To confirm the relationship between sex and the progression of Coronavirus Disease-19 (COVID-19), and its potential mechanism, among severe patients. For this retrospective study, we included 168 consecutive severe patients with pathogen-confirmed COVID-19 who were hospitalized between January 16th and February 4th, 2020, at Tongji Hospital in Wuhan, China. Clinical characteristics, laboratory parameters, and outcomes were compared and analyzed between males and females. In the present study, we analyzed 168 severe patients with COVID-19, including 86 males and 82 females, and 48 patients (28.6%) were diagnosed as critically ill. Of 86 male patients, 12.8% (11/86) died and 75.6% (65/86) were discharged; of 82 female patients, 7.3% (6/82) died and 86.6% (71/82) were discharged. Eleven laboratory parameters showed significant differences between male and female patients, and six of them were higher during the whole clinical course in patients who died than in patients who were discharged. In adjusted logistic regression analysis, males with comorbidities presented a higher risk of being critically ill than males without comorbidities (OR = 3.824, 95% CI = 1.279–11.435). However, this association attenuated to null in female patients (OR = 2.992, 95% CI = 0.937–9.558). A similar sex-specific trend was observed in the relation between age and critically ill conditions. We highlighted sex-specific differences in clinical characteristics and prognosis. Male patients appeared to be more susceptible to age and comorbidities. Sex is an important biological variable that should be considered in the prevention and treatment of COVID-19. Overall, our results highlight sex-specific differences in clinical characteristics and prognosis to COVID-19, which are consistent with the sex-bias observed in other COVID-19 related studies. We also provided more evidence and explored the underlying mechanism with epidemiological analysis. Six candidate laboratory indicators with significant sex differences were considered as potential mediators affecting the prognosis of COVID-19. The age-specific risk distributions of COVID-19 showed a positive correlation between the prognosis and age/ comorbidities, which was significantly affected by sex. We also emphasize that sex is a biological variable that should be considered in the prevention and therapy of COVID-19. It is our hope that these methods may serve as a guide to the clinician in providing timely and specific therapy. Obviously, future studies are warranted to elucidate the different pathways and cellular responses between women and men. The key challenge is how best to use this disparity for providing adequate protection in both males and females.

Relapse following chemeric antigen receptor (CAR) T-cell therapy can arise from progressive loss of the CAR T cells or from loss of the target antigen by tumor cells. Wang et al report that using a mix of CAR T cells targeting CD19 and CD22 reduces relapse with antigen-negative tumor cells. However, a lack of CAR T-cell persistence leads to increased relapse with antigen-positive cells.

Chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) have great potentials in autoimmune diseases and could be novel therapeutics for relapsed/refractory neuromyelitis optica spectrum disorder (NMOSD). To evaluate the safety and efficacy of the CT103A, a self-developed BCMA-targeting CAR construct against BCMA, in patients with AQP4-IgG seropositive NMOSD, an ongoing, investigator-initiated, open-label, single-arm, phase 1 clinical trial is conducted at our center. In total, 12 patients were administered with a CAR-BCMA infusion. Ten of the 12 patients dosed were women (83.3%), with a median age of 49.5 years (range, 30–67). were The most common events of grade 3 or higher were hematologic toxic effects. Seven patients (58%) developed infections, but no grade 4 infections occurred. Cytokine release syndrome was reported in all patients with only events of grade 1 or 2 observed. During the follow-up of a median 5.5 months, 11 patients had no relapse; all patients generally reported improvement in disabilities and quality-of-life outcomes; 11 patients’ AQP-4 antibodies in serum showed a downward trend by the cutoff date. CAR T-cell expansion was associated with responses, and persisted more than 6 months post-infusion in 17% of the patients. In summary, CAR T-cell therapy shows a manageable safety profile and therapeutic potentials for patients with relapsed/refractory AQP4-IgG seropositive NMOSD. Another expansion phase is currently underway to determine the safety and efficacy of CAR T-BCMA infusion in patients with other neuro-inflammatory diseases.

Chimeric antigen receptor T (CAR-T) cell therapy has shown promise in treating hematological malignancies and certain solid tumors. However, its efficacy is often hindered by negative relapses resulting from antigen escape. This review firstly elucidates the mechanisms underlying antigen escape during CAR-T cell therapy, including the enrichment of pre-existing target-negative tumor clones, antigen gene mutations or alternative splicing, deficits in antigen processing, antigen redistribution, lineage switch, epitope masking, and trogocytosis-mediated antigen loss. Furthermore, we summarize various strategies to overcome antigen escape, evaluate their advantages and limitations, and propose future research directions. Thus, we aim to provide valuable insights to enhance the effectiveness of CAR-T cell therapy.