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Aims Clubroot, caused by the soil-borne protist Plasmodiophora brassicae , is one of the most destructive disease for Brassica oleracea worldwide. However, the molecular mechanism of clubroot resistance still remains poorly elucidated. Therefore, we aim at identifying key genes responsive to P. brassicae infection and deducing possible molecular mechanism regulating clubroot resistance in cabbage. Methods A clubroot-resistant line (XG) and a clubroot-susceptible line (JF) were employed to conduct histological observation and transcriptome analysis at 7 and 28 DAI (days after inoculation) following inoculation with P. brassicae . Differentially expressed genes (DEGs) obtained by comparing infected roots with mock-infected roots were assigned to Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for enrichment analysis. Results TEM observation showed obvious histological differences of root cells between JF and XG after inoculation with P. brassicae . At 7 DAI, the number of DEGs identified in JF was much higher than that of XG, and most of them were enriched in metabolic pathways, metabolites biosynthesis and starch, sucrose metabolism. More DEGs were identified at 28 DAI compared to 7 DAI in XG, and most of these DEGs involved in biosynthesis of secondary metabolites, plant-pathogen interaction and plant hormone transduction. Genes related to cell wall biosynthesis, pattern recognition receptors (PRRs), disease resistance proteins, SA signal transduction, calcium influx, respiratory burst oxidase homolog (RBOH), MAPK cascades, transcription factors and chitinase were mainly up-regulated in XG at 28 DAI, while most of them were repressed in JF. Conclusions Our research work suggest drastic and complex defense response to P. brassicae infection at 28 DAI (secondary infection stage) at transcriptional level. Results generated in the present study could provide comprehensive insights into the transcriptomic landscape for better understanding of molecular regulatory mechanism of clubroot resistance in cabbage.

PurposeTo investigate the prevalence, incidence and characteristics of bacterial infections and their impact on outcome in critically ill patients infected with COVID-19. MethodsWe conducted a prospective observational study in eight Italian ICUs from February to May 2020; data were collected through an interactive electronic database. Kaplan–Meier analysis (limit product method) was used to identify the occurrence of infections and risk of acquisition.ResultsDuring the study period 248 patients were recruited in the eight participating ICUs. Ninety (36.3%) patients developed at least one episode of secondary infection. An ICU length of stay between 7 and 14 days was characterized by a higher occurrence of infectious complications, with ventilator-associated pneumonia being the most frequent. At least one course of antibiotic therapy was given to 161 (64.9%) patients. Overall ICU and hospital mortality were 33.9% and 42.9%, respectively. Patients developing bacteremia had a higher risk of ICU mortality [45.9% vs. 31.6%, odds ratio 1.8 (95% CI 0.9–3.7), p = 0.069] and hospital mortality [56.8% vs. 40.3%, odds ratio 1.9 (95% CI 1.1–3.9), p = 0.04].ConclusionIn critically ill patients infected with COVID-19 the incidence of bacterial infections is high and associated with worse outcomes. Regular microbiological surveillance and strict infection control measures are mandated.

Objective This study aimed to develop a predictive model for secondary infections in patients with severe or critical COVID-19 by analyzing clinical characteristics and laboratory indicators. Method A total of 307 patients with severe or critical COVID-19 admitted to Peking University Third Hospital from December 2022 to February 2023 were retrospectively analyzed, including 156 patients with secondary infection and 151 patients without secondary infection. The Boruta algorithm identified significant variables, and eight machine learning models were evaluated based on area under the curve (AUC) performance. The optimal model selected was further assessed, with model interpretability provided using SHapley Additive exPlanations (SHAP). Result Nine predictive factors were identified: Mechanical Ventilation, Procalcitonin (PCT), Interleukin-8 (IL-8), Interleukin-6 (IL-6), Blood Urea Nitrogen, Glucose, Creatine Kinase, Lactate Dehydrogenase, and Mean Platelet Volume (MPV). The random forest model demonstrated the best performance, with further evaluation showing an average AUC of 0.981 (CI 0.965–0.998) on the training set and 0.836 (CI 0.761–0.912) on the test set. SHAP analysis identified MPV, PCT, and IL-8 as the strongest predictors of secondary infections. Conclusion We developed an effective predictive model for secondary infection risk in severe COVID-19 patients using readily available clinical parameters, enabling early clinical intervention. This machine learning approach demonstrates potential for improving patient management. Clinical trial This study does not involve clinical trial interventions. Therefore, clinical trial registration was not applicable.

