Vaccination against COVID-19 among healthcare workers as a cocoon strategy for people living with HIV.

Introduction: Healthcare professionals working in infectious disease units are often engaged in the care of patients with HIV infection. A cocoon vaccination strategy may protect those who are immunocompromised from a severe course of COVID-19. Methods: The research was conducted between January 2021 and June 2022. The study participants were 450 healthcare workers (HCWs) from the Hospital for Infectious Diseases in Warsaw who were vaccinated against COVID-19 with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) -, thefirst available type of vaccine in Poland. Sera were collected according to the schedule of the study. Statistical analyses were performed with non-parametric tests: Wilcoxon's test was used to compare dependent numerical variables, and Fisher's exact test and the Chi-squared test to compare categorical variables. A p value of <0.05 was considered statistically significant. Results: Among the 450 HCWs working in the Hospital for Infectious Diseases in Warsaw 412 (91,5 %) were vaccinated against COVID-19. In total 170 (41,3 %) vaccinated HCWs were included in the final analysis. Their median age was 51 years [interquartile range (IQR): 41-60 years] and median body mass index (BMI) was 25.10 [IQR: 22.68-29.03]. Most of the cohort consisted of women (n = 137, 80.59 %), with the majority working directly with patients (n = 137, 73.21 %). It was found that as early as 14 days after the second dose of the vaccine, 100 % of the study participants achieved a positive result for SARS CoV-2 S-RBD antibodies. There were 168 subjects who had had a COVID-19 diagnosis before entering study and after vaccination 65 HCWs was diagnosed with COVID-19. Conclusions: Due to the fact that people living with HIV with severe immunodeficiency may have an incomplete immune response to COVID vaccination and be at risk of a severe course of the disease, the cocoon strategy of vaccinating medical personnel may be beneficial for these patients.

Cardiovascular complications in the course of COVID-19 - lessons learned and implications for the future care of patients with viral respiratory diseases: Data from a single center retrospective observational study.

BACKGROUND: Factors associated with cardiovascular complications of COVID-19 remain understudied. OBJECTIVES: Here we investigate the occurrence and risk factors of arrythmias, myocardial infarction and/or stroke, and thromboembolism in the course of COVID-19. METHODS: We have performed an observational study with prospectively designed data collection. Data of patients diagnosed with COVID-19 who were admitted from March 6th 2020 to November 30th 2021 in our Hospital were analyzed. Logistic regression was used to identify variables associated with the odds of early hospital death due to COVID-19. RESULTS: Fourteen-point three percent of 1964 patients had cardiovascular complications, 6.36 % arrhythmias, 5.5 % thromboembolic events and 2.39 % myocardial infarction and/or stroke. Factors independently increasing the odds of arrhythmia were older age (OR=1.49 [95 % CI: 1.17-1.92], p = 0.02), longer time between admission and the first onset of symptoms (1.02 [0.99-1.05], p = 0.049), concomitant atrial fibrillation/flutter (2.84 [1.37-5.70], p = 0.004), nicotinism (2.49 [1.37-4.49], p = 0.002), and eGFR<60 ml/min/1.73m2 (2.44 [1.08-5.59], p = 0.033). Factors independently increasing the odds of myocardial infarction and/or stroke were dementia (4.55 [0.97-19.3], p = 0.044), hemiplegia (12.67 [3.12-46.1], p < 0.001), nicotinism (3.36 [1.30-10.4], p = 0.013) and higher C-reactive protein concentration (1.01 [1.00-1.01], p = 0.040). Factors independently increasing the odds of thromboembolic events were longer hospitalization (1.08 [1.05-1.10], p < 0.001) and higher d-dimers (1.04 [1.02-1.05], <0.001). CONCLUSIONS: The risk of cardiovascular complications was especially pronounced in patients with older age, pre-existing cardiovascular disease and more sever pneumonia at presentation to care. This underlines the importance of close and careful clinical follow-up in the course of COVID-19 for specific patients' populations, including a pro-active approach in diagnosis.

