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Dynamic monitoring of immune function indexes in COVID-19 patients.

ABSTRACT: We conducted a retrospective analysis of the clinical characteristics and dynamic variations of immune indexes in nine COVID-19 patients in Zigong, China. We used flow cytometry and enzyme-linked immunosorbent assays to measure the absolute levels of CD4 and CD8 lymphocytes and SARS-CoV-2 antibodies, respectively. We found that CRP, LDH, HBDH, CD4/CD8 and IgE levels were increased in 6/9 patients, while PA and the absolute numbers of CD4 and CD8 lymphocytes decreased in 7/9 patients. From disease onset through 63 days of follow-up, SARS-CoV-2 IgG levels were consistently higher than those of SARS-CoV-2 IgM, reaching peaks on days 28 and 13, respectively. IgM levels decreased to normal 35 days after disease onset, while IgG levels remained elevated through day 63. IgE levels varied similarly to SARS-CoV-2 IgM. Our results suggest that SARS-CoV-2 may elicit allergic immune responses in patients and that the levels of CRP, PA, LDH, and HBDH, as well as the absolute numbers of CD4 and CD8 lymphocytes could be used as early diagnostic markers of SARS-CoV-2 infection. Lastly, the dynamic variation of SARS-CoV-2 antibodies could guide the timing of blood collection for plasma exchange.

SUBMITTER: Song Y

PROVIDER: S-EPMC7803549 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Dynamic monitoring of immune function indexes in COVID-19 patients.

Song Yaohui Y Zhong Huixiu H Li Lin L Yin Minggang M Yin Yi Y Guo Xiaolong X Zhang Bo B Liu Weiping W

Aging 20201223 24

We conducted a retrospective analysis of the clinical characteristics and dynamic variations of immune indexes in nine COVID-19 patients in Zigong, China. We used flow cytometry and enzyme-linked immunosorbent assays to measure the absolute levels of CD4 and CD8 lymphocytes and SARS-CoV-2 antibodies, respectively. We found that CRP, LDH, HBDH, CD4/CD8 and IgE levels were increased in 6/9 patients, while PA and the absolute numbers of CD4 and CD8 lymphocytes decreased in 7/9 patients. From diseas ...[more]

PMID: 33361525

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Project description:The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus' pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5' gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.

Project description:Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocytosis, sepsis or cytokine release syndrome, their exact nature remains unknown. This is severely impeding the ability to treat patients facing severe stages of the disease. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune signature of disease severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found monocyte and neutro-phil immune suppression loss associated with fatal clinical outcome in severe patients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allele, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of my-eloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis that supports secondary bacteria and virus infection and can progress to “immune silence” in patients facing death.

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Dynamic monitoring of immune function indexes in COVID-19 patients.

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Dynamic monitoring of immune function indexes in COVID-19 patients.

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