Infection Research Articles

Favipiravir pharmacokinetics in Thai adults with mild COVID-19: A sub-study of interpatient variability and ethnic differences in exposure.

This sub-study sought to characterize the pharmacokinetics (PK) of favipiravir (FPV) within Thai adults and quantitatively assess differences in exposure to those previously reported in other populations as a basis to understand putative differences in efficacy between studies conducted in different regions. It was nested within a prospective trial of adults with symptomatic COVID-19 infection without pneumonia receiving 1800 mg FPV twice-daily on day 1 and 800 mg twice-daily thereafter. Individual PK profiles were fitted with a one-compartment disposition model (first-order absorption). Eight adults (seven female) with a median age of 39 years and BMI of 27.9 kg/m2 were included. Seven adults achieved plasma concentrations above the EC90 invitro target (25 mg/L), with minimum-maximum concentrations decreasing with repeat dosing. The mean FPV apparent clearance observed in this study was 1.1 L/h (coefficient of variation [CV]: 60%), apparent volume of distribution 20.6 L (CV: 40%), absorption rate constant 6.1 h (CV: 100%), and 2.4 daily % change in apparent clearance (CV: 315%). Higher exposures were observed in these Thai adults compared with data from previous studies in Chinese, Japanese, and Turkish populations, respectively. Current FPV doses recommended in Thailand achieved target plasma concentrations with higher exposures than those described previously in other populations. The limited sample size prohibits firm conclusions from being drawn but the presented data warrants confirmation with a view to interrogate the appropriateness of doses used in randomized clinical trials that failed to demonstrate efficacy.

Dual RNA-seq study of the dynamics of coding and non-coding RNA expression during Clostridioides difficile infection in a mouse model.

Clostridioides difficile is the leading cause of healthcare-associated diarrhea in industrialized countries. Many questions remain to be answered about the mechanisms governing its interaction with the host during infection. Non-coding RNAs (ncRNAs) contribute to shape virulence in many pathogens and modulate host responses; however, their role in C. difficile infection (CDI) has not been explored. To better understand the dynamics of ncRNA expression contributing to C. difficile infectious cycle and host response, we used a dual RNA-seq approach in a conventional murine model. From the pathogen side, this transcriptomic analysis revealed the upregulation of virulence factors, metabolism, and sporulation genes, as well as the identification of 61 ncRNAs differentially expressed during infection that correlated with the analysis of available raw RNA-seq data sets from two independent studies. From these data, we identified 118 potential new transcripts in C. difficile, including 106 new ncRNA genes. From the host side, we observed the induction of several pro-inflammatory pathways, and among the 185 differentially expressed ncRNAs, the overexpression of microRNAs (miRNAs) previously associated to inflammatory responses or unknown long ncRNAs and miRNAs. A particular host gene expression profile could be associated to the symptomatic infection. In accordance, the metatranscriptomic analysis revealed specific microbiota changes accompanying CDI and specific species associated with symptomatic infection in mice. This first adaptation of in vivo dual RNA-seq to C. difficile contributes to unravelling the regulatory networks involved in C. difficile infectious cycle and host response and provides valuable resources for further studies of RNA-based mechanisms during CDI.IMPORTANCEClostridioides difficile is a major cause of nosocomial infections associated with antibiotic therapy classified as an urgent antibiotic resistance threat. This pathogen interacts with host and gut microbial communities during infection, but the mechanisms of these interactions remain largely to be uncovered. Noncoding RNAs contribute to bacterial virulence and host responses, but their expression has not been explored during C. difficile infection. We took advantage of the conventional mouse model of C. difficile infection to look simultaneously to the dynamics of gene expression in pathogen, its host, and gut microbiota composition, providing valuable resources for future studies. We identified a number of ncRNAs that could mediate the adaptation of C. difficile inside the host and the crosstalk with the host immune response. Promising inflammation markers and potential therapeutic targets emerged from this work open new directions for RNA-based and microbiota-modulatory strategies to improve the efficiency of C. difficile infection treatments.

