Infection-related Symptoms Research Articles

PCSK9 Inhibitors and Infection-Related Adverse Events: A Pharmacovigilance Study Using the World Health Organization VigiBase.

Protein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are novel lipid-lowering agents used in patients with cardiovascular disease. Despite reassuring safety data from pivotal trials, increasing evidence from real-world studies suggests that PCSK9i increase the risk of bacterial and viral infections. Therefore, this study aimed to identify signals of infection-related adverse events (AEs) associated with PCSK9i. We performed an observational pharmacovigilance study using the World Health Organization's VigiBase, recorded up to December 2022. We included individual case safety reports (ICSRs) of PCSK9 inhibitors, alirocumab and evolocumab, and compared them with those of other drugs. Infection-related ICSRs were retrieved from the Medical Dictionary for Regulatory Activities System Organ Class 'infections and infestations.' Among 114,293 reports (258,099 drug-AE pairs) related to PCSK9 inhibitors, 54% included female patients, 41% included patients aged ≥65 years, and 82% included patients who received evolocumab. Additionally, beyond AEs recognized by regulatory authorities, organ infections such as influenza (reporting odds ratio [ROR] 2.89, 95% confidence interval [CI] 2.74-3.05), gastric infections (ROR 2.47, 95% CI 1.63-3.75), and kidney infections (ROR 1.36, 95% CI 1.06-1.73) were observed. Sensitivity analysis indicated a heightened risk of infection-related AEs associated with PCSK9i regardless of the specific drug type. In addition to the labelled respiratory infections, six infection-related symptoms in the gastrointestinal, urinary, and renal organs were identified. Our findings support the need for systematic surveillance of infections among PCSK9i users.

Exploring the Prevalence of Tinnitus and Ear-Related Symptoms in China After the COVID-19 Pandemic: Online Cross-Sectional Survey.

Tinnitus is a complex and heterogeneous disease that has been identified as a common manifestation of COVID-19. To gain a comprehensive understanding of tinnitus symptoms in individuals following COVID-19 infection, we conducted an online survey called the China Ear Nose and Throat Symptom Survey in the COVID-19 Pandemic (CENTSS) among the Chinese population. Our objective was to investigate tinnitus and ear-related symptoms after COVID-19 infection in the Chinese population, with the aim of providing a solid empirical foundation for improved health care. The findings from CENTSS can contribute to the development of enhanced management strategies for tinnitus in the context of long COVID. By gaining a better understanding of the factors contributing to tinnitus in individuals with COVID-19, health care providers can tailor interventions to address the specific needs of affected patients. Furthermore, this study serves as a basis for research on the long-term consequences of COVID-19 infection and its associated tinnitus symptoms. A quantitative, online, cross-sectional survey study design was used to explore the impact of the COVID-19 pandemic on experiences with tinnitus in China. Data were collected through an online questionnaire designed to identify the presence of tinnitus and its impacts. Descriptive statistics were used to analyze individuals' demographic characteristics, COVID-19 infection-related ear symptoms, and the cognitive and emotional implications of tinnitus. Univariable and multivariable logistic regression analyses were used to model the cross-sectional baseline associations between demographic characteristics, noise exposure, educational level, health and lifestyle factors, and the occurrence of tinnitus. Between December 19, 2022, and February 1, 2023, we obtained responses from 1262 Chinese participants representing 24 regions, with an average age of 37 years. Among them, 540 patients (42.8%) reported experiencing ear-related symptoms after COVID-19 infection. Only 114 (9%) of these patients sought medical attention specifically for their ear symptoms, while 426 (33.8%) did not seek hospital care. Tinnitus emerged as the most prevalent and impactful symptom among all ear-related symptoms experienced after COVID-19 infection. Of the respondents, female participants (688/888, 77.78%), younger individuals (<30 years), individuals with lower education levels, participants residing in western China, and those with a history of otolaryngology diseases were more likely to develop tinnitus following COVID-19 infection. In summary, tinnitus was identified as the most common ear-related symptom during COVID-19 infection. Individuals experiencing tinnitus after COVID-19 infection were found to have poorer cognitive and emotional well-being. Different ear-related symptoms in patients post-COVID-19 infection may suggest viral invasion of various parts of the ear. It is therefore crucial to monitor and manage hearing-related changes resulting from COVID-19 as clinical services resume.

