The number of coronavirus infections in Santa Clara County could be between 50 and 80 times higher than the officially confirmed count, preliminary results from a community-based study by a team of Stanford University researchers indicates.
The prevalence study, led by Stanford Assistant Professor Eran Bendavid, has not been formally published and is still undergoing peer reviews. It has, however, been published on the preprint server medRxiv. As such, it is effectively a first draft, subject to change based on input before formal publication.
That said, the early findings indicate that between 48,000 and 81,000 residents in Santa Clara County were infected as of April 1, back when the official count was 956. The estimate is based on 3,330 blood samples that were taken from volunteers in Mountain View, Los Gatos and San Jose on April 3 and April 4 and tested for antibodies to SARS-CoV-2.
When adjusted for Santa Clara County's population and demographics, the number of positive results suggests that between 2.49% and 4.16% of county residents have had COVID-19.
The study’s results "represent the first large-scale community-based prevalence study in a major U.S. county completed during a rapidly changing pandemic, and with newly available test kits," the authors wrote.
The most important implication, the preprint notes, is that "the number of infections is much greater than the reported number of cases."
"The population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection is much more widespread than indicated by the number of confirmed cases," the researchers concluded. "Population prevalence estimates can now be used to calibrate epidemic and mortality projections."
Jay Bhattacharya, a professor of medicine at Stanford University and one of the study’s authors, said the goal of the study is to understand how widespread the disease is.
"To do that, we need to understand how many people are infected," Bhattacharya told this new organization on April 4, as the second day of tests was kicking off. "The current test people use to check whether they have the condition – the PCR (polymerase chain reaction) test – it just checks whether you currently have the virus in you. It doesn't check whether you had it and recovered. An antibody test does both."
Participants in the prevalence study were targeted through Facebook ads, with the goal of getting a representative sample of the county by demographic and geographic characteristics, the study states. Because the sampling strategy relied on people who have access to Facebook and a car, there was an overrepresentation of white women between 19 and 64, as well as an under-representation of Hispanic and Asian populations, relative to the community, according to the study. The study attempted to compensate for that by weighting the results for race, sex and ZIP code so that they better reflect the countywide population.
The group’s analysis indicated 50 blood samples from the study, or 1.5% of the total, tested positive for either immunoglobulin M (IgM), the antibody that the body produces when the infection occurs and that disappears after several weeks, or immunoglobulin G (IgG), the antibody that appears later, stays longer and provides the basis for immunity.
After weighting to match the county population by race, sex and ZIP code, the prevalence rate was adjusted to 2.81%, according to the study. Other factors, including uncertainties relating to the sensitivity of the tests that were used, contributed to the range of up to 4.16%.
County, state and federal health experts have consistently acknowledged that the number of COVID-19 cases is far higher than the official statistics show, a problem they attribute largely to the lack of widespread testing. Even though California is looking to greatly ramp up serological (blood) testing and to establish new community-testing sites, the state continues to experience both a shortage of tests and a backlog in processing tests.
As of April 15, more than 246,400 tests had been conducted in California. In Santa Clara County, there were 17,061 tests completed as of April 16, with 10.79% testing positive for the coronavirus.
The new study suggests that the undercounting of COVID-19 infections -- the extent to which they vary from official case numbers -- is far greater than has been assumed.
"The under-ascertainment of infections is central for better estimation of the fatality rate from COVID-19," the study states. "Many estimates of fatality rate use a ratio of deaths to lagged cases (because of duration from case confirmation to death), with an infections-to-cases ratio in the 1-to-5-fold range as an estimate of underascertainment. Our study suggests that adjustments for under-ascertainment may need to be much higher."
The Stanford study suggests that the undercounting of cases can also be attributed to a lack of widespread testing and reliance on PCR for case identification, which misses "convalescent" cases (those who have already recovered from the infection). The official count also doesn’t capture asymptomatic or lightly symptomatic infections that go undetected, the study states.
The range of results also reflects uncertainty in both test sensitivity (how good it is at correctly identifying COVID-19 antibodies) and test specificity (how likely it is to produce a false positive). Researchers relied on tests manufactured by the Minnesota-based company Premier Biotech, rather than the newly developed serological test by Stanford, which has been used to test health care workers.
