“Our Santa Clara seroprevalence study is now out. It shows 50-85 times underestimated number of infections, therefore 50-85 times overestimated infection rate fatality. True infection rate fatality is in the ballpark of seasonal influenza.” – John Ioannidis, Stanford University School of Medicine
COVID-19 Antibody Seroprevalence in Santa Clara County, California
Eran Bendavid 1, Bianca Mulaney 2, Neeraj Sood 3, Soleil Shah 2, Emilia Ling 2, Rebecca Bromley-Dulfano 2, Cara Lai 2, Zoe Weissberg 2, Rodrigo Saavedra-Walker 4, Jim Tedrow 5, Dona Tversky 6, Andrew Bogan 7, Thomas Kupiec 8, Daniel Eichner 9, Ribhav Gupta 10, John P.A. Ioannidis 1,10, Jay Bhattacharya 1
April 11, 2020
1. Department of Medicine, Stanford University School of Medicine, Stanford CA
2. Stanford University School of Medicine, Stanford CA
3. Sol Price School of Public Policy, University of Southern California, Los Angeles CA
4. Health Education is Power, Inc., Palo Alto CA
5. The Compliance Resource Group, Inc., Oklahoma City OK
6. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford CA
7. Bogan Associates, LLC, Palo Alto CA
8. ARL BioPharma, Inc. , OklahomaCity OK
9. Sports Medicine Research and Testing Laboratory, Salt Lake City UT
10. Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford CA
The unadjusted prevalence of antibodies to SARS-CoV-2 in Santa Clara County was 1.5% (exact binomial 95CI 1.11-1.97%), and the population-weighted prevalence was 2.81% (95CI 2.24-3.37%).
Under the three scenarios for test performance characteristics, the population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%).
These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April, 50-85-fold more than the number of confirmed cases (956 confirmed cases in Santa Clara County as of 4/1/2020 KB).
The most important implication of these findings is that the number of infections is much greater than the reported number of cases.
Our data imply that, by April 1 (three days prior to the end of our survey) between 48,000 and 81,000 people had been infected in Santa Clara County.
The reported number of confirmed positive cases in the county on April 1 was 956, 50-85-fold lower than the number of infections predicted by this study.
The infection to case ratio, also referred to as an under-ascertainment rate, of at least 50,is meaningfully higher than current estimates.
This ascertainment rate is a fundamental parameter of many projection and epidemiologic models, and is used as a calibration target for understanding epidemic stage and calculating fatality rates.
The under-ascertainment for COVID-19 is likely a function of reliance on PCR for case identification which misses convalescent cases, early spread in the absence of systematic testing, and asymptomatic or lightly symptomatic infections that go undetected.
We can use our prevalence estimates to approximate the infection fatality rate from COVID-19 in Santa Clara County. As of April 10, 2020, 50 people have died of COVID-19 in the County, with an average increase of 6% daily in the number of deaths.
If our estimates of48,000-81,000 infections represent the cumulative total on April 1, and we project deaths to April 22 (a 3 week lag from time of infection to death), we estimate about 100 deaths in the county.
A hundred deaths out of 48,000-81,000 infections corresponds to an infection fatality rate of 0.12-0.2%.
If antibodies take longer than 3 days to appear, if the average duration from case identification to death is less than 3 weeks, or if the epidemic wave has peaked and growth in deaths is less than 6% daily, then the infection fatality rate would be lower.
These straightforward estimations of infection fatality rate fail to account for age structure and changing treatment approaches to COVID-19.
Nevertheless,our prevalence estimates can be used to update existing fatality rates given the large upwards revision of under-ascertainment.
We conclude that based on seroprevalence sampling of a large regional population, the prevalence of SARS-CoV-2 antibodies in Santa Clara County was between 2.49% and 4.16%by early April.
While this prevalence may be far smaller than the theoretical final size of the epidemic, it suggests that the number of infections is 50-85-fold larger than the number of cases currently detected in Santa Clara County.
These new data should allow for better modeling of this pandemic and its progression under various scenarios of non-pharmaceutical interventions.