Potential infection foci in the oral cavity and their impact on the formation of central nervous system abscesses: A literature review.

Despite advancements in preventive, diagnostic, and therapeutic activities in medicine, inflammatory processes of the central nervous system remain a significant problem, posing a serious threat to life and health. Purulent central nervous system infections are unique, including abscesses of the brain and spine, which are severe infections occurring in 0.4% to 0.9% of 1000 patients worldwide. Central nervous system abscesses have varying etiology. For example, organized, encapsulated abscesses of the brain are a unique group of inflammatory processes in the central nervous system caused by inflammation around the teeth in 3% to 10% of cases. Sometimes, the condition of patients with brain abscesses is severe and life-threatening. Therefore, detecting and eliminating all causes early, including those potentially resulting from odontogenic infections, is important; accurate and early diagnosis enables appropriate treatment. This paper presents a review of the information available in the literature on brain abscesses and their relationship with odontogenic foci of infection in the oral cavity.

Hospital Admission Factors Independently Affecting the Risk of Mortality of COVID-19 Patients.

INTRODUCTION: COVID-19 is a disease characterized by high in-hospital mortality, which seems to be dependent on many predisposing factors. OBJECTIVES: The aim of this study was to analyze the clinical symptoms, abnormalities in the results of laboratory tests, and coexisting chronic diseases that independently affected the risk of in-hospital mortality in patients with COVID-19. PATIENTS AND METHODS: We analyzed the records of patients with COVID-19 who were hospitalized from 6 March 2020 to 30 November 2021. RESULTS: Out of the entire group of 2138 patients who were analyzed, 12.82% died during hospitalization. In-hospital mortality was independently associated with older age (OR 1.53, 95% CI 1.20-1.97); lower arterial blood oxygen saturation (OR 0.95, 95% CI 0.92-0.99); the presence of a neoplasm (OR 4.45, 95% CI 2.01-9.62), a stomach ulcer (OR 3.35, 95% CI 0.94-11.31), and dementia (OR 3.40, 95% CI 1.36-8.26); a higher score on the SOFA scale (OR 1.73, 95% CI 1.52-1.99); higher lactate dehydrogenase (LDH) (OR 1.08, 95% CI 1.05-1.12); higher N-terminal pro-brain natriuretic peptide (NT pro BNP) (OR 1.06, 95% CI 1.01-1.11); and lower total bilirubin in blood concentration (OR 0.94, 95% CI 0.90-0.99). CONCLUSIONS: We found that low oxygen saturation, old age, and the coexistence of cancer, gastric ulcers, and dementia syndrome were variables that independently increased mortality during hospitalization due to COVID-19. Moreover, we found that decreased platelet count and bilirubin concentration and increased levels of LDH and NT-proBNP were laboratory test results that independently indicated a higher risk of mortality. We also confirmed the usefulness of the SOFA scale in predicting treatment results. The ability to identify mortality risk factors on admission to hospital will facilitate both adjusting the intensity of treatment and the monitoring of patients infected with SARS-CoV-2.

Enteroviral central nervous system infections in patients with Lyme neuroborreliosis.

Patients with Lyme neuroborreliosis (LNB) are rarely tested for the presence of neurovirulent viruses other than tick-borne encephalitis virus (TBEV); however, such coinfections could be of clinical importance. The aim of the study was to search for the presence of neurotropic viruses in a LNB patients. Fourteen patients admitted with signs and symptoms of neuroinfection who were eventually diagnosed to have LNB (according to the guidelines of the European Federation of Neurological Societies) were subjects of the study. Sera and cerebrospinal fluid (CSF) collected at the time of initial presentation were tested for viral pathogens most common in our geographical area: human enteroviruses (EV), herpes simplex virus type 1 and 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus type 6, human adenoviruses, and TBEV using PCR/RT-PCR and serological assays. RNA and DNA-based metagenomic next-generation sequencing (mNGS) was used to detect other viral pathogens. EV was detected in CSF from two (14 %) LNB patients and viral loads were similar (220 and 270 copies/ml). The mMGS analysis were performed on CSFs from 10 patients and generated a total 213,750,885 NGS reads, 0.05 % of which were viral. However, none of potential pathogens fulfilled the criteria for positive viral detection by mNGS. Using a number of PCR/RT-PCR assays and mNGS we identified EV infection in two out of 14 LNB patients. The possible co-occurrence of enterovirus and Lyme neuroborreliosis infections may warrant further research.

