Risk factors for complicated course and recurrence of Clostridioides Difficile infections during COVID-19 pandemic.

INTRODUCTION: The primary symptom of Clostridioides difficile infection (CDI) is diarrhea of varying severity. Both malnutrition and clinical nutrition increase the risk for contracting Clostridioides difficile (C. difficile) infection and the likelihood of relapses. Moreover, the risk for recurrence is higher if there is infection with a hypervirulent strain (NAP1/BI/027). Hypoalbuminemia predisposes to a severe course of the disease and morbidity. MATERIAL AND METHODS: Analysis was carried out of the data regarding patients hospitalized at the Regional Hospital for Infectious Diseases in Warsaw from 01 January 2020 to 31 December 2021 who were diagnosed with C. difficile infection. A severe course of infection was diagnosed when a blood test showed a leukocyte count greater than or equal to 15,000/µl and/or a creatinine concentration >1.5 mg/dl (>132.6 mmol/l). RESULTS: Clostridioides difficile infection was the reason for 185 hospitalizations (involving 108 women and 77 men), of 167 patients aged from 22 to 93 years old. There were 68 (37%) cases of recurrent infection. Seventy-five (41%) infections met the study's criteria for severe CDI, and 12 (7%) patients died. Out of the total number of hospitalizations, 41 (22%) were due SARS-CoV-2 co-infection. PCR tests detecting binary toxin revealed 34 (18%) positive results. Infection with a hypervirulent strain was an independent risk factor for the recurrence of diarrhea which had C. difficile etiology. Overall, during an episode of diarrhea, one antibacterial drug was used in 139 cases (75%), two in 27 (15%), three in 14 (8%) situations, and four - twice (1%). Among these, drugs not recommended for the treatment of CDI were used in 21 (11%) cases. The number of antibacterial drugs administered during an episode of diarrhea was an independent risk factor for the death of the infected person. Clinical nutrition was applied during 19 hospitalizations (10%), out of which 12 (63%) cases showed a severe course of C. difficile infection, while four patients (21%) died. Using clinical nutrition methods was an independent risk factor for a severe course of the disease and patient death. CONCLUSIONS: Clinical nutrition and the number of antibiotics used during an episode of diarrhea are independent risk factors for the death of a patient with CDI. Infection with a hypervirulent strain increases the risk for relapse.

HIV treatment strategies across Central, Eastern and Southeastern Europe: New times, old problems.

INTRODUCTION: In the last decade, substantial differences in the epidemiology of, antiretroviral therapy (ART) for, cascade of care in and support to people with HIV in vulnerable populations have been observed between countries in Western Europe, Central Europe (CE) and Eastern Europe (EE). The aim of this study was to use a survey to explore whether ART availability and therapies have evolved in CE and EE according to European guidelines. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group conducted two identical multicentre cross-sectional online surveys in 2019 and 2021 concerning the availability and use of antiretroviral drugs (boosted protease inhibitors [bPIs], integrase inhibitors [INSTIs] and nucleoside reverse transcriptase inhibitors [NRTIs]), the introduction of a rapid ART start strategy and the use of two-drug regimens (2DRs) for starting or switching ART. We also investigated barriers to the implementation of these strategies in each region. RESULTS: In total, 18 centres participated in the study: four from CE, six from EE and eight from Southeastern Europe (SEE). Between those 2 years, older PIs were less frequently used and darunavir-based regimens were the main PIs (83%); bictegravir-based and tenofovir alafenamide-based regimens were introduced in CE and SEE but not in EE. The COVID-19 pandemic did not significantly interrupt delivery of ART in most centres. Two-thirds of centres adopted a rapid ART start strategy, mainly in pregnant women and to improve linkage of care in vulnerable populations. The main obstacle to rapid ART start was that national guidelines in several countries from all three regions did not support such as strategy or required laboratory tests first; an INSTI/NRTI combination was the most commonly prescribed regimen (75%) and was exclusively prescribed in SEE. 2DRs are increasingly used for starting or switching ART (58%), and an INSTI/NRTI was the preferred regimen (75%) in all regions and exclusively prescribed in SEE, whereas the use of bPIs declined. Metabolic disorders and adverse drug reactions were the main reasons for starting a 2DR; in the second survey, HIV RNA <500 000 c/ml and high cluster of differentiation (CD)-4 count emerged as additional important reasons. CONCLUSIONS: In just 2 years and in spite of the emergence of the COVID-19 pandemic, significant achievements concerning ART availability and strategies have occurred in CE, EE and SEE that facilitate the harmonization of those strategies with the European AIDS Clinical Society guidelines. Few exceptions exist, especially in EE. Continuous effort is needed to overcome various obstacles (administrative, financial, national guideline restrictions) in some countries.