COVID-19 in Female and Male Athletes: Symptoms, Clinical Findings, Outcome, and Prolonged Exercise Intolerance—A Prospective, Observational, Multicenter Cohort Study (CoSmo-S)

BackgroundAn infection with SARS-CoV-2 can lead to a variety of symptoms and complications, which can impair athletic activity.ObjectiveWe aimed to assess the clinical symptom patterns, diagnostic findings, and the extent of impairment in sport practice in a large cohort of athletes infected with SARS-CoV-2, both initially after infection and at follow-up. Additionally, we investigated whether baseline factors that may contribute to reduced exercise tolerance at follow-up can be identified.MethodsIn this prospective, observational, multicenter study, we recruited German COVID elite-athletes (cEAs, n = 444) and COVID non-elite athletes (cNEAs, n = 481) who tested positive for SARS-CoV-2 by PCR (polymerase chain reaction test). Athletes from the federal squad with no evidence of SARS-CoV-2 infection served as healthy controls (EAcon, n = 501). Questionnaires were used to assess load and duration of infectious symptoms, other complaints, exercise tolerance, and duration of training interruption at baseline and at follow-up 6 months after baseline. Diagnostic tests conducted at baseline included resting and exercise electrocardiogram (ECG), echocardiography, spirometry, and blood analyses.ResultsMost acute and infection-related symptoms and other complaints were more prevalent in cNEA than in cEAs. Compared to cEAs, EAcon had a low symptom load. In cNEAs, female athletes had a higher prevalence of complaints such as palpitations, dizziness, chest pain, myalgia, sleeping disturbances, mood swings, and concentration problems compared to male athletes (p < 0.05). Until follow-up, leading symptoms were drop in performance, concentration problems, and dyspnea on exertion. Female athletes had significantly higher prevalence for symptoms until follow-up compared to male. Pathological findings in ECG, echocardiography, and spirometry, attributed to SARS-CoV-2 infection, were rare in infected athletes. Most athletes reported a training interruption between 2 and 4 weeks (cNEAs: 52.9%, cEAs: 52.4%), while more cNEAs (27.1%) compared to cEAs (5.1%) had a training interruption lasting more than 4 weeks (p < 0.001). At follow-up, 13.8% of cNEAs and 9.9% of cEAs (p = 0.24) reported their current exercise tolerance to be under 70% compared to pre-infection state. A persistent loss of exercise tolerance at follow-up was associated with persistent complaints at baseline, female sex, a longer break in training, and age > 38 years. Periodical dichotomization of the data set showed a higher prevalence of infectious symptoms such as cough, sore throat, and coryza in the second phase of the pandemic, while a number of neuropsychiatric symptoms as well as dyspnea on exertion were less frequent in this period.ConclusionsCompared to recreational athletes, elite athletes seem to be at lower risk of being or remaining symptomatic after SARS-CoV-2 infection. It remains to be determined whether persistent complaints after SARS-CoV-2 infection without evidence of accompanying organ damage may have a negative impact on further health and career in athletes. Identifying risk factors for an extended recovery period such as female sex and ongoing neuropsychological symptoms could help to identify athletes, who may require a more cautious approach to rebuilding their training regimen.Trial Registration NumberDRKS00023717; 06.15.2021—retrospectively registered.

Protection effects of mice liver and lung injury induced by coronavirus infection of Qingfei Paidu decoction involve inhibition of the NLRP3 signaling pathway

Ethnopharmacological relevanceCoronavirus Disease 2019 (COVID-19) is a grave and pervasive global infectious malady brought about by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), posing a significant menace to human well-being. Qingfei Paidu decoction (QFPD) represents a pioneering formulation derived from four classical Chinese medicine prescriptions. Substantiated evidence attests to its efficacy in alleviating clinical manifestations, mitigating the incidence of severe and critical conditions, and reducing mortality rates among COVID-19 patients. Aim of the studyThis study aims to investigate the protection effects of QFPD in mice afflicted with a coronavirus infection, with a particular focus on determining whether its mechanism involves the NLRP3 signaling pathway. Materials and methodsThe coronavirus mice model was established through intranasal infection of Kunming mice with Hepatic Mouse Virus A59 (MHV-A59). In the dose-effect experiment, normal saline, ribavirin (80 mg/kg), or QFPD (5, 10, 20 g/kg) were administered to the mice 2 h following MHV-A59 infection. In the time-effect experiment, normal saline or QFPD (20 g/kg) was administered to mice 2 h post MHV-A59 infection. Following the assessment of mouse body weights, food consumption, and water intake, intragastric administration was conducted once daily at consistent intervals over a span of 5 days. The impact of QFPD on pathological alterations in the livers and lungs of MHV-A59-infected mice was evaluated through H&E staining. The viral loads of MHV-A59 in both the liver and lung were determined using qPCR. The expression levels of genes and proteins related to the NLRP3 pathway in the liver and lung were assessed through qPCR, Western Blot analysis, and immunofluorescence. ResultsThe administration of QFPD was shown to ameliorate the reduced weight gain, decline in food consumption, and diminished water intake, all of which were repercussions of MHV-A59 infection in mice. QFPD treatment exhibited notable efficacy in safeguarding tissue integrity. The extent of hepatic and pulmonary injury, when coupled with QFPD treatment, demonstrated not only a reduction with higher treatment dosages but also a decline with prolonged treatment duration. In the dose-effect experiment, there was a notable, dose-dependent reduction in the viral loads, as well as the expression levels of IL-1β, NLRP3, ASC, Caspase 1, Caspase-1 p20, GSDMD, GSDMD-N, and NF-κB within the liver of the QFPD-treated groups. Additionally, in the time-effects experiments, the viral loads and the expression levels of genes and proteins linked to the NLRP3 pathway were consistently lower in the QFPD-treated groups compared with the model control groups, particularly during the periods when their expressions reached their zenith in the model group. Notably, IL-18 showed only a modest elevation relative to the blank control group following QFPD treatment. ConclusionsTo sum up, our current study demonstrated that QFPD treatment has the capacity to alleviate infection-related symptoms, mitigate tissue damage in infected organs, and suppress viral replication in coronavirus-infected mice. The protective attributes of QFPD in coronavirus-infected mice are plausibly associated with its modulation of the NLRP3 signaling pathway. We further infer that QFPD holds substantial promise in the context of coronavirus infection therapy.

