Infection Research Articles

Incidence of COVID-19 mRNA vaccine symptomatic breakthrough infections during Omicron circulation in adults with or without infection prior to vaccination

ObjectivesCOVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination. MethodsIn the first half of 2021, healthy adults (aged 18–45, 65–74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case-control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves. ResultsFrom January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection. ConclusionOur results highlight the need to consider immune markers of protection in association with infection and vaccination history.

Rare case of septic shock combined with meningitis caused by Pasteurella multocida without a history of cat and dog bites

BackgroundPasteurella multocida is a zoonotic pathogen that mainly causes local skin and soft tissue infections in the human body through cat and dog bites. It rarely causes bacteraemia (or sepsis) and meningitis. We reported a case of septic shock and meningitis caused by P. multocida in a patient without a history of cat and dog bites.Case presentationAn 84-year-old male patient was urgently sent to the emergency department after he was found with unclear consciousness for 8 h, accompanied by limb tremors and urinary incontinence. In the subsequent examination, P. multocida was detected in the blood culture and wound secretion samples of the patient. However, it was not detected in the cerebrospinal fluid culture, but its DNA sequence was detected. Therefore, the patient was clearly diagnosed with septic shock and meningitis caused by P. multocida. The patient had no history of cat or dog contact or bite. The patient was subsequently treated with a combination of penicillin G, doxycycline, and ceftriaxone, and he was discharged after 35 days of hospitalisation.ConclusionThis report presented a rare case of septic shock and meningitis caused by P. multocida, which was not related to a cat or dog bite. Clinical doctors should consider P. multocida as a possible cause of sepsis or meningitis and should be aware of its potential seriousness even in the absence of animal bites.

Effects of the COVID-19 Pandemic on Brief Resolved Unexplained Events (BRUEs) in Children: A Comparative Analysis of Pre-Pandemic and Pandemic Periods.

Brief Resolved Unexplained Events (BRUEs), formerly known as Apparent Life-Threatening Events (ALTEs), are concerning episodes of short duration (typically <1 min) characterized by a change in breathing, consciousness, muscle tone, and/or skin color. In some cases, SARS-CoV-2 infection has been associated with episodes of BRUEs in previously healthy children. This study aimed to compare the demographic, respiratory, perinatal, and infectious characteristics in children affected by BRUEs before the COVID-19 pandemic and after the spread of SARS-CoV-2. We conducted a retrospective observational study covering January 2018 to March 2020 (pre-COVID-19) and April 2023 (during the ongoing COVID-19 pandemic). Collected variables included clinical information during pregnancy and neonatal details of children with BRUEs. The number of children in the pre-COVID-19 period was 186 (41%); after the emergence and spread of SARS-CoV-2 this number was 268 (59%). The risk of infection at birth for children developing BRUEs was higher during the pandemic. Children were less likely to have ongoing symptomatic infection during BRUEs during the pandemic (coefficient B = 0.783; p = 0.009). Respiratory symptoms during BRUEs were more frequent during the pandemic (coefficient B = 0.654; p = 0.052). Fever during BRUEs was less likely during the pandemic (coefficient B = -0.465, p = 0.046). These findings could have significant clinical implications for managing children with BRUEs during the COVID-19 pandemic.

Inflammasomes in epithelial innate immunity: front line warriors.

Our epithelium represents a battle ground against a variety of insults including pathogens and danger signals. It encodes multiple sensors that detect and respond to such insults, playing an essential role in maintaining and defending tissue homeostasis. One key set of defense mechanisms is our inflammasomes which drive innate immune responses including, sensing and responding to pathogen attack, through the secretion of pro-inflammatory cytokines and cell death. Identification of physiologically relevant triggers for inflammasomes has greatly influenced our ability to decipher the mechanisms behind inflammasome activation. Furthermore, identification of patient mutations within inflammasome components implicates their involvement in a range of epithelial diseases. This review will focus on exploring the roles of inflammasomes in epithelial immunity and cover: the diversity and differential expression of inflammasome sensors amongst our epithelial barriers, their ability to sense local infection and damage and the contribution of the inflammasomes to epithelial homeostasis and disease.

Protective Role of NS1-Specific Antibodies in the Immune Response to Dengue Virus through Antibody-Dependent Cellular Cytotoxicity.