Biliary microbiome and gallstones: A silent friendship

With increasing evidence, the biliary tract and the gallbladder mucosa are no longer considered sterile environments devoid of bacteria. Rather a profound biofilm of resident bacterial flora is associated with the mucosal surface. The bile too harbors a resident flora. It is when a dysbiotic process ensues, that this bacterial flora either becomes opportunist or is replaced by a pathogenic one that has a strong ability to survive the challenges of the biliary environment. Although once believed a metabolic problem, recent evidence indicates a complex interaction between different species of bacteria and gallbladder mucosa and bile which may culminate in calculus formation. The resident microbiota and its several enzymes dictate the type of gallstone by the mere interplay of the constituting type of bacteria in the biofilm, even without any evidence of infection. Dysbiosis is often mediated by either intestinal dysbiosis or less probably by oral dysbiosis. The gallstones, in turn, provide a haven for the resident microbiota in which they can form their own defined niche enriched with the biofilm that can resist the biliary defense mechanisms and survive the hostile biliary environment in the background of biliary stasis and local infection. However, this process of silent friendship is more complex than said, and further research is needed to define the relationship between the two.

Plasmodium berghei liver stage parasites exploit host GABARAP proteins for TFEB activation

Plasmodium, the causative agent of malaria, infects hepatocytes prior to establishing a symptomatic blood stage infection. During this liver stage development, parasites reside in a parasitophorous vacuole (PV), whose membrane acts as the critical interface between the parasite and the host cell. It is well-established that host cell autophagy-related processes significantly impact the development of Plasmodium liver stages. Expression of genes related to autophagy and lysosomal biogenesis is orchestrated by transcription factor EB (TFEB). In this study, we explored the activation of host cell TFEB in Plasmodium berghei-infected cells during the liver stage of the parasite. Our results unveiled a critical role of proteins belonging to the Gamma-aminobutyric acid receptor-associated protein subfamily (GABARAP) of ATG8 proteins (GABARAP/L1/L2 and LC3A/B/C) in recruiting the TFEB-blocking FLCN-FNIP (Folliculin-Folliculin-interacting protein) complex to the PVM. Remarkably, the sequestration of FLCN-FNIP resulted in a robust activation of TFEB, reliant on conjugation of ATG8 proteins to single membranes (CASM) and GABARAP proteins. Our findings provide novel mechanistic insights into host cell signaling occurring at the PVM, shedding light on the complex interplay between Plasmodium parasites and the host cell during the liver stage of infection.

Association of Serum Vitamin D Level with Symptomatic Urinary Tract Infection in Pregnant Women

Background: Urinary tract infections (UTIs) are the most common bacterial infections during pregnancy. Pregnant women in Bangladesh often suffer from UTIs due to a lack of knowledge regarding proper hygiene practices. Adequate vitamin D levels have the potential to enhance the innate immune response, thereby can reduce susceptibility to bacterial infections. Therefore, vitamin D deficiency in pregnant women could increase the risk of urinary tract infections. Aim: To determine the association between maternal serum vitamin D levels and urinary tract infection in pregnancy. Method: This was a case-control study among purposively selected pregnant women attending the inpatient and outpatient department of Obstetrics and Gynaecology, ICMH, Matuail, Dhaka. A total 80 pregnant women between 18-40 years of age were included in this study at their 6-28 weeks of gestation. Among them 40 women who had urinary tract infection, confirmed by presence of ≥105/HPF pus cell in urine routine microscopic examination and a positive urine culture report, were considered as the cases and the rest of the 40 age and gestational age-matched healthy pregnant women without UTI were enrolled as the controls. Aseptically, 5 mL of venous blood was drawn to measure maternal serum vitamin D levels. Statistical analysis was done using the latest version of analytic software SPSS, where required. Results: Among 40 case respondents, Escherichia coli was found to be the most prevalent (60.0%) cause of UTI, with an average maternal serum vitamin D level of 20.5±11.94 ng/ml among those cases. The overall mean (±SD) vitamin D level was much lower among the cases than the controls, 21.1±11.25 ng/mL and 27.9±9.58 ng/ml, respectively. This difference was found statistically significant p=0.004). Considering vitamin D level of 30 ng/mL as the cut-off value, odd’s ratio calculation showed the mother with serum vitamin D level <30 ng/mL had 3.2 times more risk to develop UTI compared to those ...

