Prevalence of Non-SARS-CoV-2 Respiratory Pathogens and Co-Infection with SARS-CoV-2 in the Early Stage of COVID-19 Epidemic.

BACKGROUND: This study aims to reflect the prevalence of non-SARS-CoV-2 respiratory pathogens and co-infection with SARS-CoV-2 in the early stage of the COVID-19 epidemic, considering SARS-CoV-2 broke out during influenza season and its symptoms resemble those of influenza. METHODS: A total of 685 nucleic acid samples of respiratory pathogens were collected from 1 November 2019 to 20 January 2020 and were detected by the 13 Respiratory Pathogen Multiplex Detection Kit and Novel Coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit. RESULTS: In Wuhan, human rhinovirus was the most frequent infectious pathogen in November (31.5%) and human respiratory syncytial virus appeared the most in December and January (37.1%, 8.6%, respectively). Detection of SARS-CoV-2 first appeared from January 1 to January 10. Generally, 115 patients of 616 patients (18.7%) from Wuhan were infected with SARS-CoV-2, and only two children were co-infected with other respiratory pathogens. In Taiyuan, influenza A virus was detected most frequently in December and January (30.3%, 12%, respectively) without infection of SARS-CoV-2. CONCLUSIONS: Some cases diagnosed with influenza before routine nucleic acid testing of SARS-CoV-2 were attributed to COVID-19. Co-infection between SARS-CoV-2 and other non-SARS-CoV-2 respiratory pathogens existed in the early stage of COVID-19 epidemic.

Blockage of TIM-3 relieves lupus nephritis by expanding Treg cells and promoting their suppressive capacity in MRL/lpr mice.

T Cell Immunoglobulin and Mucin Containing Protein-3 (TIM-3) is an important immune checkpoint protein that is expressed in Tregs and affects their function. However, the expression and role of TIM-3 in modulating regulatory T cells (Tregs) in lupus nephritis (LN) are still unknown. In this study, we found that the percentage of TIM-3+ cells among spleen lymphocytes, CD4+ T cells and Tregs was higher in MRL/lpr mice than in MpJ mice. TIM-3high CD4+ T cells and TIM-3high Tregs were mainly responsible for the increase. The percentage of Tregs in TIM-3high CD4+ T cells was lower than that in TIM-3low CD4+ T cells, and the expression of CTLA-4 and IL-10 was lower in TIM-3high Tregs than in the TIM-3low Tregs in MRL/lpr mice. Blockade of TIM-3 in vivo significantly increased the Treg population and the expression of CTLA-4 and IL-10 in Tregs, thus relieving the LN symptoms and pathology in MRL/lpr mice. Additionally, bioinformatics analysis indicated that TIM-3 regulates Treg cells in LN mainly through cytokine-cytokine receptor interactions, the PI3K-Akt signaling pathway, the T cell receptor signaling pathway, Th17 cell differentiation and the FoxO signaling pathway. Together, our study has demonstrated that TIM-3 regulates Tregs in LN and that overexpression of TIM-3 in CD4+ T cells and Tregs leads to Treg quantity and quality deficiency in MRL/lpr mice. Blockade of TIM-3 protects against LN by expanding Tregs and enhancing their suppressive capacity. Finally, TIM-3 might be a potential therapeutic target for the treatment of LN.