Late diagnosis of HIV infection in Warsaw: Estimating the scale of the problem and demographic trends.

BACKGROUND: Late diagnosis of a significant number of people with HIV remains a problem. This study analysed 1711 patients from the Hospital for Infectious Diseases in Warsaw who were diagnosed with HIV infection in 2008-2010 and 2016-2018. METHODS: Patients with late diagnosis and advanced disease were distinguished on the basis of the consensus definition. In statistical analysis, non-parametric tests were used to compare the groups: the χ2 test for categorized data and the Mann-Whitney U test for the comparison of continuous variables. RESULTS: There were no statistically significant differences in the percentage of patients with early diagnosis, late diagnosis, advanced disease and patients with an indicator disease between the two analysed periods in the Warsaw centre. A much higher percentage of men than women was found. The dominant route of acquisition among newly diagnosed patients and among late presenters in both periods were men who have sex with men (MSM). The highest percentage of patients with late diagnosis was among heterosexual men and the lowest was among MSM in both periods. CONCLUSIONS: The results of the analysis of patients from the Warsaw centre confirmed that late diagnosis of HIV infection continues to be a problem, with no improvement seen over the analysed periods, although the scale of the problem is smaller than in national and European statistics. MSM and heterosexual men appear to be key groups in need of intensified testing.

Is the definition of late diagnosis correct?

BACKGROUND: The study analysed 1711 patients of the Hospital for Infectious Diseases in Warsaw diagnosed with HIV infection in 2008-2010 and 2016-2018. Research was conducted examining the changes in CD4 cell counts before starting antiretroviral (ARV) treatment in order to find people who were misclassified as late-diagnosed. METHODS: Patients with late diagnosis were distinguished on the basis of the consensus definition. The Mann-Whitney U-test was used to analyse the change in CD4 cell counts before starting ARV treatment. RESULTS: In the years 2008-2010, the CD4 count was remeasured before starting ARV treatment in 90 late-diagnosed patients. The median change in the CD4 count was 22 cells/µL. In 49 of these, the number of CD4 cells spontaneously increased before the start of treatment. We can suspect that these patients were misclassified as late-diagnosed. CONCLUSIONS: The consensus definition of late diagnosis often leads to overestimation of the number of late-diagnosed patients. The crucial problem is a transient decline in the CD4 lymphocyte count in the acute phase of HIV infection. A potential solution is to introduce serum HIV viral load measurement into the definition.

Higher Immunological Response after BNT162b2 Vaccination among COVID-19 Convalescents-The Data from the Study among Healthcare Workers in an Infectious Diseases Center.

