and resolution of SH was achieved in a similar proportion of subjects on CVC (N = 145) and placebo (N = 144; 16% vs. 19%, P = 0.52 and 8% vs. 6%, P = 0.49, respectively). However, the fibrosis endpoint was met in significantly more subjects on CVC than placebo (20% vs. 10%; P = 0.02). Treatment benefits were greater in those with higher disease activity and fibrosis stage at baseline. Biomarkers of systemic inflammation were reduced with CVC. Safety and tolerability of CVC were comparable to placebo. CONCLUSION: After 1 year of CVC treatment, twice as many subjects achieved improvement in fibrosis and no worsening of SH compared with placebo. Given the urgent need to develop antifibrotic therapies in NASH, these findings warrant phase 3 evaluation. (Hepatology 2018;67:1754-1767).

The efficacy of paritaprevir/ritonavir/ombitasvir+dasabuvir and ledipasvir/sofosbuvir is comparable in patients who failed interferon-based treatment with first generation protease inhibitors - a multicenter cohort study.

BACKGROUND: According to the EASL and AASLD guidelines, the recommended treatment for patients who failed to achieve a sustained virologic response (SVR) on prior interferon-based triple therapy with protease inhibitors (PI), is a combination of sofosbuvir and NS5A inhibitors. Polish national recommendations also allow the use of paritaprevir/ritonavir/ombitasvir+dasasbuvir±ribavirin (PrODR) in this group of patients. The aim of the study was to evaluate the efficacy and safety of PrODR vs. ledipasvir/sofosbuvir±RBV (LSR) in PI-experienced patients in real-life setting. METHODS: Our analysis included patients registered in the nationwide, investigators initiated, multicentre EpiTer-2 database. Among 4530 patients registered, 335 with genotype 1 (93% 1b) were previously treated with IFN-based regimens with PIs: 127 with boceprevir (BOC), 208 with telaprevir (TVR). Patients with advanced fibrosis (F3/F4) were significantly predominant (BOC 28.4%/61.4%, TVR 18.8%/64.4%, respectively). Subjects were assigned to IFN-free retreatment as follows: BOC - 64 (50.4%) PrODR and 63 (49.6%) LSR; TVR- 103 (49.5%) PrODR and 105 (50.5%) LSR. RESULTS: SVR rates were comparable for particular groups: BOC → PrODR- 100%; BOC → LSR - 98%; TVR → PrODR - 97%; TVR → LSR - 96% (intent-to treat analysis-ITT) and BOC → PrODR→100%; BOC → LSR - 99%; TVR → PrODR - 99%; TVR → LSR - 98% (modified intent-to treat analysis-mITT). Both treatment regimens had a favourable safety profile. Adverse events (AEs) were generally mild or moderate in severity. Three deaths were reported. The treatment was stopped due to AEs in five patients (three treated with PrODR and two with LSR). CONCLUSION: Efficacy and safety of treatment with PrODR and LSR is comparable in BOC or TVR-experienced patients.

Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study).

UNLABELLED: Entecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long-term therapy may be required. We investigated whether adding on pegylated interferon (Peg-IFN) to ETV therapy enhances serological response rates. In this global investigator-initiated, open-label, multicenter, randomized trial, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5 mg/day) and were randomized in a 1:1 ratio to either Peg-IFN add-on therapy (180 µg/week) from week 24 to 48 (n = 85) or to continue ETV monotherapy (n = 90). Response was defined as HBeAg loss with HBV DNA <200 IU/mL at week 48. Responders discontinued ETV at week 72. All patients were followed until week 96. Response was achieved in 16 of 85 (19%) patients allocated to the add-on arm versus 9 of 90 (10%) in the monotherapy arm (P = 0.095). Adjusted for HBV DNA levels before randomized therapy, Peg-IFN add-on was significantly associated with response (odds ratio: 4.8; 95% confidence interval: 1.6-14.0; P = 0.004). Eleven (13%) of the add-on-treated patients achieved disease remission after ETV cessation versus 2 of 90 (2%) of those treated with monotherapy (P = 0.007), which was 79% (11 of 14) versus 25% (2 of 8) of those who discontinued ETV (P = 0.014). At week 96, 22 (26%) patients assigned add-on versus 12 (13%) assigned monotherapy achieved HBeAg seroconversion (P = 0.036). Peg-IFN add-on led to significantly more decline in hepatitis B surface antigen, HBeAg, and HBV DNA (all P < 0.001). Combination therapy was well tolerated. CONCLUSION: Although the primary endpoint was not reached, 24 weeks of Peg-IFN add-on therapy led to a higher proportion of HBeAg response, compared to ETV monotherapy. Add-on therapy resulted in more viral decline and appeared to prevent relapse after stopping ETV. Hence, Peg-IFN add-on therapy may facilitate the discontinuation of nucleos(t)ide analogs.