Extracorporeal shockwave therapy of the perineum for male patients with chronic pelvic pain syndrome: a pilot study

BackgroundChronic pelvic pain syndrome (CPPS) is a complex condition that is often difficult to treat and may sometimes require a multidisciplinary team. Among the wide array of treatment options is extracorporeal shockwave therapy (ESWT). However, its role in CPPS remains controversial. The purpose of our study is to assess the efficacy and safety of ESWT of the perineum in male patients with CPPS. MethodsFourteen patients aged between 21 and 85 years were recruited in this single-center, single-arm prospective trial from October 2018 to October 2020. ESWT was delivered to the perineum weekly for up to 8 weeks. Assessment was done via International Index for Erectile Function, International Prostate Symptom Score, King's Health Questionnaire, National Institutes of Health – Chronic Prostatitis Symptom Index, Visual Analogue Scale, Analgesic Questionnaire, and UPOINT (urinary symptoms [U], psychosocial dysfunction [P], organ-specific symptoms [O], infection-related symptoms [I], neurological/systemic conditions [N], tenderness of skeletal muscles [T]) phenotype system. The parameters are assessed before the start and end of treatment as well as at regular time points on follow-up appointments up to 20 weeks. ResultsThirteen patients completed the study. There was improvement in the Visual Analogue Scale pain score, Tenderness domain on UPOINT, King's Health Questionnaire, and National Institutes of Health – Chronic Prostatitis Symptom Index scores. In terms of erectile function, improvement in the erectile function domain of International Index for Erectile Function was observed. There was also significant improvement in lower urinary tract symptoms assessed on International Prostate Symptom Score. There were no adverse events reported post treatment and during the follow-up period. ConclusionsESWT improved pain and quality of life of male patients with CPPS. It can be a safe and effective treatment modality in the armamentarium of CPPS.

Chitosan-Based Hydrogel in the Management of Dermal Infections: A Review.

The main objective of this review is to provide a comprehensive overview of the current evidence regarding the use of chitosan-based hydrogels to manage skin infections. Chitosan, a naturally occurring polysaccharide derived from chitin, possesses inherent antimicrobial properties, making it a promising candidate for treating various dermal infections. This review follows a systematic approach to analyze relevant studies that have investigated the effectiveness of chitosan-based hydrogels in the context of dermal infections. By examining the available evidence, this review aims to evaluate these hydrogels' overall efficacy, safety, and potential applications for managing dermal infections. This review's primary focus is to gather and analyze data from different recent studies about chitosan-based hydrogels combating dermal infections; this includes assessing their ability to inhibit the growth of microorganisms and reduce infection-related symptoms. Furthermore, this review also considers the safety profile of chitosan-based hydrogels, examining any potential adverse effects associated with their use. This evaluation is crucial to ensure that these hydrogels can be safely utilized in the management of dermal infections without causing harm to patients. The review aims to provide healthcare professionals and researchers with a comprehensive understanding of the current evidence regarding the use of chitosan-based hydrogels for dermal infection management. The findings from this review can contribute to informed decision-making and the development of potential treatment strategies in this field.

Using Health-Related Social Media to Understand the Experiences of Adults With Lung Cancer in the Era of Immuno-Oncology and Targeted Therapies: Observational Study.

