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2.
Front Pharmacol ; 12: 730567, 2021.
Article in English | MEDLINE | ID: covidwho-1505033

ABSTRACT

Background and aims: Xuanfei Baidu decoction (XFBD), a traditional Chinese medicine formulation, was designed and successfully applied for COVID-19 disease treatment in China, while the mechanism is still not clear. Methods: To evaluate the protective effect of XFBD on immunosuppression in cyclophosphamide (CY)-treated mice, XFBD was orally administrated, the body weight was measured, and the immune organ index was calculated. HE staining was performed to analyze the pathological structures of the liver, spleen, and thymus. The levels of cytokines and immunoglobulin in the serum and spleen were evaluated by ELISA and RT-PCR. Splenic lymphocytes were isolated, and LPS-stimulated cell proliferation and the number of CD4+ and CD8+ T lymphocytes were evaluated. Results: XFBD significantly suppressed body weight loss and increased the indices of spleen and thymus. The pathological alteration was much improved after XFBD administration. The reductions of TNF-α, IFN-γ, IgG, and IgM levels in serum and IL-2, IL-4, and IL-6 expressions in the spleen were all significantly alleviated by XFBD. Splenic lymphocyte proliferation in response to LPS was further enhanced after treatment with XFBD. The reduction of CD4+ and CD8+ T lymphocytes in CY-treated mice was also highly increased in XFBD groups. Conclusion: Our findings suggested that XFBD played a crucial role in protection against immunosuppression in CY-treated mice and could be a potential candidate for immune modification and therapy.

3.
Engineering (Beijing) ; 2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1487711

ABSTRACT

Traditional Chinese medicine (TCM) has been successfully applied worldwide in the treatment of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacological mechanisms underlying this success remain unclear. Hence, the aim of this review is to combine pharmacological assays based on the theory of TCM in order to elucidate the potential signaling pathways, targets, active compounds, and formulas of herbs that are involved in the TCM treatment of COVID-19, which exhibits combatting viral infections, immune regulation, and amelioration of lung injury and fibrosis. Extensive reports on target screening are elucidated using virtual prediction via docking analysis or network pharmacology based on existing data. The results of these reports indicate that an intricate regulatory mechanism is involved in the pathogenesis of COVID-19. Therefore, more pharmacological research on the natural herbs used in TCM should be conducted in order to determine the association between TCM and COVID-19 and account for the observed therapeutic effects of TCM against COVID-19.

4.
Signal Transduct Target Ther ; 6(1): 195, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1232065

ABSTRACT

B cell response plays a critical role against SARS-CoV-2 infection. However, little is known about the diversity and frequency of the paired SARS-CoV-2 antigen-specific BCR repertoire after SARS-CoV-2 infection. Here, we performed single-cell RNA sequencing and VDJ sequencing using the memory and plasma B cells isolated from five convalescent COVID-19 patients, and analyzed the spectrum and transcriptional heterogeneity of antibody immune responses. Via linking BCR to antigen specificity through sequencing (LIBRA-seq), we identified a distinct activated memory B cell subgroup (CD11chigh CD95high) had a higher proportion of SARS-CoV-2 antigen-labeled cells compared with memory B cells. Our results revealed the diversity of paired BCR repertoire and the non-stochastic pairing of SARS-CoV-2 antigen-specific immunoglobulin heavy and light chains after SARS-CoV-2 infection. The public antibody clonotypes were shared by distinct convalescent individuals. Moreover, several antibodies isolated by LIBRA-seq showed high binding affinity against SARS-CoV-2 receptor-binding domain (RBD) or nucleoprotein (NP) via ELISA assay. Two RBD-reactive antibodies C14646P3S and C2767P3S isolated by LIBRA-seq exhibited high neutralizing activities against both pseudotyped and authentic SARS-CoV-2 viruses in vitro. Our study provides fundamental insights into B cell response following SARS-CoV-2 infection at the single-cell level.


Subject(s)
B-Lymphocytes/immunology , COVID-19/immunology , Convalescence , Immunologic Memory , RNA-Seq , SARS-CoV-2/immunology , Animals , B-Lymphocytes/pathology , COVID-19/genetics , COVID-19/pathology , Cell Line, Tumor , Cell Separation , Chlorocebus aethiops , HEK293 Cells , Humans , SARS-CoV-2/genetics , Vero Cells
5.
J Mol Cell Biol ; 13(3): 197-209, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1145182