The Clinical Effectiveness and Safety of Vaccinations against COVID-19 in HIV-Positive Patients: Data from Observational Study in Poland.

People living with HIV (PLWH) are a heterogeneous group of immunocompromised persons, yet underrepresented in randomized clinical trials leading to vaccination registration. Detectable HIV viral load and having chronic comorbidities may increase the risk of severe COVID-19 outcomes in this group of patients. We aimed to assess the efficacy and safety of vaccinations against COVID-19 in PLWH. MATERIALS AND METHODS: We performed a retrospective analysis of medical records of HIV-positive individuals routinely followed up between 1 January 2021 and 30 April 2022 that were at the HIV Outpatient Clinic in Warsaw. The analysis included data on the type and date of administration of subsequent doses of COVID-19 vaccination, adverse vaccine reactions, and the history of SARS-CoV-2 infection. RESULTS: In total, 217 patients were included in the analysis, with a median age of 43 years (IQR: 35.5-51.5 years) and median CD4+ count of 591 cells/uL (IQR: 459.5-745.0 cells/uL). Most of the patients were male (191/217, 88.0%) and were vaccinated with the BNT162b2 vaccine (143/217, 65.9%). None of the patients diagnosed with COVID-19 required hospitalization. Vaccine adverse events (VAE) mostly occurred after the 1st dose (in 33/217 (15.2%)), and none of them were severe or required medical care. CONCLUSIONS: In our cohort of patients, vaccination against COVID-19 proved to be safe and effective against a severe course of the disease among people living with HIV. However, vaccination, to a lesser degree, protects against mild SARS-CoV-2 infection. Longer observations are required in order to assess the sustainability of protection against severe COVID-19 in this group of patients.

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.

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 Management of HIV Care Services in Central and Eastern Europe: Data from the Euroguidelines in Central and Eastern Europe Network Group.

INTRODUCTION: The COVID-19 pandemic has been challenging time for medical care, especially in the field of infectious diseases (ID), but it has also provided an opportunity to introduce new solutions in HIV management. Here, we investigated the changes in HIV service provision across Central and Eastern European (CEE) countries before and after the COVID-19 outbreak. METHODS: The Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of ID from 24 countries within the CEE region. Between 11 September and 29 September 2021, the group produced an on-line survey, consisting of 32 questions on models of care among HIV clinics before and after the SARS-CoV-2 outbreak. RESULTS: Twenty-three HIV centers from 19 countries (79.2% of all countries invited) participated in the survey. In 69.5% of the countries, there were more than four HIV centers, in three countries there were four centers (21%), and in four countries there was only one HIV center in each country. HIV care was based in ID hospitals plus out-patient clinics (52%), was centralized in big cities (52%), and was publicly financed (96%). Integrated services were available in 21 clinics (91%) with access to specialists other than ID, including psychologists in 71.5% of the centers, psychiatrists in 43%, gynecologists in 47.5%, dermatologists in 52.5%, and social workers in 62% of all clinics. Patient-centered care was provided in 17 centers (74%), allowing consultations and tests to be planned for the same day. Telehealth tools were used in 11 centers (47%) before the COVID-19 pandemic outbreak, and in 18 (78%) after (p = 0.36), but were represented mostly by consultations over the telephone or via e-mail. After the COVID-19 outbreak, telehealth was introduced as a new medical tool in nine centers (39%). In five centers (28%), no new services or tools were introduced. CONCLUSIONS: As a consequence of the COVID-19 pandemic, tools such as telehealth have become popularized in CEE countries, challenging the traditional approach to HIV care. These implications need to be further evaluated in order to ascertain the best adaptations, especially for HIV medicine.

How sex and gender matter in infectious diseases - outcomes of the first Polish conference "A woman in an infectious diseases circle".

Occurrence of infectious disease in a woman is an interdisciplinary area of medicine. The common problem of lower recruitment of women to clinical trials leads to the necessity to rely in clinical practice on the exchange of practical experiences, specialist consultations and individualization of treatment. As the COVID-19 pandemic shows, there is a close relationship between infectious diseases and civilization diseases. People suffering from chronic diseases are both more susceptible to infection and the more severe course of an infectious disease. On the other hand, infection may accelerate or initiate the onset of a noncommunicable disease. Women, especially those living with HIV, are a group with an underestimated risk of high blood pressure or some cancers. Therefore, one of the main goals of the conference is to break the stereotypes of thinking about health, in which gender is the main determinant of some screening tests. Late presentation of women to medical care is a significant problem that is of great importance in the diagnosis and treatment of both communicable and non-communicable diseases. Women put family and professional responsibilities in the first place, and they are known to downplay their own health problems. It leads to the diagnosis of cardiovascular diseases or cancer at the stage of advanced changes, limiting the possibilities of effective therapy. Understanding gender attributed differences in the etiology and epidemiology of diseases allows for the improvement of patient care, as well as determines the right direction of reforms in the area of healthcare. It is essential to build models of care based on an interdisciplinary and patient-centered approach, with broad support from both stakeholders and NGOs. Each contact of the patient with the health care system should be seen as an opportunity for screening both in the area of civilization diseases, women's health, and infectious diseases corresponding to her lifestyle.

