News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
Sign In

US Works with Clinical Laboratories to Launch Several Large-Scale COVID-19 Serological Surveys to Track Undetected COVID-19 in the Nation’s Population

Though some experts claim widespread antibody testing is key to effective public health safety, the WHO warns positive serological tests may not indicate immunity from reinfection or transmission of SARS-CoV-2

It may be the largest program of clinical laboratory testing ever conducted in the United States. Health officials are preparing to undertake large-scale serological surveys (serosurveys) to detect and track previously undetected cases of SARS-CoV-2, the novel coronavirus, that causes the COVID-19 illness.

Microbiologists, epidemiologists, and medical laboratory leaders will be interested in these studies, which are aimed at determining how many adults in the US with no confirmed history of SARS-CoV-2 infection actually possess antibodies to the coronavirus.

Serological screening testing may also enable employers to identify employees who can safely return to their job. And researchers may be able to identify communities and populations that have been most affected by the virus.

Serological Study of COVID-19 Taking Place in Five States

In an interview with Science, Michael Busch, MD, PhD, Senior Vice President, Research and Scientific Affairs of Vitalant (formerly Blood Systems), one of the nation’s oldest and largest nonprofit community blood service providers, and Director of the Vitalant Research Institute, discussed several serological studies in which he is involved. The first study, which he said is being funded by the National Institutes of Health (NIH), is taking place in six metropolitan regions in the US: Seattle, New York City, San Francisco, Los Angeles, Boston, and Minneapolis.

The interesting twist in these studies is that they will test blood samples from people donating blood. In March, participating blood centers in each region started saving 1,000 donor samples per month. Six thousand samples will be assessed monthly for a six-month period using an antibody testing algorithm that enables researchers to monitor how people develop SARS-CoV-2 antibodies over time.

Busch told Science this regional study will evolve into three “national, fully representative serosurveys of the US population using blood donors.” This particular national serosurvey will study 50,000 donations in September and December of 2020 and in November 2021.

“We’re going to be estimating overall antibody prevalence to SARS-CoV-2 within each state, but also map it down within the states to regions and metropolitan urban areas, and look at the differences,” Busch told Science, which called the serosurvey “unprecedented.”

“It’s certainly the largest serosurvey I’ve ever been involved with,” Busch said.

Serological versus PCR Testing for COVID-19

Unlike polymerase-chain-reaction (PCR)-based COVID-19 diagnostic testing, which uses nasopharyngeal swabs to detect the presence of viral RNA, serological testing such as LabCorp’s 164055 IgG test looks for the presence of SARS-CoV-2 antibodies in blood samples. A positive test indicates a previous infection.

In the third NIH serosurvey, according to Busch, NIH blood-donor serosurveys will be compared with results from population serosurveys taking place through the University of Washington and University of California San Francisco, which involve neighborhood door knocking and sampling from hematology labs.

“An antibody test is looking back into the immune system’s history with a rearview mirror,” said Matthew J. Memoli, MD (above,) an infection disease specialist with the NIH and Director of the National Institute of Allergy and Infectious Diseases (NIAID), in a news release. “By analyzing an individual’s blood, we can determine if that person has encountered SARS-CoV-2 previously.” (Photo copyright: National Institutes of Health.)

Some of the SARS-CoV-2 serological surveys underway include:

  • The National Institutes of Health serosurvey involving as many as 10,000 adults in the US who have no confirmed history of infection with SARS-CoV-2, which will analyze blood samples for two types of antibodies—anti-SARS-CoV-2 protein IgG and IgM. Researchers also may perform additional tests to evaluate volunteers’ immune responses to the virus.
  • A World Health Organization (WHO) coordinated follow-up study to its Solidarity Trial named Solidarity 2, which will “pool data from research groups in different countries to compare rates of infection,” which WHO officials say is ‘critical’ to understanding the true extent of the pandemic and to inform policy, Research Professionals News reported.
  • In Germany, the Robert Koch Institute, the country’s disease control and prevention agency, is tackling Europe’s first large-scale COVID-19 antibody testing. Its three-phase study will include serological testing on blood from donation centers, followed by testing on blood samples from coronavirus regional hotspots and then the country’s broader population.

But Can Serological Testing Prove Immunity to COVID-19?

Dark Daily previously reported on the critical role serology testing played in Singapore to help officials use contact tracing to identify people involved in COVID-19 outbreaks. (See, “Asian Cities, Countries Stand Out in the World’s Fight Against COVID-19, US Clinical Laboratory Testing in the Spotlight,” March 30, 2020.)