Introduction: The BNT162b2 vaccination studies did not specifically focus on groups that were heavily exposed to SARS-CoV-2 infection. Therefore, we aimed to assess the safety and efficacy of the BNT162b2 vaccine among healthcare workers (HCWs). Methods: Study participants were recruited from hospital employees who received BNT162b2 vaccination at the Hospital for Infectious Diseases in Warsaw. Blood samples were collected before and after each vaccination dose. At each timepoint, the levels of anti-SARS CoV-2 IgM, anti-n SARS-CoV-2 IgG, and S-RBD antibodies were measured. Data on concomitant diseases and the vaccine's adverse events (VAE) were collected after each vaccination dose. In the statistical analyses, non-parametric tests were used. Results: In total, 170 healthcare workers were included in the analysis. Their median age was 51 years (interquartile range (IQR): 41−60 years); most of them were women (n = 137, 80.6%) working in direct contact with patients (n = 137, 73.2%); and 46 (27.0%) had concomitant diseases. More than one fifth of subjects had COVID-19 before their first dose of vaccination (n = 38, 22.6%). In terms of immunological responses, our investigations showed a high level of efficacy for the BNT162b2 mRNA vaccination as measured by S-RBD antibody concentrations: these were positive in 100% of participants 14 days after the second dose of the vaccine. It was also observed that employees with high S-RBD antibodies (>=433 BAU/mL) were more likely to be COVID-19 convalescents before receiving the first vaccine dose (p < 0.001). Conclusion: The BNT162b2 vaccine is safe and effective among HCWs. Vaccine adverse events occurred, but serious events were not observed. Moreover, the BNT162b2 vaccine is effective against symptomatic and severe COVID-19­none of the workers that acquired a SARS-CoV-2 infection after vaccination required hospitalization or medical care. We also observed higher immunological responses among COVID-19 convalescents.

The Clinical Course and Outcomes of Patients Hospitalized Due to COVID-19 during Three Pandemic Waves in Poland: A Single Center Observational Study.

Background: The first case of coronavirus disease 2019 (COVID-19) in Poland was reported on 4 March 2020. We aim to compare the clinical course and outcomes of patients hospitalized in the Hospital for Infectious Diseases in Warsaw due to COVID-19 during three pandemic waves. Materials and methods: The medical data were collected for all patients diagnosed with COVID-19 hospitalized in our hospital from 6 March 2020 till 30 November 2021. COVID-19 diagnosis was confirmed by nasopharyngeal swabs using real-time polymerase chain reaction assay (RT-PCR) or SARS-CoV-2 antigen test. COVID-19 waves were defined based on the number and dynamics of cases. Results: Altogether, 2138 patient medical records were analyzed. The majority of the cohort was male (1235/2138, 57.8%), and the median age was 65 years [IQR: 50−74 years]. Patients hospitalized during the third wave had lower oxygen saturation on admission (p < 0.001) and were more likely to receive oxygen supplementation (p < 0.001). Serious complications, including pneumothorax (p < 0.001) and thromboembolic complications (p < 0.001), intensive care unit admission (p = 0.034), and death (p = 0.003), occurred more often in patients of the third wave. Conclusions: During the third wave, patients in our cohort experienced a more severe course of the disease and poorer outcomes.

The effectiveness of erysipelas prophylaxis depends on the cumulative dose of benzathine penicillin G.

Erysipelas is an acute infection due to S. pyogenes and is characterized by a high risk of relapses. The number of patients suffering from one or more recurrences varied depending on the study and accounted for between 16% and 47% of the total number of those affected. Antibiotic prophylaxis with the use of penicillin can reduce the risk of recurrence by 47%. A number of 873 patients with erysipelas treated at the Hospital for Infectious Diseases in Warsaw from 2010 to 2018 was enrolled in the study. Benzathine-penicillin G was given intramuscularly at a dose of 1.2 MU or 2.4 MU or 3.6 MU. The earliest moment that prophylactic treatment was administered was the first episode of erysipelas recurrence. The decision to administer the antibiotic and the dose to use was discretionally made by the examining physician. Altogether 104 (11.9%) persons experienced at least one episode of erysipelas recurrence during the study period. A total of 2976 doses of benzathine- penicillin G (BP) were administered. The most common dose was that of 2.4 MU (2380, 80%). The dose of 1.2 MU was given 567 times (19%). The highest dose, i.e. 3.6 MU, was administered to only 5 patients (8 applications, 0.2%). No effect was shown by either the number of benzathine- penicillin G administered doses (p=0.07) or the median dose (p=0.65), whereas patients without relapse received a statistically higher cumulative dose of the antibiotic (p=0.047). Age was a risk factor of recurrence only in the group of diabetic patients (p=0.03). Benzathine penicillin G given in an appropriate cumulative dose is effective in preventing erysipelas recurrence.