The treatment of non-small cell lung cancer (NSCLC) has evolved dramatically with the approval of immuno-oncology (IO) and targeted therapies (TTs). Insights on the patient experience with these therapies and their impacts are lacking. Health-related social media has been increasingly used by patients to share their disease and treatment experiences, thus representing a valuable source of real-world data to understand the patient's voice and uncover potential unmet needs. This study aimed to describe the experiences of patients with NSCLC as reported in discussions posted on lung cancer-specific social media with respect to their disease symptoms and associated impacts. Publicly available posts (2010-2019) were extracted from selected lung cancer- or NSCLC-specific websites. Social media users (patients and caregivers posting on these websites) were stratified by metastatic- and adjuvant-eligible subgroups and treatment received using natural language processing (NLP) and machine learning methods. Automated identification of symptoms was conducted using NLP. Qualitative data analysis (QDA) was conducted on random samples of posts mentioning pain-related, fatigue-related, respiratory-related, or infection-related symptoms to capture the patient experience with these and associated impacts. Overall, 1724 users (50,390 posts) and 574 users (4531 posts) were included in the metastatic group and adjuvant group, respectively. Among users in the metastatic group, pain, discomfort, and fatigue were the most commonly mentioned symptoms (49.7% and 39.6%, respectively), and in the QDA (258 posts from 134 users), the most frequent impacts related to physical impairments, sleep, and eating habits. Among users in the adjuvant group, pain, discomfort, and respiratory symptoms were the most commonly mentioned (44.8% and 23.9%, respectively), and impacts identified in the QDA (154 posts from 92 users) were mostly related to physical functioning. Findings from this exploratory observational analysis of social media among patients and caregivers informed the lived experience of NSCLC in the era of novel therapies, shedding light on most reported symptoms and their impacts. These findings can be used to inform future research on NSCLC treatment development and patient management.

Assessment of Reported Adverse Events After Interchanging Between TNF-α Inhibitor Biosimilars in the WHO Pharmacovigilance Database.

Observational studies have shown that a significant proportion of patients interchanging between tumor necrosis factor-α inhibitor biosimilars withdraws from the new treatment because of adverse effects. We aim to analyze adverse events related to interchanging from tumor necrosis factor-α (TNF-α) inhibitor reference products to biosimilars and between biosimilars reported in the World Health Organization pharmacovigilance database. We extracted all cases reporting the Medical Dictionary for Regulatory Activities term "Product substitution issue (PT)" for TNF-α inhibitors. Then, we analyzed and categorized all adverse events reported in more than 1% of cases. We compared the adverse events reported according to reporter qualification, type of switch, and type of TNF-α inhibitor using Chi2 tests. We conducted a network analysis coupled with a clustering approach to identify syndromes of co-reported adverse events. In the World Health Organization pharmacovigilance database, 2543 cases and 6807 adverse events related to TNF-α inhibitor interchangeability have been reported up to October 2022. Injection-site reactions were the most reported adverse events with 940 cases (37.0%), followed by modifications in drug effect in 607 cases (23.9%). Musculoskeletal, cutaneous, and gastrointestinal disorders linked to the underlying disease were reported in 505 (20.0%), 145 (5.7%), and 207 (8.1%) cases, respectively. Adverse events non-related to the underlying disease were nonspecific (n = 458, 18.0%), neurologic (n = 224, 8.8%), respiratory (n = 132, 5.2%), and psychological disorders (n = 64, 2.5%). Injection-site reactions and infection-related symptoms (e.g., nasopharyngitis, urinary tract infection, lower respiratory tract infection) were more reported by non-healthcare professionals while adverse events related to reduced clinical efficacy (e.g., drug ineffective, arthralgia, psoriasis) were more reported by healthcare professionals. The proportions of injection-site reactions were higher when switching between biosimilars of the same reference product, but the proportions of adverse events related to reduced clinical efficacy (e.g., psoriasis, arthritis, psoriatic arthropathy) were more reported when switching from a reference product. The main differences in the proportions of reported cases between adalimumab, infliximab, and etanercept were driven by symptoms related to the underlying targeted diseases, except for a higher reporting rate of injection-site pain with adalimumab. Adverse events evocative of hypersensitivity reactions were reported in 192 (7.6%) cases. Most of the network clusters concerned non-specific adverse events or were related to reduced clinical efficacy. This analysis highlights the burden of patient-reported adverse events when interchanging between TNF-α inhibitor biosimilars, notably injection-site reactions, non-specific adverse events, and symptoms related to reduced clinical efficacy. Our study also highlights differences in reporting patterns between patients and healthcare professionals and depending on the type of switch. The results are limited by missing data, the lack of precision of the coded Medical Dictionary for Regulatory Activities terms, and by the variability of reporting rate of adverse events. Thus, incidence rates of adverse events cannot be inferred from these results.

Isolation and characterization of porcine epidemic diarrhea virus with a novel continuous mutation in the S10 domain.

Porcine epidemic diarrhea virus (PEDV), which re-emerged in China in 2010, has caused severe economic losses to the global pig industry. In this study, a PEDV strain, designated PEDV WMB, was isolated from piglets with severe diarrhea on a pig farm in Henan Province of China. Whole-genome sequencing and analysis revealed that the PEDV WMB strain belongs to subtype G2c and has a unique continuous mutation in the S10 antigenic epitope of the S protein. Moreover, the virus-neutralization (VN) test indicated that polyclonal antibodies against the S10 protein of other G1 and G2 strains showed reduced VN reactivity to PEDV WMB. The pathogenicity of PEDV WMB was further investigated in 3 day-old piglets. PEDV infection-related clinical symptoms and morphological lesions were observed and confirmed by histopathological and immunohistochemical examination (IHC). These results illustrated that continuous mutation of the S10 epitope might affect the immunogenicity or pathogenicity of PEDV, providing evidence of the need to monitor the genetic diversity of the virus and develop effective measures to prevent and control PEDV.