Tissue laser biostimulation promotes post-extraction neoangiogenesis in HIV-infected patients.

The aim of the study was to assess the rate of neoangiogenesis in extraction wound healing following exposure to biostimulating laser therapy and to analyze the correlation between parameters of neoangiogenesis as reflected by the number and surface area of newly formed blood vessels and clinical parameters such as gender, position of a tooth in the oral cavity, and CD4 lymphocyte count. Twenty-seven patients with confirmed HIV infection were enrolled in the study (6 women, 21 men). Eighty-nine teeth were extracted; 45 sockets were exposed to 6 J laser radiation (laser parameters were set as follows: wavelength, 820 nm; output, 200 mW; dose, 6 J/cm(2); spot size, 38 mm(2); continuous radiation) for five consecutive days following tooth extraction, and the remaining extraction wounds were left to heal spontaneously without laser irradiation. Antigen CD34 was assessed by immunohistochemistry as a marker of angiogenesis, and its expression was examined by computer-assisted histomorphometric image analysis. As a result, we report that biostimulating laser therapy in HIV-infected patients of varying degrees of immunodeficiency greatly accelerated post-extraction neoangiogenesis, regardless of the patient's gender, tooth position, number of roots, or number of CD4 lymphocytes in the blood. Application of low-level laser therapy for the treatment of tooth extraction wounds in HIV(+) patients greatly enhanced the formation of new blood vessels, which in turn promoted wound healing.

Impact of vaccination against HBV on hepatitis B incidence in Opolskie province in 2007-2011.

OBJECTIVE: This article aimed at evaluating the impact of HBV vaccination in population included and not listed in the National Immunization Programme (NIP) on hepatitis B incidence in Opolskie province in 2007 - 2011. MATERIALAND METHODS: Analysis was based on data provided by the Sanitary and Epidemiological Inspection under epidemiological surveillance conducted, i.e. MZ-56, MZ-57 reports (reports on cases of infectious diseases), MZ-54 reports (reports on vaccinations) and 'Questionnaires on hepatitis type B and C'. A total of 446 records of detected and confirmed hepatitis B cases, registered in 2007-2011 in district sanitary and epidemiological stations, were subject to analysis. RESULTS: In 2007-2011, hepatitis B incidence in Opolskie province was higher compared to the average incidence in Poland and was increasing in the successive years (5.8; 6.6; 7.9; 11.8; 11.0 per 100,000 population). An increase of incidence resulted from increasing number of patients with chronic hepatitis B (chronic HBV), i.e. from 47 in 2007 to 119 in 2010 and 110 in 2011 compared to decreasing number of acute infections (acute HBV). In the analyzed period, no new infections were reported in the following age group 0-9 years in Opolskie province. Only 3 cases (chronic stage) were noted in the age group 10-14 years. Of 446 patients, diagnosed with hepatitis B, 309 (69.3%) were not vaccinated. The remaining cases of acute or chronic hepatitis B were vaccinated, including 124 (27.8%) and 13 individuals with complete and incomplete vaccination, respectively. CONCLUSIONS: This analysis suggests an important role of HBV vaccination in the prevention of HBV infections. In case of individuals at the age older than that specified in the NIP, especially adults, it is recommended to perform diagnostic tests for HBV infection prior to vaccination. Furthermore, it is required to undertake activities aimed at promoting HBV vaccination in populations which are not included in the NIP.

DRESS syndrome as a complication of treatment of hepatitis C virus-associated post-inflammatory liver cirrhosis with peginterferon α2a and ribavirin.

