A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

Clinical characteristics and epidemiological significance of coronavirus disease 2019 in children and adolescents. / 儿童和青少年2019å† çŠ¶ç— æ¯’ç— çš„ä¸´åºŠè¡¨çŽ°åŠæµè¡Œç— å­¦æ„ä¹‰.

The epidemic of coronavirus disease 2019 (COVID-19) started in late December 2019, and spread rapidly throughout the world. In March 2020, the World Health Organization (WHO) declared global epidemic of COVID-19. According to the American Academy of Pediatrics, nearly 13 million children have been diagnosed with COVID-19 since the outbreak. In general, children and teens have milder symptoms and fewer deaths from COVID-19 than adults. Understanding the symptoms, infectivity, and transmission patterns of COVID-19 in children and adolescents is of great significance for timely identifying suspected patients and developing effective control measures. Considering that some children will not be vaccinated for quite some time in the future, it is more important to improve the understanding of the clinical and epidemiological significance of COVID-19 in children and adolescents. This article summarizes the current understanding of the clinical manifestations and epidemiological significance of COVID-19 in children and adolescents to provide a reference for clinical diagnosis and treatment and the formulation of epidemic prevention and control strategies in children's gathering institutions such as kindergartens and schools.