Journal of Infection最新文献

Background: COVID-19 symptoms may persist beyond acute SARS-CoV-2 infection, as ongoing symptomatic COVID-19 [OSC] (symptom duration 4-12 weeks) and post-COVID syndrome [PCS] (symptom duration ≥12 weeks). Vaccination against SARS-CoV-2 decreases OSC/PCS in individuals subsequently infected with SARS-CoV-2 post-vaccination. Whether vaccination against SARS-CoV-2, or any other vaccinations (such as against influenza) affects symptoms in individuals already experiencing OSC/PCS, more than natural symptom evolution, is unknown.

Method: Using data from the ZOE COVID Symptom Study app, two comparative analyses were carried out, both in prospectively-reporting individuals with OSC/PCS: A) symptoms in individuals receiving first vaccination against SARS-CoV-2, compared with unvaccinated individuals, matched for age, sex, BMI and week of test (n=1679 in each group); B) symptoms in individuals receiving vaccination against influenza, compared with unvaccinated individuals, matched for age, sex, BMI, week of test and number of SARS-CoV-2 vaccinations (n=692 in each group). In both analyses, vaccination date (or equivalent time from start of symptoms in the unvaccinated group) was considered as the index time, and symptom evolution was measured by comparing symptoms during the second week before and second week after vaccination. Symptoms were considered by prevalence and burden over the considered periods; all results were adjusted for multiple comparisons.

Results: After first vaccination against SARS-CoV-2, many symptoms in individuals with OSC/PCS improved more rapidly than natural history resolution, including the commonly reported symptoms of fatigue (p<0.0001, β=--0.9 [95% CI: -1.86; -0.67]) and myalgia (p<0.001, β=-0.3 [95% CI: -0.50; -0.12]). No symptom worsened after vaccination. In contrast, there was no improvement in OSC/PCS symptoms beyond natural history resolution after vaccination against influenza.

Conclusion: In individuals with OSC/PCS, vaccination against SARS-CoV-2 improved symptom resolution; this effect was not observed, however, after other vaccinations.

Objectives: Convalescent plasma (CP) treatment of COVID-19 has shown significant therapeutic effect only when administered early. We investigated the importance of patient and CP seroprofiles on treatment outcome in REMAP-CAP CP trial.

Methods: We evaluated neutralising antibodies (nAb), anti-spike (S) IgM, IgG, IgG avidity, IgG fucosylation and respiratory viral loads in a sub-set of patients (n=80) and controls (n=51) before and after transfusion, comparing them to those in the CP units (n=157) they received.

Results: Most patients were SARS-CoV-2 seropositive pre-transfusion (72% nAb; 89% S-IgG seropositivity). The majority (80%) had higher pre-transfusion S-IgG levels (median 1.7×10⁶ arbitrary units (AU); 56%) or S-IgG production rates (median 1.1×10⁶AU/day; 64%) than they received from CP (median 2.2×10⁵AU). Only 22% of the patients demonstrated significant (median 24-fold) increase in their S-IgG levels acquired from transfusion. Better outcomes, measured by organ support-free days, were associated with increase in S-IgM levels (p=0.007), decreased S-IgG fucosylation (p<0.001), lower patient age (p<0.001) but not with receiving CP (p=0.337).

Conclusions: Based on our data, increased S-antibody levels linked to transfused CP were only observed in pre-seroconversion or immunodeficient patients lacking their own SARS-CoV-2 antibodies, representing the groups where CP treatment has previously shown most benefit.

Background: Severe pulmonary hemorrhagic syndrome (SPHS) remains a fatal complication of leptospirosis with poorly understood mechanisms and an urgent need for effective biomarkers.

Methods: A nested case-control analysis was conducted using blood specimens from two previous Thai leptospirosis cohorts. Candidate microRNAs were initially discovered through a global profiling of 798 serum microRNAs in five SPHS and seven non-SPHS patients, and then validated using real-time polymerase chain reactions in 168 patients. Pathways enriched from microRNA targets were compared to those from an integrated transcriptomic-proteomic analysis. Proteins pertaining to the key resulting pathway were measured to validate significance and reveal correlation with microRNA biomarkers.

Results: Serum microRNA profiling revealed a total of 81 significantly expressed microRNAs, of which seven were selected for further validation in the whole cohort of 168 leptospirosis patients, including 28 in SPHS and 140 nonSPHS groups. Among the selected microRNAs, miR-5010-3p and miR-147b-3p had significantly higher expression in SPHS group compared to nonSPHS group, with consistently higher expression after adjusting for age, sex, days of illness, comorbidity, smoking status or recruitment site. The two had area under the curve (AUC) values of 0.76 (95% CI: 0.67-0.85) and 0.70 (95% CI: 0.56-0.81) for discriminating SPHS, respectively. These microRNAs also exhibited consistent AUC values in patients tested before chest radiograph shadows manifested. Combination of miR-5010-3p with miR-548ai and miR-224-5p, as selected by Bayesian Model Average algorithm, substantially boosts the AUC value to 0.86 (95% CI: 0.77-0.94). The miRNA biomarkers also enhanced the predictive values of a previously validated clinical model, increasing AUC value from 0.87 to 0.92 with a significant reclassification net index. Multi-omics pathway analysis incorporating microRNA targets and transcriptomic-proteomic data suggested TNF signaling as among the key pathways. In validation, seven out of ten pathway proteins were significantly different between groups, with principal components correlated with severity and miR-5010-3p.

