Understanding clinical outcomes and factors influencing mortality in intensive care unit patients with COVID-19-associated candidemia.

BACKGROUND: During the COVID pandemic, research has shown an increase in candidemia cases following severe COVID infection and the identification of risk factors associated with candidemia. However, there is a lack of studies that specifically explore clinical outcomes and mortality rates related to candidemia after COVID infection. OBJECTIVES: The aim of this international study was to evaluate the clinical outcomes and identify factors influencing mortality in patients who developed candidemia during their COVID infection. PATIENTS/METHODS: This study included adult patients (18 years of age or older) admitted to the intensive care unit (ICU) and diagnosed with COVID-associated candidemia (CAC). The research was conducted through ID-IRI network and in collaboration with 34 medical centres across 18 countries retrospectively, spanning from the beginning of the COVID pandemic until December 2021. RESULTS: A total of 293 patients diagnosed with CAC were included. The median age of the patients was 67, and 63% of them were male. The most common Candida species detected was C. albicans. The crude 30-day mortality rate was recorded at 62.4%. The logistic regression analysis identified several factors significantly impacting mortality, including age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07, p < .0005), SOFA score (OR 1.307, 95% CI 1.17-1.45, p < .0005), invasive mechanical ventilation (OR 7.95, 95% CI 1.44-43.83, p < .017) and duration of mechanical ventilation (OR 0.98, 95% CI 0.96-0.99, p < .020). CONCLUSIONS: By recognising these prognostic factors, medical professionals can customise their treatment approaches to offer more targeted care, leading to improved patient outcomes and higher survival rates for individuals with COVID-associated candidemia.

Laboratory parameters predicting mortality of adult in-patients with COVID-19 associated cytokine release syndrome treated with high-dose tocilizumab.

Large randomized clinical trials in severe Coronavirus Disease 2019 (COVID-19) patients have proven efficacy of intravenous tocilizumab. Our aim was to describe the laboratory parameters predicting in-hospital mortality of patients with tocilizumab administration in COVID-19 associated cytokine release syndrome (CRS).We evaluated high-dose (8 mg/kg) intravenous tocilizumab administration in severe and critically ill COVID-19 adult patients fulfilling predefined strict CRS criteria. A single-centre, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between April 1 and December 31, 2020. The primary endpoint was 28-day all-cause mortality. The changes in laboratory parameters from baseline on day 7 and 14 after administration of tocilizumab were analysed.In total, 1801 patients were admitted to our centre during the study period. One hundred and six patients received tocilizumab, and among them 62 (58.5%) required intensive care unit admittance while 25 (23.6%) deceased. At day 7 after tocilizumab administration, inflammatory markers (CRP, IL-6, ferritin) and lactate dehydrogenase (LDH) values were significantly lower among survivors. Subsequently, at day 14, differences of IL-6 and LDH levels has become more pronounced between subgroups. Restoration of absolute lymphocyte count (ALC) by day 7 and 14 was insufficient among patients who died.In our cohort, administration of high-dose tocilizumab for COVID-19 patients with CRS demonstrated clinical and sustained biochemical parameter improvement in 76.4%. In this patient population high and increasing LDH, IL-6, and low ALC levels had a predictive role for mortality.

A novel id-iri score: development and internal validation of the multivariable community acquired sepsis clinical risk prediction model.

We aimed to develop a scoring system for predicting in-hospital mortality of community-acquired (CA) sepsis patients. This was a prospective, observational multicenter study performed to analyze CA sepsis among adult patients through ID-IRI (Infectious Diseases International Research Initiative) at 32 centers in 10 countries between December 1, 2015, and May 15, 2016. After baseline evaluation, we used univariate analysis at the second and logistic regression analysis at the third phase. In this prospective observational study, data of 373 cases with CA sepsis or septic shock were submitted from 32 referral centers in 10 countries. The median age was 68 (51-77) years, and 174 (46,6%) of the patients were females. The median hospitalization time of the patients was 15 (10-21) days. Overall mortality rate due to CA sepsis was 17.7% (n = 66). The possible predictors which have strong correlation and the variables that cause collinearity are acute oliguria, altered consciousness, persistent hypotension, fever, serum creatinine, age, and serum total protein. CAS (%) is a new scoring system and works in accordance with the parameters in third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The system has yielded successful results in terms of predicting mortality in CA sepsis patients.

