Background: The study aimed to describe all diagnosed cases of Legionnaire's disease (LD) in south Sweden, regarding incidence, patient characteristics, diagnostics, outcomes, and infection control investigations.
Methods: This population-based retrospective study was conducted in Skåne, on patients with LD between 2011-2021. Inclusion criteria were positive polymerase chain reaction (PCR) for L. pneumophila/Legionella spp. or a positive urinary antigen test (UAT), combined with a clinical presentation consistent with Legionella infection and radiological evidence of pulmonary infiltrates.
Results: A total of 280 patients met the inclusion criteria, with a mean incidence of 2.00 per 100,000 person-years (95% CI: 1.23-2.78). Empiric treatment covering Legionella was administered in 15% of cases. Mortality rates were 13%, 15% and 23% at 30-, 90- and 365 days, respectively. UAT was performed in 88% of patients, with a 66% positivity rate. Lower respiratory tract PCR was performed in 76% of patients with a 90% positivity rate. Bacterial culture was positive in 43% of cases. Out of these, L. pneumophila serogroup 1 was most common (58%), though a significant proportion were serogroups 2-14 (30%), which are not generally detected by UAT. Genetic matches between environmental and patient strains were established in 5% of cases.
Conclusion: Legionnaires' disease in Skåne is an uncommon but clinically significant condition. Few patients received appropriate empiric antibiotic treatment. Reliance on UAT alone is insufficient for establishing diagnosis, and species-specific PCR, particularly from lower respiratory samples, enhances detection. Environmental investigations frequently identified Legionella in suspected settings; however, a definitive source of infection was rarely established.
Background: The relationship between the initial viral load in respiratory specimens and the severity of COVID-19 is not fully elucidated. Studies on the impact of patient age on the SARS-CoV-2 load have yielded divergent results.
Objective: We aimed to investigate the impact of viral load in COVID-19.
Methods: We mined a dataset of 259,511 SARS-CoV-2-infected individuals 0-105 years old in which virus RNA was quantified in nasopharyngeal swabs (viral load) using PCR at first healthcare contact. Subjects were stratified by vaccination and pandemic variant wave. Severity was assessed by hospital admission or death. Multivariable models analysed the influence of age on viral load, and viral load on severity.
Results: Among non-vaccinated (n = 140,905), viral loads of SARS-CoV-2 were lowest in children 1-9 years old and highest in infants (<1 year old) and in subjects 70-105 years, with similar results across pandemic waves and in vaccinated individuals. High viral load (≥9log10viral RNA copies/swab) associated with elevated risk of hospital admission across age groups. In adults (20-69 years old), mortality was largely confined to those with high viral load (odds ratio [OR] 5.3, 95%CI 3.6-7.3). Among subjects ≥ 70 years old, deaths occurred across viral loads but were more frequent at high viral loads (OR 2.2, 95% CI 1.9-2.6). High viral load associated with hospitalisation and mortality also in vaccinated individuals (n = 118,606).
Conclusions: This study identified high viral load at first sampling as a predictor of severe infection and/or death across age groups of SARS-CoV-2-infected patients.
Background: The natural history of HBV infection is highly heterogeneous. Failure to clear the virus during the acute phase of infection allows for viral persistence and progression to chronicity. Investigating the immune mechanisms involved in this process is crucial for effectively managing infection outcome. HLA-Ib molecules (HLA-G, HLA-E and HLA-F) play a critical role in regulating the immune response.
Objectives: primary objective: we investigate the potential impact of functional polymorphisms in HLA-F*01:03 (rs1736924), HLA-E*01:01/01:03 (rs1264457), and two selected HLA-G polymorphisms in Exon 2 (+292 A > T (rs41551813) and +372 G > A (rs1130355)) on HBV infection outcome. Secondary objective: we evaluate the expression of soluble HLA-E in our cohort.
Methods: We evaluated these polymorphisms in a cohort of 200 patients with chronic HBV infection and 100 individuals who spontaneously resolved the infection, using SSP-PCR and Sanger sequencing. Additionally, we measured soluble HLA-E (sHLA-E) levels using ELISA.
Results: Our results showed a significant association of HLA-G (rs41551813) and HLA-E (rs1264457) polymorphisms with HBV infection outcome, where carriers of the A allele in both HLA-G (rs41551813) and HLA-E (rs1264457) had a significantly higher likelihood of spontaneous HBV clearance (all p < 0.01). Furthermore, we demonstrate that elevated sHLA-E expression favours HBV persistence. Additionally, our findings has revealed that the HLA-G + 292 A > T polymorphism (rs41551813) is associated with regulation of sHLA-G expression. Haplotype analysis further identified the 'TAAA' haplotype as linked to spontaneous HBV clearance.