Conclusions: MiR-5010-3p and miR-147b-3p are novel biomarkers with good predictability and potential relevance with TNF signaling pathway, an important host response mechanism in leptospirosis SPHS.

Objectives: To investigate if receipt of measles-mumps-rubella (MMR) vaccine following the third dose of diphtheria-tetanus-acellular pertussis (DTaP3) is associated with reduced rates of non-targeted infectious disease hospitalisations.

Methods: Register based cohort study following 1,397,027 children born in Denmark, Finland, Norway, and Sweden until 2 years of age. Rates of infectious disease hospitalisations with minimum one overnight stay according to time-varying vaccination status were compared using Cox proportional hazards regression analysis with age as the underlying timescale and including multiple covariates. Summary estimates were calculated using random-effects meta-analysis.

Results: Compared with DTaP3 and no MMR vaccine, MMR after DTaP3 was associated with reduced rates of infectious disease hospitalisations: aHR was 0.86 (0.83-0.89) in Denmark, 0.70 (0.64-0.75) in Finland, 0.71 (0.68-0.74) in Norway, and 0.71 (0.65-0.77) in Sweden: summary estimate was 0.75 (0.65 to 0.84). A beneficial association was also seen in a negative control exposure analysis (3 vs. 2 DTaP doses): summary estimate aHR was 0.81 (0.75-0.87).

Conclusions: Having MMR as the most recent vaccine was consistently associated with reduced rated of infectious disease hospitalization. However, bias may account for at least some of the observed association. Randomised controlled trials are warranted to inform the optimal timing of MMR for both its specific and potential non-specific effects.

Objectives: In this ecological study, we describe SARS-CoV-2 case incidence for school age and adult populations, COVID-19 hospitalisation and death rates during Delta and the early Omicron periods, before and after schools reopened in five countries.

Methods: Data were extracted from government websites. Cases and COVID-19 hospitalisation and death incidence rates were calculated during the Delta and early Omicron periods in Australia, Canada, Denmark, Finland and the United Kingdom, for two weeks preceding and six weeks after schools reopened. We summarised stringency of public health measures (GRI), vaccination by age and testing rates.

Results: During Delta, cases increased in 2/7 sites after schools reopened, hospitalisations increased in 1/5 sites, while deaths decreased in one and increased then decreased in another. During Omicron, cases increased in 2/8 sites, hospitalisations increased in 1/6 sites and deaths increased in 1/4 sites. The hospitalisation and death rate trends that commenced before schools reopened continued on the same trajectory after schools reopened. Vaccination rates in ≥70-year-olds were 75-100% during Delta and 95-100% during Omicron. Wide variations in testing rates may explain differences in case incidence. GRI were higher during Delta with more variation than during Omicron.

Conclusions: Reopening schools did not change the existing trajectory of COVID-19 rates.

Background: A Parvovirus B19 (B19V) outbreak has been reported in Europe in 2023-2024. The aims of this study were 1) to describe the incidence of primary cases from 2012 to 2024 in one French hospital 2) to analyze the genome of 2023 strains 3) to identify virological profiles according to the clinical presentations of B19V infection.

Methods: The incidence of B19V primary cases was studied through an interrupted time-series analysis. Genomes of 2023 strains were sequenced in the NS1-VP1u region. Blood viral loads, IgG and IgM levels were analyzed in 158 cases according to clinical manifestations with Kruskal-Wallis test and a machine learning approach based on k-nearest neighbors.

Results: During the 2023-2024 B19V outbreak, there was an 8-time increase in the incidence of B19V infections compared with pre-pandemic levels (8.25 (95%CI: 5.79-11.76)). The 2023 strains belonged to genotype 1a and were closely related to pre-2019 strains. Blood viral loads were significantly different between clinical presentations (p<0.0001). Machine learning allowed us to classify 68.8% (95% CI: 60.9-75.9) patients into the correct clinical group.

Conclusions: The 2023-24 epidemic is probably due to the reemergence of the pre-2019 strain. The virological profiles highlighted in this study could assist in accurately interpreting virology results.

Objectives: There is conflicting evidence as to whether the combined administration of two vaccines can lead to poorer immunogenicity and reactogenicity. The co-administration of the Omicron-adapted COVID-19 vaccine from Novavax (NVX-CoV2601) and a 20-valent pneumococcal conjugate vaccine (PCV20) has not been previously investigated.

