Association of Molnupiravir and Nirmatrelvir-Ritonavir with reduced mortality and sepsis in hospitalized omicron patients: a territory-wide study.

This study evaluates the association between antivirals (Molnupiravir and Nirmatrelvir-Ritonavir) and all-cause and respiratory mortality and organ dysfunction among high-risk COVID-19 patients during an Omicron outbreak. Two cohorts, Nirmatrelvir-Ritonavir versus control and Molnupiravir versus control, were constructed with inverse probability treatment weighting to balance baseline characteristics. Cox proportional hazards models evaluated the association of their use with all-cause mortality, respiratory mortality, and all-cause sepsis (a composite of circulatory shock, respiratory failure, acute liver injury, coagulopathy, and acute liver impairment). Patients recruited were hospitalized and diagnosed with the COVID-19 Omicron variant between February 22, 2022 and April 15, 2022, and followed up until May 15, 2022. The study included 17,704 patients. There were 4.67 and 22.7 total mortalities per 1000 person-days in the Nirmatrelvir-Ritonavir and control groups respectively before adjustment (weighted incidence rate ratio, - 18.1 [95% CI - 23.0 to - 13.2]; hazard ratio, 0.18 [95% CI, 0.11-0.29]). There were 6.64 and 25.9 total mortalities per 1000 person-days in the Molnupiravir and control groups respectively before adjustment (weighted incidence rate ratio per 1000 person-days, - 19.3 [95% CI - 22.6 to - 15.9]; hazard ratio, 0.23 [95% CI 0.18-0.30]). In all-cause sepsis, there were 13.7 and 35.4 organ dysfunction events per 1000 person-days in the Nirmatrelvir-Ritonavir and control groups respectively before adjustment (weighted incidence rate ratio per 1000 person-days, - 21.7 [95% CI - 26.3 to - 17.1]; hazard ratio, 0.44 [95% CI 0.38-0.52]). There were 23.7 and 40.8 organ dysfunction events in the Molnupiravir and control groups respectively before adjustment (weighted incidence ratio per 1000 person-days, - 17.1 [95% CI, - 20.6 to - 13.6]; hazard ratio, 0.63 [95% CI 0.58-0.69]). Among COVID-19 hospitalized patients, use of either Nirmatrelvir-Ritonavir or Molnupiravir compared with no antiviral use was associated with a significantly lower incidence of 28-days all-cause and respiratory mortality and sepsis.

Covid-period-associated changes in organism profile of neonatal sepsis in a tertiary center from East India.

INTRODUCTION: Neonatal sepsis is a major cause of morbidity and mortality with a higher burden from the low- and middle-income countries. The coronavirus disease 2019 (Covid 19) pandemic has impacted healthcare in various ways including healthcare-associated infections (HAI). The objective of the present study was to determine changes in organism profile and incidence rates of HAI in neonates admitted to the index hospital during the pandemic and compared it with the data from the pre-pandemic period. MATERIALS AND METHODS: The study design was a retrospective, observational analysis of data from neonates with culture-positive sepsis, in a tertiary care children's hospital, between January 2018 and December 2021. Pre-Covid (January 2018 to December 2019) and Covid period data (January 2020 to December 2021) were analyzed for the significance of change. RESULTS: The prevalence of culture-positive sepsis, in pre-Covid and Covid periods, was 19.55% [95% confidence interval (95% CI) 17.13-21.52)] and 18.36% (CI 16.05-20.74), respectively. HAI rates/1000 patient days increased slightly during the Covid pandemic [7.2% (95% CI 6.98-10.08) to 9.8% (95% CI 9.78-13.67)] mainly due to an increase in fungal HAI (26% pre- vs. 41.5% Covid period). However, the proportion of Gram-negative (GN) infections fell significantly (70.5% vs. 48.6%) during the same period. In the pre-Covid period, Klebsiella followed by Burkholderia cepacia, Acinetobacter spp and Pseudomonas, were the major HAI isolates. During the Covid period, there was a decline in these isolates and Burkholderia spp was not detected. All fungal isolates were Candida species. The case fatality ratio (CFR) from HAI decreased significantly from 38% to 15.45%, mainly due to a decrease in GN HAI. CONCLUSION: During Covid pandemic, there was a significant decline in GN HAI and CFR from HAI, due to improved compliance with infection control measures in the neonatal intensive care unit (NICU). At the same time, there was a rise in the fungal HAI, possibly because of a higher proportion of premature, and sick neonates with longer hospital stay and more invasive procedures. Consolidations of gains in infection control and restriction of invasive procedures could help to minimize HAI in NICUs.