Patients with Infections of The Central Nervous System Have Lowered Gut Microbiota Alpha Diversity.

There are multiple lines of evidence for the existence of communication between the central nervous system (CNS), gut, and intestinal microbiome. Despite extensive analysis conducted on various neurological disorders, the gut microbiome was not yet analyzed in neuroinfections. In the current study, we analyzed the gut microbiome in 47 consecutive patients hospitalized with neuroinfection (26 patients had viral encephalitis/meningitis; 8 patients had bacterial meningitis) and in 20 matched for age and gender health controls. Using the QIIME pipeline, 16S rRNA sequencing and classification into operational taxonomic units (OTUs) were performed on the earliest stool sample available. Bacterial taxa such as Clostridium, Anaerostipes, Lachnobacterium, Lachnospira, and Roseburia were decreased in patients with neuroinfection when compared to controls. Alpha diversity metrics showed lower within-sample diversity in patients with neuroinfections, though there were no differences in beta diversity. Furthermore, there was no significant change by short-term (1-3 days) antibiotic treatment on the gut microbiota, although alpha diversity metrics, such as Chao1 and Shannon's index, were close to being statistically significant. The cause of differences between patients with neuroinfections and controls is unclear and could be due to inflammation accompanying the disease; however, the effect of diet modification and/or hospitalization cannot be excluded.

Factors associated with the risk of upper respiratory tract bacterial infections among HIV-positive patients.

BACKGROUND: The risk and characteristics of upper respiratory tract (URT) bacterial infections (URT-BI) among HIV (+) patients is understudied. We analyzed factors associated with its occurrence and the spectrum of culturable pathogens among patients routinely followed at the HIV Out-Patient Clinic in Warsaw. METHODS: All HIV (+) patients with available URT swab culture were included into analyses. Patients were followed from the day of registration in the clinic until first positive URT swab culture or last clinical visit from January 1, 2007 to July 31, 2016. Cox proportional hazard models were used to identify factors associated with positive URT swabs culture (those with p<0.1 in univariate included into multivariable). RESULTS: In total 474 patients were included into the analyses, 166 with culturable URT swab. In general, 416 (87.8%) patients were male, 342 (72.1%) were infected through MSM contact, 253 (53.4%) were on antiretroviral therapy. Median follow-up time was 3.4 (1.3-5.7) years, age 35.2 (30.6-42.6) years and CD4+ count 528 (400-685) cells/µl. The most common cultured bacteria were S. aureus (40.4%) and S. pyogenes (13.9%) (Table 1). Patients with culturable URT-BI were more likely to be MSM (68.5% vs 78.9%; p<0.016), have detectable viral load (20.9% vs 12.0%; p<0.0001) and CD4+ cell count <500 cells/µl (55.2% vs 39.0%; p = 0.003) (Table 2). In multivariate survival analyses detectable viral load (HR3.13; 95%Cl: 2.34-4.19) and MSM (1.63;1.09-2.42) were increasing, but older age (0.63;0.58-0.69, per 5 years older) and higher CD4+ count (0.90;0.85-0.95, per 100 cells/µl) decreasing the risk of culturable URT-BI (Table 2). CONCLUSIONS: Culturable URT-BI are common among HIV-positive patients with high CD4+ count. Similarly to general population most common cultured bacteria were S. aureus and S. pyogenes. Risk factors identified in multivariate survival analysis indicate that younger MSM patients with detectable HIV viral load are at highest risk. In clinical practice this group of patients requires special attention.

The Beneficial Effect of the COVID-19 Vaccine Booster Dose among Healthcare Workers in an Infectious Diseases Center.