Background Patients with COVID-19 receiving mechanical ventilation may become aggravated with a secondary respiratory infection. The aim of this study was to describe secondary respiratory infections, their predictive factors, and outcomes in patients with COVID-19 requiring mechanical ventilation. Methods A cohort study was carried out in a single tertiary hospital in Santiago, Chile, from 1st June to 31st July 2020. All patients with COVID-19 admitted to the intensive care unit that required mechanical ventilation were included. Results A total of 175 patients were enrolled, of which 71 (40.6%) developed at least one secondary respiratory infection during follow-up. Early and late secondary infections were diagnosed in 1.7% and 31.4% respectively. Within late secondary infections, 88% were bacterial, 10% were fungal, and 2% were of viral origin. One-third of isolated bacteria were multidrug-resistant. Bivariate analysis showed that the history of corticosteroids used before admission and the use of dexamethasone during hospitalization were associated with a higher risk of secondary infections (p = 0.041 and p = 0.019 respectively). Multivariate analysis showed that for each additional day of mechanical ventilation, the risk of secondary infection increases 1.1 times ( ad OR = 1.07; 95% CI 1.02–1.13, p = 0.008) Conclusions Patients with COVID-19 admitted to the intensive care unit and requiring mechanical ventilation had a high rate of secondary infections during their hospital stay. The number of days on MV was a risk factor for acquiring secondary respiratory infections.

PurposeCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread around the world. Differentiation between pure viral COVID-19 pneumonia and secondary infection can be challenging. In patients with elevated C-reactive protein (CRP) on admission physicians often decide to prescribe antibiotic therapy. However, overuse of anti-infective therapy in the pandemic should be avoided to prevent increasing antimicrobial resistance. Procalcitonin (PCT) and CRP have proven useful in other lower respiratory tract infections and might help to differentiate between pure viral or secondary infection.MethodsWe performed a retrospective study of patients admitted with COVID-19 between 6th March and 30th October 2020. Patient background, clinical course, laboratory findings with focus on PCT and CRP levels and microbiology results were evaluated. Patients with and without secondary bacterial infection in relation to PCT and CRP were compared. Using receiver operating characteristic (ROC) analysis, the best discriminating cut-off value of PCT and CRP with the corresponding sensitivity and specificity was calculated.ResultsOut of 99 inpatients (52 ICU, 47 Non-ICU) with COVID-19, 32 (32%) presented with secondary bacterial infection during hospitalization. Patients with secondary bacterial infection had higher PCT (0.4 versus 0.1 ng/mL; p = 0.016) and CRP (131 versus 73 mg/L; p = 0.001) levels at admission and during the hospital stay (2.9 versus 0.1 ng/mL; p < 0.001 resp. 293 versus 94 mg/L; p < 0.001). The majority of patients on general ward had no secondary bacterial infection (93%). More than half of patients admitted to the ICU developed secondary bacterial infection (56%). ROC analysis of highest PCT resp. CRP and secondary infection yielded AUCs of 0.88 (p < 0.001) resp. 0.86 (p < 0.001) for the entire cohort. With a PCT cut-off value at 0.55 ng/mL, the sensitivity was 91% with a specificity of 81%; a CRP cut-off value at 172 mg/L yielded a sensitivity of 81% with a specificity of 76%.ConclusionPCT and CRP measurement on admission and during the course of the disease in patients with COVID-19 may be helpful in identifying secondary bacterial infections and guiding the use of antibiotic therapy.