However, whether having COVID-19 antibodies will make people immune to reinfection or unable to spread the disease is not yet known.

“We don’t have nearly the immunological or biological data at this point to say that if someone has a strong enough immune response that they are protected from symptoms, … that they cannot be transmitters,” Michael Mina, MD, PhD, Assistant Professor of Epidemiology at Harvard’s T.H. Chan School of Public Health and Associate Medical Director in Clinical Microbiology (molecular diagnostics) in the Department of Pathology at Brigham and Women’s Hospital, told STAT.

The Times of Sweden reported the WHO warned in mid-April that there is no proof recovering from COVID-19 provides immunity.

“There are a lot of countries that are suggesting using rapid diagnostic serological tests to be able to capture what they think will be a measure of immunity,” said Maria Van Kerkhove, PhD, the WHO’s Technical Lead for COVID-19, at a news conference in Geneva, Switzerland, the Times of Sweden reported.

“Right now, we have no evidence that the use of a serological test can show that an individual has immunity or is protected from reinfection,” she said, adding, “These antibody tests will be able to measure that level of seroprevalence—that level of antibodies—but that does not mean that somebody with antibodies [is] immune.”

In addition, the reliability and quality of some serological tests produced in China, as well as some being manufactured in the US, have come into question, the Financial Times reported.

Nevertheless, as serological testing for COVID-19 becomes more widespread, clinical laboratories should plan to play an ever-increasing role in the battle to stop a second wave of the epidemic in this country.

—Andrea Downing Peck

Related Information:

Unprecedented Nationwide Blood Studies Seek to Track U.S. Coronavirus Spread

WHO Marshalls Global Study of Coronavirus Infection

Population-based Age-stratified Seroepidemiological Investigation Protocol for COVID-19 Virus Investigation

How Many People Are Immune to the New Corona Virus? Robert Koch Institute Starts Nationwide Antibody Studies

Everything We Know About Coronavirus Immunity and Antibodies–and Plenty We Still Don’t

The WHO Warns ‘No Evidence’ of Immunity to Corona Virus for Recovered Patients

Quest for Accurate Antibody Tests in Fight Against COVID-19

Asian Cities, Countries Stand Out in the World’s Fight Against COVID-19, US Clinical Laboratory Testing in the Spotlight

Serological Antibody Tests a ‘Potential Game Changer’ and Next Phase in Efforts to Combat the Spread of COVID-19 That Give Clinical Laboratories an Essential Role

IVD Companies and medical laboratories are developing serological survey testing that will enable them to determine how widespread COVID-19 has become

While medical laboratories gear up for testing to detect SARS-CoV-2—the novel coronavirus that causes the COVID-19 illness—efforts also are underway for expanded use of serological tests that can detect whether an individual’s immune systems has developed antibodies against the SARS-CoV-2 virus, as well as serological surveys that epidemiologists will use to determine the extent of the infection in whole populations.

It can take up to eight days after onset of symptoms for a person’s immune system to develop antibodies, so serological tests are not designed for diagnosing recent or active infections, stated a Mayo Clinic news story. However, Reuters reported that the availability of serological tests is “a potential game changer” because they could identify people who are immune even if they had no symptoms or only mild symptoms.

“Ultimately, this might help us figure out who can get the country back to normal,” Florian Krammer, PhD, told Reuters. Krammer’s lab at the Icahn School of Medicine at Mount Sinai in New York City has developed a serological test. “People who are immune could be the first people to go back to normal life and start everything up again,” he said.

However, some experts advise that the presence of antibodies is not necessarily a “get out of jail free” card when it comes to the coronavirus. “Infectious disease experts say immunity against COVID-19 may last for several months and perhaps a year or more based on their studies of other coronaviruses, including Severe Acute Respiratory Syndrome (SARS), which emerged in 2003,” reported Reuters. “But [the experts] caution that there is no way to know precisely how long immunity would last with COVID-19, and it may vary person to person.”

Additionally, it is also “uncertain whether antibodies would be sufficient protection if a person were to be re-exposed to the virus in very large amounts,” such as in an emergency room or ICU, Reuters reported.

Serological Survey Studies Get Underway Worldwide

Aside from detecting potential immunity, the World Health Organization (WHO) says serological tests could be useful for widespread disease surveillance and epidemiological research.

In the US, the Vitalant Research Institute is leading several large serological survey or “serosurvey” studies in which regional blood centers save samples of donated blood for antibody testing, Science reported.