Bias and negative values of COVID-19 vaccine effectiveness estimates from a test-negative design without controlling for prior SARS-CoV-2 infection

Test-negative designs (TNDs) are used to assess vaccine effectiveness (VE). Protection from infection-induced immunity may confound the association between case and vaccination status, but collecting reliable infection history can be challenging. If vaccinated individuals have less infection-induced protection than unvaccinated individuals, failure to account for infection history could underestimate VE, though the bias is not well understood. We simulated individual-level SARS-CoV-2 infection and COVID-19 vaccination histories and a TND. VE against symptomatic infection and VE against severe disease estimates unadjusted for infection history underestimated VE compared to estimates adjusted for infection history, and unadjusted estimates were more likely to be below 0%, which could lead to an incorrect interpretation that COVID-19 vaccines are harmful. TNDs assessing VE immediately following vaccine rollout introduced the largest bias and potential for negative VE against symptomatic infection. Despite the potential for bias, VE estimates from TNDs without prior infection information are useful because underestimation is rarely more than 8 percentage points.

Closing the gap in race-based inequities for seasonal influenza hospitalizations: a modeling study.

BIPOC (Black, Indigenous, and other People of Color) communities bear a disproportional burden of seasonal influenza hospitalizations in the United States. We developed a race-stratified (5 racial-ethnic groups) agent-based model of seasonal influenza transmission and quantify the effects of 5 idealized interventions aimed at reducing inequities in symptomatic infections and hospitalizations. The interventions assumed (i) equalized vaccination rates, (ii) equalized comorbidities, (iii) work-risk distribution proportional to the distribution of the population, (iv) reduced work contacts for all, or (v) a combination of equalizing vaccination rates and comorbidities and reducing work contacts. Our analysis suggests that symptomatic infections could be greatly reduced (by up to 17% in BIPOC adults aged 18-49) by strategies reducing work contacts or equalizing vaccination rates. All tested interventions reduced the inequity in influenza hospitalizations in all racial-ethnic groups, but interventions equalizing comorbidities were the most effective, with over 40% less hospitalizations in BIPOC groups. Inequities in hospitalizations in different racial-ethnic groups responded differently to interventions, pointing to the need of tailored interventions for different populations. Notably, these interventions resulted in better outcomes across all racial-ethnic groups, not only those prioritized by the interventions. In this simulation modeling study, equalizing vaccination rates and reducing number of work contacts (e.g., improving air filtration systems, tailored vaccination campaigns) reduced both inequity and the total number of symptomatic infections and hospitalizations in all age and racial-ethnic groups. Reducing inequity in influenza hospitalizations requires different interventions for different groups.

Erectile dysfunction after COVID-19 infection: A cross-sectional study in a male sample from Brazil

Introduction: COVID-19 infection may cause erectile dysfunction due to local viral infection and impairing mental health. Objective: To analyze the erectile function in Brazilian sample patients during pandemics with and without COVID-19 infection and compare with results from a sample obtained before the pandemic. Methods: Internet survey with epidemiologic questions, data on COVID-19 infection, and the International Index for Erectile Function (IIEF). Patients were divided into those with and without infections. A control group with results obtained before the pandemic was also included. Results: Four hundred twenty-two males were studied 210 with data obtained before the pandemic; 208 with data obtained during the pandemic (84 with COVID-19 infection and 124 without). Patients with COVID-19 infection had worse results of IIEF than those without (in the pandemics and before pandemics) with p=0.01 and used more sexual stimulants (p=0.02). The results were worse in the first month after the infection. Conclusion: Patients with COVID-19 infection had impairment in erectile function that is more severe in the first month after infection.

