Amantadine in unvaccinated patients with early, mild to moderate COVID-19: A randomized, placebo-controlled, double-blind trial.

BACKGROUND AND PURPOSE: Adamantanes were listed as an interesting option as an early intervention against COVID-19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID-19 and its neurological sequelae. METHODS: Unvaccinated patients with confirmed SARS-CoV-2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI-WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15. RESULTS: We enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI-WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI-WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated. CONCLUSION: The central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID-19 patients.

The Association of Chronic Hepatitis C with Respiratory Microbiota Disturbance on the Basis of Decreased Haemophilus Spp. Colonization.

BACKGROUND Haemophilus species are the most common microbiota in humans. The aim of this paper was to investigate Haemophilus spp., mainly H. parainfluenzae prevalence, in the upper respiratory tract of chronic hepatitis C (CHC-positive) patients with or without therapy using pegylated interferon alfa and ribavirin. MATERIAL AND METHODS We collected 462 samples from 54 healthy people and 100 CHC-positive patients at various stages: before (group A), during (group B), and after (group C) antiviral therapy. Identification of bacterial isolates including biotypes and antimicrobials susceptibility was accomplished by means of standard microbiological methods. RESULTS In 70.4% of healthy people (control group) and in 27.0% of CHC-positive patients, the presence of haemophili, mainly H. parainfluenzae was observed, and those differences were statistically significant (p<0.0001). Statistically significant differences in Haemophilus spp. colonization were also observed among healthy people and CHC-positive patients from group A (p=0.0012) and from B or C groups (p<0.0001). Resistance to ampicillin in beta-lactamase-positive isolates and multidrug resistance (MDR) of H. parainfluenzae was detected mainly in group A. CONCLUSIONS The obtained data suggest that chronic hepatitis C, together with antiviral therapy, may influence the respiratory tract microbiota composition as found using haemophili, mainly H. parainfluenzae.

The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design.

BACKGROUND: COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications. METHODS AND RESULTS: The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine. CONCLUSIONS: Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).

Risk factors and outcomes for acute respiratory failure in coronavirus disease 2019: An observational cohort study.

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout Europe. However, there is a lack of data on the full clinical course of patients infected with SARS-CoV-2 in Europe, especially in the population that developed acute respiratory failure (ARF). OBJECTIVES: To identify risk factors associated with developing ARF during SARS-CoV-2 infection. MATERIAL AND METHODS: This was an observational study of 60 adult patients with laboratory-confirmed SARS-CoV-2 infection. Data were collected from March 26, 2020 to May 26, 2020 in a tertiary academic hospital in Poland. All patients reached final outcome (discharge from the hospital or death). We divided patients into 2 groups based on whether they developed ARF, compared their clinical data, and performed multivariate logistic regression. RESULTS: Twenty-two patients (36%) from the observed cohort developed ARF. Logistic regression identified that a high sequential organ failure assessment score at admission (odds ratio (OR) = 6.97 (1.57-30.90, p = 0.011)), and a long time from admission until pneumonia (OR = 1.41 (1.06-1.87, p = 0.016)), correlated with ARF development. D-dimer, lactate dehydrogenase, neutrophil to lymphocyte ratio, C-reactive protein (CRP), and interleukin 6 (IL-6) differed both statistically and clinically between ARF and non-ARF groups. The mortality rate in the observed cohort of patients was 13.3%, and it was 32% in the group that developed ARF. CONCLUSIONS: Routine vigilant examination of the above markers may identify patients at the highest risk of ARF early on during COVID-19 infection.

Neutrophil-lymphocyte ratio and mean platelet volume as predictive factors for liver fibrosis and steatosis in patients with chronic hepatitis B.

OBJECTIVE: Evaluation of the neutrophil-lymphocyte ratio and mean platelet volume as predictive factors for liver fibrosis and steatosis in HBV patients qualified for antiviral treatment. MATERIAL AND METHODS: The study comprised 38 CHB patients who had commenced antiviral treatment, and 20 healthy volunteers who constituted the clinical control group. All patients had their blood count taken and underwent hepatic assessment using transient elastography with CAP (controlled attenuation parameter). RESULTS: It was found that the mean hepatic fibrosis was 8.7 kPa (±8.8) and the mean liver steatosis - 286 db/m (±64). Mean NLR - 2.78(±1.1), whereas in the control group the mean NLR value was 1.64(±0.98). A negative linear correlation (r= -0.34; p=0.035) was found between liver fibrosis and the NLR value in the study group. No correlation was observed between hepatic steatosis and the NLR. Mean MPV - 12.6fl (±3.1), which was considerably higher in the CBH patients than in the control group. A positive correlation (r= 0.79, p= 0.001) was found between MPV and disease severity evaluated with transient elastography. CONCLUSIONS: The NLR and the MPV were significantly higher in the CHB patients than in the healthy volunteers. Both the NLR and the MPV can be treated as predictive factors for liver fibrosis in this group of patients.

