COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection. It is currently unknown as to the correlation between the magnitude of neutralizing antibody (NAb) responses and the disease severity in COVID-19 patients. In a cohort of 59 recovered patients with disease severity including severe, moderate, mild, and asymptomatic, we observed the positive correlation between serum neutralizing capacity and disease severity, in particular, the highest NAb capacity in sera from the patients with severe disease, while a lack of ability of asymptomatic patients to mount competent NAbs. Furthermore, the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-tomoderate symptoms. These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity, highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.

Background/Aims: Interleukin-29 (IL-29), a critical member of type III interferons (IFNs) family, has been implicated in protecting against viral infection and modulating autoimmune inflammation. Toll-like receptor 4 (TLR4) plays a crucial role in synovial inflammation and may contribute to the pathogenesis of rheumatology arthritis (RA). However, little is known about the modifying effect of IL-29 on TLR4-mediated inflammation in RA. We aim to investigate the potential association between IL-29 and TLR4 in RA. Methods: Peripheral blood mononuclear cells (PBMCs) and serum from 77 patients with RA and 70 controls were collected to determine levels of IL-29 and TLR4 mRNA by real-time polymerase chain reaction (PCR). Levels of IL-29 and TLR4 in synovial tissues and fluid from 25 RA patients and 24 controls were detected by enzyme-linked immunosorbent assay (ELISA) or western blot assay, respectively. RAW264.7 cells were stimulated by lipopolysaccharide (LPS) and/or IL-29. The production of inflammatory cytokines including IL-6, IL-8 as well as TNF-a and the activation of nuclear factor-κB (NF-κB) signaling were determined. Results: In comparison with controls, increased IL-29 was observed in PBMCs, synovial tissue, serum and synovial fluid of patients with RA. Besides, TLR4 was significantly elevated in PBMCs and synovium of RA patients. Moreover, IL-29 was positively associated with TLR4 in RA, suggested by Pearson's correlation analysis. When RAW264.7 cells were stimulated by LPS with or without IL-29 in vitro, IL-29 could enhance LPS-mediated TLR4 expression and the production of IL-6, IL-8 and TNF-a in RAW264.7 cells via the activation of NF-κB signaling. Conclusion: The present study suggests, for the first time, that IL-29 can aggravate LPS/TLR4-mediated inflammation in RA depending on NF-κB signaling activation.

Macrophages play a crucial role in the control and elimination of invading Mycobacterium tuberculosis (Mtb), and also serve as the major residence for Mtb. However, the interaction between macrophages and Mtb remains to be clearly determined. Although long noncoding RNAs (lncRNAs) have emerged as key regulators in many biological processes, their roles in anti-mycobacterial responses of macrophages remain to be elucidated. Here, we applied microarray analysis to examine lncRNA and mRNA expression profiles in human primary macrophages after 72 h of infection with H37Ra or H37Rv. Our results revealed that many lncRNAs were differentially expressed in macrophages after H37Ra or H37Rv infection, indicating a possible role for lncRNAs in immune responses induced by Mtb infection and providing important cues for further functional studies. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis of the differentially expressed mRNAs showed the potential functions and pathways related to the pathogenesis of Mtb infection. Finally, two lncRNAs, MIR3945HG V1 and MIR3945HG V2, were identified as novel candidate diagnostic markers for tuberculosis. Our results provide novel insight into the mechanisms of the pivotal Mtb-macrophage interactions, and reveal potential targets for diagnostics and the treatment of tuberculosis.

COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection. It is currently unknown as to the correlation between the magnitude of neutralizing antibody (NAb) responses and the disease severity in COVID-19 patients. In a cohort of 59 recovered patients with disease severity including severe, moderate, mild and asymptomatic, we observed the positive correlation between serum neutralizing capacity and disease severity, in particular, the highest NAb capacity in sera from the patients with severe disease, while a lack of ability of asymptomatic patients to mount competent NAbs. Furthermore, the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-to-moderate symptoms. These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity, highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.

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Background: The cellular form of the prion protein (PrPC) is implicated in Alzheimer disease as a receptor for amyloid-β (Aβ).Results: An assay was developed capable of identifying inhibitors of Aβ binding to PrPC.Conclusion: Chicago Sky Blue inhibits Aβ binding to PrPC.Significance: This is the first small molecule shown to disrupt the binding of Aβ to PrPC.