Dengue virus (DENV) non-structural protein 1 (NS1) has multiple functions within infected cells, on the cell surface, and in secreted form, and is highly immunogenic. Immunity from previous DENV infections is known to exert both positive and negative effects on subsequent DENV infections, but the contribution of NS1-specific antibodies to these effects is incompletely understood. We investigated the functions of NS1-specific antibodies and their significance in DENV infection. We analyzed plasma samples collected in a prospective cohort study prior to symptomatic or subclinical secondary DENV infection. We measured binding to purified recombinant NS1 protein and to NS1-expressing CEM cells, antibody-mediated NK cell activation by plate-bound NS1 protein, and antibody-dependent cellular cytotoxicity (ADCC) of NS1-expressing target cells. We found that antibody responses to NS1 were highly serotype-cross-reactive and that subjects who experienced subclinical DENV infection had significantly higher antibody responses to NS1 in pre-infection plasma than subjects who experienced symptomatic infection. We observed strong positive correlations between antibody binding and NK activation. These findings demonstrate the involvement of NS1-specific antibodies in ADCC and provide evidence for a protective effect of NS1-specific antibodies in secondary DENV infection.

Prediction of key amino acids of Salmonella phage endolysin LysST-3 and detection of its mutants' activity.

Salmonella Typhimurium, a zoonotic pathogen, causes systemic and localized infection. The emergence of drug-resistant S. Typhimurium has increased; treating bacterial infections remains challenging. Phage endolysins derived from phages have a broader spectrum of bacteriolysis and better bacteriolytic activity than phages, and are less likely to induce drug resistance than antibiotics. LysST-3, the endolysin of Salmonella phage ST-3, was chosen in our study for its high lytic activity, broad cleavage spectrum, excellent bioactivity, and moderate safety profile. LysST-3 is a promising antimicrobial agent for inhibiting the development of drug resistance in Salmonella. The aim of this study is to investigate the molecular characteristics of LysST-3 through the prediction of key amino acid sites of LysST-3 and detection of its mutants' activity. We investigated its lytic effect on Salmonella and identified its key amino acid sites of interaction with substrate. LysST-3 may be a Ca2+, Mg2+ - dependent metalloenzyme. Its concave structure of the bottom "gripper" was found to be an important part of its amino acid active site. We identified its key sites (29P, 30T, 86D, 88L, and 89V) for substrate binding and activity using amino acid-targeted mutagenesis. Alterations in these sites did not affect protein secondary structure, but led to a significant reduction in the cleavage activity of the mutant proteins. Our study provides a basis for phage endolysin modification to target drug-resistant bacteria. Identifying the key amino acid site of the endolysin LysST-3 provides theoretical support for the functional modification of the endolysin and the development of subsequent effective therapeutic solutions.

Missed foreign body falsely interpreted as glass in surgery

Retained Foreign Bodies (FBs) in soft tissues are typically a complication of open wounds from trauma, accidents, and surgery, for which plenty of patients seek acute medical care. The importance of localizing these FBs is vital to patient health because it reduces the detrimental complications of loss of function, local tissue damage, infection, and sepsis. In today’s modern age, many automobile taillights are composed of three components: the polycarbonate outer shell, the light bulb, and various metal casings. Occasionally, patients present with one of these objects retained in their body. Here, we present the case of a FB that was dictated as a hematoma; however, it was a piece of polycarbonate that was reported as a piece of glass in the operating room transcript. Based upon imaging a piece of taillight polycarbonate at our institution, the Hounsfield Units (HU) averaged to be 88.62. Nonetheless, if there is acute blood in soft tissues, taillight plastic could be an appropriate differential; however, a hematoma is less likely to be polycarbonate from car rear lights based on the HU.

Hydrogenated Soy Phosphatidylcholine Liposomes Stimulate Differential Expression of Chemokines And Cytokines by Rat Alveolar Macrophages In Vitro

Liposomes are being developed as inhalable drug delivery systems, but concerns remain about their impact on the lungs. To better understand the impact of liposomes and their physicochemical properties on alveolar macrophages, the cytokine and chemokine expression profile of rat alveolar Nr8383 macrophages exposed to 0.1 and 1 mg/ml hydrogenated soy phosphatidylcholine (HSPC) liposomes was examined. Expression patterns varied considerably between liposomes in a concentration-dependent manner, with both anti- and pro-inflammatory chemokines/cytokines produced. Uncharged liposomes induce the greatest production of cytokines and chemokines, followed by PEGylated liposomes. The most significant increase in cytokine/chemokine expression was seen for IL-2 (up to 24-fold), IL-4 (up to 5-fold), IL-18 and VEGF (up to 10-fold), while liposome exposure significantly reduced MIP1 expression (5-fold). In summary, we demonstrate that liposome surface properties promote variable patterns of cytokine and chemokine secretion by alveolar macrophages. This suggests that the type of liposome employed may influence the type of immune response generated in the lung and by extension, dictate how inhaled liposomal nanomedicines affect the lungs response to inhaled toxicants and local infections.