The Management of HIV Care Services in Central and Eastern Europe: Data from the Euroguidelines in Central and Eastern Europe Network Group

Introduction: The COVID-19 pandemic has been challenging time for medical care, especially in the field of infectious diseases (ID), but it has also provided an opportunity to introduce new solutions in HIV management. Here, we investigated the changes in HIV service provision across Central and Eastern European (CEE) countries before and after the COVID-19 outbreak. Methods: The Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of ID from 24 countries within the CEE region. Between September 11 and September 29, 2021, the group produced an on-line survey, consisting of 32 questions on models of care among HIV clinics before and after the SARS-CoV-2 outbreak. Results: Twenty-three HIV centers from 19 countries (79.2% of all countries invited) participated in the survey. In 69.5% of the countries, there were more than four HIV centers, in three countries there were four centers (21%), and in four countries there was only one HIV center in each country. HIV care was based in ID hospitals plus out-patient clinics (52%), was centralized in big cities (52%), and was publicly financed (96%). Integrated services were available in 21 clinics (91%) with access to specialists other than ID, including psychologists in 71.5% of the centers, psychiatrists in 43%, gynecologists in 47.5%, dermatologists in 52.5%, and social workers in 62% of all clinics. Patient-centered care was provided in 17 centers (74%), allowing consultations and tests to be planned for the same day. Telehealth tools were used in 11 centers (47%) before the COVID-19 pandemic outbreak, and in 18 (78%) after (p = 0.36), but were represented mostly by consultations over the telephone or via e-mail. After the COVID-19 outbreak, telehealth was introduced as a new medical tool in nine centers (39%). In five centers (28%), no new services or tools were introduced. Conclusions: As a consequence of the COVID-19 pandemic, tools such as telehealth have become popularized in CEE countries, challenging the traditional approach to HIV care. These implications need to be further evaluated in order to ascertain the best adaptations, especially for HIV medicine.

The Presence of Either Typical or Atypical Radiological Changes Predicts Poor COVID-19 Outcomes in HIV-Positive Patients from a Multinational Observational Study: Data from Euroguidelines in Central and Eastern Europe Network Group.

HIV-positive patients may present lungs with multiple infections, which may hinder differential diagnoses and the choice of treatment in the course of COVID-19, especially in countries with limited access to high-standard healthcare. Here, we aim to investigate the association between radiological changes and poor COVID-19 outcomes among HIV-positive patients from Central and Eastern Europe. Between November 2020 and May 2021, the Euroguidelines in Central and Eastern Europe Network Group started collecting observational data on HIV and COVID-19 co-infections. In total, 16 countries from Central and Eastern European submitted data (eCRF) on 557 HIV-positive patients. The current analyses included patients who had a radiological examination performed. Logistic regression models were used to identify the factors associated with death, ICU admission, and partial recovery (poor COVID-19 outcomes). Factors that were significant in the univariate models (p < 0.1) were included in the multivariate model. Radiological data were available for 224 (40.2%) patients, 108 (48.2%) had computed tomography, and 116 (51.8%) had a chest X-ray. Of these, 211 (94.2%) were diagnosed using RT-PCR tests, 212 (94.6%) were symptomatic, 123 (55.6%) were hospitalized, 37 (16.6%) required oxygen therapy, and 28 (13.1%) either died, were admitted to ICU, or only partially recovered. From the radiologist's description, 138 (61.6%) patients had typical radiological changes, 18 (8.0%) atypical changes, and 68 (30.4%) no changes. In the univariate models, CD4 count (OR = 0.86 [95% CI: 0.76-0.98]), having a comorbidity (2.33 [1.43-3.80]), HCV and/or HBV co-infection (3.17 [1.32-7.60]), being currently employed (0.31 [0.13-0.70]), being on antiretroviral therapy (0.22 [0.08-0.63]), and having typical (3.90 [1.12-13.65]) or atypical (10.8 [2.23-52.5]) radiological changes were all significantly associated with poor COVID-19 outcomes. In the multivariate model, being on antiretroviral therapy (OR = 0.20 [95% CI:0.05-0.80]) decreased the odds of poor COVID-19 outcomes, while having a comorbidity (2.12 [1.20-3.72]) or either typical (4.23 [1.05-17.0]) or atypical (6.39 [1.03-39.7]) radiological changes (vs. no changes) increased the odds of poor COVID-19 outcomes. Among HIV patients diagnosed with symptomatic SARS-CoV-2 infection, the presence of either typical or atypical radiological COVID-19 changes independently predicted poorer outcomes.

