Shanghai has been experiencing the Omicron wave since March 2022. Though several studies have evaluated the risk factors of severe infections, the analyses of BA.2 infection risk and protective factors among geriatric people were much limited. This multicentre cohort study described clinical characteristics, and assessed risk and protective factors for geriatric Omicron severe infections. A total of 1377 patients older than 60 were enrolled, with 75.96% having comorbidities. The median viral shedding time and hospitalization time were nine and eight days, respectively. Severe and critical were associated with longer virus clearance time (aOR [95%CI]:0.706 (0.533–0.935), P = .015), while fully vaccinated/booster and paxlovid use shortened viral shedding time (1.229 [1.076–1.402], P = .002; 1.140 [0.019–1.274], P = .022, respectively). Older age (>80), cerebrovascular disease, and chronic kidney disease were risk factors of severe/critical. Fully vaccination was a significant protective factor against severe infections (0.237 [0.071–0.793], P = .019). We found patients with more than two comorbidities were more likely to get serious outcomes. These findings demonstrated that in the elderly older than 60 years old, older age (aged over 80), cerebrovascular disease, and chronic kidney disease were risk factors for severe infection. Patients with more than two comorbidities were more likely to get serious outcomes. Fully vaccinated/booster patients were less likely to be severe and vaccinations could shorten viral shedding time. The limitation of lacking an overall spectrum of COVID-19 infections among elders could be compensated in other larger-scale studies in the future.

The early and accurate diagnosis of tuberculosis (TB) is critical for controlling the global TB epidemic. Although early studies have supported the potential role of cytokine biomarkers in blood for the diagnosis of TB, this method requires further investigation and validation in different populations. A set of biomarkers that can discriminate between active TB (ATB) and latent TB infection (LTBI) remains elusive. In the current study, we organized two retrospective cohorts and one prospective cohort to investigate the immune responses at different clinical stages of TB infection, as determined by candidate cytokine biomarkers detected with a multiplex cytokine platform. Using a pre-established diagnostic algorithm, participants were classified as ATB, LTBI, and TB uninfected controls (CON). Based on our multiplex cytokine assay, a multi-cytokine biosignature was modelled for the optimal recognition of the different TB infection status. Our analysis identified a six-cytokine biosignature of TB-antigen stimulated IFN-γ, IP-10, and IL-1Ra, and unstimulated IP-10, VEGF, and IL-12 (p70) for a biomarker screening group (n = 88). The diagnostic performance of the biosignature was then validated using a biomarker validation cohort (n = 216) and resulted in a sensitivity of 88.2% and a specificity of 92.1%. In a prospectively recruited clinical validation cohort (n = 194), the six-cytokine biosignature was further evaluated, and displayed a sensitivity of 85.7%, a specificity of 91.3% and an overall accuracy of 88.7%. We have identified a six-cytokine biosignature for accurately differentiating ATB patients from subjects with LTBI and CON. This approach holds promise as an early and rapid diagnostic test for ATB.

When SARS-CoV-2 became regional epidemics, a substantial number of patients suffered from post-acute sequelae of COVID-19 (PASC, aka long COVID). Exploring the pathogenesis and especially the heterogenicity features of long COVID subgroups is of paramount importance for understanding its etiology. In this study, through integrative multi-omics analyses encompassing transcriptomics, proteomics, and metabolomics, long COVID patients exhibited overall elevated MAPK pathway activation, while patients who have recovered from long COVID showed down-regulation of this response. Long COVID heterogenicity is described by multi-omics distinct signatures for each subgroup. The Multisystemic (MULTI) symptom subgroup is characterized by enhanced glycerophospholipid and ether lipid metabolism, Neurological (NEU) by augmented glycoprotein synthesis metabolism, Cardio cerebral (CACRB) by increased pyruvate metabolism and suppressed macrophage polarization, Musculoskeletal + Systemic (MSK + SYST) by elevated glycerophospholipid metabolism, and Cardiopulmonary (CAPM) by inhibited NF-κB signaling pathways. ABHD17A, CSNK1D, PSME4 and SYVN1 were general long COVID combination biomarkers, while CRH (MULTI), FPGT (NEU), CBX6 (CACRB) and RBBP4 (CAPM) were selected as serum-specific subgroup proteins. Our study provides a commonly shared and distinct pathophysiological explanation underpinning PASC, paving the way for future diagnosis and therapeutic interventions.