Conclusion: this study demonstrates, for the first time, the critical role of HLA-Ib on HBV infection outcome, providing insights for potential therapeutic interventions.
Background: Inborn errors of immunity (IEI) are congenital disorders of the immune system. Due to impaired immune system, they are at a higher risk to develop a more severe COVID-19 course compared to general population.
Objectives: Herein, we aimed to systematically review various aspects of IEI patients infected with SARS-CoV-2. Moreover, we performed a meta-analysis to determine the frequency of COVID-19 in patients with different IEI.
Methods: Embase, Web of Science, PubMed, and Scopus were searched introducing terms related to IEI and COVID-19.
Results: 3646 IEI cases with a history of COVID-19 infection were enrolled. The majority of patients had critical infections (1013 cases, 27.8%). The highest frequency of critical and severe cases was observed in phenocopies of IEI (95.2%), defects in intrinsic and innate immunity (69.4%) and immune dysregulation (23.9%). 446 cases (12.2%) succumbed to the disease and the highest mortality was observed in IEI phenocopies (34.6%). COVID-19 frequency in immunodeficient patients was 11.9% (95% CI: 8.3 to 15.5%) with innate immunodeficiency having the highest COVID-19 frequency [34.1% (12.1 to 56.0%)]. COVID-19 case fatality rate among IEI patients was estimated as 5.4% (95% CI: 3.5-8.3%, n = 8 studies, I2 = 17.5%).
Conclusion: IEI with underlying defects in specific branches of the immune system responding to RNA virus infection experience a higher frequency and mortality of COVID-19 infection. Increasing awareness about these entities and underlying genetic defects, adherence to prophylactic strategies and allocating more clinical attention to these patients could lead to a decrease in COVID-19 frequency and mortality in these patients.
Background: Congenital Cytomegalovirus (cCMV) is the most common prenatal infection and the main infectious cause of neurodevelopmental abnormalities in developed countries. Long-term neuropsychological outcome of cCMV infection is yet not well understood, and follow-up studies on adults screened for CMV at birth are few. The aim of this study was to investigate self-reported executive functioning (EF) in adults with cCMV infection in relation to uninfected controls.
Method: All individuals from a universal newborn CMV screening study conducted in Southern Sweden and sampled 1977-85, was invited to participate in a follow-up study. 45/71 individuals (63%) with cCMV infection and 25/46 controls (54%) were enrolled. Participants were aged 34-43 years. Neurological symptoms and neuropsychiatric disabilities were documented through written reports from the original study and a semi-structured study protocol. Executive functioning was evaluated with BRIEF-A (questionnaire).
Results: No statistically significant differences were found between groups in self-reported executive functioning, although greater variability in outcomes was observed in the cCMV group.
Conclusion: Everyday executive functioning might not be affected at the group level in adults with cCMV infection or may not be adequately captured through self-reports alone. The variability in executive functioning results suggests that individuals with cCMV infection represent a more heterogeneous group compared to the controls.
Background: Throat carriage of methicillin-resistant Staphylococcus aureus (MRSA) has previously been associated with lower decolonisation treatment success rates.
Objectives: To characterise decolonisation treatment and outcome in Danish MRSA throat carriers.
Methods: This retrospective population-based cohort study included MRSA throat carriers between July, 2018 and June, 2019, in the Capital Region of Denmark. Logistic regression analysis was performed to assess variables associated with becoming MRSA free.
Results: Of 178 patients included, 129 (72%) were MRSA free by the end of the study. Overall, 78 (44%) of patients became MRSA free following a treatment attempt. Twenty-six (15%) patients became MRSA free without treatment and 25 (14%) became MRSA free unrelated to a treatment attempt. The success rate of the first decolonisation treatment, mainly nasal mupirocin and chlorhexidine body wash, was 23%. Systemic clindamycin was given in 52 cases and had a success rate of 52%. Logistic regression showed that residing in a household with three to four additional MRSA carriers was negatively associated with becoming MRSA free, although not significant after adjustment. Having MRSA in a clinical sample prior to decolonisation was associated with a lower chance of becoming MRSA free after adjustment. Topical decolonisation treatment was associated with a lower probability of becoming MRSA free.
Conclusion: In this Danish cohort of MRSA throat carriers, the overall success rate of decolonisation treatment was 44% and for systemic clindamycin 52%. A higher number of household MRSA carriers and a previous clinical MRSA infection were associated with a lower chance of becoming MRSA free.