Implications of Asymptomatic Carriers for Tuberculosis Transmission and Control in Thailand: A Modelling Approach

Tuberculosis (TB) is a regional and global bacterial illness that has been expanding and affecting individuals in every generation. An unknown percentage of asymptomatic hosts have TB, and the infection can spread while exhibiting no symptoms. These asymptomatic TB carriers, who contribute to the spread of the illness yet go mostly undetected, may make it more difficult to prevent transmission. In this study, we utilized the concept of symmetry to construct a manageable disease modelling framework for TB transmission and control. We developed a TB model to investigate the potential influence of asymptomatic carriers, symptomatic infections, and the entirety of TB prevalence on different approaches to treatment and prevention in Thailand. Annual TB incidence data from Thailand from 2000 to 2022 were used to calibrate the model parameters. We assessed the potential for reaching conflicting results about the management and spread of tuberculosis in Thailand. Our results showed that some TB strategies that were thought to be effective in reducing transmission may have the opposite impact, or that an intervention’s effectiveness might be overestimated, making it seem unfeasible in certain scenarios. For example, the objective of TB treatment, which attempts to decrease the occurrence of symptomatic TB infections, is to decrease the TB infection and propagation rates if the relative carrier (η) is less than one. Nonetheless, our results indicate that this strategy may increase the frequency of asymptomatic TB patients, symptomatic TB viral infections, and overall TB prevalence if η has been sufficiently understated. We also found that reducing only the progression rate of symptomatic TB infections cannot stop asymptomatic TB carriers and total TB prevalence, even when the relative infection of carriers (η) is less than unity. Our research provides a better understanding of the role of asymptomatic patients in spreading TB and highlights the need to accurately include bearers in models that guide Thailand’s TB control strategy.

Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda

BackgroundPlasmodium falciparum (P. falciparum) remains a significant public health challenge globally, especially in sub-Saharan Africa (SSA), where it accounts for 99% of all malaria infections. The outcomes of P. falciparum infection vary, ranging from asymptomatic to severe, and are associated with factors such as host immunity, parasite genetic diversity, and multiplicity of infection (MOI). Using seven neutral microsatellite markers, the current study investigated P. falciparum genetic diversity and MOI in both asymptomatic and symptomatic malaria individuals in Uganda.MethodsThis cross-sectional study analyzed 225 P. falciparum isolates from both asymptomatic and symptomatic malaria patients, ranging in age from 6 months to ≥ 18 years. P. falciparum genetic diversity, MOI, and multi-locus linkage disequilibrium (LD) were assessed through genotyping of seven neutral microsatellite markers: Poly-α, TA1, TA109, PfPK2, 2490, C2M34–313, and C3M69–383. Genetic data analysis was performed using appropriate genetic analysis software.ResultsP. falciparum infections exhibited high genetic diversity in both asymptomatic and symptomatic individuals. The mean expected heterozygosity (He) ranged from 0.79 in symptomatic uncomplicated malaria cases to 0.81 in asymptomatic individuals. There was no significant difference (p = 0.33) in MOI between individuals with asymptomatic and symptomatic infections, with the mean MOI ranging from 1.92 in symptomatic complicated cases to 2.10 in asymptomatic individuals. Polyclonal infections were prevalent, varying from 58.5% in symptomatic complicated malaria to 63% in symptomatic uncomplicated malaria cases. A significant linkage disequilibrium (LD) was observed between asymptomatic and symptomatic uncomplicated/complicated infections (p < 0.01). Genetic differentiation was low, with FST values ranging from 0.0034 to 0.0105 among P. falciparum parasite populations in asymptomatic and symptomatic uncomplicated/complicated infections.ConclusionThere is a high level of P. falciparum genetic diversity and MOI among both symptomatic and asymptomatic individuals in Uganda. Asymptomatic carriers harbor a diverse range of parasites, which poses challenges for malaria control and necessitates targeted interventions to develop effective strategies.

A potential platform for future vaccine trials identifies high incidence of symptomatic and asymptomatic influenza infection among children aged 6-23 months in South Africa.

