NEW YORK – With initial results from serology testing indicating that upwards of 14 percent of New York residents have been exposed to SARS-CoV-2, the state continues to expand its serology survey as it works to establish the scope of the virus's spread.
The New York effort is one of a number of similar projects reporting results as researchers around the country and globe turn to antibody testing to assess the prevalence of infection.
Thus far, these efforts have found wide variations in prevalence depending on location, with, for instance, the New York State survey finding a 21.2 percent positive rate for New York City residents, while a survey of 3,330 people in Santa Clara County, California, estimated a population prevalence of between 2.5 percent and 4.2 percent.
These findings suggest that the spread of the virus has varied widely with geography and correlate roughly with the severity of the outbreak observed in these two localities: New York City (population 8.4 million) had reported 153,204 COVID-19 cases and 11,460 deaths as of April 26, while Santa Clara County (population 1.9 million) had reported 2,084 cases and 100 deaths as of the same date.
The New York study findings also found wide variations in prevalence throughout the state, with, for instance, Long Island reporting 16.7 percent positive, Westchester and Rockland counties reporting 11.7 percent, and the rest of the state excluding these areas and New York City reporting 3.6 percent positive.
The studies indicate that the number of infected people may be much larger than the confirmed case counts. However, there are questions about the accuracy of these findings, with sampling biases and test performance issues possibly skewing the results.
The New York figures were based on testing of 3,000 people statewide, with sampling done at grocery stores around the state. In total, the state has now tested more than 8,000 people, said Jonah Bruno, director of public information for the NYS Department of Health.
Developed by the Wadsworth Center, the NYSDOH's public health lab, the serology test used fingerstick samples to measure IgG antibodies against SARS-CoV-2. IgG antibodies are associated with the longer-term immune response and typically develop several weeks after infection.
Bruno said the state chose to do sampling at grocery stores as it believed it would allow researchers to access a random and diverse sample of the population as quickly as possible without creating large crowds at a particular location.
He added that the goal was to recruit between 100 and 200 subjects per store and that "store locations were selected to maximize the chances that racially [and] ethnically diverse population was reached."
Selecting an unbiased cohort is a challenge for clinical research generally and SARS-CoV-2 studies are no exception. Gov. Andrew Cuomo acknowledged this as a potential limitation during a press conference last week, noting that the survey captured people who, "by definition, are out of the home and not at work," as opposed to people who had quarantined at home who might have a lower rate of infection."
The Santa Clara study has likewise drawn criticism for its sampling approach, which used Facebook ads targeted by zip code and sociodemographic characteristics. The researchers noted that their sample was imbalanced for zip code, sex, and race/ethnicity, which led them to reweight their sample based on these characteristics during their analysis. They also acknowledged that bias "favoring individuals in good health capable of attending our testing sites, or bias favoring those with prior COVID-like illnesses seeking antibody confirmation are also possible."
Test performance is also a question. Test specificity is a particular challenge given the relatively low prevalence of positive cases even in areas with severe outbreaks like New York City. When testing for a disease with low prevalence, tests without extremely high specificity levels can generate significant amounts of false positive results.
In a press release, the NYSDOH said the test used in its survey has a specificity ranging between 93 and 100 percent. Bruno declined to provide an explanation of what accounted for that range of specificities or to give additional information about the validation process for the test.
At the high end of the specificity range, the test would generate few to no false positives. However, if specificity were at the 93 percent level, then around a quarter of positive results would be expected to be false positives assuming a prevalence of 20 percent (similar to that estimated to New York City). At the 3 percent prevalence seen throughout much of the state, around two-thirds of positive results could be false.
False positives could be problematic for the Santa Clara study, as well. While the test showed high specificity (99.5 percent) in validation work, the authors noted that if that specificity were to slip to 97.9 percent, their COVID-19 prevalence estimate would fall to below 1 percent. Validation studies for the test, produced by Premier Biotech, are still ongoing.
Other serology studies are also underway. Researchers from the University of Southern California and the Los Angeles County Department of Public Health last week released initial data from an ongoing serology study of county residents that found that between 2.8 percent and 5.6 percent of subjects had antibodies to SARS-CoV-2. The subjects were selected using a database provided by market research firm LRW Group and testing using drive-through tests at six sites across the county. The researchers did not provide information on how many subjects were tested or the characteristics or the test used and have not published the data in a paper or preprint.
Officials in Colorado's San Miguel County are working to do serology testing on every one of the county's 8,191 residents. As of April 21, the county had processed 4,757 tests, with 26 positives, 4,661 negatives, 70 indeterminant results, and 695 results still pending.
The US National Institutes of Health is also recruiting for a serology study. Conducted by the National Institute of Allergy and Infectious Diseases and the National Institute of Biomedical Imaging and Bioengineering, with additional support from the National Center for Advancing Translational Sciences and the National Cancer Institute, the study will collect and analyze blood samples from up to 10,000 volunteers. Healthy adults over the age of 18 from across the US who have no confirmed history of COVID-19 and have no current symptoms are eligible to participate and will be enrolled over the phone.