Haematological Scoring System: An Early Predictor of Newborn Sepsis as Compared to Blood Culture at tertiary care centre

Background: Newborn sepsis is a clinical syndrome characterised by infection-related signs and symptoms in the first month of life, with or without bacteraemia. Sepsis is defined by the Brazilian Health Surveillance Agency (ANVISA) as a systemic reaction with at least two or more of the following signs and symptoms: thermal instability, bradycardia, apnea, intolerance, worsening of respiratory discomfort, hypoactivity and lethargy. Materials and Methods: This cross-sectional study was conducted in the Bal Chikitsalaya, M. B. Government Hospital, Udaipur (Rajasthan). A total of 100 sample sizes were included in between 6-month periods from March 2019 to August 2019. Blood culture reports were compared to haematological scoring parameters, C-reactive protein (CRP) levels, and other factors. Results: 27% of the 100 cases under investigation had positive blood cultures. There were 65% male. 35% of neonates had very low birth weights and 60% were premature. 74% of cases of septicemia had an early onset, compared to 26% of cases with a late onset. In 37.1% of cases, klebsiella was the most frequent organism identified, followed by E. coli and Coagulase Positive Staphylococcus. It has a higher sensitivity and a lesser specificity. The PPV range of the haematological grading criteria was 47% to 65%. C-reactive protein has extremely high sensitivity (81.5%) and extremely low specificity (9.6%), respectively. Conclusion: The early diagnosis of newborn sepsis can be made with the help of the Haematological Scoring System (HSS), which is a rapid, easy-to-use, readily accessible, bedside, cost-effective diagnostic. As opposed to blood cultures, haematological scoring factors are effective early diagnostic and treatment tools. Since the indicators have excellent sensitivity and specificity, antibiotics can be administered to asymptomatic patients with negative culture results. The accuracy of the sepsis diagnosis is improved.

Lactate Dehydrogenase and Risk of Readmission with Gastric Cancer: A Propensity Score Matching Analysis

Purpose Readmission is one of the measures of quality of care and potential costs. This study aimed to determine whether lactate dehydrogenase (LDH) is associated with an increased risk of 30-day readmission in gastric cancer. Methods We performed a retrospective study of patients who underwent radical gastrectomy for gastric cancer at our institution between July 2014 and May 2018. Balanced cohorts were created by propensity score matching (PSM) with a 1:1 ratio to generate the elevated LDH (ELDH) group (n = 151) and the low LDH group (Control) (n = 302). To determine the incidence, causes, and risk factors of 30-day readmission, subgroup analyzes were performed and used to develop an efficient prediction model. Results A total of 788 patients met the criteria to be included in the study. The cutoff value for serum LDH was 215.5. After PSM, a total of 302 patients were matched in pairs (ELDH group, n = 151, Control group, n = 151). ELDH levels had a higher risk of readmission (p = 0.005, Odds ratio 3.768, 95% confidence interval 1.493–9.510). The pre-match 30-day readmission rate was 7.2 percent, and common causes of post-match readmission included infection-related symptoms, gastrointestinal symptoms, and gastrointestinal bleeding. Conclusions Patients with preoperative ELDH levels, postoperative complications, and high preoperative American Society of Anesthesiologists Scores had a higher risk of readmission 30 days after surgery.

Isolation, identification and antibiotic susceptibility pattern of coagulase –negative staphylococci (cons) in various clinical specimens

Coagulase Negative (CoNS) have been recognized as an important agent of human infection since the past five decadesSignificance of CoNS in human infection is increasing these days.CoNS are the indigenous flora of the skin and mucous membrane. They have long been considered as non pathogenic and were rarely reported to cause severe infections. However, as a result of the combination of increased use of intravascular devices and an increase in the number of hospitalized immunocompromised patients, CoNS have become the major cause of Nosocomial blood stream infections and they account for 9% of nosocomial infections. This study has been done to identify clinically significant CoNS associated with different human infections and also study their antibiotic susceptibility pattern isolated from clinical samples. : The present study was conducted in a teaching hospital of Punjab, India. A total 52 strains of CoNS isolated as a sole agent with a significant growth from various clinical samples were included in the study. The speciation of CoNS was done based gram staining, catalase test, coagulase test and VITEK – 2 Compact system.: Out of 52 sample, 61.5% is male and 38.5% female coming. The most common CoNS species isolated were S. hemolyticus 28(54%), S. epidermitidis 8(15%), S.hominis 8(15%) and 8(15%). The current study shown that pathogenic CoNS cause infection-related signs and symptoms. CoNS was discovered to be isolated from blood, urine, and pus, and were the most often found species in patients.