Approaches for determining whether influenza vaccination prevents infection, attenuates illness, or both, are important for developing improved vaccines. We estimated influenza infection incidence, and evaluated symptom ascertainment methodologies in children to inform future vaccine trial design. We conducted a prospective cohort study among children aged 6-23 months from May-October 2022. Study nurses collected symptom and temperature data and mid-turbinate nasal swabs twice-weekly irrespective of symptoms; caregivers entered symptom data daily and collected nasal swabs weekly. Samples were tested for influenza using PCR. Of 230 healthy, screened children, 93 were enrolled of whom 87 (94%) completed 6-months follow-up. 95% (4245/4476) of scheduled nurse, 90% (2045/2276) of caregiver swabs, 99% (92/93) of baseline blood collections and 67% (9245/13768) of scheduled symptom diaries were completed. PCR-confirmed influenza incidence was 65% (60/93) for ≥1 infection; 11 (18%) individuals had 2 and 1 (2%) had 3 episodes. Of 73 episodes, 55 (75%) had ≥1 symptom and 37 (51%) had fever (measured and/or reported). Median infection duration was 7 days (interquartile range 4-9). Human RNase P gene was detected in 99% (2032/2045) of caregiver-collected swabs, through which 5 additional episodes were identified. Per episode, caregiver's diaries of reported and measured fever were 19%(25/73,34%) and 11%(15/73,21%) higher than nurse-reported (11/73,15%) and -measured fevers (7/73,10%), respectively. The incidence of influenza infection was high and mainly symptomatic suggesting that this platform could be suitable for future trials of vaccine efficacy and correlates of protection against infection and illness in children.

Health care workers hospitalized for COVID-19 in Liberia: who were they, and what were their outcomes?

Background Sustaining a ‘fit-for-purpose’ health workforce requires a better understanding of the health care worker cadres that are affected during pandemics and their outcomes. In hospitalized health care workers with confirmed COVID-19 between March 2020 and May 2023 in Liberia, we determined the hospitalization and case fatality rates, type of health care worker cadres affected, their demographic and clinical characteristics and hospital exit outcomes. Methods This was a cohort study using routine data extracted from hospitalization forms for health care workers in 24 designated COVID-19 treatment facilities. Results Of the 424 health care workers with COVID-19, hospitalization rates progressively declined between 2020 and 2023, (P&lt;0.001) with the highest rates in 2020 (24/1,000 health care workers) and 2021 (14/1,000 health care workers). Case fatality was 2% in both 2020 and 2021 with no deaths thereafter. Among those hospitalized, the highest proportions were nursing cadres with 191(45%), physicians with 63 (15%) and laboratory technicians with 42 (10%). The most frequent reported site for COVID-19 infection was the health facility (326, 89%). COVID-19 vaccination coverage in health care workers was 20%. The majority (91%) of hospitalizations were for mild symptomatic infections. Even in referral centres (n-52), 18 (35%) were for mild infections. Of the 424 who were hospitalized, 412 (97%) recovered, 9 (2%) died and 3 (1%) either left against medical advice or absconded. Of the nine deaths, none were vaccinated, seven had moderate-to-severe disease but were not referred to specialized COVID-19 treatment centers. Conclusions The hospitalized health care workers for COVID-19 were predominantly clinical and laboratory personnel who were mostly unvaccinated, and health facilities were hot-spots for contracting infections. The triage and referral system was weak with unnecessary hospitalization of mild infections. This study provides useful insights for outbreak preparedness including priority vaccination and improving health care worker safety in Liberia.

Emergency wound site infection caused by Gulosibacter massiliensis: a case report

BackgroundGulosibacter massiliensis is a new species of gram-positive, short rod-shaped, aerobic, oxidase-negative, and catalase-positive bacteria, which was discovered in human peripheral blood and named recently in 2022. Currently, the clinical reports on G. massiliensis are limited, and its pathogenic ability and infectivity remain unclear.Case presentationWe isolated G. massiliensis from the exudate of an emergency traumatic wound of the right foot of a 54-year-old man. The patient stepped into a gutter with the right foot, causing a wound with exposed bone, oozing blood, and local infection. Through timely surgical treatment and active debridement and nursing, the wound healed smoothly, and the patient was discharged from the hospital uneventfully. This strain could not be accurately identified using conventional biochemical reactions or matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis in our clinical laboratory. Finally, the strain was identified correctly using 16 S ribosomal RNA gene sequencing and historical data of Gulosibacter spp., and its drug susceptibility results were reported.ConclusionReports on clinical infection or isolation of G. massiliensis are limited. This is the first study reporting its isolation from wound secretions. It is a rare opportunistic infectious bacterium. Further clinical research will help us understand its infectivity and pathogenicity. This report could guide the treatment and laboratory detection of local wound infections caused by G. massiliensis.