Bendavid told this news organization earlier this week that the tests were chosen because they are very easy to use (they produce a line reading similar to a pregnancy test) and produce results within 15 minutes. They are, however, less precise than laboratory-based tests and give you an underestimate of how many people have coronavirus – a shortcoming that was factored in the study.
To determine their accuracy, the research team used the kits it received from Premier Biotech to test blood samples from Stanford Hospital patients that were shown to be positive through a DNA test, as well as samples that were known to be negative because they were taken before the pandemic. These results led researchers to conclude that the sensitivity is about 91.8%, a rate that was factored in to produce the final range.
The authors acknowledge the study’s other limitations. While they factored in sex, race and ZIP code, the survey does not account for age imbalances or a potential bias favoring individuals who were in good health and, therefore, able to volunteer. The effect of such biases, the study notes, is hard to ascertain.
Bendavid and Bhattacharya had both argued in the past that the COVID-19 fatality rate is far lower than many experts had assumed. That’s because the number of actual infections far exceeds the official case counts.
"If the number of actual infections is much larger than the number of cases – orders of magnitude larger – then the true fatality rate is much lower as well. That's not only plausible but likely based on what we know so far," Bendavid and Bhattacharya wrote in a Wall Street Journal opinion piece on March 24.
As of April 10, the study notes, 50 people in Santa Clara County had died of COVID-19 in the county, with an average increase of 6% daily in the number of deaths. Given the trajectory, the study estimates that the county will see about 100 deaths by April 22 (the county had reported 69 deaths as of April 16).
Given the study's estimate of 48,000 to 81,000 infections in early April – and a three-week lag from infection to death – the 100 deaths suggest that the infection fatality rate is between 0.12% and 0.2%.
The study states that the new data "should allow for better modeling of this pandemic and its progression under various scenarios of non-pharmaceutical interventions."
"While our study was limited to Santa Clara County, it demonstrates the feasibility of seroprevalence surveys of population samples now, and in the future, to inform our understanding of this pandemic’s progression, project estimates of community vulnerability, and monitor infection fatality rates in different populations over time," the study states.
Find comprehensive coverage on the Midpeninsula's response to the new coronavirus by Palo Alto Online, the Mountain View Voice and the Almanac here.
Comments
Cuesta Park
on Apr 17, 2020 at 9:29 pm
on Apr 17, 2020 at 9:29 pm
This is very good news! 0.12% to 0.2% is only a little more than the flu, and it looks like we are well on our way to herd immunity.
This is consistent with the predictions of Dr. Knut Wittkowski. He is an epidemiologist who makes some persuasive arguments that COVID-19 behaves much like a seasonal flu. A fascinating interview with him here: Web Link
If anyone knows of a good refutation of Dr. W. or of the Stanford study please share it.
Another Mountain View Neighborhood
on Apr 17, 2020 at 10:20 pm
on Apr 17, 2020 at 10:20 pm
So disappointed in Stanford for contributing to the mass confusion. Those who wish to diminish the dangers of COVID-19 are going to latch on to this "study," which was not a random sample, but rather a self-selected group.
Already people are saying the nation has overreacted by using this study to suggest COVID19 is no more dangerous than the flu. Look at real data from NYC on the death rates last year and now, and it's clear this is not just a flu. Web Link Look at the overcrowded hospitals in hot zones. Look at those who lost someone. These flawed studies add to their injury and imperil all the wider community.
Castro City
on Apr 17, 2020 at 10:42 pm
on Apr 17, 2020 at 10:42 pm
In response to Stanford should do better you said:
“So disappointed in Stanford for contributing to the mass confusion. Those who wish to diminish the dangers of COVID-19 are going to latch on to this "study," which was not a random sample, but rather a self-selected group.”
However, given the SEVERE shortage of testing equipment and agents, we are STUCK. IF the PRESIDENT would use his power under the act he claims to be using, there would be government mandated manufacturing of testing supplies, agents, and equipment. Surely by NOW we should have had at least 30,000,000 tests made and performed. So you are attacking the wrong problem. You said:
“Already people are saying the nation has overreacted by using this study to suggest COVID19 is no more dangerous than the flu. Look at real data from NYC on the death rates last year and now, and it's clear this is not just a flu. Web Link Look at the overcrowded hospitals in hot zones. Look at those who lost someone. These flawed studies add to their injury and imperil all the wider community.”