[Thrombocytopenia in HCV infection. Natural interferon as an alternative therapy]. / Maloplytkowosc w zakazeniu HCV. Interferon naturalny jako terapia alternatywna.

The current standard of care for the treatment of hepatitis C virus (HCV) infection is the combination of pegylated interferon and ribavirin. The interferon-based therapy is contraindicated in patients with HCV-associated thrombocytopenia. The pathogenesis of HCV-associated thrombocytopenia is still unclear. In this paper the main aspects of HCV-associated thrombocytopenia and alternative therapy with natural interferon (Alfaferone) are presented.

Assessing the consistency of liver fibrosis results obtained through biopsy and transient elastography in patients suffering from chronic hepatitis C.

Until recently, core-needle liver biopsy was used as the gold standard in chronic hepatitis C diagnostics. Information on the inflammatory activity grade and the staging of liver fibrosis or steatosis, obtained through biopsy, constituted an indispensable element in the process of determining patients' eligibility for antiviral treatment. The histological profile of the samples examined was decisive in determining the time for commencing treatment. Given that this procedure involves the risk of complications and temporarily reduces patient living comfort, it was deemed necessary to search for other ways to assess liver fibrosis. Transient elastography is a non-invasive alternative to liver biopsy. The current chronic hepatitis C treatment programme provides the possibility to perform transient elastography instead of liver biopsy. The test result is expressed in kPa. However, liver biopsy is still recommended in certain cases of unclear aetiology, or if discrepancies are found between the elastography results and patient clinical condition. The aim of this study was to compare two methods of liver fibrosis assessment in terms of consistency of results, and to analyse any inconsistent results.

Autoimmune reactions in the course of the hepatitis C virus (HCV) infection.

The immune response to the presence of the virus, both specific and non-specific, plays a decisive role in the natural history of the infection, and influences the intensity of lesions in the liver. Despite the great progress which we were able to observe over the last several years, many issues still require clarification. The problem of autoimmune reactions during hepatitis C virus (HCV) infection includes at least two issues. First, the risk of exacerbating reactions against the organism's own tissues that existed before the treatment. There is also an increased risk of the development of de novo autoimmune reactions, triggered mostly by interferon α. Hepatitis C virus infection predisposes to the development of diseases characterised as being certainly or probably immune-mediated. Currently the situation has changed due to introducing non-interferon therapies for HCV treatment, which eliminate the risk associated with immunotherapy in patients with autoimmune diseases, yet the therapies are not widely available.

[Serum copper and zinc level in patients suffering from infectious mononucleosis and after the regression of clinical symptoms]. / Stezenie miedzi i cynku w surowicy oraz wartosc wskaznika miedziowo-cynkowego w przebiegu mononukleozy zakaznej i po ustapieniu objawów klinicznych.

UNLABELLED: The aim of this work was to assess the serum copper (Cu) and zinc (Zn) level and ratio Cu/Zn in the acute, symptomatic period of infectious mononucleosis and during the convalescence period, when no clinical symptoms were present. MATERIAL AND METHODS: We examined 50 persons, including 26 patients (14 women and 12 men) in the age of 16 to 27 years, examined in the acute, symptomatic period of the disease. The diagnosis of infectious mononucleosis was based on the clinical, haematological, biochemical and serologic criteria. Cu and Zn concentration was measured 3 times: on the 1st day and the 2nd week of hospitalisation, and also after the regression of clinical symptoms. The control group consisted of 24 healthy individuals (13 men and 11 women) in the age of 17 to 26 years. Cu and Zn concentration was measured once in this group. All measurements of Cu and Zn serum concentration were done using the method of atomic absorption spectrophotometry (AAS) with AAS-3 spectrophotometer of Carl Zeiss-Jena production, at the wavelength for Cu--324.8, Zn--213.9 nm. We observed the Cu and Zn serum concentration and ratio Cu/Zn in patients with acute, symptomatic infectious mononucleosis and also after the regression of clinical symptoms to be statistically higher that the results from the healthy individuals. CONCLUSION: The statistical significant elevated serum Cu and Zn concentration observed during the course of infectious mononucleosis and after clinical symptoms regression in comparison to healthy persons expressed the perturbation of trace elements homeostasis. If copper to zinc ratio reflects myeloproliferative diseases activity, the practical value for infectious mononucleosis monitoring is the same as copper and zinc serum level measurement.