Alum/CpG adjuvant promotes immunogenicity of inactivated SARS-CoV-2 Omicron vaccine through enhanced humoral and cellular immunity

The SARS-CoV-2 Omicron variant, which was classified as a variant of concern (VOC) by the World Health Organization on 26 November 2021, has attracted worldwide attention for its high transmissibility and immune evasion ability. The existing COVID-19 vaccine has been shown to be less effective in preventing Omicron variant infection and symptomatic infection, which brings new challenges to vaccine development and application. Here, we evaluated the immunogenicity and safety of an Omicron variant COVID-19 inactivated vaccine containing aluminum and CpG adjuvants in a variety of animal models. The results showed that the vaccine candidate could induce high levels of neutralizing antibodies against the Omicron variant virus and binding antibodies, and significantly promoted cellular immune response. Meanwhile, the vaccine candidate was safe. Therefore, it provided more foundation for the development of aluminum and CpG as a combination adjuvant in human vaccines.

Mortality and Costs of Cardiac Implantable Electronic Device (CIED) Infections According to the Therapeutic Approach: A Single-Center Cohort Study.

Background: Cardiac device infections are serious adverse events associated with considerable morbidity and mortality, significant costs, and increased healthcare utilization. The aim of this study is to calculate the costs of treatment of cardiac implantable electrostimulation device (CIED)-related infections for different types of infection (local or systemic) and therapeutic approaches. Patients and Methods: Single-center cohort (1985-2018). The costs of the CIED-related infections were analyzed according to initial treatment (antimicrobial treatment exclusively, local approach, or transvenous lead extraction (TLE)). Total costs (including those for hospitalization stay, drugs, extraction material, and newly implanted devices) were assigned to each case until its final resolution. Results: A total of 380 cases (233 local and 147 systemic infections) were analyzed. The average cost of systemic infection was EUR 34,086, mainly due to hospitalization (78.5%; mean: 24 ± 14 days), with a mortality rate of 10.8%. Local infection had a mortality rate of 2.5% (mainly related to the extraction procedure) and an average cost of EUR 21,790, which was higher in patients with resynchronization therapy devices and defibrillators (46% of total costs). Surgical procedures limited to the pocket for local infections resulted in a high rate of recurrence (87%), evolved to systemic infections in 48 patients, and had a higher cost compared to TLE (EUR 42,978 vs. EUR 24,699; p < 0.01). Conclusions: The costs of treating CIED-related infections are high and mainly related to the type of treatment and length of hospitalization. Complete device removal is always the most effective approach and is a cost-saving strategy.

