For decades, the incidence and clinical characteristics of Pneumocystis jirovecii (P. jirovecii) colonization in patients with severe pneumonia was remained unclear. What are the clinical features and outcomes associated with P. jirovecii colonization in individuals diagnosed with severe pneumonia? In this multicenter, retrospective, matched study, severe pneumonia patients who underwent bronchoalveolar lavage clinical metagenomics from 2019 to 2023 in the ICUs of 17 medical centers were enrolled. Patients were diagnosed based on clinical metagenomics, pulmonary CT scans, and clinical presentations. Clinical data were collected retrospectively, and according to propensity score matching and Cox multivariate regression analysis, the prognosis of patients with P. jirovecii colonization was compared to that of P. jirovecii-negative patients. 40% of P. jirovecii positive patients are considered to have P. jirovecii colonization. P. jirovecii colonization group had a higher proportion of patients with immunosuppression and a lower lymphocyte count compared to P. jirovecii-negative group. More frequent detection of cytomegalovirus, Epstein-Barr virus, human herpesvirus-6B, human herpesvirus-7, and torque teno virus in the lungs was associated with P. jirovecii colonization than with P. jirovecii negativity. By constructing two cohorts through propensity score matching, we incorporated codetected microorganisms and clinical features into a Cox proportional hazards model and revealed that P. jirovecii colonization was an independent risk factor for mortality in severe pneumonia patients. According to sensitivity analyses, which included or excluded codetected microorganisms, as well as patients not receiving TMP-SMX treatment, similar conclusions were reached. Immunosuppression and a reduced lymphocyte count were identified as risk factors for P. jirovecii colonization in non-PCP patients. More frequent detection of various viruses was observed in P. jirovecii colonization patients, and P. jirovecii colonization was associated with an increased 28-day mortality in patients with severe pneumonia.

Purpose: The significance of detecting human herpesvirus 7 (HHV-7) in the lower respiratory tract of patients with severe pneumonia is unclear. This study aims to evaluate the clinical characteristics and prognosis of detecting HHV-7 in the lower respiratory tract of patients with severe pneumonia. Methods: Patients with severe pneumonia requiring invasive mechanical ventilation and underwent commercial metagenomic next-generation sequencing (mNGS) testing of bronchoalveolar lavage fluid from January 2019 to March 2023 were enrolled in 12 medical centers. Clinical data of patients were collected retrospectively, and propensity score matching was used for subgroup analysis and mortality assessment. Results: In a total number of 721 patients, 45 cases (6.24%) were identified with HHV-7 positive in lower respiratory tract. HHV-7 positive patients were younger (59.2 vs 64.4, p = 0.032) and had a higher rate of co-detection with Cytomegalovirus (42.2% vs 20.7%, p = 0.001) and Epstein–Barr virus (35.6% vs 18.2%, p = 0.008). After propensity score matching for gender, age, SOFA score at ICU admission, and days from ICU admission to mNGS assay, there was no statistically significant difference in the 28-day mortality rate between HHV-7 positive and negative patients (46.2% vs 36.0%, p = 0.395). Multivariate Cox regression analysis adjusting for gender, age, and SOFA score showed that HHV-7 positive was not an independent risk factor for 28-day mortality (HR 1.783, 95%CI 0.936–3.400, p = 0.079). Conclusion: HHV-7 was detected in the lungs of 6.24% of patients with severe pneumonia. The presence of HHV-7 in patients with severe pneumonia requiring invasive mechanical ventilation is associated with a younger age and co-detected of Cytomegalovirus and Epstein–Barr virus. While HHV-7 positivity was not found to be an independent risk factor for mortality in this cohort, this result may have been influenced by the relatively small sample size of the study.

Alzheimer’s disease has escalated into a critical public health concern, marked by its neurodegenerative nature that progressively diminishes cognitive abilities. Recognized as a continuously advancing and presently incurable condition, AD underscores the necessity for early-stage diagnosis and interventions aimed at delaying the decline in mental function. Despite the proven efficacy of cerebrospinal fluid and positron emission tomography in diagnosing AD, their broader utility is constrained by significant costs and the invasive nature of these procedures. Consequently, the innovation of blood biomarkers such as Amyloid-beta, phosphorylated-tau, total-tau et al, distinguished by their high sensitivity, minimal invasiveness, accessibility, and cost-efficiency, emerges as a promising avenue for AD diagnosis. The advent of ultra-sensitive detection methodologies, including single-molecule enzyme-linked immunosorbent assay and immunoprecipitation-mass spectrometry, has revolutionized the detection of AD plasma biomarkers, supplanting previous low-sensitivity techniques. This rapid advancement in detection technology facilitates the more accurate quantification of pathological brain proteins and AD-associated biomarkers in the bloodstream. This manuscript meticulously reviews the landscape of current research on immunological markers for AD, anchored in the National Institute on Aging—Alzheimer’s Association AT(N) research framework. It highlights a selection of forefront ultra-sensitive detection technologies now integral to assessing AD blood immunological markers. Additionally, this review examines the crucial pre-analytical processing steps for AD blood samples that significantly impact research outcomes and addresses the practical challenges faced during clinical testing. These discussions are crucial for enhancing our comprehension and refining the diagnostic precision of AD using blood-based biomarkers. The review aims to shed light on potential avenues for innovation and improvement in the techniques employed for detecting and investigating AD, thereby contributing to the broader field of neurodegenerative disease research.