[Dynamics of changes in magnesium (Mg) serum levels in patients suffering from infectious mononucleosis]. / Ocena dynamiki zmian poziomu magnezu (Mg) w surowicy krwi chorych na mononukleoze zakazna.

The aim of the study was to assess the dynamics of changes in magnesium (Mg) serum levels in the acute, symptomatic period of infectious mononucleosis and during the convalescence period, when clinical symptoms were no longer present. 50 subjects were included, among them 26 patients (14 women and 12 men) at the age of 16 to 27 years in the acute, symptomatic stage of the disease. The diagnosis of infectious mononucleosis was based on the clinical, hematological, biochemical and serologic criteria. Mg concentration was measured 3 times: on the 1st day and in the 2nd week of hospitalization, and also in the convalescence period--3 weeks after the regression of clinical symptoms. The control group consisted of 24 healthy individuals (5 men and 5 women) at the age of 17 to 26 years. Mg concentration was measured once in this group. All measurements of Mg serum concentration were performed using the method of atomic absorption spectrophotometry (AAS) at the wavelength of 285.2 nm. We observed significantly higher Mg serum concentrations in patients with acute, symptomatic infectious mononucleosis than in healthy individuals. During the convalescence period Mg serum concentrations were lower but still statistically higher than in the control group.

[Ramsay Hunt syndrome--a case study]. / Zespól Ramsaya Hunta--opis przypadku.

In this work we present a patient, aged 40 with Ramsay Hunt syndrome, who was treated at the Department of Infectious Disease, Medical Academy in Lublin (Poland). The diagnosis of the disease was based on the anamnesis concerning epidemiology of the disease, the course and three major symptoms: facial paralysis, neuralgia, herpetic eruption in the mouth and on the ear. The combined treatment with antiviral drugs and corticosteroids was partially successful and did not resolve the seventh nerve palsy.

Pregnancy during lamivudine therapy in chronic hepatitis B--case report.

In case of a pregnancy in a patient infected with hepatitis B virus there is a risk of intrauterine fetus infection, which rises significantly with the serological profile of positive hepatitis B surface antigen, hepatitis Be antigen and in the presence of HBV DNA in serum. Therefore, in clinical practice the monitoring of antiviral therapy in chronic hepatitis B in women of reproductive age is becoming especially important. The safety of lamivudine use in pregnant women infected with hepatitis B virus has not yet been proven. In this case, the patient became pregnant during the treatment with lamivudine and when hepatitis B virus replication markers were present in the serum (hepatitis B surface antigen, hepatitis Be antigen, hepatitis B virus DNA). Treatment with lamivudine lasted through the first 6 weeks of pregnancy, which was complicated by a possibility of intrauterine hepatitis B virus infection, did not cause any fetus injury.

Prolactin concentration in the serum of male patients with chronic hepatitis C.

In this work we analysed the dynamics of prolactin serum concentration in male patients with chronic hepatitis C. A group of 52 men were included in the study, 26 of them constituted the control group. The diagnosis of the disease was confirmed by the presence of HCV-RNA in the serum and by the histological examination of the liver. None of the examined men was diagnosed with any co-existing disease nor any infection markers of HAV and HBV were found. The prolactin concentration was determined in the serum of patients twice: on the 2nd day of hospitalisation and after 4 weeks of hospitalisation by the use of radioimmunological method (RIA) applying a prepared set of reagents RIA-PROL-CTK-4 (Sorin Biomedica, Italy). The results were statistically analysed. An analysis of the dynamics of prolactin serum concentration in male patients with chronic hepatitis C shows a statistically important increase in this hormone serum concentration.

Dehydroepiandrosterone sulphate and androstenedione concentration in the serum of male patients with chronic hepatitis C.

In this study the dynamics of DHEAS and androstenedione serum concentration in male patients with CHC infection were analyzed. The study group consisted of 52 men, 26 of them being the control group of healthy men. The DHEAS and androstenedione serum concentration was determined twice with radioimmunological method (RIA). 1. Mean values of suprarenal androgens serum concentration in male patients with CHC infection were lower than in healthy men and the observed differences were incidental, 2. There was no correlation between dehydroepiandrosterone and androstenedione serum concentration in male patients with CHC infection.