Blood stream infections in children less than 4 weeks old are known as neonatal sepsis. Several predisposing factors can make a neonate (less than 4 weeks) more prone to sepsis, such as prematurity, male gender, cultural practices, presence of underlying medical or surgical conditions, hospitalization, antibiotic use and invasive treatment. Neonatal sepsis in a hospitalized child can be either­pre-harbored infection (PHI), which means infection acquired prior to hospital admission or it could be healthcare-associated infection (HAI), where the infection is acquired during the hospital stay. Organisms causing neonatal sepsis in hospitalized neonates include bacteria and fungi. The coronavirus disease 2019 (Covid 19) pandemic impacted all aspects of life including healthcare. The investigators conducted the present study to look into the changes in the incidence rate as well as in the type of organisms causing healthcare-associated blood stream infections in neonates in the pre-Covid and during the Covid period.

Trends in sepsis and pneumonia during COVID-19: lessons from BPCIA.

OBJECTIVES: The COVID-19 pandemic affected care delivery nationwide for all patients, influencing cost and utilization for patients both with and without COVID-19. Our first analysis assessed changes in utilization for patients with sepsis without COVID-19 prior to vs during the pandemic. Our second analysis assessed cost and utilization changes during the pandemic for patients with sepsis or pneumonia both with and without COVID-19. STUDY DESIGN: A retrospective case-control study was utilized to determine differences in cost and utilization for patients with sepsis or pneumonia, relative to a COVID-19 diagnosis. METHODS: Claims data from 8 teaching hospitals participating in sepsis and pneumonia episodes in the Bundled Payments for Care Improvement Advanced (BPCIA) model were utilized. BPCIA is a Medicare value-based care bundled payment program that aims to decrease costs and increase quality of care through a 90-day total cost of care model. RESULTS: The first analysis (N = 1092) found that non-COVID-19 patients with sepsis had 26% higher hospice utilization (P < .05) and 38% higher mortality (P < .0001) during the pandemic vs the prepandemic period. The second analysis (N = 640) found that during the pandemic, patients with sepsis or pneumonia with COVID-19 had 70% more skilled nursing facility (SNF) use (P < .0001), 132% higher SNF costs (P < .0001), and 21% higher total episode costs (P < .0001) compared with patients without COVID-19. CONCLUSIONS: COVID-19 has affected care patterns for all patients. Patients without COVID-19 postponed care and used lower-acuity care settings, whereas patients with COVID-19 were more costly and utilized postacute care at a higher rate. These analyses inform future care coordination initiatives, given the ongoing pandemic.

Metapneumovirus Infections are Uncommon in Infants Younger than 60 Days of Age Admitted for Sepsis Evaluation.

The epidemiology and clinical manifestations of human metapneumovirus are not well studied in infants younger than 60 days of age. In this retrospective review of infants admitted for sepsis evaluation, we identified HMPV less frequently than other viral etiologies via nasopharyngeal multiplex polymerase chain reaction testing; in only 16 (1.9%) infants. Two infants had apneic episodes, but none had wheezing.

Gram-negative ESKAPE bacteria bloodstream infections in patients during the COVID-19 pandemic.