Background: When chest tube drainage does not adequately resolve thoracic empyema, video assisted thoracoscopic surgery (VATS) is often needed. However, the proper duration of antibiotics after VATS is poorly defined. Consequently, the objective of this study was to evaluate if short antibiotic durations post-VATS was equally effective compared to longer durations.
Methods: Patients with thoracic empyema treated with VATS were identified retrospectively by a query of the hospital billing database. The bacterial causes of the empyema were divided into 8 different categories while the antibiotic duration after VATS was divided into two groups which included antibiotics ˂ 14 days and antibiotics >14 days. The primary outcome measured was rates of empyema recurrence. Statistical comparisons were conducted between the antibiotic duration groups overall and when stratified based on the different bacterial causes.
Results: 137 patients were included in this study with the main cause of empyema being culture negative empyema (37.2%) while alpha haemolytic Streptococcus spp. was the most cultured bacteria (26.3%). There was no statistical difference (p = 0.5168), in the rates of empyema recurrence, when short antibiotic durations (median 11.6 days)were compared to longer antibiotic durations (median 29.1 days)post-VATS. Nor was there a statistical difference in recurrence rates when stratifying based on bacterial cause.
Conclusion: This study reinforces that antibiotic durations less than 14 days post-VATS are equally effective as prolonged antibiotic durations. However, to determine the proper duration of antibiotic therapy post-VATS, a prospective clinical trial is needed to reduce complications of prolonged antibiotic therapies for these patients.
Background: The overuse of antibiotics may lead to complications such as increased resistance, adverse events, and toxicities. Literature demonstrates a negative Methicillin-resistant Staphylococcus aureus (MRSA) nares polymerase chain reaction (PCR) may be used to streamline antibiotic therapy prior to respiratory culture results based on a negative predictive value (NPV) of 95-99%. Additional literature supports a high NPV when MRSA nares PCR is evaluated in non-respiratory cultures; however, this use in critically ill patients has not been studied.
Objectives: The purpose of this study was to evaluate the clinical utility of MRSA nares PCR in non-respiratory cultures in critically ill patients.
Methods: This was a single centre, retrospective, cohort evaluation. Outcomes evaluated were NPV, positive predictive value (PPV), sensitivity, and specificity of MRSA nares PCR in critically ill patients. A sub-group analysis based on the site of culture (blood, urine, and wound) was also conducted.
Results: Of the 325 patients screened, 200 critically ill patients were included for analysis. A total of 259 cultures were evaluated with blood being the most common source (n = 124). The MRSA nares PCR was positive in 34 (17%) patients and thirteen (5%) of the 259 cultures were positive for MRSA. For all cultures, the MRSA nares PCR demonstrated an NPV 99%, PPV 28%, sensitivity 77%, and specificity 85%. The subgroup analysis for the individual culture types reflected similar findings.
Conclusions: A negative MRSA nares PCR may be used to withhold initiation or allow for timely de-escalation of anti-MRSA antibiotics in critically ill patients if clinically applicable.
Background: Respiratory syncytial virus (RSV) significantly impacts not only children but also adults. However, knowledge of the severity and outcomes among adult RSV inpatients is still limited.
Objectives: To clarify the short- and long-term health threats associated with adult RSV infections.
Methods: This retrospective observational study included 56,980 adult inpatients aged 18 years and older due to RSV or influenza infection between April 2010 and March 2022. After inverse probability weighting adjustment, we used Poisson's regression to estimate the risk of outcomes.
Results: The RSV group had a higher risk of requiring mechanical ventilation during hospitalization compared to the influenza group (9.7% vs. 7.0%; risk ratio (RR), 1.35; 95% confidence interval (CI), 1.08-1.67). In-hospital mortality was comparable between RSV and influenza groups (7.5% vs. 6.6%; RR, 1.05; 95% CI, 0.82-1.34). RSV group was associated with increased risk of readmission within 1 year after surviving discharge (34.0% vs. 28.9%; RR, 1.19; 95% CI, 1.07-1.32) and all-cause mortality within 1 year of admission (12.9% vs. 10.3%; RR, 1.17; 95% CI, 1.02-1.36). In the age-stratified analysis, the RSV group aged 60 years and older had a higher risk than the influenza group for in-hospital death, readmission and all-cause mortality within one year.
Conclusions: RSV infections demonstrated comparable or greater health threats than influenza infections not only during hospitalization but also in long-term outcomes. The findings underscore the threat of RSV in adults, the impact on healthcare systems and the need for continued development of public health counter measures against RSV.