Clinical and microbiological characteristics and outcomes of community-acquired sepsis among adults: a single center, 1-year retrospective observational cohort study from Hungary.

BACKGROUND: Community-acquired sepsis is a life-threatening systemic reaction, which starts within ≤72 h of hospital admittance in an infected patient without recent exposure to healthcare risks. Our aim was to evaluate the characteristics and the outcomes concerning community-acquired sepsis among patients admitted to a Hungarian high-influx national medical center. METHODS: A retrospective, observational cohort study of consecutive adult patients hospitalized with community-acquired sepsis during a 1-year period was executed. Clinical and microbiological data were collected, patients with pre-defined healthcare associations were excluded. Sepsis definitions and severity were given according to ACCP/SCCM criteria. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were intensive care unit (ICU) admittance, length-of-stay (LOS), source control and bacteraemia rates. Statistical differences were explored with classical comparison tests, predictors of in-hospital all-cause mortality were modelled by multivariate logistic regression. RESULTS: 214 patients (median age 60.0 ± 33.1 years, 57% female, median Charlson score 4.0 ± 5.0) were included, 32.7% of them (70/214) had severe sepsis, and 28.5% (61/214) had septic shock. Prevalent sources of infections were genitourinary (53/214, 24.8%) and abdominal (52/214, 24.3%). The causative organisms were dominantly E. coli (60/214, 28.0%), S. pneumoniae (18/214, 8.4%) and S. aureus (14/214, 6.5%), and bacteraemia was documented in 50.9% of the cases (109/214). In-hospital mortality was high (30/214, 14.0%), and independently associated with shock, absence of fever, male gender and the need for ICU admittance, but source control and de-escalation of empirical antimicrobial therapy were protective. ICU admittance was 27.1% (58/214), source control was achieved in 18.2% (39/214). Median LOS was 10.0 ± 8.0, ICU LOS was 8.0 ± 10.8 days. CONCLUSIONS: Community-acquired sepsis poses a significant burden of disease with characteristic causative agents and sources. Patients at a higher risk for poor outcomes might be identified earlier by the contributing factors shown above.

Clinical and microbiological characteristics of adult invasive Haemophilus influenzae infections: results of a 14-year single-center experience from Hungary.

To describe the characteristics of adult invasive H. influenzae disease, 34 patients diagnosed at a single tertiary center between 2004 and 2017 were analyzed in a retrospective case series study. The annual estimated incidence was 0.1 cases/100.000 inhabitants. Dominant source of infection was pneumonia accompanied by sepsis (62%) and caused by nontypeable strains (74%) with low ampicillin resistance (14%). Survival (94%) and complication rates were high (35%). Main empirical treatments were ceftriaxone or levofloxacine.

[Thousand faces of Streptococcus pneumonia (pneumococcus) infections]. / A Streptococcus pneumoniae (pneumococcus) -infekciók ezer arca.

Incidence and mortality rates of infections caused by Streptococcus pneumoniae (pneumococcus) are high worldwide and in Hungary among paediatric as well as adult populations. Pneumococci account for 35-40% of community acquired adult pneumonias requiring hospitalization, while 25-30% of Streptococcus pneumoniae pneumonias are accompanied by bacteraemia. 5-7% of all infections are fatal but this rate is exponentially higher in high risk patients and elderly people. Mortality could reach 20% among patients with severe invasive pneumococcal infections. Complications may develop despite administration of adequate antibiotics. The authors summarize the epidemiology of pneumococcal infections, pathogenesis of non-invasive and invasive disease and present basic clinical aspects through demonstration of four cases. Early risk stratification, sampling of hemocultures, administration of antibiotics and wider application of active immunization could reduce the mortality of invasive disease. Anti-pneumococcal vaccination is advisable for adults of ≥50 years and high risk patients of ≥18 years who are susceptible to pneumococcal disease.

Characteristics of Enterococcus species bloodstream infections among adults with and without onco-hematological malignancies: Experiences from the national center of Hungary.