Bloodstream infections due to bacteria are a highly consequential nosocomial occurrences and the organisms responsible for them are usually multidrug-resistant. The aims of this study were to describe the incidence of bacteremia caused by Gram-negative ESKAPE bacilli during the COVID-19 pandemic and characterize the clinical and microbiological findings including antimicrobial resistance. A total of 115 Gram-negative ESKAPE isolates were collected from patients with nosocomial bacteremia (18% of the total bacteremias) in a tertiary care center in Mexico City from February 2020 to January 2021. These isolates were more frequently derived from the Respiratory Diseases Ward (27), followed by the Neurosurgery (12), Intensive Care Unit (11), Internal Medicine (11), and Infectious Diseases Unit (7). The most frequently isolated bacteria were Acinetobacter baumannii (34%), followed by Klebsiella pneumoniae (28%), Pseudomonas aeruginosa (23%) and Enterobacter spp (16%). A. baumannii showed the highest levels of multidrug-resistance (100%), followed by K. pneumoniae (87%), Enterobacter spp (34%) and P. aeruginosa (20%). The bla CTX-M-15 and bla TEM-1 genes were identified in all beta-lactam-resistant K. pneumoniae (27), while bla TEM-1 was found in 84.6% (33/39) of A. baumannii isolates. The carbapenemase gene bla OXA-398 was predominant among carbapenem-resistant A. baumannii (74%, 29/39) and bla OXA-24was detected in four isolates. One P. aeruginosa isolate was bla VIM-2 gene carrier, while two K. pneumoniae and one Enterobacter spp were bla NDM gene carriers. Among colistin-resistant isolates mcr-1 gene was not detected. Clonal diversity was observed in K. pneumoniae, P. aeruginosa and Enterobacter spp. Two outbreaks caused by A. baumannii ST208 and ST369 were detected, both belonging to the clonal complex CC92 and IC2. A. baumannii was associated with a death rate of 72% (28/32), most of them (86%, 24/28) extensively drug-resistant or pandrug-resistant isolates, mainly in patients with COVID-19 (86%, 24/28) in the Respiratory Diseases Ward. A. baumannii isolates had a higher mortality rate (72%), which was higher in patients with COVID-19. There was no statistically significant association between the multidrug-resistant profile in Gram-negative ESKAPE bacilli and COVID-19 disease. The results point to the important role of multidrug-resistant Gram-negative ESKAPE bacteria causing bacteremia in nosocomial settings before and during the COVID-19 epidemic. Additionally, we were unable to identify a local impact of the COVID-19 pandemic on antimicrobial resistance rates, at least in the short term.

Update on Sepsis Epidemiology in the Era of COVID-19.

Timely and accurate data on the epidemiology of sepsis is essential to inform public policy, clinical practice, and research priorities. Recent studies have illuminated several ongoing questions about sepsis epidemiology, including the incidence and outcomes of sepsis in non-Western countries and in specialized populations such as surgical patients, patients with cancer, and the elderly. There have also been new insights into the limitations of current surveillance methods using administrative data and increasing experience tracking sepsis incidence and outcomes using "big data" approaches that take advantage of detailed electronic health record data. The COVID-19 pandemic, however, has fundamentally changed the landscape of sepsis epidemiology. It has increased sepsis rates, helped highlight ongoing controversies about how to define sepsis, and intensified debate about the possible unintended consequences of overly rigid sepsis care bundles. Despite these controversies, there is a growing consensus that severe COVID-19 causing organ dysfunction is appropriate to label as sepsis, even though it is treated very differently from bacterial sepsis, and that surveillance strategies need to be modified to reliably identify these cases to fully capture and delineate the current burden of sepsis. This review will summarize recent insights into the epidemiology of sepsis and highlight several urgent questions and priorities catalyzed by COVID-19.

Reduction of early surgical site and other care related infections in 3553 hip fracture patients: lessons learned from the 5-year Safe Hands project.

