CD8+ T-Cell Epitope Variations Suggest a Potential Antigen HLA-A2 Binding Deficiency for Spike Protein of SARS-CoV-2.

We identified SARS-CoV-2 specific antigen epitopes by HLA-A2 binding affinity analysis and characterized their ability to activate T cells. As the pandemic continues, variations in SARS-CoV-2 virus strains have been found in many countries. In this study, we directly assess the immune response to SARS-CoV-2 epitope variants. We first predicted potential HLA-A*02:01-restricted CD8+ T-cell epitopes of SARS-CoV-2. Using the T2 cell model, HLA-A*02:01-restricted T-cell epitopes were screened for their binding affinity and ability to activate T cells. Subsequently, we examined the identified epitope variations and analyzed their impact on immune response. Here, we identified specific HLA-A2-restricted T-cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides were confirmed to bind with HLA-A*02:01 and potentially be presented by antigen-presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8+ T cells from convalescent COVID-19 patients, and one dominant epitope (n-Sp1) was defined. These epitopes could activate and generate epitope-specific T cells in vitro, and those activated T cells showed cytolytic activity toward target cells. Meanwhile, n-Sp1 epitope variant 5L>F significantly decreased the proportion of specific T-cell activation; n-Sp1 epitope 8L>V variant showed significantly reduced binding to HLA-A*02:01 and decreased proportion of n-Sp1-specific CD8+ T cell, which potentially contributes to the immune escape of SARS-CoV-2. Our data indicate that the variation of a dominant epitope will cause the deficiency of HLA-A*02:01 binding and T-cell activation, which subsequently requires the formation of a new CD8+ T-cell immune response in COVID-19 patients.

Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors - CX3CR1 and L-selectin - were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.

Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia.

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

Psychological impact in non-infectious disease specialists who had direct contact with patients with COVID-19

Background: The coronavirus disease 2019 (COVID-19) outbreak has become a pandemic. Obstetricians and midwives, among other medical staff, are tackling COVID-19 and are under immense psychological stress. Aims We aimed to survey the mental health of non-infectious disease specialist staff, specifically obstetricians and midwives, working in officially designated hospitals treating patients with COVID-19. Method: A nationwide online survey was conducted from 7 March to 17 March 2020 investigating the mental health of obstetricians and midwives (who were not themselves infected with COVID-19) working in hospitals treating patients with COVID-19. We used the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder (GAD-7) scale and the 7-item Insomnia Severity Index (ISI) to assess their symptoms of depression, anxiety and insomnia. Results: A total of 885 (41.6%), 609 (28.6%) and 729 (34.3%) obstetricians and midwives reported depression (PHQ-9 >= 5), anxiety (GAD-7 >= 5) and insomnia (ISI >= 8), respectively, during the COVID-19 pandemic. Regardless of whether or not they had direct contact with patients with COVID-19, obstetricians and midwives were more likely to report mild and moderate depression and anxiety during the COVID-19 pandemic when compared with before the pandemic. Those who had direct contact with patients with COVID-19 were more likely to report depression and insomnia than those who did not. Those who had sufficient protective equipment or training were less likely to report depression, anxiety and insomnia than those who did not. Conclusions: Our data suggest that non-infectious disease specialist staff have experienced varying, but increased levels of depression, anxiety and insomnia during this COVID-19 pandemic, which could be reduced by sufficient levels of protective equipment and occupational COVID-19 workplace training. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Psychological impact in non-infectious disease specialists who had direct contact with patients with COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has become a pandemic. Obstetricians and midwives, among other medical staff, are tackling COVID-19 and are under immense psychological stress. AIMS: We aimed to survey the mental health of non-infectious disease specialist staff, specifically obstetricians and midwives, working in officially designated hospitals treating patients with COVID-19. METHOD: A nationwide online survey was conducted from 7 March to 17 March 2020 investigating the mental health of obstetricians and midwives (who were not themselves infected with COVID-19) working in hospitals treating patients with COVID-19. We used the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder (GAD-7) scale and the 7-item Insomnia Severity Index (ISI) to assess their symptoms of depression, anxiety and insomnia. RESULTS: A total of 885 (41.6%), 609 (28.6%) and 729 (34.3%) obstetricians and midwives reported depression (PHQ-9 ≥ 5), anxiety (GAD-7 ≥ 5) and insomnia (ISI ≥ 8), respectively, during the COVID-19 pandemic. Regardless of whether or not they had direct contact with patients with COVID-19, obstetricians and midwives were more likely to report mild and moderate depression and anxiety during the COVID-19 pandemic when compared with before the pandemic. Those who had direct contact with patients with COVID-19 were more likely to report depression and insomnia than those who did not. Those who had sufficient protective equipment or training were less likely to report depression, anxiety and insomnia than those who did not. CONCLUSIONS: Our data suggest that non-infectious disease specialist staff have experienced varying, but increased levels of depression, anxiety and insomnia during this COVID-19 pandemic, which could be reduced by sufficient levels of protective equipment and occupational COVID-19 workplace training.

A Comprehensive Summary of the Knowledge on COVID-19 Treatment.

Currently, the world is challenged by the coronavirus disease 2019 (COVID-19) pandemic. Epidemiologists and researchers worldwide are invariably trying to understand and combat this precarious new disease. Scrutinizing available drug options and developing potential new drugs are urgent needs to subdue this pandemic. Several intervention strategies are being considered and handled worldwide with limited success, and many drug candidates are yet in the trial phase. Despite these limitations, the development of COVID-19 treatment strategies has been accelerated to improve the clinical outcome of patients with COVID-19, and some countries have efficiently kept it under control. Recently, the use of natural and traditional medicine has also set the trend in coronavirus treatment. This review aimed to discuss the prevailing COVID-19 treatment strategies available globally by examining their efficacy, potential mechanisms, limitations, and challenges in predicting a future potential treatment candidate and bridging them with the effective traditional Chinese medicine (TCM). The findings might enrich the knowledge on traditional alternative medication and its complementary role with Western medicine in managing the COVID-19 epidemic.