Introduction: Healthcare workers in Poland received a booster dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech, Manufacturer: Pfizer, Inc., and BioNTech; Moguncja, Germany) at the beginning of October 2021. Here, we report on the preliminary results of an ongoing clinical study into the antibody response to SARS-CoV-2 of healthcare workers previously exposed to the virus, with or without evidence of past infection, in the Hospital for Infectious Diseases in Warsaw before and after the vaccine booster dose. Methods: Blood samples were collected on the day the vaccine booster dose was administered and again 14 days later. The levels of SARS-CoV-2 IgG antibodies (against the n-protein, indicative of disease) and S-RBD (indicative of a response to vaccination) were measured. Results: One hundred and ten health care workers from the Hospital for Infectious Diseases were included in the study. The percentage of subjects with a positive test for anti-n-protein IgG antibodies at both time points remained unchanged (16, 14%), while a statistically significant increase in the percentage of subjects producing high levels of S-RBD antibodies (i.e., >433 BAU/mL) was observed (from 23, 21% to 109, 99%; p = 0.00001). Conclusions: The results of the study indicate that the booster dose of the vaccine significantly increases the percentage of people with high levels of S-RBD antibodies, regardless of previous contact with the virus, which may indicate greater protection against both the disease and a severe course of COVID-19.

Analysis of the occurrence of hemophagocytic lymphohistiocytosis (HLH) features in patients with sepsis: a prospective study.

HLH syndrome may mimic sepsis but requires entirely different treatment. The aim of the study was to assess the occurrence of HLH features in patients with sepsis and the influence these exert on the patients' prognosis. The prospective study included 108 patients with suspected sepsis who were routinely evaluated according to HLH criteria. They were divided into group I (SOFA = 2, n = 57) and group II (SOFA ≥ 3, n = 51). Four patients were excluded from analysis: 1 with real HLH, 2 with Still's disease and 1 with lymphoma. The median (IQR) concentration of ferritin was 613.4 (850.3) ng/mL, however 6 patients revealed a remarkedly high ferritin concentration > 3000 ng/mL, including 2 with ferritin > 10,000 ng/mL. In total, 21 patients met ≥ 4/8 HLH criteria and were found to have sepsis with HLH-like syndrome (SHLS). Out of these, 19 responded to antimicrobials, 2 died due to infection. The sepsis patients presented with the following HLH criteria: fever (95.2%), hyperferritinemia (57.3%), splenomegaly (43.4%), reduced NK cell activity (35.2%), high sCD25 activity (27.4%) and rarely: hypertriglyceridemia (14.4%), duopenia (5.8%), hypofibrinogenemia (1.9%). Although group II patients had higher odds for SHLS presentation (OR 3.26, p = 0.026) and for death (OR 14.3, p = 0.013), SHLS occurrence had no impact on the risk of death (OR 0.77, p = 0.75). Sepsis patients can present with SHLS exclusively due to severe infection. Duopenia, hypertriglyceridemia, hypofibrinogenemia and high level of sCD25 are unusual in sepsis and might indicate real HLH syndrome. Hyperferritinemia, even as high as in real HLH syndrome, can occur in sepsis patients.

Search for Viral Infections in Cerebrospinal Fluid From Patients With Autoimmune Encephalitis.

