1 2 UW COVID-19 testing data suggest successful flattening of the curve in both Seattle region and Washington State 3 4 5 6 April Kaur Randhawa, PhD1, Leigh H. Fisher, PhD1, Alexander L. Greninger, MD, PhD1,2, Shuying Sue Li, PhD1, Jessica Andriesen, PhD1, Lawrence Corey, MD1,2,3, Keith R. Jerome, MD, PhD1,2 7 8 9 1 10 11 2 12 3 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, WA, USA Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA 13 14 Address correspondence to: 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Alex Greninger University of Washington Department of Laboratory Medicine Box 357110 1959 NE Pacific Street, NW120 Seattle, WA 98195-7110 Phone: (415) 439-3448 agrening@uw.edu 36 Manuscript word count: 599 or Keith R. Jerome Fred Hutchinson Cancer Research Center 1100 Fairview Ave N, E5-110 Seattle, WA 98109 Phone: 206-667-6793 kjerome@fredhutch.org 1 37 The first reported case of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2; 38 COVID-19) in the United States occurred January 20, 2020 in Snohomish County, Washington1. 39 University of Washington (UW) Virology was one of the first US laboratories to begin testing for 40 SARS-CoV-2 and has tested samples from >60,000 patients. Over 90% of samples tested are 41 from health care organizations in Washington state, representing inpatients, outpatients, 42 employees, and community health patients. The orders from individual locations vary, but most 43 come from clinical facilities within the same health system or established outreach clients of the 44 laboratory. This is especially true for the regional emergency rooms and primary care clinics that 45 utilized the laboratory during this study period. We reasoned that analysis of outpatient and ER 46 facilities with established connections to the laboratory would allow estimates of COVID-19 47 prevalence in our region. 48 49 Clinical specimens were >95% nasopharyngeal swabs. Samples were analyzed by a lab- 50 developed RT-PCR test using either the WHO RT-PCR E/RdRp primer set2 or the CDC N1 and 51 N2 primer sets3,4, or by FDA EUA RT-PCR tests from Hologic (Panther Fusion), Diasorin 52 (Simplexa), and Roche (cobas). Test results were aligned to the day of the sample collection, 53 with a study period of March 1 through April 8, 2020. Data analyzed used the date of the first 54 positive sample. Penalized cubic regression splines were fit to the positive test rate for each of 55 the analyzed time series5. Analyses were run in R 3.6.1 and the smoothed models were fit 56 using the mgcv package. Our study was approved by the Institutional Review Boards at 57 University of Washington and Fred Hutchinson Cancer Research Center. 58 59 The demographic characteristics of the patient population and the overall positivity rates are 60 illustrated in Table 1 and Figure 1. Positivity rates were higher in ER vs outpatient clinics and in 2 61 men vs women. The positivity rate for SARS-CoV-2 detection over time in shown in Figure 1. 62 Non-linear trends were seen in the estimated smooth curves for the Seattle area (Figure 1A) 63 and greater Washington state (Figure 1B) outpatient populations, with initially increasing 64 positivity rates, followed by a peak positivity around March 27-28, after which positivity rates 65 declined for both populations. For ER facilities, the trend in positive rates was flatter, but 66 showed a similar pattern, reaching a peak slightly earlier (March 26) followed by a more gradual 67 trend downward (Figure 1C). Self-selection in persons visiting ERs in the community may be a 68 factor in influencing these differences. Based on the outpatient and ER data, we extrapolated 69 the estimated smoothed trend for positive rates within the Washington state outpatient 70 population (Figure 1D). While the confidence limits are large, these projections indicate that if 71 the current trend