Identification and assessment of TCR-T cells targeting an epitope conserved in SARS-CoV-2 variants for the treatment of COVID-19

Background Coronavirus disease 2019 (COVID-19) continues to be a major global public health challenge, with the emergence of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current vaccines or monoclonal antibodies may not well be protect against infection with new SARS-CoV-2 variants. Unlike antibody-based treatment, T cell-based therapies such as TCR-T cells can target epitopes that are highly conserved across different SARS-CoV-2 variants. Reportedly, T cell-based immunity alone can restrict SARS-CoV-2 replication. Methods In this study, we identified two TCRs targeting the RNA-dependent RNA polymerase (RdRp) protein in CD8+ T cells. Functional evaluation by transducing these TCRs into CD8+ or CD4+ T cells confirmed their specificity. Results Combinations of inflammatory and anti-inflammatory cytokines secreted by CD8+ and CD4+ T cells can help control COVID-19 in patients. Moreover, the targeted epitope is highly conserved in all emerged SARS-CoV-2 variants, including the Omicron. It is also conserved in the seven coronaviruses that infect humans and more broadly in the subfamily Coronavirinae. Conclusions The pan-genera coverage of mutant epitopes from the Coronavirinae subfamily by the two TCRs highlights the unique strengths of TCR-T cell therapies in controlling the ongoing pandemic and in preparing for the next coronavirus outbreak.

The Influence of Family Function on State and Trait Anxiety of Chinese College Students During the Epidemic of COVID-19 (preprint)

BACKGROUND: COVID-19 has a terrible impact worldwide, and more than 0.8 million people had died of it before September 2020. Many countries had taken many measures to against it, and one of the most effective methods was "stay-at-home" order. But staying at home for a long time is not good for human beings with social features, and that may lead to the occurrence of psychological diseases. Because of COVID-19, many people were forced to stay at home and spend more time with family members. As a special group of population, Chinese college student are more dependent on families, and their psychology, such as anxiety, may be more affected by family during the outbreak of COVID-19.METHODS: This cross-sectional study was conducted online from March 14, 2020 to March 21, 2020.The State-Trait Anxiety Inventory (ST-AI) and Chinese Family Function Scale (FAD-18) were used in this study. ANOVA was used in basic information. Path analysis was used to estimate the relationship among family function, state anxiety and trait anxiety.RESULTS: A total of 1039 respondents (695 females and 344 males) were included in the study. Their state anxiety scores were 39.28 and 36.84, respectively. The trait anxiety scores were 40.66 and 38.36, respectively. There were significant differences (p<0.01). But compared with the healthy norm, there was no significant difference. Except gender, there were significant differences (p<0.01) in state anxiety and trait anxiety between college students of medicine and art majors. In path analysis, the standard direct effect of family function on trait anxiety was 0.434(p< 0.001) in male group, 0.271(p< 0.001) in female group. While the standard direct and indirect effect of family function on state anxiety were not significant.CONCLUSIONS: This study found that during the outbreak of COVID-19, the state anxiety and trait anxiety of Chinese college students were related to gender and major. What’s more, family function had a great influence on anxiety. It is very important to pay attention to health function of family and psychological counseling for different genders and majors.

On the Time Trend of COVID-19: A Panel Data Study (preprint)

In this paper, we study the trending behaviour of COVID-19 data at country level, and draw attention to some existing econometric tools which are potentially helpful to understand the trend better in future studies. In our empirical study, we find that European countries overall flatten the curves more effectively compared to the other regions, while Asia & Oceania also achieve some success, but the situations are not as optimistic elsewhere. Africa and America are still facing serious challenges in terms of managing the spread of the virus, and reducing the death rate, although in Africa the virus spreads slower and has a lower death rate than the other regions. By comparing the performances of different countries, our results incidentally agree with Gu et al. (2020), though different approaches and models are considered. For example, both works agree that countries such as USA, UK and Italy perform relatively poorly; on the other hand, Australia, China, Japan, Korea, and Singapore perform relatively better.

The production of antibodies for SARS-CoV-2 and its clinical implication (preprint)

Background: Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), a novel betacoronavirus, has caused an outburst of pneumonia cases in Wuhan, China. We report the production of specific IgM and IgG antibodies after the infection of SARS-CoV-2 and its implication for the diagnosis, pathology and the course of the disease as well as the recurrence of positive nucleic acid tests after discharge. Methods: Test results for SARS-CoV-2 IgM and IgG antibodies of 221 confirmed COVID-19 patients were retrospectively examined, and their clinical data were collected and analyzed based on various subgroups. SARS-CoV-2 IgM and IgG antibodies were determined with the chemiluminescence method. Findings: The concentration (S/CO) of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, with a median of 17.38 (IQR 4.39-36.4) for IgM and 5.59 (IQR 0.73-13.65) for IgG. Detection rates reached highest on day 16-18 and day 19-21 for IgM and IgG, which were 73.6% and 98.6%, respectively, with significantly higher concentration of IgG in critically ill patients than in those with mild to moderate disease (P=0.027). The concentration of the antibodies on day 16-21 is not correlated with the course or outcome of the disease (Spearman r < 0.20, P > 0.05). Nasopharyngeal swabs revealed positive SARS-CoV-2 RNA in up to 52.7% of recovered patients after discharge, whose IgG proved to be significantly lower than that of those with negative RNA results (P = 0.009). IgG and IgM were tested twice within 14 days after discharge with a 7-day interval, and the second testing of these antibodies displayed a decrease in concentration of 21.2% (IQR, 11.2%34.48%) for IgG and 23.05% (IQR, -27.96%46.13%) for IgM, without statistical significance between the patients with re-detectable positive RNA results and those with negative RNA results after discharge. However, those with positive results experienced a count decrease in lymphocyte subsets. Interpretation: The concentration of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, and antibody testing on day 16-21 is associated with increased detection rates, but the antibody concentration does not affect the course and outcome of the infection. Recovering patients with re-detectable positive SARS-CoV-2 RNA displayed lower concentration of IgG, but the downward trend of IgG during recovery indicated its limited duration of protection, and the protective effect of IgG remains to be investigated.

Molecular Basis for Treating COVID-19 with Official Chinese Herbal Formula LCTE (preprint)

Chinese herbal formulas, notably the lung-cleaning and toxicity-excluding (LCTE) soup has played an important role in treating an ongoing and life-threating worldwide pandemic, COVID-19 (caused by SARS-CoV-2). Applying LCTE outside of China may be difficult for medical society to approach due to the unfamiliar rationale behind its application in terms of Traditional Chinese Medicine. To overcome this barrier, we illuminate the chemical and biological mechanisms behind LCTE’s effects, by exploring the chemical compounds contained in LCTE ingredients, the proteins targeted by these compounds as well as undertaking the network pharmacology analysis. The results disclosed that LCTE contains compounds with the potential to directly inhibit SARS-CoV-2 and inflammation, and that the compounds targeted proteins significantly related to the main symptoms seen in COVID-19. The general effect of LCTE was to affect the pathways involved in viral and other microbe infection, inflammation/cytokine response, and lung diseases. Our work provided chemical biological explanations for using LCTE to treat COVID-19.