Methods: In this randomised, double-blind, placebo-controlled, non-inferiority trial, immunocompetent participants aged ≥60 years were randomised in a 1:1:1:1 ratio to four groups: NVX-CoV2601 plus PCV20 (combination group); NVX-CoV2601 plus placebo (NVX-only group); PCV20 plus placebo (PCV20-only group); or placebo plus placebo (placebo group). The primary outcome was Omicron-specific anti-spike protein IgG ELISA units at day 28 in the combination group compared with the NVX-only group. Non-inferiority was established if the lower limit of the two-sided 95% CI of the geometric mean titre ratio was above the non-inferiority margin of 0.67. Secondary outcomes included anti-pneumococcal capsular polysaccharide (PCP) IgG ELISA units. Solicited local and systemic adverse events were collected for 7 days after vaccination. This study was registered with ClinicalTrials.gov, number NCT05767606, and the EU Clinical Trials Register, EudraCT number 2022-004118-12.

Results: All 256 randomised participants completed the study. The baseline characteristics were similar in the four groups. Overall, the median age was 64 (IQR 61 to 69) and 105 (41%) of 256 were male. At day 28, the geometric mean anti-spike protein IgG ELISA units were 534 U/mL (95% CI 432-660) in the combination group and 556 U/mL (95% CI 460-672) in the NVX-only group, resulting in a geometric mean titre ratio of 0.96 (95% CI 0.73-1.27), thereby meeting the criteria for non-inferiority. Anti-PCP IgG ELISA units at day 28 were 507 U/mL (95% CI 416-619) in the combination group and 592 U/mL (95% CI 485-723) in the PCV20-only group. Local and systemic reactogenicity was similar in the three active treatment groups. No safety concerns or serious adverse events were observed.

Conclusions: Immunogenicity following co-administration of NVX-CoV2601 with PCV20 was non-inferior to administration of NVX-CoV2601 alone. Given the similar safety and reactogenicity profile, our findings may help to overcome concerns about concomitant vaccination and pave the way for combination vaccines.

Funding: Novavax.

Background: Dengue, a mosquito-borne viral infection, poses a rapidly growing burden, particularly in low- and middle-income countries. Without early identification of patients at risk of severe outcomes (dengue haemorrhagic fever, severe dengue, and plasma leakage- the latter typically occurring on days 5-7 of illness), untriaged admissions lead to hospital overcrowding and suboptimal care.

Methods: This nested case-control study compared early-stage plasma samples (within the first 96 hours of fever) from dengue patients with and without plasma leakage. Thirty-four potential biomarkers, selected through systematic review, were tested on a multiplex bead-based immunoassay platform. Subgroup analysis stratified patients by primary or secondary dengue infection.

Findings: A total of 228 patient samples (114 had plasma leakage) were tested. Elevated Vascular cell adhesion molecule-1 (OR:3.289, 95% CI: 1.090-9.926, p<0.05), and Interleukin 33 receptor levels (OR: 2.677, 95% CI: 1.244-5.856, p<0.05) were associated with an increased risk of plasma leakage while eotaxin-1 was associated with a decreased risk (OR: 0.166, 95% CI: 0.057-0.483, p<0.05). When adjusted for prior dengue exposure, additional biomarkers (C-X-C motif chemokine 11, serum amyloid A) were also associated with plasma leakage.

Interpretation: Plasma leakage in dengue, being more objectively measurable than other severe outcomes, offers a reliable endpoint for biomarker studies. Identifying biomarkers that predict plasma leakage strengthens the evidence base in dengue research. These biomarkers could improve clinical assessment and patient care in dengue cases.

Objective: To assess the characteristics, risk factors and clinical impact of penicillin and other antibiotic allergies labels in general practice in the UK.

Design: Population-based cohort study.

Setting: Primary care in the UK, 2000-2018.

Participants: Adults aged 18-100 years who were registered with their general practice for at least 12 months between 01-Jan-2000 and 31-Dec-2018 and followed until 25-Sep-2019.

Main outcome measures: The main outcomes include the annual prevalence and incidence of penicillin and other antibiotic allergies labels. Multinominal logistic regression was used to examine the characteristics associated with receiving an allergy label to different antibiotics. Cox regression modelling was used to compare the risk of resistant infections (methicillin resistant Staphylococcus aureus [MRSA] and vancomycin resistant enterococci) as well as Clostridioides difficile (C.difficile) infection between patients with and without allergy labels. The monthly proportion of patients who had a penicillin allergy test, either before their allergy label was recorded or within one year, was calculated to assess any impact of NICE penicillin allergy assessment recommendations (Clinical guideline [CG183]) in September 2014.

Results: Both the prevalence and incidence of penicillin allergy label showed a pattern of initial growth followed by a decline. The prevalence reached a maximum of 8.25% in 2011, and the incidence peaked at 0.46% in 2004. Older age, being female, living in less deprived areas, belonging to a larger general practice, and having co-morbidities were associated with a higher chance of receiving a penicillin or other antibiotic allergy label. Patients with antibiotic allergy labels were more likely to receive alternative broad-spectrum antibiotics and had a higher risk of MRSA and C.difficile infections. The introduction of NICE drug allergy guideline did not alter the proportion of patients undergoing penicillin allergy assessment.

Conclusion: Penicillin and other antibiotic allergy labels are common and lead to radical change in the antibiotic prescribing practices and are associated with resistant and healthcare associated infections.