[Application of immunosuppressive agents in crtical coronavirus disease].

The outbreak of novel coronavirus (SARS-CoV-2) infection has brought great harm to people's life and social development. Although SARS-CoV-2 infection is more common in mild patients at present, considering the characteristics of crtical disease, rapid progress and high mortality, the treatment of critical patients are the focus of clinical attention. Immune imbalance which is characterized by cytokine storm plays a vital role in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS), extrapulmonary multiple organ failure and even death. Therefore, the application of immunosuppressive agent in crtical coronavirus disease patients has a promising prospect. In this paper, different immunosuppressive agents and their application in crtical SARS-CoV-2 infection are reviewed, so as to provide reference for crtical coronavirus disease therapy.

The Role of Cellular Immunity in the Protective Efficacy of the SARS-CoV-2 Vaccines.

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been approved for clinical use. SARS-CoV-2 neutralizing antibody titers after immunization are widely used as an evaluation indicator, and the roles of cellular immune responses in the protective efficacy of vaccines are rarely mentioned. However, therapeutic monoclonal neutralizing antibodies have shown limited efficacy in improving the outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19), suggesting a passive role of cellular immunity in SARS-CoV-2 vaccines. The synergistic effect of virus-specific humoral and cellular immune responses helps the host to fight against viral infection. In fact, it has been observed that the early appearance of specific T-cell responses is strongly correlated with mild symptoms of COVID-19 patients and that individuals with pre-existing SARS-CoV-2 nonstructural-protein-specific T cells are more resistant to SARS-CoV-2 infection. These findings suggest the important contribution of the cellular immune response to the fight against SARS-CoV-2 infection and severe COVID-19. Nowadays, new SARS-CoV-2 variants that can escape from the neutralization of antibodies are rapidly increasing. However, the epitopes of these variants recognized by T cells are largely preserved. Paying more attention to cellular immune responses may provide new instructions for designing effective vaccines for the prevention of severe disease induced by the break-through infection of new variants and the sequelae caused by virus latency. In this review, we deliberate on the role of cellular immunity against COVID-19 and summarize recent advances in the development of SARS-CoV-2 vaccines and the immune responses induced by vaccines to improve the design of new vaccines and immunization strategies.

CD4+ T Cells Play a Critical Role in Microbiota-Maintained Anti-HBV Immunity in a Mouse Model.

The ability of the host to clear hepatitis B virus (HBV) is closely correlated to the establishment of commensal microbiota. However, how microbiota affects anti-HBV immunity is still unclear. Using a well-known hydrodynamical HBV transfection mouse model and treatment with antibiotics (Atb), we explored the change in adaptive immunity (CD4+ cells, germinal center B cells and anti-HBs Ab). In our setting, normal mice exhibited complete clearance of HBV within 6 weeks post-hydrodynamic injection (HDI) of HBV-containing plasmid, whereas Atb-treated mice lost this capacity, showing high serum level of hepatitis B surface antigen (HBsAg) without hepatitis B surface antibodies (anti-HBs), similar as what happened in Rag1-/- mice or CD4-/- mice, suggesting that microbiota may influence the function of CD4+ T cells. Furthermore, the numbers of splenic and hepatic effector CD4+ T cells (CD44hiCD62L-CD4+ T cells) both decreased with impaired function (IFN-γ synthesis), resulting in lower frequency of germinal center B cells and CD4+ follicular helper T cells, and impaired anti-HBs production. We further tried to find the bacterial species responsible for maintaining anti-HBV immunity, and found that each antibiotic alone could not significantly influence HBV clearance compared to antibiotic combination, suggesting that global commensal microbial load is critical for promoting HBV clearance. We also confirmed that TLRs (e.g., TLR2, 4, 9) are not major players in immune clearance of HBV using their agonists and knock-out mice. These results suggest that commensal microbiota play an important role in maintaining CD4+ T cell immunity against HBV infection.