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.

Flexible Noncontact Sensing for Human-Machine Interaction.

From typical electrical appliances to thriving intelligent robots, the exchange of information between humans and machines has mainly relied on the contact sensor medium. However, this kind of contact interaction can cause severe problems, such as inevitable mechanical wear and cross-infection of bacteria or viruses between the users, especially during the COVID-19 pandemic. Therefore, revolutionary noncontact human-machine interaction (HMI) is highly desired in remote online detection and noncontact control systems. In this study, a flexible high-sensitivity humidity sensor and array are presented, fabricated by anchoring multilayer graphene (MG) into electrospun polyamide (PA) 66. The sensor works in noncontact mode for asthma detection, via monitoring the respiration rate in real time, and remote alarm systems and provides touchless interfaces in medicine delivery for bedridden patients. The physical structure of the large specific surface area and the chemical structure of the abundant water-absorbing functional groups of the PA66 nanofiber networks contribute to the high performance synergistically. This work can lead to a new era of noncontact HMI without the risk of contagiousness and provide a general and effective strategy for the development of smart electronics that require noncontact interaction.