Covid-19: First U.S. blood antibody results

“Infection much more widespread,” Stanford researchers conclude

Photo: KATE SELIG/The Stanford Daily

irst findings of antibodies to SARS-Cov-2 in the blood of ordinary Americans came last week from Contra Costa County, California and San Miguel County, Colorado.

People with antibodies are presumed to have been infected at some point in the past, possibly without knowing it, and may be immune.

In Contra Costa Country, of 2,718 adults and 612 children whose finger-prick samples were taken two weeks ago, 1.5% tested positive for either antibody IgG or IgM. The test was organized by researchers at Stanford.

In San Miguel County, Colorado, which includes the ski town of Telluride, results for 1,975 tests processed as of 14 April showed 11 with antibodies, 30 borderline, and the balance negative. “Borderline” refers to an inconclusive “high-signal flash” that did not stay positive. Excluding them gives a seropositive rate of 0.6%

The Contra Costa County study used a disposable “white stick” test originally intended for home use, but currently not approved for it by the FDA. [CORRECTED. Text originally stated the San Miguel County was also a “white stick” test. It was a lab-run ELISA, as described below.]

While laboratory-performed “ELISA” blood antibody tests are reliable and been used for years, the reliability of the new Covid-19 “white stick” tests is uncertain.

Still, dozens of companies, perhaps as many as 90, are in a rush to get theirs approved and onto the market.

“Every scientist and his dog is trying to make this test,” James Gill, a clinical lecturer at Warwick Medical School in Coventry, England, told Bloomberg Business Week on Thursday.

The white sticks suffered a setback in the UK last week when Public Health England cancelled an order for 3.5 million of them. Its evaluation committee said they weren’t good enough.

The Oxford professor who chaired the evaluation committee did add that the kits were improving and might be ready for prime time within a few months.

After describing physical hazards faced by the tests, James Gill added, “If your test can survive all that and give the accurate result, your lab is going to make an awful lot of money.”

Preliminary conclusions controversial

Given the potential for error by the sticks and near single-digit number of people testing positive, some researchers believe only tentative conclusions should be drawn from the recent results.

The authors of a report published Friday on the Stanford tests did speculate, concluding:

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

and went on to say:

it suggests that the number of infections is 50–85-fold larger than the number of cases currently detected in Santa Clara County

The Santa Clara County COVID-19 Cases Dashboard reports 1,870 confirmed cases as of 17 April.

That would place the true number of people in the county who have been infected between 90,000 and 150,000.

Applied to the United States as a whole, 50 times would put the total number of infected at 36 million, while 85 times would place it at 61 million.

Implication on infection mortality rate

If the true number of those infected in the general population is very large and been significantly underestimated, a key metric used in epidemiology, the infection mortality rate (IFR), is conversely lower.

The IFR estimates the fatality rate in all those with infection, both those with the detected disease (confirmed cases) and those who are undetected — asymptomatic and, for Covid in the U.S. today, likely not tested.

Dr. Jay Bhattachary

Diseases with low IFRs are more like flu, and less like Ebola.

Two of the co-authors of the Stanford report, Dr. Eran Bendavid of Department of Medicine and Dr. Jay Bhattachary of the Stanford Department of Epidemiology and Population Health, have argued that SARS-CoV-2 is more prevalent, but less deadly, than thought.

The two together wrote an Op-Ed that appeared in the Wall Street Journal on 24 March. They called what was then the World Health Organization’s 3% to 4% estimate of the case fatality rate for Covid-19 “deeply flawed,” and based on insufficient evidence.

The case fatality rate (CFR) is the number of reported deaths per reported cases. A good current estimate (April 12, 2020) for the Covid-19’s CFR is 0.72%, according to the Oxford Center for Evidence-Based Medicine.

In March, after the Wall Street Journal article appeared, Dr. Bhattacharya was asked to appear on “Tucker Carlson Tonight.” He told Carlson then “Per case, I don’t think it’s as deadly as people thought.”

Antibody test was performed with home-use “white stick”

The blood drawn during the drive-thru on Friday, April 3 and Saturday, April 4 went into small stoppered vials.

However, the antibody test itself was actually run on a one of the disposable “white stick” tests originally developed for home use.

The convoluted reason involves the FDA’s current position that while the white sticks are not suitable for home use, it does not object to them being used in a qualified lab, which presumably also has a “gold standard” ELISA bench test against which to validate them.

Yet except for this regulation, those driving in for the test might have had their (potentially inaccurate) results in 10 minutes.