BACKGROUND: It has been reported that virus-mediated brain tissue damage can lead to autoimmune encephalitis (AE) characterized by the presence of antibodies against neuronal surface antigens. In the study, we investigate the presence of viruses in cerebrospinal fluid (CSF) from patients with AE using reverse transcription polymerase chain reaction (RT-PCR)/PCR and shotgun metagenomics. METHODS: CSF samples collected from 200 patients with encephalitis were tested for the presence of antibodies against antiglutamate receptor (NMDAR), contactin-associated protein 2 (CASPR2), glutamate receptors (type AMPA1/2), leucine-rich glioma-inactivated protein 1 (LGI1), dipeptidyl aminopeptidase-like protein 6 (DPPX), and GABA B receptor, and those found positive were further analyzed with real-time RT-PCR/PCR for common viral neuroinfections and shotgun DNA- and RNA-based metagenomics. RESULTS: Autoantibodies against neuronal cells were detected in CSF from 8 individuals (4% of all encephalitis patients): 7 (3.5%) had anti-NMDAR and 1 (0.5%) had anti-GABA B. RT-PCR/PCR identified human herpes virus type 1 (HSV-1; 300 copies/mL) and the representative of Enterovirus genus (550 copies/mL) in 1 patient each. Torque teno virus (TTV) was found in another patient using metagenomic analysis, and its presence was confirmed by specific PCR. CONCLUSIONS: We detected the presence of HSV, TTV, and Enterovirus genus in CSF samples from 3 out of 8 AE patients. These findings support the concept of viral involvement in the pathogenesis of this disease.

Next-generation sequencing in the diagnosis of viral encephalitis: sensitivity and clinical limitations.

Identification of pathogens causing viral encephalitis remains challenging, and in over 50% of cases the etiologic factor remains undetermined. Next-generation sequencing (NGS) based metagenomics has been successfully used to detect novel and rare infections, but its value for routine diagnosis of encephalitis remains unclear. The aim of the present study was to determine the sensitivity of shotgun metagenomic sequencing protocols, which include preamplification, and testing it against cerebrospinal fluid (CSF) samples from encephalitis patients. For sensitivity testing HIV and HBV positive sera were serially diluted in CSF from an uninfected patient. NGS repeatedly detected HIV and HBV sequences present at concentrations from 105 to 102 and from 105 to 10 viral copies/reaction, respectively. However, when the same protocols were applied to RT-PCR/PCR positive CSF samples from 6 patients with enteroviral encephalitis (median viral load 47 copies/ml) and 15 patients with HSV, CMV or VZV encephalitis (median viral load 148 copies/ml), only 7 (28.6%) were identified as positive. In conclusions, while NGS has the advantage of being able to identify a wide range of potential pathogens it seems to be less sensitive compared to the standard amplification-based assays in the diagnosis of encephalitis, where low viral loads are common.

Differences and similarities in clinical manifestations of Listeria monocytogenes and Mycobacterium tuberculous meningitis.

INTRODUCTION: Tuberculous meningitis (TbM) and meningitis caused by Listeria monocytogenes (LM) require different treatment regimens and have grave prognosis if therapy is delayed. THE AIM OF THE STUDY: Comparison of clinical manifestations, laboratory features and outcome of TbM and LM. MATERIAL AND METHODS: We retrospectively analyzed records of 402 patients with community acquired bacterial meningitis (BM) who were hospitalized between January 2010 and September 2019. RESULTS: LM and TbM were diagnosed in 28 (7.0%) and 23 (5.7%) patients, respectively. Patients with TbM were more likely to present with hydrocephalus (p<0.001), scored lower on the Thwaites Index (TI) (p<0.001) and had longer duration of symptoms prior to hospitalization (p=0.001). Furthermore, TbM patients had lower concentration of c-reactive protein (CRP) (p<0.001) and lower white blood cells count (WBC) (p=0.035). When compared to BM patients with etiology other than LM and TbM (nLnTbM), TbM patients presented with lower concentration of CRP (p<0.001), and procalcitonin (PCT) (p<0.001), lower WBC (p<0.001), and lower granulocyte percentage of CSF cytosis (p<0.001), but were more likely to present with hydrocephalus (p<0.001), aphasia (p=0.003) and hemiparesis (p=0.008). In comparison with the nLnTbM group, LM patients had lower concentration of CRP (p=0.01), lower WBC (p<0.001), and lower granulocyte percentage of CSF cytosis (p<0.016). LM patients were also more likely to have concomitant cancer (p=0.008), receive immunosuppressive treatment (p<0.001) or be immunocompromised (p=0.015). CONCLUSIONS: TbM patients had less pronounced inflammation but more severe central nervous system complications compared to patients with LM and other etiologies. Furthermore, LM patients, but not TbM patients, were often immunocompromised.