Herpesviruses are widely distributed in the lower respiratory tract, yet no study has comprehensively characterized their clinical features and prognostic impact in severe pneumonia. In this multicenter, retrospective study, we included severe pneumonia patients who underwent bronchoalveolar lavage fluid (BALF) metagenomic testing in intensive care units across 17 medical centers from January 2019 to June 2023. Based on metagenomic results, patients were categorized into herpesvirus-negative, HSV-1, EBV, CMV, HHV-6B, and HHV-7 groups. Propensity score matching and multivariable Cox regression were used to compare mortality between herpesvirus-positive and -negative patients. Interaction analyses were conducted to assess the impact of co-detection of different herpesviruses. Besides, main findings were validated using data from a prospective multicenter cohort. Among 1,737 enrolled patients, the 28-day mortality rate was 41.3% (718/1,737). Herpesviruses were detected in 828 patients. Detection frequencies were: HSV-1 (26.8%), CMV (17.8%), EBV (16.6%), HHV-7 (5.3%), HHV-6B (2.2%), and VZV (0.5%). Clinical characteristics varied across herpesvirus groups. No single herpesvirus was independently associated with increased mortality compared to the negative group. However, co-detection of HSV-1 and CMV was significantly associated with higher 28-day mortality (vs. both negative: adj-HR = 1.439, 95% CI: 1.093–1.894, P = 0.009). This finding was validated in a prospective cohort (adj-HR = 1.656, 95% CI: 1.061–2.585, P = 0.026). Herpesviruses are frequently detected in the lower respiratory tract of patients with severe pneumonia, with distinct clinical features across virus types. Co-detection of HSV-1 and CMV was associated with increased 28-day mortality.

The MASS cohort comprises 2000 ICU patients with severe pneumonia, covering community‐acquired pneumonia, hospital‐acquired pneumonia, and ventilator‐associated pneumonia, sourced from 19 hospitals across 10 cities in three provinces. A wide array of samples including bronchoalveolar lavage fluid, sputum, feces, and whole blood are longitudinally collected throughout patients' ICU stays. The cohort study seeks to uncover the dynamics of lung and gut microbiomes and their associations with severe pneumonia and host susceptibility, integrating deep metagenomics and transcriptomics with detailed clinical data.

Aspergillus, the causative pathogen of invasive pulmonary aspergillosis (IPA)-a highly lethal infectious disease-produces spores with diameters that fall within the fine particulate matter (PM_2.5) range and are frequently detected in ambient PM_2.5 samples. In this study, we investigated whether pre-admission exposure to PM_2.5 is associated with an increased risk of IPA in patients with severe pneumonia. Daily PM_2.5 levels for the six months before admission were obtained from a multicenter retrospective cohort and a multicenter prospective cohort. Multivariable logistic regression was used to assess whether pre-admission PM_2.5 exposure is an independent risk factor of IPA in both cohorts. Pooled concentration-response curves determined the dose-response relationship. Mediation analysis was used to assess whether the presence of Aspergillus acts as a mediator between PM_2.5 exposure and 28-day mortality. Among 2287 patients, higher average daily PM_2.5 exposure over six-month before admission was independently associated with an increased risk of IPA. For every 10 μg/m³ increase in average daily PM_2.5 exposure during the six months before admission, the risk of IPA increased by 21% (95% CI: 10%-32%). The dose-response relationship was linear, and results remained robust across subgroups and sensitivity analyses. Mediation analysis showed that Aspergillus positivity was found to mediate 21.26% (95% CI: 4.5%-48%; P = 0.008) of the relationship between daily PM_2.5 exposure in the 90 days preceding admission and 28-day mortality. In this study, we evaluate the association between pre-admission PM_2.5 exposure and IPA. Our findings demonstrate that higher concentrations of PM_2.5 prior to admission are associated with an increased risk of IPA among ICU-admitted patients with severe pneumonia. In addition, our findings suggest that Aspergillus mediate the association between PM_2.5 exposure and mortality in this population. This work was supported by National Science and Technology Major Project of China (2025ZD0549000), National Natural Science Foundation of China (grant no. 82202356, 82341109, and 82173645), the Zhejiang Provincial Natural Science Fund (grant no. LTGY24H190001), "Pioneer" and "Leading Goose" R&D Program of Zhejiang (grant no. 2025C02090).