I cannot argue this. I am in TOTAL agreement.
Rex Manor
on Apr 18, 2020 at 6:18 am
on Apr 18, 2020 at 6:18 am
@Stanford should do better
"So disappointed in Stanford for contributing to the mass confusion."
More honest data leads to less confusion, well, until the news media and politicians step in of course.
"Those who wish to diminish the dangers of COVID-19 are going to latch on to this "study,""
Of course, because the chicken-littles from day one were claiming the mortality rate of people once infected was between 4-10%. But that flawed data had no clue what the true infection rate was, so the "data" if you can call it that was simply a ratio of those self-selected as known to be sick or known to have had contact with the sick on one side of the calculation and those who died on the other side.
That's what was flawed and confusing.
Stanford is trying to do a wider testing and then make a closer to the truth calculation of the mortality rate for those infected.
That's what we need more of not less.
"which was not a random sample, but rather a self-selected group."
ALL prior data has been self-selected and misleading.
"Already people are saying the nation has overreacted by using this study to suggest COVID19 is no more dangerous than the flu."
Which is probably going to turn out to be close, once all the full data for:
people exposed,
people infected,
people with no symptoms,
people with minimal symptoms,
people needing minor medical intervention,
people needing extreme medical measures, and finally, the
people who actually died of the virus.
Right now, we only have so-so numbers on the number of dead and nothing remotely close to any idea of any of the other numbers we need to make a valid calculation of mortality rate. It's irrational to think this specific coronavirus has a 10x to 1000x greater mortality than any prior coronavirus has ever had and a 10,000x worse than the flu is beyond any rational science.
"Look at real data from NYC on the death rates last year and now,"
That is utterly meaningless in calculating the true mortality rate.
Those sorts of things make for great TV headlines to scare people, but serve zero scientific purpose.
"and it's clear this is not just a flu."
No, but the mortality rate is probably a lot closer than 10x to 10,000x as so many "experts" have claimed on TV.
"Look at the overcrowded hospitals in hot zones."
Irrelevant to the science and of no use in determining the mortality rate.
"Look at those who lost someone."
When you have to appeal to raw emotion, that only proves you don't have anything valid to say.
"These flawed studies add to their injury and imperil all the wider community. "
By causing governments to react too much and in counter-productive ways.
ALL the prior studies so far are deeply flawed and utterly useless for science, nothing we know so far is of any use in scientifically calculating the true mortality rate.
The fact is, until we have enough, as in billions of, active infection and anti-body test kits deployed and results returned and tabulated, until we have all the numbers I listed above, we cannot do anything meaningful about determining the true mortality rate.
At least Standford and the Navy are trying to get some wide-net date.
Each time we see new data, the estimated mortality rate goes DOWN, NO new data has pointed to a higher mortality rate.
When all the numbers are going in the same direction, you might want to reconsider your position.
Rengstorff Park
on Apr 18, 2020 at 11:20 am
on Apr 18, 2020 at 11:20 am
> "Look at real data from NYC on the death rates last year and now,"
> That is utterly meaningless in calculating the true mortality rate.
Wrong. It is absolutely meaningful data. Add in Madrid, Italy, and the rural areas and it gives a good glimpse into what's happening.
> until we have enough, as in billions of, active infection and anti-body test kits deployed and results returned
True. And it's pure negligence that America is behind so many other countries in per capita testing.
Another Mountain View Neighborhood
on Apr 18, 2020 at 11:29 am
on Apr 18, 2020 at 11:29 am
Did you look at the New York Times article:
Web Link
When people say the death rates are skewed by over labeling deaths as COVID19 related, just look to see how many more people are dying in NYC these last 30 days than any other 30 days in modern history of NYC including 9/11, what else explains that jump if not COVID19 being very deadly to a small but still important subset of people?
I know people who died in NYC these last 30 days, and hearing people say it wasn't COVID19 is like hearing people say 9/11 didn't happen.
