Immunogenicity profiling and distinct immune response in liver transplant recipients vaccinated with SARS-CoV-2 inactivated vaccines.

SARS-CoV-2 vaccination has been recommended for liver transplant (LT) recipients. However, our understanding of inactivated vaccine stimulation of the immune system in regulating humoral and cellular immunity among LT recipients is inadequate. Forty-six LT recipients who received two-dose inactivated vaccines according to the national vaccination schedule were enrolled. The clinical characteristics, antibody responses, single-cell peripheral immune profiling, and plasma cytokine/chemokine/growth factor levels were recorded. Sixteen (34.78%) LT recipients with positive neutralizing antibody (nAb) were present in the Type 1 group. Fourteen and 16 LT recipients with undetected nAb were present in the Type 2 and Type 3 groups, respectively. Time from transplant and lymphocyte count were different among the three groups. The levels of anti-RBD and anti-S1S2 decreased with decreasing neutralizing inhibition rates. Compared to the Type 2 and Type 3 groups, the Type 1 group had an enhanced innate immune response. The proportions of B, DNT, and CD3+CD19+ cells were increased in the Type 1 group, whereas monocytes and CD4+ T cells were decreased. High CD19, high CD8+CD45RA+ cells, and low effector memory CD4+/naïve CD4+ cells of the T-cell populations were present in the Type 1 group. The Type 1 group had higher concentrations of plasma CXCL10, MIP-1 beta, and TNF-alpha. No severe adverse events were reported in all LT recipients. We identified the immune responses induced by inactivated vaccines among LT recipients and provided insights into the identification of immunotypes associated with the responders.

Immunogenicity profiling and distinct immune response in liver transplant recipients vaccinated with SARS-CoV-2 inactivated vaccines

SARS-CoV-2 vaccination has been recommended for liver transplant (LT) recipients. However, our understanding of inactivated vaccine stimulation of the immune system in regulating humoral and cellular immunity among LT recipients is inadequate. Forty-six LT recipients who received two-dose inactivated vaccines according to the national vaccination schedule were enrolled. The clinical characteristics, antibody responses, single-cell peripheral immune profiling, and plasma cytokine/chemokine/growth factor levels were recorded. Sixteen (34.78%) LT recipients with positive neutralizing antibody (nAb) were present in the Type 1 group. Fourteen and 16 LT recipients with undetected nAb were present in the Type 2 and Type 3 groups, respectively. Time from transplant and lymphocyte count were different among the three groups. The levels of anti-RBD and anti-S1S2 decreased with decreasing neutralizing inhibition rates. Compared to the Type 2 and Type 3 groups, the Type 1 group had an enhanced innate immune response. The proportions of B, DNT, and CD3+CD19+ cells were increased in the Type 1 group, whereas monocytes and CD4+ T cells were decreased. High CD19, high CD8+CD45RA+ cells, and low effector memory CD4+/naïve CD4+ cells of the T-cell populations were present in the Type 1 group. The Type 1 group had higher concentrations of plasma CXCL10, MIP-1 beta, and TNF-alpha. No severe adverse events were reported in all LT recipients. We identified the immune responses induced by inactivated vaccines among LT recipients and provided insights into the identification of immunotypes associated with the responders.

Immune responses and pathogenesis in persistently PCR-positive patients with SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 emerged in China in December 2019 and then rapidly spread worldwide. Why COVID-19 patients with the same clinical condition have different outcomes remains unclear. This study aimed to examine the differences in the phenotype and functions of major populations of immune cells between COVID-19 patients with same severity but different outcomes. Four common type adult inpatients with laboratory confirmed COVID-19 from Beijing YouAn Hospital, Capital Medical University were included in this study. The patients were divided into two groups based on whether or not COVID-19 polymerase chain reaction (PCR)-negative conversion occurred within 3 weeks. Peripheral blood samples were collected to compare the differences in the phenotype and functions of major populations of immune cells between the two groups of patients. The result shows that the proportions of CD3+ CD8+ CD38+ HLA-DR+ CD27- effector T killer cells generally declined, whereas that of CD3+ CD4+ CD8+ double-positive T cells (DPTs) increased in the persistently PCR-positive patients. In summary, considering the imbalance between effector T killer cells/CD3+CD4+CD8+ DPTs was a possible key factor for PCR-negative conversion in patients with COVID-19.

Downregulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in Patients With COVID-19.