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.

Management of SARS-CoV-2 infection: recommendations of the Polish Association of Epidemiologists and Infectiologists as of February 23, 2022.

The first Polish recommendations regarding the management of patients with COVID-19 were published by the Polish Society of Epidemiologists and Infectiologists (PTEiLChZ) on March 31, 2020, and the last annex was dated November 12, 2021. The ongoing state of pandemic, the emergence of new variants of the virus, and the availability of new drugs necessitate their updating. Changes introduced in the current version of recommendations for the management of COVID-19 comprised the possibility of using remedesivir in an outpatient setting, previously reserved for inpatient treatment, as well as other antiviral drugs-molnupiravir and nirmatrelvir / ritonavir. We revised the possibility of using monoclonal antibodies due to the resistance of the currently dominant Omicron variant. Anakinra, an antagonist of interleukin 1 receptors, has been added as a treatment option in advanced stages of the disease, and the recommended daily dose of glucocorticosteroids used in the most severe forms of COVID-19 has been increased. Information on vaccination and pre-exposure prophylaxis in specific populations has also been updated.

DIC, SIC or CAC - the haemostatic profile in COVID-19 patients hospitalised in the intensive care unit: a single-centre retrospective analysis.

INTRODUCTION: Infection with SARS-CoV-2 in its most severe form leads to acute respiratory distress syndrome requiring mechanical ventilation under the conditions of the Intensive Care Unit (ICU). The state of hypercoagulation described in COVID-19 may deepen respiratory failure, leading to increased mortality. The aim of the presented study is to characterise the haemostatic profile based on the results of clotting system parameters and risk assessment of thromboembolic complications of patients hospitalised in the ICU. MATERIAL AND METHODS: This retrospective study covered the first 10 adult patients hospitalised in the ICU of the Hospital for Infectious Diseases in Warsaw in the second quarter of 2020. Demographic, clinical and laboratory parameters of the coagulation system and the risk of thromboembolic complications were assessed. Well known criteria of haemostatic disorders were used to classify the observed derangements. RESULTS: The most frequently observed deviations in the coagulation system were high concentrations of D-dimer and fibrinogen. In select cases the clotting time was prolonged. No severe thrombocytopenia was observed. All patients presented a high risk of thromboembolic complications as assesed by the Padua score. The observed clotting abnormalities did not meet the criteria for DIC (disseminated intravascular coagulation) and SIC (sepsis-induced coagulopathy) diagnosis. CONCLUSIONS: The main elements of coagulopathy that were observed in our cases differ from those usually seen in patients with recognised sepsis. The unique haemostatic profile of COVID-19 patients treated in the ICU has been described as CAC (COVID-19-associated coagulopathy).

Tocilizumab for patients with severe COVID-19: a retrospective, multi-center study.

BACKGROUND: Tocilizumab, an inhibitor of the interleukin-6 receptor, may decrease the inflammatory response and control the symptoms of severe coronavirus disease 2019 (COVID-19), but the evidence is scarce. METHODS: This retrospective study included patients with severe COVID-19 requiring oxygen therapy who received tocilizumab in seven centers across Poland. We assessed on-treatment changes in clinical status and inflammatory markers. RESULTS: Twenty-eight patients were included (19 male), with a mean age of 61.7 ± 12.4 years. The mean time from symptom onset to the first tocilizumab dose was 10.5 ± 5.7 days. Clinical status improved within 24 hours in 11 (39%) patients, within one week in 23 (82%) patients, and within two weeks in 25 (89%); one (4%) patient showed no change and two (7%) patients died. Sixteen patients (57%) no longer needed oxygen therapy within a week (p < 0.001). The serum concentrations of C-reactive protein, procalcitonin, and fibrinogen decreased significantly (p ≤ 0.001). Lung changes improved in 21 (84%) patients within two weeks of treatment; 19 had minimal or no changes upon final examination. CONCLUSIONS: Tocilizumab can control the symptoms of severe COVID-19 by reducing the inflammatory response and rapidly improves the clinical status in most patients.