BACKGROUND: Surgical site infection (SSI) after acute hip fracture surgery is a devastating complication associated with increased suffering and mortality. The aim of the study was to investigate early SSI, sepsis, pneumonia and urinary tract infections over five years, before and after the implementation of the Safe Hands project. METHODS: This was a single-centre observational study with a 5-year longitudinal design, investigating the effects of an infection-prevention intervention targeting the clinical care pathway of individuals with acute hip fracture. Statistical analyses were based on routinely collected patient outcome data comprising 3553 patients. The study conforms to the criteria of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). RESULTS: The incidence of early SSIs decreased from 2.5% in years 1-2 to 1.1% in years 4-5. Similar results were observed for sepsis (2.7% to 1.3%) and urinary tract infections (14.2% to 4.2%). The multivariable regression results suggest that, for every observed year, the odds of early SSIs decreased. Male gender, procedure time, sepsis and preoperative skin damage increased the odds significantly. CONCLUSIONS: Our preventive bundle, based on partnership between researchers, managers and clinicians and a strong commitment to change from the involved professions, appear to be effective in reducing the frequency of potentially devastating SSIs and other hospital acquired infections after hip fracture surgery. The use of external and internal facilitators was crucial to enable individual and organisational learning and overcoming barriers to improvements. TRIAL REGISTRATION: Clinical Trials.gov ID: NCT02983136 Registered 6 December 2016-Retrospectively registered.

Impact of the COVID-19 pandemic on the incidence of healthcare facility-onset Clostridioides difficile infection in hospitalized patients with sepsis: Interrupted time series analysis using Japanese Diagnosis Procedure Combination data.

OBJECTIVES: Healthcare facility-onset Clostridioides difficile infection (HO-CDI) is a major nosocomial infection associated with high mortality and healthcare costs. We aimed to determine if HO-CDI incidence decreased due to the COVID-19 pandemic. We hypothesized that the pandemic decreased HO-CDI as healthcare workers became more diligent in handwashing and sanitization. METHODS: In this retrospective cohort study, adult patients with sepsis hospitalized in general wards from January 2018 to February 2021 were identified using a nationwide Japanese administrative database. Patients were divided into two groups according to the hospitalization date (before and after the first declaration of a state of emergency). The primary outcome was a change in the level of the HO-CDI monthly incidence ratio (per 10000 patient-days). RESULTS: Of the 49,156 eligible hospitalizations for sepsis, 41,870 were before and 7,283 were after the first state of emergency declaration. Interrupted time-series (ITS) analysis showed no significant difference in the HO-CDI incidence ratio after Japan's first state of emergency declaration (level change -1.0, 95% confidence interval (CI) -8.6 to 6.6, p = 0.8, slope change 0.06, 95% CI -0.17 to 0.3, p = 0.6). The overall HO-CDI incidence ratio was 3.86/10000 patient-days (interquartile range 2.97-4.53); higher incidence existed in subgroups with older adults or a lower Barthel index at admission. CONCLUSIONS: No significant change in HO-CDI incidence was observed in patients with sepsis hospitalized in general wards before and after Japan's first state of emergency declaration. Our study revealed that HO-CDI in general wards in Japan had been consistently decreasing since before the COVID-19 pandemic.

Bloodstream infections in the COVID-19 era: results from an Italian multi-centre study.

BACKGROUND: Correlation between coronavirus disease 2019 (COVID-19) and superinfections has been investigated, but remains to be fully assessed. This multi-centre study reports the impact of the pandemic on bloodstream infections (BSIs). METHODS: This study included all patients with BSIs admitted to four Italian hospitals between 1 January and 30 June 2020. Clinical, demographic and microbiologic data were compared with data for patients hospitalized during the same period in 2019. RESULTS: Among 26,012 patients admitted between 1 January and 30 June 2020, 1182 had COVID-19. Among the patients with COVID-19, 107 BSIs were observed, with an incidence rate of 8.19 episodes per 1000 patient-days. The incidence of BSI was significantly higher in these patients compared with patients without COVID-19 (2.72/1000 patient-days) and patients admitted in 2019 (2.76/1000 patient-days). In comparison with patients without COVID-19, BSI onset in patients with COVID-19 was delayed during the course of hospitalization (16.0 vs 5 days, respectively). Thirty-day mortality among patients with COVID-19 was 40.2%, which was significantly higher compared with patients without COVID-19 (23.7%). BSIs in patients with COVID-19 were frequently caused by multi-drug-resistant pathogens, which were often centre-dependent. CONCLUSIONS: BSIs are a common secondary infection in patients with COVID-19, characterized by increased risk during hospitalization and potentially burdened with high mortality.