BACKGROUND: The World Health Organization characterizes novel coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a pandemic. Here, we investigated the clinical, cytokine levels; T-cell proportion; and related gene expression occurring in patients with COVID-19 on admission and after initial treatment. METHODS: Eleven patients diagnosed with COVID-19 with similar initial treatment regimens were enrolled in the hospital. Plasma cytokine, peripheral T cell proportions, and microfluidic quantitative polymerase chain reaction analyses for gene expression were conducted. RESULTS: Five patients with mild and 6 with severe disease were included. Cough and fever were the primary symptoms in the 11 COVID-19 cases. Older age, higher neutrophil count, and higher C-reactive protein levels were found in severe cases. IL-10 level significantly varied with disease progression and treatment. Decreased T-cell proportions were observed in patients with COVID-19, especially in severe cases, and all were returned to normal in patients with mild disease after initial treatment, but only CD4+ T cells returned to normal in severe cases. The number of differentially expressed genes (DEGs) increased with the disease progression, and decreased after initial treatment. All downregulated DEGs in severe cases mainly involved Th17-cell differentiation, cytokine-mediated signaling pathways, and T-cell activation. After initial treatment in severe cases, MAP2K7 and SOS1 were upregulated relative to that on admission. CONCLUSIONS: Our findings show that a decreased T-cell proportion with downregulated gene expression related to T-cell activation and differentiation occurred in patients with severe COVID-19, which may help to provide effective treatment strategies for COVID-19.

Dysregulation of the immune response affects the outcome of critical COVID-19 patients.

Critical cases of coronavirus disease 2019 (COVID-19) are associated with a high risk of mortality. It remains unclear why patients with the same critical condition have different outcomes. We aimed to explore relevant factors that may affect the prognosis of critical COVID-19 patients. Six critical COVID-19 inpatients were included in our study. The six patients were divided into two groups based on whether they had a good or poor prognosis. We collected peripheral blood samples at admission and the time point of exacerbation to compare differences in the phenotypes and functions of major populations of immune cells between the groups. On admission, compared to patients with poor prognoses, those with good prognoses had significantly higher counts of monocytes (P < .05), macrophages (P < .05), higher frequency of CD3+ CD4+ CD45RO+ CXCR3+ subsets (P < .05), higher frequency of CD14+ CD11C+ HLA-DR+ subset of dendritic cells (P < .05), and a lower count of neutrophils (P < .05). At the time point of exacerbation, the proportions of naïve CD4+ T cells (P < .05), Tregs, and Th2 cells in the poor prognosis group were relatively higher than those in the good prognosis group, and CD4+ memory T cells were relatively lower (P < .05). According to our results, the poor prognosis group showed a worse immune response than the good prognosis group at the time of admission and at exacerbation. Dysregulation of the immune response affects the outcome of critical COVID-19 patients.

Preliminary Exploration of the Cause of Liver Disorders During Early Stages in COVID-19 Patients.

Background: Abnormal liver function is a common indication of coronavirus disease 2019 (COVID-19) patients. Two proposed mechanisms are liver injury mediated by angiotensin-converting enzyme 2 (ACE2) and the involvement of the systemic immune response. We investigated the role played by these to determine the cause of liver abnormality in the early stages of COVID-19. Methods: A cross-sectional study was conducted among confirmed cases of COVID-19 at Beijing Youan Hospital from January 21, 2020, to February 24, 2020. We compared clinical characteristics, viremia status, and cytokine profile on admission between patients with and without liver disorder. Results: Of the 44 COVID-19 patients analyzed, there were no differences in the clinical symptoms and signs, disease severity, or computed tomography (CT) image features between the two groups. Lymphopenia was more common in the liver disorder group. Further, C-reactive protein levels were much higher in the hepatic disorder group, with significantly higher concentrations of IL-6, IL-10, and M-CSF. Viremia was detected in only 7% of patients. Conclusions: Due to the infrequency of viremia, ACE2-mediated viral hepatitis does not seem to account for the commonly observed liver disorders in COVID-19 patients. By contrast, a dysregulated immune response may be a crucial pathogenic factor for liver disorder in the early stages of COVID-19.

The inhibition of IL-2/IL-2R gives rise to CD8+ T cell and lymphocyte decrease through JAK1-STAT5 in critical patients with COVID-19 pneumonia.

Although most patients with COVID-19 pneumonia have a good prognosis, some patients develop to severe or critical illness, and the mortality of critical cases is up to 61.5%. However, specific molecular information about immune response in critical patients with COVID-19 is poorly understood. A total of 54 patients were enrolled and divided into three groups, among which 34 were common, 14 were severe, and 6 were critical. The constitution of peripheral blood mononuclear cells (PBMC) in patients was analyzed by CyTOF. The profile of cytokines was examined in plasma of patients using luminex. The IL-2 signaling pathway was investigated in the PBMC of patients by qRT-PCR. The count and percentage of lymphocytes were significantly decreased in critical patients compared to common and severe patients with COVID-19 pneumonia. The count of T cells, B cells, and NK cells was remarkably decreased in critical patients compared to normal controls. The percentage of CD8+ T cells was significantly lower in critical patients than that in common and severe patients with COVID-19 pneumonia. The expression of IL-2R, JAK1, and STAT5 decreased in PBMC of common, severe, and critical patients, but IL-2 level was elevated in severe patients and decreased in critical patients with COVID-19 pneumonia. The decrease of CD8+ T cells in critical patients with COVID-19 pneumonia may be related to the IL-2 signaling pathway. The inhibition of IL-2/IL-2R gives rise to CD8+ T cell and lymphocyte decrease through JAK1-STAT5 in critical patients with COVID-19 pneumonia.