Various skin and systemic symptoms may develop as a complication of treatment with different medications and medicinal substances. One of them is a relatively rare drug reaction with eosinophilia and systemic symptoms, referred to as DRESS syndrome. The morphology of skin lesions and the patient's general health can differ; the management involves withdrawal of drugs suspected of triggering DRESS syndrome, and administration of local and systemic glucocorticosteroids. In this paper we present a case of a patient with HCV associated chronic hepatitis, treated with peginterferon α2a (PEG-IFN-α2a) and ribavirin, who developed skin lesions and systemic symptoms typical of DRESS syndrome.

Complexity and Diversity of the Neurological Spectrum of SARS-CoV-2 over Three Waves of COVID-19.

Background/Objectives: SARS-CoV-2 continually mutates, with five identified variants. Many neurological manifestations were observed during the COVID-19 pandemic, with differences between virus variants. The aim of this study is to assess the frequency and characteristics of neurological manifestations during COVID-19 in hospitalized patients over three waves in Poland with comparison and analysis correlation with the course of infection. Methods: This retrospective single-center study included 600 consecutive adults with confirmed COVID-19, hospitalized during 3 waves (pre-Delta, Delta and Omicron) in Poland. Demographic and clinical information and neurological manifestations were collected and compared across three periods. Results: The median age of the study group was 68, lower during the Delta wave. In the Omicron period, the disease severity at admission and inflammatory markers concentration were the lowest. Neurological manifestations were observed in 49%. The most common were altered mentation, headache, myalgia, mood disorder, ischemic stroke and encephalopathy. Smell and taste disturbances (STDs) were less frequent in the Omicron period. Neurological complications were predominant in the pre-Delta and Omicron periods. Ischemic stroke was observed more often in pre-Delta period. Altered mentation was related to higher severity at admission, worse lab test results, higher admission to ICU and mortality, while headache reduced mortality. Pre-existing dementia was related to higher mortality. Conclusions: Neurological manifestations of COVID-19 are frequent, with a lower rate of STDs in the Omicron period and more often cerebrovascular diseases in the pre-Delta period. Headache improves the course of COVID-19, while altered mentation, stroke and neurological comorbidities increase severity and mortality.

Presence of precore and core promoter mutants limits the probability of response to peginterferon in hepatitis B e antigen-positive chronic hepatitis B.

UNLABELLED: Peginterferon (PEG-IFN) treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) results in HBeAg loss in 30% of patients, but clearance of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) from serum is less often achieved. We investigated whether the presence of precore (PC) and basal core promoter (BCP) mutants before PEG-IFN treatment affects serological and virological response. A total of 214 HBeAg-positive CHB patients treated with PEG-IFN ± lamivudine for 52 weeks in a global randomized trial were classified at baseline as wildtype (WT) or non-WT (detectable mutants at PC/BCP) by line-probe assay. Response was assessed at 6 months posttreatment and through long-term follow-up (LTFU). Mutants were detected in 64% of patients, in varying frequencies across HBV genotypes A through D. Patients with WT had higher baseline HBV DNA, HBeAg, and HBsAg levels than patients with non-WT. Patients with WT were more likely to achieve HBeAg loss with HBV DNA <10,000 copies/mL (response, 34 versus 11%, P < 0.001) and HBsAg clearance (18 versus 2%, P < 0.001) at week 78 than non-WT patients. Among WT patients who achieved HBeAg clearance at week 78, 78% had undetectable HBV DNA and 61% achieved HBsAg clearance at LTFU (versus 26% and 15% in non-WT patients, P < 0.001 for both). The presence of WT virus at baseline was an independent predictor of response (odds ratio [OR] 2.90, 95% confidence interval [CI]: 1.15-7.31, P = 0.023) and HBsAg clearance (OR 5.58, 95% CI: 1.26-24.63, P = 0.013) and patients with non-A genotypes with detectable mutants had a low probability of response. CONCLUSION: The presence of only WT virus at baseline is a strong predictor of response (HBeAg loss with HBV DNA <10,000 copies/mL) to PEG-IFN for HBeAg-positive CHB. Patients with detectable PC and/or BCP mutants have a lower probability of response and are less optimal candidates for PEG-IFN therapy.