Visitor behavior during hospital inpatient visitation.

The common target audience of the current guidelines for the prevention of healthcare-associated infections is represented by healthcare workers. Behavioral protocols for visitors and caregivers that aim to prevent healthcare-associated infections are still not available. The aim of this study was to determine the behavior of the visitors and to determine possible behavior that would contribute to the transmission of pathogenic microorganisms, in order to provide suggestions for visitors in the post-pandemic period. A survey about visitor behavior was administered to 621 visitors. The survey consisted of questions regarding the demographic features and the behavior of the patient visitors. Seventy-seven visitors (12.4%) had at least one infection-related symptoms. Overall, 426 (68.6%) visitors stated that they would cancel their visit if they had any infection-related symptoms. The location of the hand washbasin to wash or sanitize the hands at the patient's unit was not known by 142 (22.9%) visitors. The number of visitors performing all hand hygiene steps was 351 (56.5%). Compliance with hand hygiene was not affected by age, gender, living in the same house as the visited patient, or visiting an adult or pediatric patient. The visitors should be queried about symptoms of infectious disease at the entrance of the hospital. The knowledge level of the visitors about hand hygiene is not sufficient. Clear recommendations about when and how often visitors should practice hand hygiene and providing information at the entrance of the hospital will improve the hand hygiene compliance of the visitors.

Molecular, cellular and neurological consequences of infection by the neglected human pathogen Nocardia

BackgroundNocardia is a facultative intracellular pathogen that infects the lungs and brains of immunocompromised patients with consequences that can be fatal. The incidence of such infections is rising, immunocompetent individuals are also being infected, and there is a need to learn more about this neglected bacterial pathogen and the interaction with its human host.ResultsWe have applied dual RNA-seq to assess the global transcriptome changes that occur simultaneously in Nocardia farcinica (N. farcinica) and infected human epithelial alveolar host cells, and have tested a series of mutants in this in vitro system to identify candidate determinants of virulence. Using a mouse model, we revealed the profiles of inflammation-related factors in the lung after intranasal infection and confirmed that nbtB and nbtS are key virulence genes for Nocardia infection in vivo. Regarding the host response to infection, we found that the expression of many histones was dysregulated during the infection of lung cells, indicating that epigenetic modification might play a crucial role in the host during Nocardia infection. In our mouse model, Nocardia infection led to neurological symptoms and we found that 15 of 22 Nocardia clinical strains tested could cause obvious PD-like symptoms. Further experiments indicated that Nocardia infection could activate microglia and drive M1 microglial polarization, promote iNOS and CXCL-10 production, and cause neuroinflammation in the substantia nigra, all of which may be involved in causing PD-like symptoms. Importantly, the deletion of nbtS in N. farcinica completely attenuated the neurological symptoms.ConclusionsOur data contribute to an in-depth understanding of the characteristics of both the host and Nocardia during infection and provide valuable clues for future studies of this neglected human pathogen, especially those addressing the underlying causes of infection-related neurological symptoms.

Correlation between serum IgM antibody and viral load with clinical symptoms in neonates infected with cytomegalovirus

To investigate the correlation between serum cytomegalovirus (CMV) IgM antibody/viral load and infection-related clinical symptoms in neonates infected with CMV, and provide basis for clinical assessment and monitoring of neonatal CMV infection. A total of 70 neonates with CMV infection admitted to neonatology in Women's Hospital, School of Medicine Zhejiang University, from January 2014 to December 2020 were included in this study. Using real-time quantitative PCR as the diagnostic criteria, congenital cytomegalovirus-infected neonates (n=29) was diagnosed within the first 3 weeks of life, otherwise, it was postnatally acquired cytomegalovirus infection (n=41). The differences in general information and clinical indicators between IgM antibody positive and negative patients were analyzed, combined with the PCR result, the correlation between the IgM/viral load and the occurrence of symptoms were analyzed. T-test and non-parametric test were used to compare the differences of indicators between groups, logistic regression was used for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of relevant indicators. In the congenital CMV infection group and the postnatally acquired CMV infection group, viral load and the proportion of symptomatic patients in IgM positive group were significantly higher than IgM negative group (Z=-2.616, P=0.008; 80% vs. 21%, P=0.005) (Z=-2.405, P=0.016; 56% vs. 19%, P=0.025). Logistic regression analysis of the included population showed the risk factors of CMV infection-related symptoms were IgM positive (OR 4.562, 95%CI:1.461-14.246,P=0.009) and viral load (OR 1.728, 95%CI:1.068-2.798,P=0.026). Regressive analysis for single symptom with correction showed IgM antibody positive was associated with hearing dysfunction(OR 3.954, 95%CI:1.066-14.677,P=0.040),the CMV viral load was associated with thrombocytopenia (OR 2.228, 95%CI:1.124-4.413,P=0.022), and brain imaging abnormalities (OR 3.956, 95%CI:1.421-11.011, P=0.008). Receiver operating characteristic (ROC) analysis showed the area under ROC curve of CMV viral load for brain imaging abnormalities was 0.883 (P<0.001), with a sensitivity of 75.0% and specificity of 90.3%. For neonates infected with CMV, the risk of infection-related clinical symptoms and hearing dysfunction may be increased when IgM antibody was positive. Meanwhile, the higher the CMV viral load at diagnosis, the higher the risk of thrombocytopenia and abnormal brain imaging.

