Identification of cross-reactive CD8+ T cell receptors with high functional avidity to a SARS-CoV-2 immunodominant epitope and its natural mutant variants.

Despite the growing knowledge of T cell responses in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Here, with a predicted peptide library from SARS-CoV-2 S and N proteins, we found that specific CD8+ T cell responses were identified in over 75% of COVID-19 convalescent patients (15/20) and an epitope from the N protein, N361-369 (KTFPPTEPK), was the most dominant epitope from our selected peptide library. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity that were independent of the CD8 co-receptor. These TCRs exhibited complementary cross-reactivity to several presently reported N361-369 mutant variants, as to the wild-type epitope. Further, the natural functions of these TCRs in the cytotoxic immunity against SARS-CoV-2 were determined with dendritic cells (DCs) and the lung organoid model. We found that the N361-369 epitope could be normally processed and endogenously presented by these different types of antigen presenting cells, to elicit successful activation and effective cytotoxicity of CD8+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, and illuminated potential ways of viral clearance in COVID-19 patients. These results indicate that utilizing CD8-independent TCRs against SARS-CoV-2-associated antigens may provide functional superiority that is beneficial for the adoptive cell immunotherapies based on natural or genetically engineered T cells. Additionally, this information is highly relevant for the development of the next-generation vaccines with protections against continuously emerged SARS-CoV-2 mutant strains.

The Attitude towards Preventive Measures and Knowledge of COVID-19 Inpatients with Severe Mental Illness in Economically Underdeveloped Areas of China.

Patients with severe mental illnesses (SMI) were at high risk of infection during Coronavirus Diseases 2019 (COVID-19) pandemic. This study examined hospitalized SMI patients' attitude and knowledge towards the COVID-19 infection. A cross-sectional survey was conducted in five psychiatric hospitals located in Gansu province, the most economically underdeveloped area in China. Patients' attitude towards preventive measures and knowledge of COVID-19 were measured by a self-report questionnaire. A total of 925 hospitalized patients with SMI were recruited. Of them, 84.8% (95%CI: 82.4%-87.1%) had positive attitudes towards preventive measures of the COVID-19 outbreak. Being married (OR: 1.55, 95%CI: 1.05-2.30) and a higher educational level (OR: 1.63, 95%CI: 1.12-2.38) were independently associated with positive attitudes towards COVID-19 preventive measures, whereas higher educational level was associated with better knowledge of the COVID-19 outbreak (ß: 0.231, P < 0.001). Patients mainly received COVID-19 relevant knowledge from public media (58.9%), followed by their clinicians (33.2%). Most hospitalized SMI patients in economically underdeveloped areas in China showed positive attitudes towards COVID-19 preventive measures. However, public health education on COVID-19 relevant knowledge by mental health professionals was inadequate to reduce the risk of transmission and infection.