The white sticks used in Santa Clara County came from Premier Biotech of Minneapolis, Minn., who is US distributor for a kit manufactured by Hangzhou Biotest Biotech, Co., Ltd.

How the test is given (Premier Biotech; 1:13)
Premier Biotech kits in the box.

Hangzhou Biotest Biotech is one of many companies making the tests. Many of the Chinese firms are located in Hangzhou.

Hangzhou Biotest Biotech does not appear to have any connection with “Safecare Bio-Tech,” a different Hangzhou company whose early kits were rejected as detective by the Spain’s Health Minister.

However, it is the same kit that got a Huntington Beach, Calif. — based marketeer, Wellness Matrix Group, in trouble for advertising it as “FDA Approved” in late March. Wellness Matrix was offering the kits online for $49.95.

The FDA does not appear likely to approve any of the white stick kits for home use anytime soon, although on Saturday afternoon 4 April, while blood samples were still being taken in Palo Alto, California Gov. Gavin Newsom created some confusion about that in a press briefing.

Newsom said he had been talking with the FDA and anticipated approval for the “Stanford test” in “a matter of hours.”

Newsom was apparently referring an entirely different test, a molecular (PCR) test developed by Stanford Health Care Clinical Virology Laboratory. That lab had earlier asked for FDA approval of that test. The FDA did on 8 April.

Colorado contortions

The FDA requirement that tests be performed in a lab also contributed to delay and confusion in San Miguel County, Colorado.

Two part-time residents of Telluride, Mei Mei Hu and her husband, Lou Reese, are owners of privately-held United Biomedical Inc. based in Hauppauge, Long Island, New York.

The couple offered to provide blood antibody testing for Telluride and the surrounding county, which has roughly 8,000 residents.

By the end of March, volunteers had collected 4,285 blood samples from county residents, but per FDA rules the samples had to be shipped back to the lab in Hauppauge. That village, along with the rest of New York, was then being put under lockdown.

An early round of tests on 645 San Miguel County first-responders and health care workers was expedited. All tested negative. Additional results have appeared at irregular intervals.

Die „Heinsberg Protokolls“

In Europe, Germany is leading in large-scale blood antibody tests.

The first was in the German district of Heinsberg, in North Rhine-Westphalia, bordering the Netherlands. In February, a local carnival in the Old Town of Gangelt transformed the area into the site of one of Germany’s largest outbreaks.

Researchers from the University Hopsital Bonn started taking blood in the area 31 March.

The 1,000 participants invited were statistically selected to mirror all Germany demographically. They included children and came from approximately 400 households.

The participants filled out questionnaires, had throat swabs taken, and blood drawn. The blood test were lab-run for antibodies IgG and IgA.

Preliminary results announced 9 April for 500 tests found that 14% had antibodies while 2% proved to be actively infected at the time they were interviewed.

A much larger test for Munich, with 3,000 participants, was announced 3 April using what the Germans now call the „Heinsberg Protokolls“. That test will be under the direction of Michael Holscher, Director of the Tropical Institute at Munich University Hospital.

Blood Banks

Blood banks are an obvious place to find blood to test for antibodies, although finding blood donated recently enough to be of interest may be a challenge.

Oxford Immunology Consortium tested 1,000 donations from Scotland, 500 taken 17 March 2020 and the remainder 21–23 March. It found 6 in the 21–23 March 2020 cohort containing anti-SARS-CoV-2 antibodies. These were lab tests were performed by both pseudotype neutralization assay and ELISA.

The CDC is planning to do something like that in the U.S., but not until this fall. It as said it will study blood banked from donors in six major urban areas, including New York City, Seattle and Minneapolis.

Editorial Commentary (Will Bates)

  1. It is regretful that we don’t have more information from the 50 positives. What did they think they had, and when?
  2. The “white stick” market is becoming something of a Wild West. We need to be careful the valuable baby, blood antibody testing, doesn't get thrown out with the bathwater.
  3. There are already some Consumer Reports type efforts to rate the white sticks. One ranking I’ve seen by manufacturer is: AutoBio Diagnostics > Dynamiker Biotechnology = CTK Biotech > Artron Laboratories > Acro Biotech ≥ Hangzhou Alltest Biotech. I have no idea of Hangzhou Alltest Biotech is the same as one of the other Hangzhous.

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Will Bates writes about science, technology, and business. His journalism has appeared in the New York Times, the Wall Street Journal, and numerous magazines.