Abstract 4135466: Feasibility of Using Existing Infection Surveillance Methods for Percutaneous Coronary Intervention-related Infections

Background: Percutaneous coronary intervention (PCI) is a treatment that requires attention in terms of infection control, as it necessitates aseptic procedures similar to surgical operations. However, surveillance practices for PCI-related infections are uncommon, and no standardized surveillance program has been established. Purpose: To assess the feasibility of using existing surveillance methods to detect PCI-related infectious diseases. Method: To identify PCI-related bloodstream infections of local access sites, four existing case definitions, namely, laboratory-confirmed bloodstream infections (LCBI), clinical sepsis (CSEP), local access site infection (LASI), and exit site infection (ESI), were retrospectively applied to 1,037 patients who underwent PCI between April 2018 and March 2021. Of these, 167 experienced fever, underwent blood culture testing, and/or received antibiotics within 6 days of PCI. To confirm consistent evaluation, two independent infection control experts evaluated each case record according to the four case definitions. Results: Twenty-three patients (2.2%) were diagnosed with PCI-related infections, including two patients according to LCBI, 21 according to CSEP, and none according to LASI and ESI. Thirteen patients (LCBI: 1, CSEP: 12) received circulatory assist devices such as intra-aortic balloon pumping. Of the remaining 11 patients, 10 underwent emergency PCI, and one underwent elective PCI ( P =0.0001). The average length of hospital stay was 16.1 days for patients with PCI-related infections and 4.7 days for non-infected patients ( P &lt;0.05). Conclusion: The positive diagnosis of PCI-related infections was predominantly based on CSEP. Many of these positive patients underwent emergency PCI and/or received circulatory assist devices. The results of the present study warrant further investigations with larger patient cohorts.

Giardia lamblia risk factors and burden in children with acute gastroenteritis in a Nicaraguan birth cohort.

Giardia lamblia is an intestinal protozoan estimated to cause ~200 million symptomatic infections annually, mainly in children in low- and middle-income countries associated with intestinal damage, increased permeability, and malabsorption. We describe here the epidemiology, incidence, clinical characteristics, and risk factors of acute gastroenteritis episodes (AGE) with G. lamblia detection (GAGE) using a birth cohort of 443 Nicaraguan children followed weekly until 36 months of life. From June 2017 to July 2021, 1385 AGE samples were tested by qPCR. G. lamblia was detected in 104 (7.5%) of AGE episodes. In all, 69 (15.6%) children experienced at least one GAGE episode, and 25 of them (36.2%) experienced more than one episode. The incidence rate of the first episode of GAGE was 6.8/100 child-years (95% CI, 4.5-9.1). During GAGE, bloody stools, vomiting, and fever were uncommon, and children were less likely to be treated at a primary care clinic, suggesting that GAGE is typically mild and most cases did not receive medical attention, which could facilitate higher parasite loads with increased possibilities of establishing chronic carriage. GAGE was more common in children 12-24 months of age (13.9/100 child-years [95% CI, 10.7-17.1]) as compared to other age groups. In our birth-cohort, children living in a home with an indoor toilet (aHR, 0.52 [95%CI, 0.29-0.92]), and being breastfed in the first year of life (aHR: 0.10 [95%IC, 0.02, 0.57]) had a lower incidence of GAGE. In contrast, being breastfed for ≤ 6 months was associated with a higher incidence if the children were living in houses without indoor toilets and earthen floors (HR, 7.79 [95% CI, 2.07, 29.3]). Taken together, GAGE is more frequent under poor household conditions. However, breastfeeding significantly reduces the incidence of GAGE in those children.

