BACKGROUND: The coronavirus disease 2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak throughout the world. The host immunity of COVID-19 patients is unknown. METHODS: The routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission. RESULTS: A total of 65 SARS-CoV-2–positive patients were classified as having mild ( n = 30), severe ( n = 20), and extremely severe ( n = 15) illness. Many routine laboratory tests, such as ferritin, lactate dehydrogenase, and D-dimer, were increased in severe and extremely severe patients. The absolute numbers of CD4 ⁺ T cells, CD8 ⁺ T cells, and B cells were gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4 ⁺ and CD8 ⁺ T cells were increased in severe and extremely severe patients compared with mild patients. The costimulatory molecule CD28 had opposite results. The percentage of natural Tregs was decreased in extremely severe patients. The percentage of IFN-γ–producing CD8 ⁺ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-γ–producing CD4 ⁺ T cells was increased in extremely severe patients. IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients. CONCLUSION: The number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4 ⁺ and CD8 ⁺ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection. FUNDING: This work was funded by the National Mega Project on Major Infectious Disease Prevention (2017ZX10103005-007) and the Fundamental Research Funds for the Central Universities (2019kfyRCPY098).

Objectives: This study aimed to determine the IgM and IgG responses against severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2 in coronavirus disease 2019 (COVID‐19) patients with varying illness severities.Methods: IgM and IgG antibody levels were assessed via chemiluminescence immunoassay in 338 COVID‐19 patients.Results: IgM levels increased during the first week after SARS‐CoV‐2 infection, peaked 2 weeks and then reduced to near‐background levels in most patients. IgG was detectable after 1 week and was maintained at a high level for a long period. The positive rates of IgM and/or IgG antibody detections were not significantly different among the mild, severe and critical disease groups. Severe and critical cases had higher IgM levels than mild cases, whereas the IgG level in critical cases was lower than those in both mild and severe cases. This might be because of the high disease activity and/or a compromised immune response in critical cases. The IgM antibody levels were slightly higher in deceased patients than recovered patients, but IgG levels in these groups did not significantly differ. A longitudinal detection of antibodies revealed that IgM levels decreased rapidly in recovered patients, whereas in deceased cases, either IgM levels remained high or both IgM and IgG were undetectable during the disease course.Conclusion: Quantitative detection of IgM and IgG antibodies against SARS‐CoV‐2 quantitatively has potential significance for evaluating the severity and prognosis of COVID‐19.

Dietary methionine interventions are beneficial to apoptosis-inducing chemotherapy and radiotherapy for cancer, while their effects on ferroptosis-targeting therapy and immunotherapy are unknown. Here we show the length of time methionine deprivation affects tumoral ferroptosis differently. Prolonged methionine deprivation prevents glutathione (GSH) depletion from exceeding the death threshold by blocking cation transport regulator homolog 1 (CHAC1) protein synthesis. Whereas, short-term methionine starvation accelerates ferroptosis by stimulating CHAC1 transcription. In vivo, dietary methionine with intermittent but not sustained deprivation augments tumoral ferroptosis. Intermittent methionine deprivation also sensitizes tumor cells against CD8⁺ T cell-mediated cytotoxicity and synergize checkpoint blockade therapy by CHAC1 upregulation. Clinically, tumor CHAC1 correlates with clinical benefits and improved survival in cancer patients treated with checkpoint blockades. Lastly, the triple combination of methionine intermittent deprivation, system x_c^- inhibitor and PD-1 blockade shows superior antitumor efficacy. Thus, intermittent methionine deprivation is a promising regimen to target ferroptosis and augment cancer immunotherapy.

Accurate monitoring of host immunity is hampered by the flaws of conventional tests. The relationship between lymphocyte number and function is unknown. The function of lymphocytes was analyzed based on IFN-γ secretion assay. Lymphocyte number and function was investigated in individuals under various states. The number of CD4+ and CD8+ T cells was gradually decreased, whereas the function of them was gradually increased with increasing age. A significantly negative correlation existed between the number and function of both CD4+ and CD8+ T cells. Differently, both the number and function of NK cells are maintained at a high level after birth. Staying up all night was found to impair the function of CD4+, CD8+ T cells, or NK cells. Lymphocyte number and function were both decreased in patients with immunosuppressive conditions or opportunistic infections, while the opposite phenomenon was observed in patients with some autoimmune diseases (except for NK cells). In kidney transplant recipients, the number and function of CD4+ and CD8+ T cells were increased or decreased when rejection or infection occurred. We demonstrated that evaluation of host immunity based on combination of lymphocyte number and function plays an important role in the diagnosis, treatment, and prognosis of diseases.