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OBJECTIVES: To investigate the changes in the disease spectrum among hospitalized children in the pediatric intensive care units (PICU) within 2 years before and after the outbreak of coronavirus disease 2019 (COVID-19). METHODS: The related data on disease diagnosis were collected from all children who were hospitalized in the PICU of Affiliated Hospital of Jining Medical College from January 2018 to December 2019 (pre-COVID-19 group) and from January 2020 to December 2021 (post-COVID-19 group). A statistical analysis was performed for the disease spectrum of the two groups. RESULTS: There were 2 368 children in the pre-COVID-19 group and 1 653 children in the post-COVID-19 group. The number of children in the post-COVID-19 group was reduced by 30.19% compared with that in the pre-COVID-19 group. There was a significant difference in age composition between the two groups (P<0.05). The top 10 diseases in the pre-COVID-19 group by number of cases were respiratory diseases, neurological diseases, sepsis, critical illness, circulatory system diseases, severe neurosurgical diseases, digestive system diseases, unintentional injuries, endocrine system diseases, and tumors. The top 10 diseases in the post-COVID-19 group by number of cases were respiratory diseases, neurological diseases, sepsis, circulatory system diseases, unintentional injuries, endocrine system diseases, severe neurosurgical diseases, acute abdomen, trauma surgical diseases, and digestive system diseases. The proportions of respiratory diseases, critical illness and severe neurosurgical diseases in the post-COVID-19 group were lower than those in the pre-COVID-19 group (P<0.05), while the proportions of unintentional injuries, acute abdomen, endocrine system diseases, trauma surgical diseases and sepsis were higher than those in the pre-COVID-19 group (P<0.05). CONCLUSIONS: COVID-19 epidemic has led to a significant reduction in the number of children admitted to the PICU, and there are significant changes in the disease spectrum within 2 years before and after the outbreak of COVID-19. Relevant prevention and control measures taken during the COVID-19 epidemic can reduce the incidence of respiratory diseases, neurological diseases, and other critical illness in children, but it is necessary to strengthen the prevention of unintentional injuries and chronic disease management during the epidemic.

Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study.

BACKGROUND: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. METHODS: We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients' characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. RESULTS: A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49-2.45). CONCLUSIONS: We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245 . Registered 3 May 2019.

A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome.

Severe Coronavirus disease 2019 (COVID-19) is associated with several pre-existing comorbidities and demographic factors. Similar factors are linked to critical sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that age and comorbidities are more generically linked to critical illness mortality than a specific disease state. We used national databases to identify ICU patients and to retrieve comorbidities. The relative importance of risk factors for 60-day mortality was evaluated using the interaction with disease group (Sepsis, ARDS or COVID-19) in logistic regression models. We included 32,501 adult ICU patients. In the model on 60-day mortality in sepsis and COVID-19 there were significant interactions with disease group for age, sex and asthma. In the model on 60-day mortality in ARDS and COVID-19 significant interactions with cohort were found for acute disease severity, age and chronic renal failure. In conclusion, age and sex play particular roles in COVID-19 mortality during intensive care but the burden of comorbidity was similar between sepsis and COVID-19 and ARDS and COVID-19.

Pneumonia and Related Conditions in Critically Ill Patients-Insights from Basic and Experimental Studies.