Abstract Background The case-fatality rate of dengue in travelers is low. Secondary dengue virus (DENV) infections are considered a risk factor for fatal outcome in endemic populations; however, the impact of secondary infections on mortality in travelers has not been studied systematically. We performed a descriptive analysis of case reports of dengue fatalities in travelers. Methods We searched Medline for clinical case reports, using the free terms and MeSH headings: ‘Dengue’ OR ‘Severe Dengue’ AND ‘Travel-Related Illness’ OR ‘travel’ AND ‘Mortality’ OR ‘Fatal Outcome’. We analyzed case reports of fatal dengue in returning travelers published from 1995 to 2020, with the objective to detail risk factors for dengue mortality in this population. We verified the authors’ classifications of primary or secondary dengue infections; infections were considered as primary by absence of anti-DENV immunoglobulin (Ig)G or by IgM-to-IgG ratios greater than or equal to 1.8 in the first 7 days post symptom onset. Results We identified nine detailed reports of dengue with fatal outcome among travelers from non-endemic countries. Eight fatalities were female. The median age was 32 years (range 21–63). Out of nine fatal cases, seven travelers had a primary DENV infection, one had a secondary infection and, in one, these data were not reported. The infecting DENV serotypes were DENV-1 (n = 2), DENV-2 (n = 2) and DENV-3 (n = 3); DENV-1 or 2 (n = 1) and in one case, the serotype could not be determined. Conclusions Dengue-related deaths in travelers are rare. Most dengue cases in travelers are primary infections. Contrary to prevailing conceptions, we found that fatal outcomes of dengue in travelers from non-endemic countries were reported mainly with primary DENV infections. We alert health care providers that primary DENV infections are not always harmless and that in adult travelers from non-endemic countries, primary infections may contribute more to dengue-related mortality than secondary infections.

Background This study identified the risk factors for severe acute respiratory syndrome coronavirus 2 infection among household contacts of index patients and determined the incubation period (IP), serial interval, and estimates of secondary infection rate in Kerala, India. Methods We conducted a cohort study in three districts of Kerala among the inhabitants of households of reverse transcriptase polymerase chain reaction‐positive coronavirus disease 2019 patients between January and July 2021. About 147 index patients and 362 household contacts were followed up for 28 days to determine reverse transcriptase polymerase chain reaction positivity and the presence of total antibodies against SARS‐CoV‐2 on days 1, 7, 14, and 28. Results The mean IP, serial interval, and generation time were 1.6, 3, and 3.9 days, respectively. The secondary infection rate at 14 days was 43.0%. According to multivariable regression analysis persons who worked outside the home were protected (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.24–0.85), whereas those who had kissed the coronavirus disease 2019‐positive patients during illness were more than twice at risk of infection (aOR, 2.23; 95% CI, 1.01–5.2) than those who had not kissed the patients. Sharing a toilet with the index patient increased the risk by more than twice (aOR, 2.5; 95% CI, 1.42–4.64) than not sharing a toilet. However, the contacts who reported using masks (aOR, 2.5; 95% CI, 1.4–4.4) were at a higher risk of infection in household settings. Conclusions Household settings have a high secondary infection rate and the changing transmissibility dynamics such as IP, serial interval should be considered in the prevention and control of SARS‐CoV‐2.