ABSTRACT

Although millions of patients have clinically recovered from COVID-19, little is known about the immune status of lymphocytes in these individuals. In this study, the peripheral blood mononuclear cells of a clinically recovered (CR) cohort were comparatively analyzed with those of an age- and sex-matched healthy donor cohort. We found that CD8+ T cells in the CR cohort had higher numbers of effector T cells and effector memory T cells but lower Tc1 (IFN-γ+), Tc2 (IL-4+), and Tc17 (IL-17A+) cell frequencies. The CD4+ T cells of the CR cohort were decreased in frequency, especially the central memory T cell subset. Moreover, CD4+ T cells in the CR cohort showed lower programmed cell death protein 1 (PD-1) expression and had lower frequencies of Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17A+), and circulating follicular helper T (CXCR5+PD-1+) cells. Accordingly, the proportion of isotype-switched memory B cells (IgM-CD20hi) among B cells in the CR cohort showed a significantly lower proportion, although the level of the activation marker CD71 was elevated. For CD3-HLA-DR- lymphocytes in the CR cohort, in addition to lower levels of IFN-γ, granzyme B and T-bet, the correlation between T-bet and IFN-γ was not observed. Additionally, by taking into account the number of days after discharge, all the phenotypes associated with reduced function did not show a tendency toward recovery within 4‒11 weeks. The remarkable phenotypic alterations in lymphocytes in the CR cohort suggest that  severe acute respiratory syndrome coronavirus 2 infection profoundly affects lymphocytes and potentially results in dysfunction even after clinical recovery.


Subject(s)
CD8-Positive T-Lymphocytes/virology , COVID-19/blood , Leukocytes, Mononuclear/virology , SARS-CoV-2/pathogenicity , Adult , Aged , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Cell Lineage/genetics , Cell Lineage/immunology , Female , Gene Expression Regulation/immunology , Granzymes/genetics , Humans , Interferon-gamma/genetics , Leukocytes, Mononuclear/pathology , Male , Middle Aged , T-Box Domain Proteins/genetics , Th1 Cells/immunology , Th1 Cells/virology , Th17 Cells/immunology , Th17 Cells/virology , Th2 Cells/immunology , Th2 Cells/virology
6.
Clin Transl Immunology ; 10(3): e1259, 2021.
Article in English | MEDLINE | ID: covidwho-1120286

ABSTRACT

OBJECTIVE: SARS-CoV-2 has caused a worldwide pandemic of COVID-19. The existence of prolonged SARS-CoV-2 positivity (PP) has further increased the burden on the health system. Since T cells are vital for viral control, we aimed to evaluate the characteristics of T-cell responses associated with PP. METHODS: We established a PP cohort and two age- and sex-matched control cohorts: a regular clinical recovery (CR) cohort and a healthy donor (HD) cohort. The mean time for RNA negativity conversion in the PP cohort was markedly longer than that in the CR cohort (66.2 vs 25.3 days), while the time from illness onset to sampling was not significantly different. T-cell responses in the PP cohort were assayed, analysed and compared with those in the CR and HD cohorts by flow cytometry and ELISpot analysis of peripheral blood mononuclear cells. RESULTS: Compared with the CR cohort, the proliferation, activation and functional potential of CD8+ and CD4+ T cells in the PP cohort were not significantly different. However, the frequencies and counts of Teff and Tem in CD8+ but not in CD4+ T cells of the PP cohort were prominently lower. Moreover, a weaker SARS-CoV-2 N protein-specific IFN-γ+ T-cell response and a higher frequency of Tregs were detected in the PP cohort. CONCLUSION: Suppressed CD8+ T-cell differentiation is associated with PP and may be an indicator for the prediction of prolonged SARS-CoV-2 positivity in COVID-19 patients. The association between suppressed CD8+ T-cell differentiation and elevated Tregs warrants studies in the future.

7.
Virol Sin ; 36(5): 859-868, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1070952

ABSTRACT

The COVID-19 pandemic, caused by the SARS-CoV-2 infection, is a global health crisis. While many patients have clinically recovered, little is known about long-term alterations in T cell responses of COVID-19 convalescents. In this study, T cell responses in peripheral blood mononuclear cells of a long-time COVID-19 clinically recovered (20-26 weeks) cohort (LCR) were measured via flow cytometry and ELISpot. The T cell responses of LCR were comparatively analyzed against an age and sex matched short-time clinically recovered (4-9 weeks) cohort (SCR) and a healthy donor cohort (HD). All volunteers were recruited from Wuhan Jinyintan Hospital, China. Phenotypic analysis showed that activation marker PD-1 expressing on CD4+ T cells of LCR was still significantly lower than that of HD. Functional analysis indicated that frequencies of Tc2, Th2 and Th17 in LCR were comparable to those of HD, but Tc17 was higher than that of HD. In LCR, compared to the HD, there were fewer IFN-γ producing T cells but more IL-2 secreting T cells. In addition, the circulating Tfh cells in LCR were still slightly lower compared to HD, though the subsets composition had recovered. Remarkably, SARS-CoV-2 specific T cell responses in LCR were comparable to that of SCR. Collectively, T cell responses experienced long-term alterations in phenotype and functional potential of LCR cohort. However, after clinical recovery, SARS-CoV-2 specific T cell responses could be sustained at least for six months, which may be helpful in resisting re-infection.


Subject(s)
COVID-19 , Cohort Studies , Humans , Leukocytes, Mononuclear , Pandemics , Phenotype , SARS-CoV-2
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