Cardiovascular sequelae in symptomatic SARS-CoV-2 infection survivors.

SARS-CoV-2 infection may lead to myocardial and endothelial damage. The present study sought to characterize the cardiovascular sequel in a large group of consecutive patients admitted for out-patient cardiovascular follow-up after a symptomatic COVID-19 infection. The aims of this study were as follows: to evaluate the presence of post-covid cardiovascular symptoms in an unselected population of outpatients referred to a post-COVID outpatient cardiology clinic and to characterize the long-term abnormalities associated with a more severe COVID-19 infection clinical course. A total of 914 patients were included in this single-center, observational, cross-sectional study, of which 163 were hospitalized and 149 required mechanical ventilation for COVID-19 pneumonia. Patients were analyzed at follow-up according to the care setting during the initial presentation. The median time to follow-up was 126 days. At that time, only 3.5% of patients reported no persistent dyspnea, chest pain, or fatigue on exertion. In a follow-up echocardiographic assessment, patients who required hospitalization showed slight alterations in the pulmonary acceleration time and the tricuspid regurgitation pressure gradient, as well as reduced exercise tolerance during treadmill exercise testing when compared to patients with a benign clinical course. 24-hour Holter EKG monitoring or 24-hour blood pressure monitoring did not identify significant differences between the analyzed subgroups. The current study reports on an association between COVID-19 severity and the presence of cardiovascular alterations at follow-up. A simple diagnostic protocol, comprising an exercise treadmill test and transthoracic echocardiography is useful in identifying patients who may benefit from regular, structured cardiovascular medical care.

“On-demand” nanosystem-integrated microneedles for amplified triple therapy against recalcitrant bacteria and biofilm growth

Phototherapy has emerged to eradicate recalcitrant bacteria without causing drug resistance, but it is often accompanied by considerable limitations owing to a high tolerance of recalcitrant bacteria to heat and oxidative damage, leading to low efficiency of monotherapy and unwanted side effects. Assuming that employing antimicrobial peptides (AMPs) to disrupt bacterial membranes could reduce bacterial tolerance, a multifunctional “on-demand” nanosystem based on zeolitic imidazolate framework-8 (ZIF-8) with metal ions for intrinsic antibacterial activity was constructed to potently kill methicillin-resistant Staphylococcus aureus (MRSA). Then, microneedles (MNs) were used to transdermally deliver the ZIF-8-based nanosystem for localized skin infection. After MNs insertion, the nanoplatform could specifically deliver the loaded therapeutic components to bacterial infection sites through employing hyaluronic acid (HA) as a capping agent, thus realizing the “on-demand” payload release triggered by excess hyaluronidase secreted by MRSA. The prepared nanosystem and MNs were confirmed to exert an amplified triple therapy originating from membranolytic effect, phototherapy, and ion therapy, thus displaying a powerful bactericidal and MRSA biofilm destruction ability. This intelligent antimicrobial strategy may bring a dawn of hope for eradicating multidrug-resistant bacteria and biofilms.

Adapting COVID-19 research infrastructure to capture influenza and respiratory syncytial virus alongside SARS-CoV-2 in UK healthcare workers winter 2022/23 and beyond: protocol for a pragmatic sub-study

