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PurposeLong COVID, also known as post-acute sequelae of COVID-19, refers to the constellation of long-term symptoms experienced by people suffering persistent symptoms for one or more months after SARS-CoV-2 infection. Blood biomarkers can be altered in long COVID patients; however, biomarkers associated with long COVID symptoms and their roles in disease progression remain undetermined. This study aims to systematically evaluate blood biomarkers that may act as indicators or therapeutic targets for long COVID.MethodsA systematic literature review in PubMed, Embase, and CINAHL was performed on 18 August 2022. The search keywords long COVID-19 symptoms and biomarkers were used to filter out the eligible studies, which were then carefully evaluated.ResultsIdentified from 28 studies and representing six biological classifications, 113 biomarkers were significantly associated with long COVID: (1) Cytokine/Chemokine (38, 33.6%); (2) Biochemical markers (24, 21.2%); (3) Vascular markers (20, 17.7%); (4) Neurological markers (6, 5.3%); (5) Acute phase protein (5, 4.4%); and (6) Others (20, 17.7%). Compared with healthy control or recovered patients without long COVID symptoms, 79 biomarkers were increased, 29 were decreased, and 5 required further determination in the long COVID patients. Of these, up-regulated Interleukin 6, C-reactive protein, and tumor necrosis factor alpha might serve as the potential diagnostic biomarkers for long COVID. Moreover, long COVID patients with neurological symptoms exhibited higher levels of neurofilament light chain and glial fibrillary acidic protein whereas those with pulmonary symptoms exhibited a higher level of transforming growth factor beta.ConclusionLong COVID patients present elevated inflammatory biomarkers after initial infection. Our study found significant associations between specific biomarkers and long COVID symptoms. Further investigations are warranted to identify a core set of blood biomarkers that can be used to diagnose and manage long COVID patients in clinical practice.

Background: Unclear pathogenesis existed for nasopharyngeal carcinoma. Aims: to analyze the role of bile acids in the pathogenesis of nasopharyngeal carcinoma. Methods: 20 healthy volunteers and 20 patients with nasopharyngeal carcinoma were enrolled between January 1

Triple-negative breast cancer (TNBC) is the most aggressive and challenging breast cancer subtype, which does not respond to traditional endocrine and anti-HER2-targeted therapies. PD-L1 is highly enriched in TNBC and has been considered a therapeutic target. Despite the excellent anti-cancer activity, the atezolizumab-based chimeric antigen receptor (CAR) T cells showed a robust off-target effect. In addition, the treatment of solid tumors with CAR-T is limited by abnormal glycosylation in malignant tumors. Targeting glycosylated PD-L1 (gPD-L1) provided tissue specificity against TNBC, implying it can prevent antigen escape and off-target effect. In this study, we generated gPD-L1 CAR-T cells using lentiviral vectors expressing the scFv regions of the anti-gPD-L1 antibody. The gPD-L1 CAR-T cells exhibited antigen-specific activation, cytokine production, and cytolytic activity against TNBCs in vitro and in the xenograft tumors model. CyTOF and single-cell RNA sequencing (scRNA-seq) showed distinct IFNγ-positive cell types. Mechanistically, IFNγ crosstalked with EGFR signaling through Src activation and, in turn, triggered B3GNT3-mediated PD-L1 glycosylation. Inhibition of Src resulted in reduced gPD-L1 expression in TNBC. CRISPR/Cas9 knockout of B3GNT3 in TNBC cells impaired gPD-L1 CAR-T response. As a result of nonautonomous gPDL1 amplification in TNBCs, gPD-L1 CAR-T cells continued to annihilate TNBCs. Additionally, since gPD-L1 CAR-T cells provided higher specificity on TNBC, they had lower normal tissue toxicity. Overall, gPD-L1 CAR-T exhibits excellent anti-tumor activity against TNBCs, and it could be a promising immunotherapy tool to treat TNBCs in clinic. Furthermore, targeting glycosylation moiety on the tumor antigen is a novel approach to lessen CAR-T toxicity in patients. Citation Format: Chia-Wei Li, Shih-Han Wang, Yun-Ju Lai, Jyun Wang, Chun-Tse Kuo, Shih-Duo Hsu Hung, Shou-Hou Liu. Non-autonomous enhancement of gPDL1 CAR-T annihilates TNBC development. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4106.