LOW-INTENSITY SHOCKWAVE TREATMENT FOR NEUROGENIC BLADDER WITH CHRONIC URINE RETENTION - CASE REPORT

We present a case of neurogenic bladder accompanied by chronic urine retention in a patient diagnosed with multiple sclerosis (MS). This condition was effectively managed by low-intensity shockwave therapy (Li-ESWT). Low-intensity focused shockwave therapy (Li-ESWT) is becoming increasingly important in the treatment of urological problems. This case study investigates the feasibility and efficacy of using Li-ESWT to reduce post-void residual volume in persons with neurogenic bladder, representing the first examination of its sort. Bladder dysfunction (BD) frequently occurs in patients who have been diagnosed with multiple sclerosis (MS). Bladder dysfunction (BD) can occur due to the impairment of nerve impulses in the central nervous system regions involved for regulating bladder function and managing the contractions of the urinary sphincters, which is caused by the lesions associated with multiple sclerosis (MS). Urinary retention can cause various symptoms, including insufficient bladder emptying, urinary incontinence, frequent urinary tract infections, urosepsis resulting in the development of kidney abscesses due to localised kidney infection, and reduced kidney function. Optimal bladder function is essential for individuals with MS, as it plays a critical role in preserving kidney health, preventing urinary tract infections and incontinence, reducing the frequency of MS episodes, and improving their overall well-being. A 31-year-old woman was referred to our urology office with a chronic urinary tract infection caused by a neurogenic bladder with a significant volume of residual urine. A kidney abscess formation was identified as a complication. Li-ESWT, which stands for low-intensity extracorporeal shockwave therapy, was used as a part of a multimodal strategy to treat the urinary bladder. This treatment was delivered off-label. The therapy was given on a weekly basis for a period of 6 weeks. The procedure included administering 2500 shocks at a rate of four pulses per second, with an energy flux density (EFD) of 0.25 millijoules per square millimetre. The EFD (Energy Flux Density) used in our study exceeded 0.32 mJmm2,4, the fR (frequency rate) was set at 8 Hz (pulses per second), the treatment sessions consisted of 12 cycles of Li-ESWT (Low-Intensity Extracorporeal Shockwave Therapy), and a total of 3000 shocks were administered. At the intervals of one week, three months, six months, nine months, and twelve months following the administration of Li-ESWT and tadalafil 2.5 mg, the post-void residual (PVR) volume was consistently below 50 ml. The Li-ESWT treatment effectively reduced the post-void residual urine volume.Low-intensity extracorporeal shockwave therapy (Li-ESWT) can safely and efficiently decrease the amount of urine left in the bladder after voiding in individuals with neurogenic bladder caused by multiple sclerosis (MS). We have effectively demonstrated that Li-ESWT is a feasible and safe treatment for chronic urine retention, resulting in a decrease of post-void residual (PVR) volume from 200 ml to 50 ml. In the future, Li-ESWT has the potential to be advanced as a more efficacious alternative therapy for individuals experiencing chronic urinary retention. Further investigation is necessary to confirm the effectiveness of ESWT in addressing the neurogenic bladder.

Gene expression analyses reveal differences in children’s response to malaria according to their age

In Bandiagara, Mali, children experience on average two clinical malaria episodes per year. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, can vary dramatically among children. We simultaneously characterize host and parasite gene expression profiles from 136 Malian children with symptomatic falciparum malaria and examine differences in the relative proportion of immune cells and parasite stages, as well as in gene expression, associated with infection and or patient characteristics. Parasitemia explains much of the variation in host and parasite gene expression, and infections with higher parasitemia display proportionally more neutrophils and fewer T cells, suggesting parasitemia-dependent neutrophil recruitment and/or T cell extravasation to secondary lymphoid organs. The child’s age also strongly correlates with variations in gene expression: Plasmodium falciparum genes associated with age suggest that older children carry more male gametocytes, while variations in host gene expression indicate a stronger innate response in younger children and stronger adaptive response in older children. These analyses highlight the variability in host responses and parasite regulation during P. falciparum symptomatic infections and emphasize the importance of considering the children’s age when studying and treating malaria infections.

Topical Use of Low-dose Tranexamic Acid Has no Effect on Drainage Volume after Medial Open Wedge High Tibial Osteotomy: A Case Control Study.

Many studies reported that tranexamic acid (TXA) was effective in reducing surgical blood loss in the perioperative period of medial open wedge high tibial osteotomy (MOWHTO). However, few studies focused on the simple topical use of TXA in MOWHTO, and the modality and dosage of topical use of TXA varied. The purpose of this study was to observe the effect of topical use of low-dose TXA on drainage volume after MOWHTO, and to analyze the related influencing factors. Data of patients who underwent MOWHTO combined with arthroscopic knee surgery in our department from January 2019 to September 2021 were retrospectively analyzed. A total of 105 patients (38 males and 67 females, aged 57.7 ± 7.5 years) were included in this study who received topical TXA or no TXA. The patients were divided into three groups: control group (39 cases), 0.5 g TXA group (40 cases), 1 g TXA group (26 cases). Postoperative drainage volume, wound healing, incidence of hematoma and deep venous thrombosis (DVT) were observed and analyzed in the three groups. The effects of gender, hypertension and diabetes on postoperative drainage volume were analyzed using a t-test. The correlation between age, body mass index (BMI), osteotomy gap and postoperative drainage volume were analyzed using the Pearson correlation coefficient. The average postoperative drainage volume of the control group was 259.54 ± 226.33 mL, that of the 0.5 g TXA group was 277.18 ± 177.68 mL, and that of the 1 g TXA group was 229.15 ± 219.93 mL. There was no statistically significant difference in postoperative drainage volume among the three groups (F = 0.423, p = 0.656). There was no local hematoma and wound infection in the three groups. The wound fat liquefaction was found in one patient of the control group. The incidence of DVT was 38.9% (7/18) and 57.1% (8/14) in the control group and 0.5 TXA group, respectively. There was no significant difference in the incidence of DVT between the above two groups (p = 0.476). The average postoperative drainage volume of male patients in the three groups was higher than that of female patients, and the differences were statistically significant (p < 0.05). There was no correlation between age, BMI, osteotomy gap and postoperative drainage volume in the three groups (p > 0.05). Topical use of low-dose TXA has no significant effect on drainage volume after MOWHTO. The drainage volume after MOWHTO in male patients was more than that in female patients. Topical administration of low-dose TXA does not increase postoperative complications, such as DVT and hematoma.