Introduction: Over the past decade, enterococcal bloodstream infection (BSI) shows increasing incidence globally among the elderly and in patients with comorbidities. In this study, we aimed to assess microbiological and clinical characteristics and long-term outcomes of BSIs caused by Enterococcus spp. in adult patients with and without active onco-hematological malignancies hospitalized at a national referral institute. Methods: A prospective analysis of consecutive enterococcal BSI cases was conducted in the National Institute of Hematology and Infectious Diseases (Budapest, Hungary) between December 2019 and April 2022. We compared characteristics and outcomes at 30-days and 1 year after diagnosis among patients with and without onco-hematological malignancies. Results: In total, 141 patients were included (median age 68 ± 21 years, female sex 36.9%), 37% (52/141) had active onco-hematological malignancies. The distribution of species was as follows: 50.4% Enterococcus faecalis, 46.1% Enterococcus faecium, 1.4% Enterococcus avium and Enterococcus gallinarum, and 0.7% Enterococcus raffinosus. No statistically significant differences in all-cause mortality rates were observed between patient subgroups at 30 days (32.7 vs. 28.1%; P = 0.57) and 1 year (75.0 vs. 60.7%; P = 0.09). Conclusion: Enterococcal bloodstream infections yielded a relevant burden of morbidity, but with no statistical difference in long-term outcomes of adult patients with and without active onco-hematological malignancies.

Favipiravir does not improve viral clearance in mild to moderate COVID-19 - A systematic review and meta-analysis of randomized controlled trials.

Purpose: Favipiravir has been used in the therapy of COVID-19, including patients with mild to moderate symptoms in certain countries. The aim of our systematic review and meta-analysis was to investigate its efficacy and safety in mild-to-moderate COVID-19 infections. Methods: The PubMed, Embase, Web of Science, and Cochrane databases were systematically reviewed for articles reporting the results of randomized controlled trials published until January 6, 2023, resulting in the identification of 20 eligible studies. Results: There were no significant differences in viral clearance time (HR = 1.20, p = 0.09) compared to those without favipiravir therapy. However, in the subgroup analyses, favipiravir treatment significantly increased viral clearance by 59 % (HR = 1.59, p < 0.01) and 42 % (HR = 1.42, p < 0.01], I2 = 20 %) compared to the comparator group in patients with moderate severity of COVID-19 and in the inpatient care setting, respectively. Favipiravir had no beneficial effects in the case of patients with mild symptoms and treated in ambulatory care. Conclusions: The use of favipiravir is questionable in the treatment of outpatients with COVID-19 with mild symptoms. Moderate beneficial effects in the case of patients with moderate symptoms and inpatients should be treated with care due to the limitations of the analysed trials.

Secondary infections and long-term outcomes among hospitalized elderly and non-elderly patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treated with baricitinib: a comparative study from the national centre of Hungary.

Baricitinib is considered a first-line treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adult patients with an associated cytokine storm syndrome (CSS). Our objective was to compare rates of secondary infections and long-term outcomes of elderly and non-elderly patients who received baricitinib for COVID-19. We conducted a single-centre observational study between November 2020 and September 2023, focusing on hospitalized adult SARS-CoV-2 patients with CSS, categorized as elderly (≥ 65 years) and non-elderly (< 65 years). Enrolment, severity stratification, and diagnosis of infectious complications followed predefined criteria. Outcomes of all-cause mortality and rates of non-severe and severe secondary infections were assessed at 1-year post-treatment initiation. Kaplan-Meier analysis was performed for survival analysis. In total, 490 patients were enrolled (median age 65 ± 23 (21-100) years (years, median ± IQR, min-max); 49.18% elderly; 59.59% male). Elderly patients were admitted to the hospital significantly earlier (7 ± 5 days vs. 8 ± 4 days; p = 0.02), experienced a higher occurrence of severe COVID-19 (121/241, 50.21% vs. 98/249, 39.36%; p = 0.02), and required the use of non-invasive ventilation at baseline (167/225, 74.22% vs. 153/236, 64.83%; p = 0.03). At 1 year, all-cause mortality was significantly higher in the elderly subgroup (111/241, 46.06% vs. 29/249, 11.65%; p < 0.01). At 90 days and 1 year, rates of any severe secondary infection were also more prevalent among the elderly (56/241, 23.24% vs. 37/249 14.86%; p = 0.02 and 58/241, 24.07% vs. 39/249, 15.66%; p = 0.02). In conclusion, elderly SARS-CoV-2-infected patients experience a more severe clinical course, higher secondary infection rates, and increased risk for long-term mortality, regardless of immunomodulatory therapy.