Long-lasting brain fog is related with severity clusters of symptoms in COVID-19 patients.

COVID-19 patients may experience Long-lasting symptoms from weeks to even months. To evaluate long-term cognitive impairment based on the severity of symptoms of COVID-19 infection in a primary health system setting. From a database of 363 patients, 83 cases aged 47 ± 15 years, (58% females) were selected from June to August 2020. In patients who survived the virus, 24 infection-related symptoms were collected to create three severity clusters (mild, moderate, and severe). The follow-up time was at least seven months. Comparing the first two clusters with the severe cluster, the existence of brain fog and risk factors (obesity, hypertension, diabetes, chronic lung disease, and hypothyroidism) were analyzed. Thirty-one patients (37%) had persistent symptoms lasting up to 240 days. Fifty-one patients (61%) experienced brain fog. Concentration was affected by symptom severity (odds ratio [OR] 3.63, 95% confidence interval [CI] 1.26-10.46, p = 0.02). Short- or long-term memory loss was not affected. Moreover, symptom severity was related to brain fog (OR 3.16, 95% CI 1.05-9.51, p = 0.04). Patients with persistent symptoms had a concentration impairment associated with severity patterns (OR 24.3, 95% CI 1.73-340.11, p = 0.03). Brain fog is associated with symptom severity in COVID-19 survivors and lasts for more than eight months.

Neonatal Sepsis and Associated Factors Among Newborns in Woldia and Dessie Comprehensive Specialized Hospitals, North-East Ethiopia, 2021.

IntroductionNeonatal sepsis is a clinical illness characterized by infection-related signs and symptoms in the first month of life, with or without bacteremia. Septicemia, meningitis, pneumonia, arthritis, osteomyelitis, and urinary tract infections are all examples of systemic illnesses that can affect newborns. Hence, the main aim of this study was to assess the prevalence and factors associated with neonatal sepsis among newborns in Woldia and Dessie Comprehensive Specialized Hospitals, northeast Ethiopia, from January 1 to July 30, 2021.MethodsThis institution-based cross-sectional study was conducted from January 1 to July 30, 2021, on 344 randomly selected neonates who visited the hospital. A systematic random sampling technique was used to select samples, and data were collected using a pre-tested standardized questionnaire. For data entry and analysis, Epi Data version 4.1 and SPSS version 24 applications were used, respectively. The goodness-of-fit was tested by the Hosmer–Lemeshow statistic test. Bivariable and multivariable binary logistic regressions were used to identify associated factors at a 95% confidence interval. Significance was considered at p-value <0.05.ResultsIn this study, the prevalence of neonatal sepsis was 79.4% (95% CI: 75.2–83.6%). Maternal UTI/STI history [AOR: 3.1; 95% CI (1.5–7.1)], gestational age <37 weeks [AOR: 4.4; 95% CI (1.0–8.9)], PROM [AOR: 4.9; 95% CI (2.5–6.8)], and new-born resuscitation history [AOR: 2.3; 95% CI (1.5–4.3)] were all significantly associated with neonatal sepsis.ConclusionThis study indicates that the proportion of neonatal sepsis is high. A history of maternal PROM, being a preterm neonate, a history of maternal UTI/STIs, and having received resuscitation at birth were identified as risk factors for neonatal sepsis.

COVID-19 Pandemic and Its Impact on Perinatal Outcomes between Symptomatic and Asymptomatic Women.