Infant Non-Secretor Histoblood Group Antigen Phenotype Reduces Susceptibility to Both Symptomatic and Asymptomatic Rotavirus Infection.

The infant non-secretor histoblood group antigen phenotype is associated with reduced risk of symptomatic rotavirus diarrhea, one of the leading global causes of severe pediatric diarrheal disease and mortality. However, little is known regarding the role of secretor status in asymptomatic rotavirus infections. Therefore, we performed a nested case-control study within a birth cohort study previously conducted in Dhaka, Bangladesh, to determine the association between infant secretor phenotype and the odds of asymptomatic rotavirus infection, in addition to the risk of rotavirus diarrhea, in unvaccinated infants. In the parent cohort, infants were enrolled in the first week of life and followed through the first two years of life with multiple clinic visits and active surveillance for diarrheal illness. Secretor phenotyping was performed on saliva. Eleven surveillance stools collected over the first year of life were tested for rotavirus by real-time RT-PCR, followed by conventional PCR and amplicon sequencing to identify the infecting P-type of positive specimens. Similar to findings for symptomatic diarrhea, infant non-secretors experienced significantly fewer primary episodes of asymptomatic rotavirus infection through the first year of life in a likely rotavirus P-genotype-dependent manner. These data suggest that non-secretors experienced reduced risk from rotavirus due to decreased susceptibility to infection rather than reduced infection severity.

Effectiveness of glutamine and arginine in wound healing of pressure ulcers: A systematic review protocol

IntroductionVarious nutrients play a physiological role in the healing process of pressure ulcers (PUs). Nutritional interventions include the administration of enteral nutritional supplements and formulas containing arginine, glutamine, and micronutrients. The aim of this systematic review is to evaluate the effectiveness of enteral nutritional supplements and formulas containing arginine and glutamine on wound-related outcomes. These include (1) time to healing, (2) changes in wound size, (3) local wound infection, (4) PU recurrence, and (5) PU-related pain. Materials and methodsThis protocol was developed according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). A search will be conducted in the Cochrane Library, EMBASE, PubMed (MEDLINE), CINAHL (EBSCOhost interface) and Web of Science. In addition, a manual search will be conducted to identify relevant records. Except for systematic reviews, no restrictions will be placed on the study design, the population studied or the setting. Studies that do not address PUs, in vitro studies and studies that do not report wound-related outcomes will be excluded. Study selection, risk of bias assessment and data extraction will be performed independently by three researchers. Depending on the extent of heterogeneity of interventions, follow-up time and populations, results will be summarised either by meta-analysis or narrative synthesis. ConclusionsThis is the first systematic review to identify, evaluate and summarise the current evidence for enteral arginine and glutamine supplementation on wound-related outcomes in PUs. The review will provide a solid basis for deriving valid and clinically relevant conclusions in this area.

Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland

Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. Fetal blood sampling at 21-28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, β2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, β2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log10/mL, and β2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. The combination of thrombocytes, β2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.

Blended BA.5 infection within 8 days after a boosted bivalent mRNA vaccination strengthens and lengthens the host immunity.

The impact of SARS-CoV-2 infection shortly after vaccination on vaccine-induced immunity is unknown, which is also one of the concerns for some vaccinees during the pandemic. Here, based on a cohort of individuals who encountered BA.5 infection within 8 days after receiving the fourth dose of a bivalent mRNA vaccine, preceded by three doses of inactivated vaccines, we show that booster mRNA vaccination provided 48% protection efficacy against symptomatic infections. At Day 7 postvaccination, the level of neutralizing antibodies (Nabs) against WT and BA.5 strains in the uninfected group trended higher than those in the symptomatic infection group. Moreover, there were greater variations in Nabs levels and a significant decrease in virus-specific CD4+ T cell response observed in the symptomatic infection group. However, symptomatic BA.5 infection significantly increased Nab levels against XBB.1.9.1 and BA.5 (symptomatic > asymptomatic > uninfected group) at Day 10 and resulted in a more gradual decrease in Nabs against BA.5 compared to the uninfected group at Day 90. Our data suggest that BA.5 infection might hinder the early generation of Nabs and the recall of the CD4+ T cell response but strengthens the Nab and virus-specific T cell response in the later phase. Our data confirmed that infection can enhance host immunity regardless of the short interval between vaccination and infection and alleviate concerns about infections shortly after vaccination, which provides valuable guidance for developing future vaccine administration strategies.

