Identification of immunomodulatory drugs that inhibit multiple inflammasomes and impair SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces mild or asymptomatic COVID-19 in most cases, but some patients develop an excessive inflammatory process that can be fatal. As the NLRP3 inflammasome and additional inflammasomes are implicated in disease aggravation, drug repositioning to target inflammasomes emerges as a strategy to treat COVID-19. Here, we performed a high-throughput screening using a 2560 small-molecule compound library and identified FDA-approved drugs that function as pan-inflammasome inhibitors. Our best hit, niclosamide (NIC), effectively inhibits both inflammasome activation and SARS-CoV-2 replication. Mechanistically, induction of autophagy by NIC partially accounts for inhibition of NLRP3 and AIM2 inflammasomes, but NIC-mediated inhibition of NAIP/NLRC4 inflammasome are autophagy independent. NIC potently inhibited inflammasome activation in human monocytes infected in vitro, in PBMCs from patients with COVID-19, and in vivo in a mouse model of SARS-CoV-2 infection. This study provides relevant information regarding the immunomodulatory functions of this promising drug for COVID-19 treatment.

Implementation of the drive-through strategy for COVID-19 vaccination: an experience report.

OBJECTIVE: To describe the experience of implementing a satellite vaccination unit in a drive-through system during a campaign against COVID-19. METHOD: This is an experience report carried out in a drive-through vaccination satellite unit. The study development was guided by the triad structure-process-results, proposed by Donabedian. RESULTS: The unit was structured in a soccer stadium, allowing it to serve large audiences safely. Care flow occurred in stages and professionals were organized by sectors, with emphasis on the nursing team' work. Initially, screening was performed; later, users went to the registration sector, and, finally, they were forwarded to the application station. The unit also had emergency sectors, a cold chain, space for professionals and a Basic Health Unit as a point of support. In 25 days of operation, 9698 doses were administered, with 1.8% of doses lost. CONCLUSION: The implementation of this system required planning, structure, process development and intense team articulation, with emphasis on the fundamental and strategic role of nurses in different points of action and leadership.