Advanced age and increased CRP concentration are independent risk factors associated with Clostridioides difficile infection mortality.

Clostridioides difficile (C.difficile) is a Gram-positive, spore-forming, toxin-producing anaerobic bacillus, which is one of the most common causes of health-care-associated infection developed mainly by elderly patients. The objective of this study was to assess mortality among the patients of the Hospital for Infectious Diseases in Warsaw related to C.difficile infection. Analysis was conducted of 1638 records reporting the medical histories of patients hospitalized for the first time due to Clostridioides difficile infection (CDI) in the Hospital for Infectious Diseases in Warsaw from 2010 to 2017. The inclusion criteria were any (principal or secondary) discharge diagnosis code for CDI according to ICD-10 and being an adult (≥ 18 years). 108 out of 1638 (7%) of the patients died. The median age in this group was 83 years. The largest number of deaths (90%) occurred in the group of patients aged 65 years or older and 81-90 years old (53% of all the deaths). In the multivariate logistic regression model relevant only to the age groups, not to sepsis-age over 80 and over 90 were independent predictors of death, increasing the risk of death by 3.4 and 1.8 times, respectively. The result of the receiver operating curve (ROC) analysis determined the age of 77 years as the threshold value, indicating the increased risk of death (AUC 0.727, standard error 0.025, 95% CI 0.678-0.776, p < 0.0001). In addition, other quantitative variables, namely CRP, creatinine and leucocytes were studied and turned out to be independent death predictors as well. The diagnosis of sepsis increased the risk of death fourfold (OR = 4.042; 95% Cl 2.4-6.7; p < 0.001). Increased inflammatory parameters, namely CRP and white blood cell count, advanced age, particularly over the age of 80, as well as a diagnosis of sepsis are independent risk factors for death and could be used as predictive markers of poor outcome in CDI.

Decrease of T-cells exhaustion markers programmed cell death-1 and T-cell immunoglobulin and mucin domain-containing protein 3 and plasma IL-10 levels after successful treatment of chronic hepatitis C.

During chronic hepatitis C virus (HCV) infection, both CD4+ and CD8+ T-cells become functionally exhausted, which is reflected by increased expression of programmed cell death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), and elevated anti-inflammatory interleukin 10 (IL-10) plasma levels. We studied 76 DAA-treated HCV-positive patients and 18 non-infected controls. Flow cytometry measured pretreatment frequencies of CD4+PD-1+, CD4+PD-1+Tim-3+ and CD8+PD-1+Tim-3+ T-cells and IL-10 levels measured by ELISA were significantly higher and CD4+PD-1-Tim-3- and CD8+PD-1-Tim-3- T-cells were significantly lower in patients than in controls. Treatment resulted in significant decrease of CD4+Tim-3+, CD8+Tim-3+, CD4+PD-1+Tim-3+ and CD8+PD-1+Tim-3+ T-cell frequencies as well as IL-10 levels and increase in CD4+PD-1-Tim-3- and CD8+PD-1-Tim-3- T-cells. There were no significant changes in the frequencies of CD4+PD-1+ T-cells, while CD8+PD-1+ T-cells increased. Patients with advanced liver fibrosis had higher PD-1 and lower Tim-3 expression on CD4+T-cells and treatment had little or no effect on the exhaustion markers. HCV-specific CD8+T-cells frequency has declined significantly after treatment, but their PD-1 and Tim-3 expression did not change. Successful treatment of chronic hepatitis C with DAA is associated with reversal of immune exhaustion phenotype, but this effect is absent in patients with advanced liver fibrosis.