Science also reported on a similar WHO initiative in which six countries will pool data from their own antibody studies. And in the Netherlands, blood banks have begun screening thousands of blood donations for presence of antibodies, Wired reported.

FDA Emergency Use Authorization

On March 16, the federal Food and Drug Administration (FDA) announced that it would allow commercial development and distribution of serological tests that “identify antibodies (e.g., IgM, IgG) to SARS-CoV-2 from clinical specimens” without an Emergency Use Authorization (EUA). The agency noted that these tests are “less complex than molecular tests” used to detect active infections, and that the policy change is limited to such testing in medical laboratories or by healthcare workers at the point-of-care. “This policy does not apply to at home testing,” the FDA reiterated.

“Serological tests can play a critical role in the fight against COVID-19 by helping healthcare professionals to identify individuals who have overcome an infection in the past and have developed an immune response,” said FDA Commissioner Stephen M. Hahn, MD (above with President Trump during a Coronavirus Task Force press briefing), in an April 7 press statement. “In the future, this may potentially be used to help determine—together with other clinical data—that such individuals are no longer susceptible to infection and can return to work. In addition, these test results can aid in determining who may donate a part of their blood called convalescent plasma, which may serve as a possible treatment for those who are seriously ill from COVID-19.” (Photo copyright: CNBC.)

FDA Issues First EUA for Rapid Diagnostic Test

Cellex Inc., based in Research Triangle Park, N.C., received the first EUA for its qSARS-CoV-2 serological test on April 1. As with other rapid diagnostic tests (RDTs) under development, the qSARS-CoV-2 test detects the presence of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in human blood. The biotechnology company’s RDT can be used to test serum, plasma, or whole-blood specimens, stated Cellex, and can produce results in 15 to 20 minutes.

The FDA has authorized use of the antibody test only by laboratories certified under CLIA to perform moderate and high complexity tests. Cellex has set up a COVID-19 website with information about the qSARS-CoV-2 test for clinical laboratories, patients, and healthcare providers.

Other Serological Tests Under Development

Mayo Clinic Laboratories announced on April 13 that it is ramping up availability of an internally-developed serological test. “Initial capacity will be 8,000 tests per day performed at laboratory locations across Mayo Clinic,” stated the announcement. “Testing will be performed 24 hours a day, and Mayo Clinic Laboratories is working to ensure turnaround time is as close as possible to 24 hours after receipt of the sample.”

Emory University in Atlanta announced on April 13 that it will begin deploying its own internally developed antibody test. Initially, testing will be limited to 300 people per day, comprised of Emory Healthcare patients, providers, and staff members. Eventually, testing will be “expanded significantly,” said Emory, with a goal of 5,000 tests per day by mid-June.

The Center for Health Security at the Johns Hopkins Bloomberg School of Public Health lists dozens of other serologic tests that are under development, approved for use in other countries, or approved for research or surveillance purposes. Most are rapid diagnostic tests, but some developers are working on enzyme-linked immunosorbent assays (ELISA).

RDTs are typically qualitative, meaning they produce a positive or negative result, stated the Center for Health Security. An ELISA test “can be qualitative or quantitative,” noted the Center, but it can take one to five hours to produce results.

A third type of serological test—the neutralization assay—involves infecting a patient’s blood with live coronavirus to determine if antibodies exist that can inhibit growth of the virus. The test takes three to five days in a level 3 biosafety laboratory to produce results. The Straits Times reported on one laboratory in Singapore that developed a neutralization assay to trace the source of COVID-19 infections that originated in Wuhan, China.

Serological testing is another important tool clinical laboratories and epidemiologists can use to fight and ultimately defeat the COVID-19 pandemic and is worth watching.

—Stephen Beale

Related Information:

Coronavirus (COVID-19) Update: Serological Tests

Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency

Advice on the Use of Point-of-Care Immunodiagnostic Tests for COVID-19

Serology-based Tests for COVID-19

FDA Officially Authorizes Its First Serological Antibody Blood Test for COVID-19

Cellex Cleared to Market Antibody Test for COVID-19

What Are Antibody Tests and What Do They Mean for the Coronavirus Pandemic?

Cellex qSARS-CoV-2 IgG/IgM Rapid Test

IgG/IgM Rapid Test Approved by FDA for EUA Use

EDI Novel Coronavirus COVID-19 ELISA Kits

Mayo Clinic Laboratories Launches Serology Testing In Support of COVID-19 Response

;