Pneumonia is an acute infectious disease with high morbidity and mortality rates. Pneumonia's development, severity and outcome depend on age, comorbidities and the host immune response. In this study, we combined theoretical and experimental investigations to characterize pneumonia and its comorbidities as well as to assess the host immune response measured by TREC/KREC levels in patients with pneumonia. The theoretical study was carried out using the Columbia Open Health Data (COHD) resource, which provides access to clinical concept prevalence and co-occurrence from electronic health records. The experimental study included TREC/KREC assays in young adults (18-40 years) with community-acquired (CAP) (n = 164) or nosocomial (NP) (n = 99) pneumonia and healthy controls (n = 170). Co-occurring rates between pneumonia, sepsis, acute respiratory distress syndrome (ARDS) and some other related conditions common in intensive care units were the top among 4170, 3382 and 963 comorbidities in pneumonia, sepsis and ARDS, respectively. CAP patients had higher TREC levels, while NP patients had lower TREC/KREC levels compared to controls. Low TREC and KREC levels were predictive for the development of NP, ARDS, sepsis and lethal outcome (AUCTREC in the range 0.71-0.82, AUCKREC in the range 0.67-0.74). TREC/KREC analysis can be considered as a potential prognostic test in patients with pneumonia.

SepsEast Registry indicates high mortality associated with COVID-19 caused acute respiratory failure in Central-Eastern European intensive care units.

The coronavirus disease (COVID-19) pandemic caused unprecedented research activity all around the world but publications from Central-Eastern European countries remain scarce. Therefore, our aim was to characterise the features of the pandemic in the intensive care units (ICUs) among members of the SepsEast (Central-Eastern European Sepsis Forum) initiative. We conducted a retrospective, international, multicentre study between March 2020 and February 2021. All adult patients admitted to the ICU with pneumonia caused by COVID-19 were enrolled. Data on baseline and treatment characteristics, organ support and mortality were collected. Eleven centres from six countries provided data from 2139 patients. Patient characteristics were: median 68, [IQR 60-75] years of age; males: 67%; body mass index: 30.1 [27.0-34.7]; and 88% comorbidities. Overall mortality was 55%, which increased from 2020 to 2021 (p = 0.004). The major causes of death were respiratory (37%), cardiovascular (26%) and sepsis with multiorgan failure (21%). 1061 patients received invasive mechanical ventilation (mortality: 66%) without extracorporeal membrane oxygenation (n = 54). The rest of the patients received non-invasive ventilation (n = 129), high flow nasal oxygen (n = 317), conventional oxygen therapy (n = 122), as the highest level of ventilatory support, with mortality of 50%, 39% and 22%, respectively. This is the largest COVID-19 dataset from Central-Eastern European ICUs to date. The high mortality observed especially in those receiving invasive mechanical ventilation renders the need of establishing national-international ICU registries and audits in the region that could provide high quality, transparent data, not only during the pandemic, but also on a regular basis.

Secondary bacterial infections are a leading factor triggering New Onset Atrial Fibrillation in intubated ICU Covid-19 ARDS patients.

BACKGROUND: Cardiac arrhythmias, mainly atrial fibrillation (AF), is frequently reported in COVID-19 patients, more often in Intensive Care Unit (ICU) patients, yet causality has not been virtually explored. Moreover, non-Covid ICU patients frequently present AF, sepsis being the major trigger. We aimed to examine whether sepsis or other factors-apart from Covid-19 myocardial involvement-contribute to elicit New Onset AF (NOAF) in intubated ICU patients. METHODS: Consecutive intubated, Covid-19ARDS patients, were prospectively studied for factors triggering NOAF. Demographics, data on Covid-19 infection duration, laboratory findings (troponin as well), severity of illness and ARDS were compared between NOAF and control group (no AF) on admission. In NOAF patients, echocardiographic findings, laboratory and secondary infection data on the AF day were compared to the preceding days and/or ICU admission data. RESULTS: Among 105 patients screened, 79 were eligible; nineteen presented NOAF (24%). Baseline characteristics did not differ between the NOAF and control groups. Troponin levels were mildly elevated upon ICU admission in both groups. Left ventricular global longitudinal strain was impaired (<16.5%) in 63% vs 78% in the two groups, respectively. The right ventricle was mildly dilated, and pericardial effusion was present in 52 vs 43%, respectively. NOAF occurred on the 18 ± 4.8 days from Covid-19 symptoms' onset, and the 8.5 ± 2.1 ICUday. A septic secondary infection episode occurred in 89.5% of the patients in the NOAF group ( vs 41.6% in the control group (p < 0.001). In fact, NOAF occurred concurrently with a secondary septic episode in 84.2% of the patients. Sepsis presence was the only factor associated to NOAF occurrence (OR 16.63, p = 0.002). Noradrenaline, lactate and inflammation biomarkers gradually increased in the days before AF (all p < 0.05). Echocardiographic findings did not change on NOAF occurrence. CONCLUSION: Secondary infections seem to be major contributors for NOAF occurrence in Covid-19 patients, probably playing the role of the "second hit" in an affected myocardium from Covid-19.