Introduction During the COVID-19 pandemic, extensive research was conducted on SARS-CoV-2; however, important questions about other respiratory pathogens remain unanswered. A severe influenza season in 2022–2023 with simultaneous circulation of SARS-CoV2 and respiratory syncytial virus is anticipated. This sub-study aims to determine the incidence and impact of these respiratory viruses on healthcare workers, the symptoms they experienced, the effectiveness of both COVID-19 and influenza vaccination and the burden of these infections on the National Health Service (NHS) workforce. Methods and analysis This is a longitudinal prospective cohort sub-study, utilising the population and infrastructure of the SARS-CoV-2 Immunity &amp; Reinfection Evaluation (SIREN) study, which focuses on hospital staff in the UK. Participants undergo fortnightly nucleic acid amplification testing on a multiplex assay including SARS-CoV-2, influenza A and B and RSV, regardless of symptoms. Questionnaires are completed every two weeks, capturing symptoms, sick days, exposures, and vaccination records. Serum samples are collected monthly or quarterly from participants associated with a SIREN site. This sub-study commenced on 28/11/22 to align with the predicted influenza season and participants’ influenza vaccine status. The SIREN Participant Involvement Panel shaped the aims and methods for the study, highlighting its acceptability. UK devolved administrations were supported to develop local protocols. Analysis plans include incidence of asymptomatic and symptomatic infection, comparisons of vaccination coverage, assessment of sick day burden, and effectiveness of seasonal influenza against infection and time off work. Data are also integrated into UKHSA nosocomial modelling. Ethics and dissemination The protocol was approved by the Berkshire Research Ethics Committee (IRAS ID 284460, REC Reference 20SC0230) on 14/11/2022. Participants were informed in advance. As the frequency and method of sampling remained the same, implied consent processes were approved by the committee. Participants returning to the study give informed consent. Regular reports to advisory groups and peer-reviewed publications are planned to disseminate findings and inform decision making. Clinical trial registration number: ISRCTN11041050; registration date: 12 January 2021. Sub study included in protocol version: v8.0, and amended in v9.0

Quality Improvement Initiatives for Pleural Infection Managed with Intrapleural Therapy.

Rationale Pleural infection is associated with significant mortality and its management is complex. Little attention has been given to care process metrics such as management delays, pleural drainage practices, and adequacy of intrapleural therapy administration despite their potential impact on outcomes. Audits revealed gaps in those care processes in our institution. Objectives To assess the impact of quality improvement initiatives on pleural effusion management in adults. Methods We performed a retrospective comparison of patients treated with intrapleural therapy for pleural infection at the McGill University Health Centre before (April 2013-April 2016, N=109) and after interventions (June 2020-June 2021, N=44). Interventions included a pleural drainage policy and order set, an intrapleural therapy protocol and pre-printed order, implementation of intrapleural therapy administration by nurses, local pleural infection guideline development, and an online learning module for physicians. Major outcomes (length of stay, mortality, surgical treatment) and care process metrics (management delays, pleural drainage practices, intrapleural therapy administration) were compared between the two periods. Results After implementation of the interventions, in-hospital mortality and length of stay were unchanged, but surgical management went from 14% to 0% (p=0,01). Delays in drain insertion and intrapleural therapy initiation were not significantly different. Insertion of drains smaller than 12Fr decreased from 51% to 7% (p<0,001). Drain blockage decreased from 20% to 2% (p=0,004). Additional drain insertions went from 62% to 48% (p=0,12). After interventions, 70% of intrapleural therapy doses were given by nurses, the intrapleural therapy protocol was more often adequately followed, less doses were missed, and less extended therapy was prescribed. Complications related to drain insertion and intrapleural therapy were similar between the two periods. Conclusions Following the implementation of multifaceted quality improvement interventions for pleural infection including involvement of nurses in pleural drain flushing and intrapleural therapy, improvements were observed in intrapleural therapy administration, chest drainage practices, and need for surgery. However, length of stay, mortality, and management delays were unchanged.

Effectiveness of Bivalent mRNA Vaccines in Preventing Symptomatic SARS-CoV-2 Infection-Increasing Community Access to Testing Program, United States, January-September 2023.

On September 2, 2022, bivalent COVID-19 mRNA vaccines, were recommended to address reduced effectiveness of COVID-19 monovalent vaccines during SARS-CoV-2 Omicron variant predominance. Using national pharmacy-based SARS-CoV-2 testing program data from January 15 to September 11, 2023, this test-negative, case-control design study assessed bivalent COVID-19 vaccine effectiveness (VE) against symptomatic infection. VE against symptomatic infection of a bivalent dose between 2 weeks and 1 month after bivalent vaccination ranged from 46% (95% CI: 38%-52%) for those aged ≥ 65 years to 61% (95% CI 41%-75%) for those aged 12-17 years. Bivalent vaccines protected against symptomatic infection. However, effectiveness waned over time, emphasizing the need to stay up to date with COVID-19 vaccination.