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The experimental CRISPR-based test, with further development, could potentially be used outside of labs.

A team studying rare kidney diseases pivoted to lung injury and identified an FDA-approved drug that’s now being tested as a potential COVID-19 treatment.

Irwin Jungreis and Manolis Kellis reanalyzed the results of a previous randomized controlled trial of calcifediol (25-hydroxyvitamin D3) as a treatment for hospitalized COVID-19 patients in Córdoba, Spain. The Córdoba study had limited impact, but through mathematical analysis, Jungreis and Kellis demonstrate that calcifediol intervention did indeed contribute to decreased ICU admissions among hospitalized COVID-19 patients. Their work suggests that the Córdoba study provides sufficient evidence to warrant immediate, well-designed pivotal clinical trials of calcifediol in a broader cohort of patients with COVID-19, and to consider broad adoption of calcifediol treatment for vitamin-D-deficient hospitalized COVID-19 patients.

Antibody engineering technologies face increasing demands for speed, reliability and scale.  Xun Chen, Aviv Regev and colleagues have developed CeVICA, a cell-free antibody engineering platform for rapid generation of divergent synthetic antibodies with tunable affinities. The team applied CeVICA to engineer antibodies against the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike proteins and identified more than 800 predicted binder families. Among 14 experimentally-tested binders, six showed inhibition of pseudotyped virus infection. CeVICA may serve as the basis for automated and highly parallel antibody generation.

To address a critical shortage of testing capacity during the early COVID-19 outbreaks in the Boston area, a team of collaborators at Ó³»­´«Ã½ and Massachusetts General Hospital (MGH) set up an emergency-use laboratory-developed test at MGH to accurately and safely diagnose SARS-CoV-2 by March 13, 2020. This test was used to diagnose many of the early cases in the community, guiding hospital care of the most critically ill patients and allowing patients to enroll in clinical trials. The team describes the process of developing the diagnostic in the hope that their experience will help lower barriers to fast and accurate testing in future crisis conditions.

Thai researchers collaborating with the lab of core institute member Feng Zhang benchmarked a SHERLOCK-based diagnostic for SARS-CoV-2 against a quantitative PCR assay using more than 500 samples collected at a large medical center in Bangkok, Thailand. The researchers found the CRISPR-Cas13-based assay to be 100 percent specific and between 96 and 100 percent sensitive across a range of viral loads, down to 42 RNA copies per reaction. The Thai team is now using SHERLOCK in their hospital for screening patients.

Mucin-1 (MUC1) is a transmembrane protein expressed in mucosal epithelial cells that when elevated predicts the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Maria Alimova, institute member Anna Greka and their colleagues mined a dataset screening 3,713 compounds at different stages of clinical development to identify FDA-approved drugs that reduce MUC1 protein abundance. They identified fostamatinib (R788), a treatment for chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo, fostamatinib reduced MUC1 abundance in lung epithelial cells in a mouse model of ALI. The work provides a rationale for a clinical trial testing clinical benefit for COVID-19 patients.

A new diagnostic protocol for SARS-CoV-2 called SHINE (SHERLOCK and HUDSON Integration to Navigate Epidemics), developed by Jon Arizti-Sanz, Catherine Freije, institute member Pardis Sabeti, and Cameron Myhrvold of the Ó³»­´«Ã½'s Infectious Disease and Microbiome Program (IDMP) and Genomic Center for Infectious Diseases (GCID), and colleagues, uses the CRISPR-based diagnostic technology SHERLOCK to detect viral RNA in a single-step reaction. SHINE avoids the need for RNA extraction on samples, and results can be visualized with a fluorescent readout without opening the sample tube, reducing the risk of contamination. The protocol's simplicity matches that of other streamlined nucleic acid diagnostics for SARS-CoV-2.

The Ó³»­´«Ã½'s is making copies of its – a collection of nearly 7,000 compounds that are either FDA-approved or proven safe in clinical trials – and sharing the with collaborators in Boston and around the world to help them hunt for existing compounds that might prove effective against COVID-19. Institute scientist Florence Wagner, director of medicinal chemistry in CDoT, talks about both near- and long-term projects.

A team led by Cheri Ackerman, Cameron Myhrvold, Catherine Freije, Gowtham Thakku, core institute member Paul Blainey, and Pardis Sabeti combined the SHERLOCK CRISPR-based diagnostic with the miniaturization of microfluidics for a flexible, sensitive diagnostic platform. The platform, called CARMEN (Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids), uses new microfluidics chips that can run thousands of tests simultaneously for same-day results, and could someday be harnessed for broad public-health efforts. Learn more in .

A team led by Jonathan Schmid-Burgk, core institute members Feng Zhang and Aviv Regev, and colleagues has developed a new diagnostic approach with the potential to dramatically scale up COVID-19 testing. The method, called LAMP-Seq, incorporates molecular barcodes into individual samples during processing, enabling labs to pool many samples together and analyze them en masse with existing next-generation sequencing infrastructure. To facilitate collaborations, the team has created a public forum on .

Limited availability of RNA extraction kits has slowed the testing of COVID-19 patient samples. Alim Ladha, Julia Joung, Feng Zhang, and colleagues at the McGovern Institute for Brain Research at MIT describe a new one-step RNA preparation method that can be carried out in five minutes, a fraction of the time taken by other approaches, and uses an alternate commercially available extraction solution. Samples prepared using this protocol are compatible with the CDC’s RT-qPCR testing protocol for SARS-CoV-2.

Hayden Metsky, Cameron Myhrvold, and their colleagues in the lab of Pardis Sabeti have created a website containing CRISPR-Cas13-based assay designs, developed using a method called ADAPT, for detecting 67 viruses, including SARS-CoV-2 and related respiratory viruses, in which users can select single or multiplex panels. The team describes these resources in this preprint, focusing on a SHERLOCK assay for SARS-CoV-2.

Feng Zhang, Omar Abudayyeh, and Jonathan Gootenberg have developed a research protocol, applicable to purified RNA, that may inform the development of CRISPR-based diagnostics for COVID-19.

The research protocol provides the basic framework for establishing a SHERLOCK-based COVID-19 test using paper strips.