continues, we estimate positivity rates dropping below 2% around late April 72 and potentially below 1% around mid-May. 73 74 To date, the UW virology lab has performed >50% of all SARS-CoV-2 PCR testing in 75 Washington State, allowing us to utilize these data to assess the local dynamics of the 76 epidemic. Among caveats to our approach, this is not a population-based sample, and the mix 77 of cases seen over time is not constant. Nevertheless, by focusing analyses to outpatient and 78 emergency settings, our data indicate a true bending of the curve in the prevalence of SARS- 79 CoV-2 in the Seattle area and the state of Washington. This suggests that the early and 80 aggressive physical distancing measures taken by government agencies and the people of 81 Washington have had success in changing the course of the COVID-19 pandemic. Whether 82 current adherence to physical distancing will continue and how any alteration of this impacts our 83 projected acquisition trends remains to be determined. 84 85 3 86 Acknowledgements 87 We thank Meei-Li Huang and the rest of the UW Virology testing lab. For Laboratory Medicine 88 Informatics, we thank Patrick Mathias, Tuan Nguyen, Nathan Breit, and Rick Clayton. From 89 Fred Hutch, we thank Nicole Espy, Mindy Miner, Lisa Bunts, Sara Thiebaud, Rich Leibfried, 90 Emily Silgard, and Raphael Gottardo. We thank all the medical professionals who performed the 91 cultures, the healthcare workers caring for these patients, the essential facilities and support 92 staff, as well as the government officials of the State of Washington and City of Seattle who 93 developed and enacted physical distancing policies for our communities. Special thanks to 94 Geoff Baird, chair of the UW Dept of Medicine, and Fred Hutch President Tom Lynch for 95 supporting the laboratories and personnel associated with this project. 96 Funding: Institutional support from the Fred Hutchinson Cancer Research Center 97 Conflict of interest 98 99 AKR, LHF, SSL, JA, LC, and KRJ declare no conflicts of interest. ALG reports personal fees from Abbott Molecular. 100 101 References 102 103 104 105 106 107 108 109 110 111 1. 2. 3. 4. 5. 112 113 114 4 Holshue ML, DeBolt C, Lindquist S, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020;382(10):929-936. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by realtime RT-PCR. Euro Surveill. 2020;25(3). CDC. Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 (COVID-19). CDC. https://www.cdc.gov/coronavirus/2019nCoV/lab/guidelines-clinical-specimens.html. Published 2020. Accessed March 1, 2020. CDC. Coronavirus Disease 2019 (COVID-19): Information for Laboratories. In:2020. Wood SN. Generalized Additive Models: An Introduction with R, Second Edition. In: New York: Chapman and Hall/CRC; 2017. 115 Table 1 Facility Type Outpatient (WA) Demographic Patient Sex Patient Age Outpatient (Seattle) Patient Sex Patient Age Emergency Room (Seattle) Patient Sex Patient Age 116 5 Group Not Detected Female 8487 Male 4940 Unknown 18 Total: 13445 0-19 715 20-39 4966 40-59 4880 60-79 2601 80-105 283 Female 5343 Male 2984 Unknown 3 Total: 8330 0-19 377 20-39 3153 40-59 2941 60-79 1656 80-105 203 Female 594 Male 784 Total: 1378 0-19 26 20-39 410 40-59 488 60-79 360 80-105 94 Unknown 0 Positive 704 576 3 1283 41 413 497 295 37 467 357 2 826 21 277 295 207 26 94 130 224 3 49 63 77 31 1 Positive Rate (%) 7.7 % 10.4 % 14.3 % 5.4% 7.7% 9.2% 10.2% 11.6% 8.0% 10.7% 40.0% 5.3% 8.1% 9.1% 11.1% 11.4% 13.7% 14.2% 10.3% 10.7% 11.4% 17.6% 24.8% 100.0% 117 118 Figure 1 119 120 121 122 Observed positivity rates (black points), estimated smooth trends, and 95% CIs (red) for A) Outpatients – Seattle Area, B) Outpatients - Washington State, and C) Emergency Room Patients. Weekends, when fewer samples are collected, are indicated in gray. D) Extrapolated smooth trend of WA outpatient positivity rate. 123 124 125 6