Rex Manor
on Apr 18, 2020 at 1:29 pm
on Apr 18, 2020 at 1:29 pm
Unfortunately, the study's results are entirely consistent with the underlying false-positive rate of the tests they're using, which would still put Santa Clara at roughly the same prevalence as the underlying case rate. Just like hydroxychloroquine, science takes time and there's not going to be a single silver bullet to get us out of this.
St. Francis Acres
on Apr 18, 2020 at 2:24 pm
on Apr 18, 2020 at 2:24 pm
Donald Trump is on tv right now (Saturday at 2:24 pm) campaigning. He cannot stay on script. When he varies from the speech written for him, Trump sounds like the know-nothing lightweight he is. If Trump is re-selected in November, buy a plot. You'll need it sooner than you are hoping.
Rengstorff Park
on Apr 18, 2020 at 2:34 pm
on Apr 18, 2020 at 2:34 pm
Trump told us we could ALL get a test, in March, when we wanted one.
I want one. Where are they, Mr. (China-Loving) Trump?
Trump, January 24, THIS YEAR:
“China has been working very hard to contain the Coronavirus, the United States greatly appreciates their efforts and transparency. It will all work out well. In particular, on behalf of the American People, I want to thank President Xi!”
I would like him to stop 'speaking' on my behalf, and actually do some WORK.
"It will all work out well."
Castro City
on Apr 18, 2020 at 3:37 pm
on Apr 18, 2020 at 3:37 pm
I agree I know EVENTUALLY we will return to some kind of normalcy.
BUT
When Trump invoked the Defense Production Act, he assumed statutory responsibility to address the current situation as of April 2.
Thus any loss of income, public suffering, and death that occurs after that date is by statute his RESPONSIBILITY.
The fact that he has not required any testing production at all is intentional.
The president is looking for PLAUSIBLE deniability regarding his responsibility under that statute. This is by DESIGN. INTENTIONAL BLINDNESS so that the people cannot hold him accountable for his failure by the NUMBERS.
When are the people of this country finally say ENOUGH IS ENOUGH regarding the lack of testing?
another community
on Apr 19, 2020 at 3:35 am
on Apr 19, 2020 at 3:35 am
@ R.F.
How are we "well on our way to herd immunity"? This data reflects that 50 out of 3,330 people tested positive for antibodies. That is 1.5% of the sample group. How is 1.5% considered well on our way to herd immunity?
When you take false positives into account (this test was not even FDA approved), and the fact that the sample pool was not random (self selection bias; these were volunteers who were more likely to have had covid like symptoms prior to the study), then the actual % of positive cases could be much lower.
Nobody is arguing that there are many more cases than the number that have been confirmed. But the 50-85x is blown way out of proportion. They took the 1.5% (which is probably over inflated to begin with), then marked it up to an even higher percentage (2.5-4.2%) and said that since x percent came back positive out of 3,330 then we have x number of cases in this county, which is y % higher than reported. The numbers they are using are too high. And you cannot extrapolate out to other areas of the country because we have such limited testing here compared to other areas like NYC. You can't say that just because our number of cases is 10x higher than reported that their number of cases is 10x higher than reported if they test 20x as many people as we do.
another community
on Apr 19, 2020 at 3:31 pm
on Apr 19, 2020 at 3:31 pm
This is really shoddy work by Stanford. As mentioned by others, opponents of the shutdowns have latched on to the study and used it as justification to lift all restrictions. The good folks who work on the front lines at Stanford Medicine must be livid with their irresponsible colleagues who have botchd the public messaging of the study results.
Monta Loma
on Apr 20, 2020 at 1:37 pm
on Apr 20, 2020 at 1:37 pm
Interestingly, the Stanford numbers do seem to hold up somewhat when looking at the Boston homeless shelter count and some aircraft carriers: Web Link
Monta Loma
on Apr 20, 2020 at 6:44 pm
on Apr 20, 2020 at 6:44 pm
mvresident, weren't you hawking hydroxychloroquine earlier? Called it the "Trump pill" and wondered why we weren't spending more money on it? Maybe you take a break from the amateur epidemiology and virology for a little bit...