Background: Interleukin-6 (IL-6) is known to be detrimental in coronavirus disease 2019 (COVID-19) because of its involvement in driving cytokine storm. This systematic review and meta-analysis aimed to assess the safety and efficacy of anti-IL-6 signaling (anti-IL6/IL-6R/JAK) agents on COVID-19 based on the current evidence. Methods: Studies were identified through systematic searches of PubMed, EMBASE, ISI Web of Science, Cochrane library, ongoing clinical trial registries ( clinicaltrials.gov ), and preprint servers (medRxiv, ChinaXiv) on August 10, 2020, as well as eligibility checks according to predefined selection criteria. Statistical analysis was performed using Review Manager (version 5.3) and STATA 12.0. Results: Thirty-one studies were included in the pooled analysis of mortality, and 12 studies were identified for the analysis of risk of secondary infections. For mortality analysis, 5630 COVID-19 cases including 2,132 treated patients and 3,498 controls were analyzed. Anti-IL-6 signaling agents plus standard of care (SOC) significantly decreased the mortality rate compared to SOC alone (pooled OR = 0.61, 95% CI 0.45–0.84, p = 0.002). For the analysis of secondary infection risk, 1,624 patients with COVID-19 including 639 treated patients and 985 controls were included, showing that anti-IL-6 signaling agents did not increase the rate of secondary infections (pooled OR = 1.21, 95% CI 0.70–2.08, p = 0.50). By contrast, for patients with critical COVID-19 disease, anti-IL-6 signaling agents failed to reduce mortality compared to SOC alone (pooled OR = 0.75, 95% CI 0.42–1.33, p = 0.33), but they tended to increase the risk of secondary infections (pooled OR = 1.85, 95% CI 0.95–3.61, p = 0.07). A blockade of IL-6 signaling failed to reduce the mechanical ventilation rate, ICU admission rate, or elevate the clinical improvement rate. Conclusion: IL-6 signaling inhibitors reduced the mortality rate without increasing secondary infections in patients with COVID-19 based on current studies. For patients with critical disease, IL-6 signaling inhibitors did not exhibit any benefit.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection. It is a disease with a high incidence, mortality, and recurrence rate and frequently results in its survivors requiring readmission into hospitals. The readmission is mainly due to recurrent sepsis. Patients with recurrent sepsis are more susceptible to secondary infections partly due to immune dysfunction, leading to a higher mortality in the long term. However, there remains a gap in the understanding of immunological characteristics and underlying mechanisms of recurrent sepsis. In this study, we used mouse models of acute and recurrent sepsis to investigate their different immunological characteristics. And then we subjected the two mouse models to a secondary influenza A virus (H1N1) infection and characterized the different immune responses. Here, we demonstrated that CD4 + T cells present an exacerbated exhaustion phenotype in response to recurrent sepsis as illustrated by the decreased frequency of CD4 + T cells, reduced co-stimulatory CD28 and increased inhibitory PD-1 and Tim-3 expression on CD4 + T cells, increased frequency of regulatory T cells, and reduced MHC-II expression on antigen-presenting cells. Moreover, we showed that antiviral immune responses decrease in the recurrent sepsis mouse model subjected to a secondary infection as illustrated by the reduced pathogen clearance and inflammatory response. This may be a consequence of the exacerbated CD4 + T cell exhaustion. In summary, recurrent sepsis exacerbates CD4 + T cell exhaustion and decreases antiviral immune responses, contributing to significant morbidity, increased late mortality, and increased health care burden in recurrent sepsis patients.

An important reason why porcine reproductive and respiratory syndrome virus (PRRSV) is difficult to control effectively is that it often causes severe secondary bacterial infections, which are usually attributed to the immunosuppression caused by PRRSV. However, the mechanism by which PRRSV infection leads to increased susceptibility of cells to bacterial infection has been largely overlooked. We revealed that PRRSV induced actin cytoskeleton rearrangement by upregulating FLNA expression, thereby aggravating bacterial invasion. PRRSV increased bacterial adhesion by promoting the ITGα5 expression, and the upregulation of ITGα5 could induce FLNA-mediated actin cytoskeleton rearrangement. Furthermore, we found that H1N1 and porcine circovirus type 2 infection also significantly promoted the expression of FLNA and ITGα5 and increased the infection of multiple bacteria. These results suggest that FLNA and ITGα5 play important roles in virus-induced secondary bacterial infection.