In a startling finding, new Stanford research reveals that the COVID-19 virus is far more widespread than presumed, with an estimated 2.5% to 4.2% of Santa Clara County residents carrying antibodies to the pathogens.
An invisible and perhaps benign companion, the virus may have infected between 48,000 and 81,000 people in the county by early April – 50 to 85 times more than the number of official cases at that date, scientists calculate.
“The most important implication is that the number of infections is much greater than the reported number of cases,” concludes the research paper, published Friday morning in the online journal medRxiv.
“Our estimate also suggests that, at this time, a large fraction of the population remains unexposed in Santa Clara County,” it adds.
The results represent the first large-scale community-based prevalence study in a major U.S. county completed during the rapidly changing pandemic, using newly available test kits. Santa Clara County, home to Stanford University and 1.9 million residents, was one of the first hotspots for the coronavirus in the country.
The news comes at a time when health experts and elected officials look to immunity as one way to blunt the impact of the pandemic. It is not yet known if antibodies prevent future infection. If so, antibody protection could offer people a safe route out of strict “sheltering.”
The research also implies that the death rate is far lower than believed. At the time of research, 69 county residents had died – a fatality rate, based on estimated infections, of only 0.12 to 0.2%. California’s assumed death rate, based only on confirmed cases, is 3%.
More encouraging news: Unlike New York, Santa Clara County’s hospitals have yet to be overwhelmed. Fewer than 600 people are being treated for the virus at hospitals throughout the Bay Area.
The project, led by Dr. Eran Bendavid, an infectious disease specialist and professor of medicine with Stanford Health Policy, shows whether someone has been infected by the virus in the past. They recruited participants by placing targeted advertisements aimed at Santa Clara County on Facebook. They used Facebook because it allows for targeting by zip code and sociodemographic characteristics.
In contrast, COVID-19 virus testing only tests people with significant symptoms. It does not measure the true number of people who have been infected by the virus, many of whom have no symptoms or very mild symptoms.
The study’s estimate that tens of thousands of Santa Clara County residents have already been infected with the virus highlights how the profound shortage of testing has plagued efforts to understand and control the spread of the disease in the U.S. Santa Clara County recorded its first case of the virus on Jan. 31, but it took more than a month for health officials to understand the scope of how far COVID-19 had spread.
Santa Clara County residents welcomed the arrival of community-based data, saying it could guide social strategies.
“The question has always been: who needs to be isolated? Why everyone?” said Rich Altmaier of Cupertino, who hopes the higher prevalence and lower fatality rate will lead officials to re-think restrictions. “I have been in heartsick fear for the number of people with no income, no savings, and soon no food.”
But Palo Alto resident Martha Shirk said “I’m actually disappointed by the low prevalence. I think that all of us who had any kind of illness this winter harbor a secret hope that we had already been infected and hence will have robust antibodies that will confer protection. I have a two-month-old granddaughter just a few miles away whom I’ve barely gotten to know.”
Several other teams worldwide have also started testing population samples. Like Stanford, they’ve found that there’s a large underestimate of infections.
Reports from the Italian town of Robbio, Italy, where the entire population was tested, suggest at least 10% rate of infections. A survey in the western Germany municipality of Gangelt, highly affected by illness, found a 14% positive rate.
A UC Berkeley project, which will begin in May, will test a large and representative swath of 5,000 East Bay residents. Scientists will take saliva, swab and blood samples from volunteers between the ages of 18 and 60 around the region. The Colorado town of Telluride — and soon, the Marin County town of Bolinas – also plan antibody testing.
Stanford’s hospitals are currently testing healthcare workers. Within two months, the university says it will offer tests to the general community.
In the U.S., a multiyear project supported by the Centers for Disease Control and Prevention is already collecting samples from blood donors in six major urban areas to create a picture of nationwide antibody prevalence.
The Stanford researchers tested 3,330 people on April 3 and April 4 at three locations spaced across Santa Clara County — two county parks in Los Gatos and San Jose, and a church in Mountain View — to gain a snapshot of how many people in the county had already been infected, but weren’t seriously sick and didn’t realize it.
“This is critical information,” said principal investigator Bendavid, in an April 3 interview.
Repeated serologic testing in different geographies, spaced a few weeks apart, could create a broader picture of the extent of infection over time, he said.
The wide range in estimates — 2.5% to 4.2% — is based on what’s known about the performance of the test kit, made by Minnesota’s Premier Biotech. Its sensitivity and specificity would push the number higher or lower.
The team’s protocol was informed by a World Health Organization protocol for population-level COVID-19 antibody testing.
Because volunteers were disproportionately white and female, relative to the county’s demographics, the team’s data scientists had to make statistical adjustments. Those imbalances were addressed by giving less computational “weight” to white women. Latino and Asian volunteers, who were underrepresented, got greater “weight.”
There are other potential biases. The research may have favored people in good health who could drive to a testing site, or those with prior COVID-like illnesses who wanted antibody confirmation.
Like all other emerging COVID-19 research papers, the work has not been peer reviewed. (Conventional publication can take as long as a year.) Santa Clara County Department of Public Health holds the copyright on the paper.
Until now, we’ve underestimated the prevalence of the illness because our current virus testing started too late, missing cases, according to the researchers. Viral testing also misses people who are newly recovering from infection – or, significantly, people who have few or no symptoms.
The test measures so-called “neutralizing antibodies,” which are proteins that prevent infection by binding to the part of a virus that latches onto and enters a person’s cell. It then hijacks the cell’s genetic machinery to make millions of copies of itself.
These are the same cells that COVID-19 survivors are donating to Bay Area blood banks in an effort to save sick patients.
Now researchers are scrambling to answer questions: Do these antibodies protect against reinfection? Are particular types of antibodies key? What level of antibodies is required for immunity? And how long do they persist?
In an ideal world, the antibodies for COVID-19 would act like those for chicken pox, providing lifetime immunity.
Early research suggests a more complicated picture, clarified by time, global cooperation — and more Stanford-like tests.
Read the study: https://www.medrxiv.org/content/10.1101/2020.04.14.20062463v1