Trends in bacterial sepsis incidence and mortality in France between 2015 and 2019 based on National Health Data System (Système National des données de Santé (SNDS)): a retrospective observational study.

OBJECTIVE: This study aims to provide a case definition of sepsis of presumed bacterial aetiology based on 10th revision of the International Classification of Diseases (ICD-10) codes, to assess trends in sepsis incidence and mortality between 2015 and 2019 in France, and to describe the characteristics of affected patients and hospital stays. DESIGN: Nationwide, population-based, retrospective observational study. SETTING: Metropolitan France between 2015 and 2019. PARTICIPANTS: Between 2015 and 2019, 1 224 433 patients with sepsis of presumed bacterial aetiology were selected from the French National Hospital Discharge Database (Programme de Médicalisation des Systèmes d'Information) and were identified from corresponding ICD-10 codes for explicit sepsis or implicit sepsis. MAIN OUTCOMES MEASURES: Annual overall and age-specific and gender-specific incidence and 95% CI, as well as trends in sepsis incidence and mortality, were estimated. Comorbidities, length of hospital stay and outcomes were described. RESULTS: The sex-standardised and age-standardised incidence per 100 000 (95% CI) increased from 357 (356.0 to 359.0) in 2015 to 403 (401.9 to 405.0) in 2019 and remained higher for males compared with females. Children under 1 year and patients over 75 years consistently had the highest incidence. The most common comorbidities were cancer and chronic heart failure. The median hospital length of stay was 12 days. Most patients came from home, but only half returned home after their hospital stay and approximately 15% were discharged to long-term care. In-hospital mortality was about 25% and declined along the study period. CONCLUSIONS: Medico-administrative databases can be used to provide nationwide estimates of the in-hospital burden of bacterial sepsis. The results confirm the high burden of sepsis in France. These data should be complemented by estimating the additional burden associated with fungal and viral infections during the COVID-19 pandemic.

Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus.

OBJECTIVES: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda. DESIGN AND METHODS: Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV. RESULTS: The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43-134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30-76.18; p = 0.003), maternal age <25 years (aOR 4.54; 95% CI 1.40-19.29; p = 0.02), and increasing neonatal age (aOR 1.08 for each day older; 95% CI 1.00-1.16; p = 0.05), were associated risk factors for CMV in neonates with clinical sepsis. We found a 2-fold higher maternal vaginal shedding in eastern (45%) vs western (22%) Uganda during parturition (n = 22/49 vs 11/50, the Fisher exact test; p = 0.02). In infants with PIH, the prevalence in blood was 24% and in infants with NPIH, it was 20%. CMV was present in the cerebrospinal fluid (CSF) of 13% of infants with PIH compared with 0.5% of infants with NPIH (n = 26/205 vs 1/194, p < 0.0001). CONCLUSIONS: Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized.

Pediatric Emergency Department Sepsis Screening Tool Accuracy During the COVID-19 Pandemic.