["When it rains, it pours" - de novo diagnosed multiple myeloma with invasive Streptococcus pneumoniae infection in severe COVID-19 complicated with cytokine storm]. / "A baj nem jár egyedül" ­ de novo diagnosztizált myeloma multiplex invazív Streptococcus pneumoniae fertozéssel citokinviharral szövodött COVID­19-ben.

With the appearance of SARS-CoV-2, the range of infections, considered the most common cause of death for people with multiple myeloma, has expanded. Although the omicron variant (PANGO B.1.1.529) of SARS-CoV-2, that dominates the world at the time of manuscript writing, is less likely to cause fatal infection in immunocompetent patients compared to the delta variant (PANGO B.1.617.2), its transmissibility did not decrease. The likelihood of a severe or critical course of COVID-19 in patients with multiple myeloma is increased by the humoral and cellular immunosuppression caused by the malignancy itself, its targeted hematological treatment, and other comorbidities associated with the disease (e.g., chronic kidney failure). Antiviral therapies, monoclonal antibody preparations used as pre- or post-exposure prophylaxis, and possibly convalescent plasma therapy, started as early as possible might prevent the clinical progression of COVID-19. While the incidence of community-acquired co-infections accompanying COVID-19 in the average population is not exceptionally high, in people with multiple myeloma, Streptococcus pneumoniae infection that follows respiratory viral diseases is approximately 150 times more likely to cause invasive disease. As a result of modern oncohematological treatment, multiple myeloma has now become a chronic disease accompanied by relapses, and those affected should be immunized against the above two pathogens. In our manuscript, we describe the case of an adult patient with severe COVID-19 complicated by cytokine storm and invasive Streptococcus pneumoniae infection who was diagnosed with de novo multiple myeloma during hospital care, and, finally, we briefly review the related literature data. Orv Hetil. 2023; 164(20): 763-769.

Outcomes of high-risk adult outpatients treated with early remdesivir therapy during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron era: experiences from the national centre of Hungary.

Emerging evidence suggests that remdesivir might improve clinical outcome of high-risk outpatients with coronavirus disease 2019 (COVID-19). Our aim was to evaluate characteristics and outcomes of nonhospitalised adults diagnosed with COVID-19 and treated with early remdesivir therapy during the omicron wave. A single-centre prospective cohort study was performed among adult patients between February and June 2022, during the circulation of phylogenetic assignment of named global outbreak (PANGO) subvariants BA.2, BA.4, and BA.5 in Hungary. Patients were enrolled based on pre-defined criteria. Clinical characteristics (demography, comorbidities, vaccination status, imaging, treatment, and disease course) and outcomes (COVID-19 related hospitalisation, oxygen supplementation, intensive care support, and all-cause death) were assessed at 28 days post-treatment. A subgroup analysis of patients with and without active haematological malignancies was also carried out. Altogether, 127 patients were enrolled: 51.2% (65/127) were female with a median age of 59 (IQR: 22, range: 21‒92) years, and 48.8% (62/127) had active haematological malignancy. At 28 days post-treatment, 7.1% (9/127) of patients required COVID-19-related hospitalisation, 2.4% (3/127) required oxygen supplementation, 1.6% (2/127) required intensive care, and 0.8% (1/127) died due to a non-COVID-19-related secondary infection at the intensive care unit, all with haematological malignancies. Early remdesivir treatment might be a feasible strategy among high-risk outpatients with COVID-19 during the omicron wave.

Clinical and Microbiological Outcomes and Follow-Up of Secondary Bacterial and Fungal Infections among Critically Ill COVID-19 Adult Patients Treated with and without Immunomodulation: A Prospective Cohort Study.