Covid-19 in cystic fibrosis patients compared to the general population: Severity and virus-host cell interactions

BackgroundPeople with cystic fibrosis (pwCF) are considered at risk of developing severe forms of respiratory viral infections. We studied the consequences of COVID-19 and virus-host cell interactions in CF vs. non-CF individuals. MethodsWe enrolled CF and non-CF individuals, with /without COVID-like symptoms, who underwent nasopharyngeal swab for detection of SARS-CoV-2. Gene expression was evaluated by RNA sequencing on the same nasopharyngeal swabs. Criteria for COVID-19 severity were hospitalization and requirement or increased need of oxygen therapy. ResultsThe study included 171 patients (65 pwCF and 106 non-CF individuals). Among them, 10 pwCF (15.4 %) and 43 people without CF (40.6 %) tested positive at RT-PCR. Symptomatic infections were observed in 8 pwCF (with 2 requiring hospitalization) and in 11 individuals without CF (6 requiring hospitalization). Host transcriptomic analysis revealed that genes involved in protein translation, particularly ribosomal components, were downregulated in CF samples irrespective of SARS-CoV-2 status. In SARS-CoV-2 negative individuals, we found a significant difference in genes involved with motile cilia expression and function, which were upregulated in CF samples. Pathway enrichment analysis indicated that interferon signaling in response to SARS-CoV-2 infection was upregulated in both pwCF and non-CF subjects. ConclusionsCOVID-19 does not seem to be more severe in CF, possibly due to factors intrinsic to this population: the lower expression of ribosomal genes may downregulate the protein translation machinery, thus creating an unfavorable environment for viral replication.

Anti-Staphylococcus aureus effects of natural antimicrobial peptides and the underlying mechanisms.

Staphylococcus aureus can cause localized infections such as abscesses and pneumonia, as well as systemic infections such as bacteremia and sepsis. Especially, methicillin-resistant S. aureus often presents multidrug resistance, which becomes a major clinical challenge. One of the most common reasons for methicillin-resistant S. aureus antibiotic resistance is the presence of biofilms. Natural antimicrobial peptides derived from different species have shown effectiveness in combating S. aureus biofilms. In this review, we summarize the inhibitory activity of antimicrobial peptides against S. aureus planktonic cells and biofilms. We also summarize the possible inhibitory mechanisms, involving cell adhesion inhibition, membrane fracture, biofilm disruption and DNA disruption. We believe this can provide the basis for further research against S. aureus biofilm-associated infections.

Early post-operative lactate increase following kidney transplant is associated with delayed graft function: A retrospective cohort study.

Delayed graft function (DGF) is a frequent complication following kidney transplant. This study aimed to assess the association between early post-operative lactate variation and DGF. This was a single center, retrospective cohort study between February 2021 and December 2022 in Saint-Louis Hospital (APHP, France). Venous lactate levels were measured immediately (H0) and 4h (H4) after kidney transplant. The primary outcome was the occurrence of DGF (need for renal replacement therapy between transplantation and day 7). Secondary outcome was the occurrence of complications (i.e., death, vascular thrombosis, hemorrhagic shock, urological complications (hematoma, urinoma), local or systemic infection) between transplant and day 7. Two hundred 12 patients were included, and 38 (17.9%) developed DGF. Venous lactate variation between H0 and H4 was higher in patients who developed DGF (-30 (IQR -83, -6)% vs. -15 (IQR -62, -11)%, p=.037), but the variation of level was more often positive (corresponding to an increased lactate production over time between H0 and H4) in patients who developed DGF ((28(85%) vs. 94(62%), p=.011). In multivariate logistic regression, positive venous lactate level variation between H0 and H4 was strongly associated with a reduced risk of developing DGF (OR .30 [.09-.79], p=.024). We did not find any association between post-operative hyperlactatemia and occurrence of complications between transplant and day 7. DGF is a frequent complication following kidney transplantation. Its early prediction could help physicians optimize treatment and protect the kidney. Early venous lactate variation after kidney transplant could help to predict the occurrence of DGF.