CD4+ T-cell immunity of SARS-CoV-2 patients determine pneumonia development (preprint)

Most humans infected with SARS-CoV-2 will recover without developing pneumonia. A few SARS-CoV-2 infected patients, however, develop pneumonia, and occasionally develop cytokine storms. In such cases, it is assumed that there is an inadequate immune response to eliminate viral infected cells and an excessive inappropriate immune response causing organ damage, but little is known about this mechanism. In this study, we used single cell RNA sequencing and mass cytometry to analyze peripheral blood T cells from patients hospitalized with proven COVID-19 infection in order to clarify the differences in host immune status among COVID-19 pneumonia cases, non-pneumonia cases, and healthy controls. The results showed that a specific CD4+ T cell cluster with chemokine receptor expression patterns, CXCR3+CCR4-CCR6+ (Th1/17), was less abundant in COVID-19 pneumonia patients. Interestingly, these CD4+ T-cell clusters were identical to those we have reported to correlate with antitumor immunity and predict programmed cell death (PD)-1 blockade treatment response in lung cancer. The Th1/17 cell percentages had biomarker performance in diagnosing pneumonia cases. In addition, CTLA-4 expression of type17 helper T cells (Th17) and regulatory T cells (Treg) was found to be significantly lower. This indicates that functional suppression of Th17 was less effective and Treg function was impaired in pneumonia cases. These results suggest that imbalance of CD4+ T-cell immunity generates excessive immunity that does not lead to viral eradication. This might be a potential therapeutic target mechanism to prevent severe viral infections.

COVID-19 testing avoidance among patients with cardiovascular disease (preprint)

Background: Rapid coronavirus 2019 (COVID-19) testing in symptomatic cases is extremely important for preventing the spread of COVID-19 infection and early therapeutic intervention. In contrast, whether symptomatic patients are tested depends largely on their health literacy, interpretation, and knowledge of COVID-19. We aimed to investigate the rate of COVID-19 testing avoidance despite having common cold symptoms in patients with cardiovascular disease and examine factors related to testing avoidance. Methods: A large-scale epidemiological questionnaire survey, the Japan COVID-19 and Society Internet Survey 2022 (JACSIS), was conducted online from April to May 2022. The rate of COVID-19 testing avoidance was investigated in patients aged 20 to 80 years with cardiovascular risk factors (hypertension, dyslipidemia, or diabetes) or a history of cardiovascular disease (angina, myocardial infarction, or stroke), only those exhibiting common cold symptoms during the 2 months in the survey. Results: Of the 1,565 eligible patients, 58% (909 patients) did not undergo COVID-19 testing. Multivariate analysis revealed that older age, obesity, non-walking regularly, long sedentary time, eating alone, frequent snacking, and having received 4 COVID-19 vaccinations were independently associated with testing avoidance. Conclusions: In the chronic phase of the COVID-19 pandemic, prompt COVID-19 testing at the time of symptomatic disease is important, and strategies to reduce testing hesitancy should be considered.