SalivaDirect: A simplified and flexible platform to enhance SARS-CoV-2 testing capacity

• Published in: Med (New York, N.Y. : Online) Vol. 2; no. 3; pp. 263 - 280.e6
• Main Authors: Vogels, Chantal B.F., Watkins, Anne E., Harden, Christina A., Brackney, Doug E., Shafer, Jared, Wang, Jianhui, Caraballo, César, Kalinich, Chaney C., Ott, Isabel M., Fauver, Joseph R., Kudo, Eriko, Lu, Peiwen, Venkataraman, Arvind, Tokuyama, Maria, Moore, Adam J., Muenker, M. Catherine, Casanovas-Massana, Arnau, Fournier, John, Bermejo, Santos, Campbell, Melissa, Datta, Rupak, Nelson, Allison, Anastasio, Kelly, Askenase, Michael H., Batsu, Maria, Bickerton, Sean, Brower, Kristina, Bucklin, Molly L., Cahill, Staci, Cao, Yiyun, Courchaine, Edward, DeIuliis, Giuseppe, Earnest, Rebecca, Geng, Bertie, Goldman-Israelow, Benjamin, Handoko, Ryan, Khoury-Hanold, William, Kim, Daniel, Knaggs, Lynda, Kuang, Maxine, Lapidus, Sarah, Lim, Joseph, Linehan, Melissa, Lu-Culligan, Alice, Martin, Anjelica, Matos, Irene, McDonald, David, Minasyan, Maksym, Nakahata, Maura, Naushad, Nida, Nouws, Jessica, Obaid, Abeer, Odio, Camila, Oh, Ji Eun, Omer, Saad, Park, Annsea, Park, Hong-Jai, Peng, Xiaohua, Petrone, Mary, Prophet, Sarah, Rice, Tyler, Rose, Kadi-Ann, Sewanan, Lorenzo, Sharma, Lokesh, Shaw, Albert C., Shepard, Denise, Smolgovsky, Mikhail, Sonnert, Nicole, Strong, Yvette, Todeasa, Codruta, Valdez, Jordan, Velazquez, Sofia, Vijayakumar, Pavithra, White, Elizabeth B., Yang, Yexin, Dela Cruz, Charles S., Ko, Albert I., Iwasaki, Akiko, Krumholz, Harlan M., Matheus, J.D., Hui, Pei, Liu, Chen, Farhadian, Shelli F., Sikka, Robby, Wyllie, Anne L., Grubaugh, Nathan D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.03.2021
• Subjects: Clinical and Translational; COVID-19; COVID-19 - diagnosis; COVID-19 Testing; Humans; Laboratories; molecular testing; population screening; Saliva; SARS-CoV-2; SARS-CoV-2 - genetics; COVID-19; saliva; SARS-CoV-2; molecular testing; Translation to Patients; population screening
• ISSN: 2666-6340; 2666-6359; 2666-6340
• DOI: 10.1016/j.medj.2020.12.010

Scaling SARS-CoV-2 testing to meet demands of safe reopenings continues to be plagued by assay costs and supply chain shortages. In response, we developed SalivaDirect, which received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA). We simplified our saliva-based diagnostic test by (1) not requiring collection tubes with preservatives, (2) replacing nucleic acid extraction with a simple enzymatic and heating step, and (3) testing specimens with a dualplex qRT-PCR assay. Moreover, we validated SalivaDirect with reagents and instruments from multiple vendors to minimize supply chain issues. From our hospital cohort, we show a high positive agreement (94%) between saliva tested with SalivaDirect and nasopharyngeal swabs tested with a commercial qRT-PCR kit. In partnership with the National Basketball Association (NBA) and National Basketball Players Association (NBPA), we tested 3,779 saliva specimens from healthy individuals and detected low rates of invalid (0.3%) and false-positive (<0.05%) results. We demonstrate that saliva is a valid alternative to swabs for SARS-CoV-2 screening and that SalivaDirect can make large-scale testing more accessible and affordable. Uniquely, we can designate other laboratories to use our sensitive, flexible, and simplified platform under our EUA (https://publichealth.yale.edu/salivadirect/). This study was funded by the NBA and NBPA (N.D.G.), the Huffman Family Donor Advised Fund (N.D.G.), a Fast Grant from Emergent Ventures at the Mercatus Center at George Mason University (N.D.G.), the Yale Institute for Global Health (N.D.G.), and the Beatrice Kleinberg Neuwirth Fund (A.I.K.). C.B.F.V. is supported by NWO Rubicon 019.181EN.004. Frequent testing is critical to limit SARS-CoV-2 transmission. In response to this need, we developed SalivaDirect, a sensitive, simplified, and flexible testing framework, which received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA). We tested saliva collected from a hospital cohort and showed a high positive agreement (94%) as compared to paired nasopharyngeal swabs tested with a commercial diagnostic kit. Then, we partnered with the National Basketball Association (NBA) to test a large cohort of mostly healthy individuals, and we detected low rates of invalid (0.3%) and false-positive (0.03%–0.05%) results. Our study shows that SalivaDirect can help to increase testing capacity by providing access to an affordable framework that is less prone to supply chain shortages. [Display omitted] SalivaDirect is a simplified saliva-based test for detection of SARS-CoV-2The testing framework is flexible to minimize the risk of supply chain issuesSalivaDirect is sensitive, with low rates of invalid and false-positive resultsLaboratories can be designated to use SalivaDirect to increase testing capacity SalivaDirect is a sensitive saliva-based COVID-19 diagnostic test, which received Emergency Use Authorization from the U.S. FDA. With the ability to designate other laboratories, the flexible and simplified framework helps to increase the capacity of existing laboratory infrastructure for SARS-CoV-2 testing.