Coronavirus disease 2019 (COVID-19) has been increasing among pregnant women worldwide. Its impact on maternal, fetal, and neonatal health is still scarce in the published literature. As a routine COVID-19 prenatal screening has been established for all women requiring hospitalization, it is not clear whether symptomatic women carry worse pregnancy outcomes than those without symptoms. We aimed to analyze perinatal outcomes between symptomatic and asymptomatic women admitted to our center. Materials and Methods. A single-center retrospective cohort study was conducted for fourteen months. All pregnant women with positive reverse transcriptase-polymerase chain reaction (RT-PCR) test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were enrolled, and their perinatal outcomes were analyzed in two groups based on whether they were symptomatic or not. The primary outcomes were composite adverse fetal, neonatal, and maternal outcomes and their comparison between study groups. Results. Out of 209 included COVID-19 positive pregnant women, 62 (30%) presented with one or more infection-related symptoms. Symptomatic women were older, multiparous, carried ≥1 comorbid condition, and attained infection at earlier gestational age (44% vs. 28%; 82% vs. 69%; 28% vs. 16%; and 34 vs. 36 weeks, respectively) (p < 0.05), when compared to asymptomatic women, respectively. Maternal composite adverse outcomes were higher in the symptomatic group and showed either one or more outcomes, positive chest radiological findings, requiring hospitalization with oxygen supplementation, or maternal death (8% vs. 0.7%) (p < 0.05). Composite fetal and neonatal adverse outcomes such as miscarriage, fetal or neonatal death, admission to neonatal intensive care unit, and neonatal COVID-19 infection were not statistically significant (p > 0.05) between symptomatic and asymptomatic women. Conclusion. COVID-19 infection among symptomatic pregnant women may carry a higher risk for adverse maternal outcomes. It may be associated with their advanced age and comorbid conditions. Maternal infection-associated symptoms per se likely do not pose an increased risk for adverse fetal or neonatal outcomes.

P-073 SARS-CoV2 infection in human testis and sperm: in vivo and in vitro studies

Study questionCan severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) enter somatic and germinal cells of human testis or ejaculated sperm, thus affecting male reproductive function?Summary answerThis research provides a biological background of the potential route for infection of SARS-CoV-2 and may enable rapid deciphering of COVID-19-induced male-related reproductive disorders.What is known alreadyEpidemiologic studies suggest a significant male sex susceptibility for severe COVID19 symptoms. SARS-CoV-2 is known to affect certain cell types based on their expression of angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease2 (TMPRSS2). ACE2 makes available the binding site for the Spike protein of SARS-CoV-2. TMPRSS2 facilitates virus entry by cleaving the S antigen into S1 (the active binding site). Several studies reported the presence of ACE2 in Leydig and Sertoli cells as well as in germ cells from spermatogonia to spermatozoa. These data suggest that the human testis and gametes are a target for SARS-CoV-2.Study design, size, durationTo address this question, we examined the gene expression profile of SARS-CoV-2-associated receptors and proteases (ACE2-TMPRSS2) as well as their protein expression and localization in testicular tissue of males undergoing diagnostic surgery and in sperm of healthy, normozoospermic donors referring to the Unit of Assisted Reproduction, Siena University Hospital, from April 2020 to January 2022.Participants/materials, setting, methodsAssays were performed on tissue biopsies (n = 3) or on freshly ejaculated sperm of men (n = 6) undergoing routine semen analysis after granting informed consent. To this end, tissue biopsies and ejaculated sperm have been co-cultivated for 5-12h with infected VERO E6 cells. Immunoelectron microscopy, in situ hybridization, and highly sensitive digital droplet PCR analysis, have been used to assess if particles containing SARS-CoV- 2 antigens can be detected in testicular tissue or spermatozoa in vitro.Main results and the role of chanceWe carefully investigated the presence of the SARS-CoV-2 virus and the possible effect on male fertility, both at the molecular and ultrastructural levels. To elucidate the mechanisms underlying virus infection in germ cells and male gametes, we analyzed the expression of both ACE2 and TMPRSS2. Both genes are expressed in testes and ejaculated sperm, confirming the possibility that SARS-CoV2 can enter these cells. We also provided evidence of the expression of the corresponding proteins in both testis and sperm by immunofluorescence assays. The immunofluorescence staining of paraffin-embedded slices of testicular tissue with anti-ACE2 antibody revealed a strong signal in Leydig cells. However, ACE2 staining was also present in human Sertoli cells and was concentrated in the adluminal half of the cell, i.e. surrounding spermatocytes and spermatids.The analysis of TRPMSS2 showed similar results. Indeed, this protease is localized mainly in the interstitium, at the level of Leydig cells. This is an intriguing datum, since, while Leydig cells may be considered as a high-risk cells because of the co-expression of TMPRSS2 and ACE2, germ cells may not be at increased risk of ACE2and TMPRSS2-mediated viral entry and spread, given the lack of co-expression in these testicular cell type.Limitations, reasons for cautionThe low number of analyzed samples may limit the statistical power of this study. Whether the SARS-CoV-2 infection change the gene expression profile of other SARS-CoV-2-associated proteases is under investigationWider implications of the findingsThis validated RT-PCR assay allows reliable screening of SARS-CoV-2 in sperm, useful for investigating the presence of the virus in patients undergoing ART, as well as for explaining the molecular and cellular mechanisms related to the gender specificity of the more severe infection-related symptoms.Trial registration numberNot applicable

Cross-sectional internet survey exploring women’s knowledge, attitudes and practice regarding urinary tract infection-related symptoms in the Netherlands

ObjectivesUrinary tract infections (UTIs) are the most prevalent cause for women to consult a general practitioner (GP) and are commonly treated with (broad-spectrum) empirical antibiotics, even though 50% of UTIs...