BACKGROUND: Automated sepsis alerts in pediatric emergency departments (EDs) can identify patients at risk for sepsis, allowing for earlier intervention with appropriate therapies. The impact of the COVID-19 pandemic on the performance of pediatric sepsis alerts is unknown. METHODS: We performed a retrospective cohort study of 59 335 ED visits before the pandemic and 51 990 ED visits during the pandemic in an ED with an automated sepsis alert based on systemic inflammatory response syndrome criteria. The sensitivity, specificity, negative predictive value, and positive predictive value of the sepsis algorithm were compared between the prepandemic and pandemic phases and between COVID-19-negative and COVID-19-positive patients during the pandemic phase. RESULTS: The proportion of ED visits triggering a sepsis alert was 7.0% (n = 4180) before and 6.1% (n = 3199) during the pandemic. The number of sepsis alerts triggered per diagnosed case of hypotensive septic shock was 24 in both periods. There was no difference in the sensitivity (74.1% vs 72.5%), specificity (93.2% vs 94.0%), positive predictive value (4.1% vs 4.1%), or negative predictive value (99.9% vs 99.9%) of the sepsis alerts between these periods. The alerts had a lower sensitivity (60% vs 73.3%) and specificity (87.3% vs 94.2%) for COVID-19-positive versus COVID-19-negative patients. CONCLUSIONS: The sepsis alert algorithm evaluated in this study did not result in excess notifications and maintained adequate performance during the COVID-19 pandemic in the pediatric ED setting.

No increase of device associated infections in German intensive care units during the start of the COVID-19 pandemic in 2020.

BACKGROUND: The COVID-19 pandemic may have had a substantial impact on the incidence of device-associated healthcare-associated infections (HAI), in particular in intensive care units (ICU). A significant increase of HAI was reported by US hospitals when comparing incidence rates from 2019 and 2020. The objective of this study was to investigate the development of the most relevant device-associated HAI in German ICUs during the year 2020 as compared to 2019. METHODS: We utilized the data of the ICU component of the German National Reference Center for Surveillance of Nosocomial Infections (KISS = Krankenhaus-Infektions-Surveillance-System) for the period 2019-2020. We focused on central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), ventilator-associated lower respiratory infections (VALRTI) and bloodstream infections associated with the use of Extracorporeal-Life-Support-Systems (ECLSABSI). Device use was defined as the number device days per 100 patient days; device-associated infection rates as the number of device-associated infections per 1000 device days. To compare the pooled means between the years and quarters we calculated rate ratios of device-associated infection rates with 95% confidence intervals by Poisson regression models. RESULTS: The number of participating ICUs in the surveillance system decreased from 982 in 2019 to 921 in 2020 (6.2%). Device utilization rates increased significantly for central lines and ventilator use. VALRTI rates and CAUTI rates decreased in 2020 compared with 2019, however, no increase was shown for CLABSI or ECLSABSI. This result was also confirmed when the corresponding quarters per year were analyzed. CONCLUSIONS: The lack of an increase in device-associated healthcare associated infections (HAI) in German ICUs may be due to the lower overall incidence of COVID-19 cases in Germany in 2020 compared with US, to a very high availability of ICU beds per 100,000 inhabitants compared with many other countries, and a change in the ICU patient mix due to numerous elective procedures that were postponed during the first two waves. The primary reason seems to be that only 7% of all ICU patients in Germany in 2020 were COVID-19 patients.

On prioritising global health's triple crisis of sepsis, COVID-19 and antimicrobial resistance: a mixed-methods study from Malawi.

Sepsis causes 20% of global deaths, particularly among children and vulnerable populations living in developing countries. This study investigated how sepsis is prioritised in Malawi's health system to inform health policy. In this mixed-methods study, twenty multisectoral stakeholders were qualitatively interviewed and asked to quantitatively rate the likelihood of sepsis-related medium-term policy outcomes being realised. Respondents indicated that sepsis is not prioritised in Malawi due to a lack of local sepsis-related evidence and policies. However, they highlighted strong linkages between sepsis and maternal health, antimicrobial resistance and COVID-19, which are already existing national priorities, and offers opportunities for sepsis researchers as policy entrepreneurs. To address the burden of sepsis, we recommend that funding should be channelled to the generation of local evidence, evidence uptake, procurement of resources and treatment of sepsis cases, development of appropriate indicators for sepsis, adherence to infection prevention and control measures, and antimicrobial stewardship.