BACKGROUND: Nearly 10% of COVID-19 cases will require admission to the intensive care unit (ICU). Our aim was to assess the clinical and microbiological outcomes of secondary infections among critically ill COVID-19 adult patients treated with/without immunomodulation. METHODS: A prospective observational cohort study was performed between 2020 and 2022 at a single ICU. The diagnosis and severity classification were established by the ECDC and WHO criteria, respectively. Eligible patients were included consecutively at admission, and followed for +30 days post-inclusion. Bloodstream-infections (BSIs), ventilator-associated bacterial pneumonia (VAP), and COVID-19-associated invasive pulmonary aspergillosis (CAPA) were defined according to international guidelines. Patient stratification was performed by immunomodulatory therapy administration (dexamethasone, tocilizumab, baricitinib/ruxolitinib). The primary outcome was any microbiologically confirmed major infectious complication, secondary outcomes were invasive mechanical ventilation (IMV) requirement and all-cause mortality. RESULTS: Altogether, 379 adults were included. At baseline, 249/379 (65.7%) required IMV and 196/379 (51.7%) had a cytokine storm. At +30 days post-inclusion, the rate of any microbiologically confirmed major infectious complication was 151/379 (39.8%), IMV requirement and all-cause mortality were 303/379 (79.9%) and 203/379 (53.6%), respectively. There were no statistically significant outcome differences after stratification. BSI, VAP, and CAPA episodes were mostly caused by Enterococcus faecalis (27/124, 22.1%), Pseudomonas aeruginosa (26/91, 28.6%), and Aspergillus fumigatus (20/20, 100%), respectively. Concerning the primary outcome, Kaplan-Meier analysis showed similar probability distributions between the treatment subgroups (118/299, 39.5% vs. 33/80, 41.3%, log-rank p = 0.22), and immunomodulation was not retained as its independent predictor in multivariate logistic regression. CONCLUSIONS: Secondary infections among critically ill COVID-19 adult patients represent a relevant burden, probably irrespective of immunomodulatory treatment.

Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study.

Background: The optimal approach for adult patients hospitalized with severe and critical coronavirus disease 2019 (COVID-19), non-responsive to antiviral and immunomodulatory drugs, is not well established. Our aim was to evaluate feasibility and safety of extracorporeal photopheresis (ECP) in this setting. Methods: A prospective, single-center investigational study was performed between 2021 and 2022 at a tertiary referral center for COVID-19. Patients diagnosed with COVID-19 were screened, and cases with severe or critical disease fulfilling pre-defined clinical and biochemical criteria of non-response for >5 days, despite remdesivir, dexamethasone and immunomodulation (tocilizumab, baricitinib, ruxolitinib), were consecutively enrolled. After patient inclusion, two ECP sessions on two consecutive days per week for 2 weeks were applied. Patients were followed-up per protocol from study inclusion, and clinical, virological and radiological outcomes were assessed at the end of treatment (EOT) +28 days. Results: A total of seven patients were enrolled. At inclusion, four out of seven (57.1%) were admitted to the ICU, all patients had ongoing cytokine storm. Additionally, 3/7 (42.9%) had radiological progression on chest CT. At EOT+28 days, 2/7 (28.6%) patients died due to non-ECP-related causes. Among the survivors, no additional requirement for intensive care unit admission or radiological progression was observed, and invasive mechanical ventilation could be weaned off in 1/5 (20.0%). All patients achieved whole-blood SARS-CoV-2 RNAemia clearance, while 3/7 (42.9%) no longer showed detectable respiratory SARS-CoV-2 RNA. According to immune biomarker profiling, ECP mainly facilitated a decrease in plasma IL-6 and IL-17A levels, as well as the physiological regeneration of peripheral blood immunocyte subpopulations, notably CD8+/CD45RO+ memory T-cells. No safety signals were identified. Conclusions: ECP appears to be a safe and feasible option for adults hospitalized with severe or critical COVID-19 who do not respond to pharmacological interventions. Further trial data are warranted to assess its optimal use. Trial registration: ClinicalTrials.gov NCT05882331 (retrospectively registered).

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID-IRI study.

OBJECTIVES: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management. METHODS: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). RESULTS: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. CONCLUSIONS: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.