Background: Klebsiella pneumoniae (K. pneumoniae) is one of the most common pathogens leading to pulmonary tuberculosis (PTB) co-infection, but the data of co-infections is scarce. This research aimed to study the clinical and microbiological characteristics of K. pneumoniae co-infections in pulmonary tuberculosis cases. Methods: Clinical manifestations and examination results of PTB cases co-infected by K. pneumoniae were retrospectively collected from the medical record database of a tertiary teaching hospital in China between November 2019 and October 2021. The K. pneumoniae strains isolated from the patients were sent for whole-genome sequencing. Statistical analyses were conducted using Stata v.14.0. Results: A total of 80 strains were collected from 76 PTB patients with K. pneumoniae co-infections (two strains were isolated from each of the four patients at different time points), including 37 primary and 39 retreated TB cases. Among these, 29 (36.3%) of the K. pneumoniae isolates were extended-spectrum β-lactamase (ESBL)-producing strains, and seven (8.8%) were determined as carbapenem-resistant Enterobacteriaceae (CRE) strains. We found that patients in the multidrug resistance (MDR)-group received more respiratory support than the non-MDR group (40.6% vs 18.2%, P= 0.031) and possessed higher elevated C-reactive protein (62.6% vs 41.8%, P=0.008) and lower haemoglobin (87.5% vs 47.7%, P=0.001). We found that 80.3% (61/76) patients had lung lesions and 57.8% (44/76) patients were immunocompromised within one month. The most common K. pneumoniae strain sequence type was ST23 (15%), followed by ST15 (12.5%) and ST273 (7.5%). Among the strains, 26.25% were classically hypervirulent K1/K2 K. pneumoniae, and all carried salmochelin and rmpA. Conclusion: This study demonstrated the important clinical features, phenotypic and genomic characteristics of isolated strains of PTB patients with K. pneumoniae co-infection. These data suggested a special attention for multidrug resistant K. pneumoniae infections with more obvious inflammatory responses which calls for more respiratory support and timely clinical management.

Several respiratory infections outbreaks have been observed in mainland China after reduction of non-pharmaceutical interventions. Other countries have seen increases in respiratory infections outside typical seasons post-COVID-19, warranting investigation into underlying causes. We established monitoring networks for suspected respiratory infection in 14 tertiary hospitals nationwide. PCR for SARS-CoV-2, influenza A and B were performed on 3708 respiratory specimens and deep sequencing were conducted to identify co-infections or newly emerging microbes in 2023. Viral evolutionary analysis was completed. We retrospectively detected serum antibody level for various respiratory pathogens from 4324 adults without respiratory infections over 7 years to observe its dynamic curves. SARS-CoV-2 and influenza A were the main pathogens during outbreaks in 2023, bacterial-virus and bacterial-bacterial co-infections were most detected, but community co-infections didn't significantly increase pneumonia incidence. Different SARS-CoV-2 and influenza variants were present in different outbreaks, and no novel pathogens were found. The epidemiological patterns of influenza A, COVID-19 and etc. were altered, exhibiting characteristics of being "staggered" compared to most global regions, and potentially led to "overlapping prevalence". Binding antibody testing showed regular fluctuation, without significant decrease against common respiratory pathogens in adults. Influenza A antibody stimulation was attenuated during the 2023 outbreak. "Misaligned" alteration in seasonal respiratory disease patterns possibly caused combined epidemics, leading to cases spike in China, 2023. In adults, antibody levels didn't show significant decline, but reduced immune response to influenza during 2020–2023 emphasizes the need for consistent vaccination during pandemics.

Background: When infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood. Methods: Forty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases. Results: We identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients. Conclusion: We reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.