Kinetics of serum C-reactive protein and procalcitonin levels and their connection to outcomes in community-acquired sepsis / A C-reaktívprotein- és -prokalcitoninszintek szérumkinetikája és a klinikai kimenetellel való kapcsolata közösségben szerzett szepszisben

Introduction and objective: Community-acquired sepsis is a life-threatening systemic reaction to infection starting 72 hours within hospital admittance. Data concerning kinetics of serum C-reactive protein (CRP) and procalcitonin (PCT) levels during disease progression are sparse. Our aim was to analyze kinetics of CRP and PCT among adults with community-acquired sepsis. Methods: We analyzed data of consecutive patients hospitalized with community-acquired sepsis at our centre during 2016. Sepsis was defined according to ACCP/SCCM criteria, community-acquisition was ascertained by a priori exclusion criteria. CRP and PCT values of days 1­14 were collected. Primary outcomes were in-hospital all-cause mortality, intensive care unit admission, secondary outcomes were septic source and the causative microorganism. Absolute (ΔabsCRP, ΔabsPCT) and relative (Δ%CRP, Δ%PCT) differences were calculated between values at the time of diagnosis and control values within 24 hours of empirical antimicrobial therapy initiation. Results: 193 patients were included. In-hospital all-cause mortality was 13.9%, intensive care unit admittance was 25.9%. Patients who died had significantly smaller median Δ%PCT decrements (­7.7 ± 127.9% vs. ­45.7 ± 88.8%, p = 0.01), compared to survivors. During hospital stay, daily absolute values of PCT on days 2­14, while those of CRP on days 5­14 were significantly higher among patients who died. Patients admitted to the intensive care unit also had smaller median Δ%PCT decrements (­19.6 ± 72.5% vs. ­49.8 ± 100.8%, p = 0.01), compared to non-admitted patients. Calculated parameters did not show significant correlations with septic focus or causative microorganisms. Discussion, conclusion: Our findings suggest that specific fluctuations of CRP and PCT are observable, and Δ%PCT might be a favourable parameter for outcome prediction among adults with community-acquired sepsis.

Use of convalescent plasma therapy in hospitalised adult patients with non-critical COVID-19: a focus on the elderly from Hungary.

Convalescent plasma therapy might be a feasible option for treatment of novel infections. During the early phases of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, several promising results were published with convalescent plasma therapy, followed by more disappointing findings of randomised controlled trials. In our single-centre, open-label, prospective, cohort study, we assessed the findings of 180 patients treated with convalescent plasma during the first four waves of the pandemic in Hungary. The primary outcome was all-cause mortality; secondary outcomes were clinical improvement and need for intensive care unit admission by day 28. Subgroup analysis comparing elderly and non-elderly (less than 65 years of age) was performed. Twenty (11.4%) patients died by day 28, at significantly higher rates in the elderly subgroup (3 vs. 17, p < 0.01). One hundred twenty-eight (72.7%) patients showed clinical improvement, and 15 (8.5%) were transferred to the intensive care unit until day 28. Non-elderly patients showed clinical improvement by day 28 in significantly higher rates (improvement 74 vs. 54, no improvement 15 vs. 11, worsening or death 4 vs. 18 patients, p < 0.01). In conclusion, we found similar clinical outcome results as randomised controlled trials, and the impact of risk factors for unfavourable clinical outcomes among patients in the elderly population.

COVID­19-associated liver enzyme elevation is probably multifactorial / A COVID-19-hez kapcsolódó májenzim-emelkedés valószínuleg multifaktoriális eredetu

Elevation of serum hepatic enzymes are common during the course of COVID­19. There are three possible mechanisms behind this phenomenon: 1) direct and indirect cytotoxic effects of SARS-CoV-2, 2) pharmacological side effects of COVID­19 drugs (e.g., remdesivir, favipiravir, tocilizumab, baricitinib, systemic corticosteroids, etc.) and 3) the progression of chronic hepatic diseases. Both the differential diagnosis and the clinical decision-making may pose difficulty for the the astute clinician, as an inappropriate treatment may result in COVID­19 progression or liver function deterioration. This review aims to provide basic guidance on the clinical decision-making for physicians managing patients with COVID­19.

Composition and changes of blood microbiota in adult patients with community-acquired sepsis: A pilot study from bench to bedside.

Background: Characteristics of the blood microbiota among adult patients with community-acquired sepsis are poorly understood. Our aim was to analyze the composition of blood microbiota in adult patients with community-acquired sepsis, and correlate changes with non-septic control patients. Methods: A prospective observational study was carried out by including adult patients hospitalized for community-acquired sepsis at our center between January and November 2019, by random selection from a pool of eligible patients. Study inclusion was done on the day of sepsis diagnosis. Community acquisition was ascertained by a priori exclusion criteria; sepsis was defined according to the SEPSIS-3 definitions. Each included patient was matched with non-septic control patients by age and gender in a 1:1 fashion enrolled from the general population. Conventional culturing with BacT/ALERT system and 16S rRNA microbiota analysis were performed from blood samples taken in a same time from a patient. Abundance data was analyzed by the CosmosID HUB Microbiome software. Results: Altogether, 13 hospitalized patients were included, 6/13 (46.2%) with sepsis and 7/13 (53.8%) with septic shock at diagnosis. The most prevalent etiopathogen isolated from blood cultures was Escherichia coli, patients mostly had intraabdominal septic source. At day 28, all-cause mortality was 15.4% (2/13). Compared to non-septic control patients, a relative scarcity of Faecalibacterium, Blautia, Coprococcus and Roseburia genera, with an abundance of Enhydrobacter, Pseudomonas and Micrococcus genera was observed among septic patients. Relative differences between septic vs. non-septic patients were more obvious at the phylum level, mainly driven by Firmicutes (25.7% vs. 63.1%; p<0.01) and Proteobacteria (36.9% vs. 16.6%; p<0.01). The alpha diversity, quantified by the Chao1 index showed statistically significant difference between septic vs. non-septic patients (126 ± 51 vs. 66 ± 26; p<0.01). The Bray-Curtis beta diversity, reported by principal coordinate analysis of total hit frequencies, revealed 2 potentially separate clusters among septic vs. non-septic patients. Conclusion: In adult patients with community-acquired sepsis, specific changes in the composition and abundance of blood microbiota could be detected by 16S rRNA metagenome sequencing, compared to non-septic control patients. Traditional blood culture results only partially correlate with microbiota test results.

Baricitinib vs tocilizumab treatment for hospitalized adult patients with severe COVID-19 and associated cytokine storm: a prospective, investigational, real-world study.

OBJECTIVES: Our aim was to compare outcomes of hospitalized adults with severe COVID-19 and cytokine storm treated with tocilizumab or baricitinib. METHODS: A prospective, investigational, real-world study was performed from April 2020 to April 2021 at our center. COVID-19 severity was classified by World Health Organization criteria, and cytokine storm was documented along predefined criteria. Eligible patients were enrolled at diagnosis if they fulfilled a priori inclusion criteria and received standard-of-care plus tocilizumab or baricitinib for >48 hours. Patients were followed per protocol for 28 days post-diagnosis. The primary outcome was all-cause mortality; secondary outcomes were invasive mechanical ventilation and major infectious complications. RESULTS: Of 463 patients, 102/463 (22.1%) received tocilizumab, and 361/463 (77.9%) baricitinib. Baseline characteristics were balanced. At 28 days, there was no difference in all-cause mortality (22/102, 21.6% vs 64/361, 17.7%; P-value = 0.38). Requirement for invasive mechanical ventilation was more frequent after tocilizumab (52/102, 50.9% vs 96/361, 26.6%; P <0.01), rate of major infectious complications was similar (32/102, 31.4% vs 96/361, 26.6%; P-value = 0.34). In logistic regression, the immunomodulatory drug was not retained as a predictor of all-cause mortality. Kaplan-Meier analysis revealed statistically similar survival distributions. CONCLUSION: All-cause mortality was similar between adults treated with baricitinib or tocilizumab for severe COVID-19 with cytokine storm.

ESCMID COVID-19 living guidelines: drug treatment and clinical management.

SCOPE: In January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: A synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon ß-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon ß-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild-moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19. SCOPE: The aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised.