If there's one thing the world has learned so far in the course of the COVID-19 pandemic, it's the important role of testing for the disease. The ability to know who has the virus and who doesn't provides critical information for people and entire regions.
Early testing involved collecting cells from the back of the throat or nasal passages of patients to detect genetic material from SARS-CoV-2, the virus that causes COVID-19. These tests, known as polymerase chain reaction (PCR) tests, can pick up the presence of viral nucleic acid. Mayo Clinic's speedily developed PCR test filled a critical need when tests were in short supply across the country.
Researchers also are interested in developing a type of testing known as serology. This kind of testing involves looking for the patient's immune response to the virus in blood samples. Specifically, these tests track down antibodies, which are small proteins created by the immune system in the process of fighting off a disease. Antibodies can be particular for one kind of disease or sometimes a disease-type, and can provide a window into a patient's infection history. The ability to detect antibodies against SARS-CoV-2 can reveal whether a patient has had COVID-19, even if they were never diagnosed or never felt sick.
For one, a serologic test can reveal whether a person might have developed immunity to COVID-19. Researchers haven't determined yet whether a person who has had and recovered from COVID-19 is protected from getting it again. But anecdotal evidence from China; preliminary studies in animal models; and experience from previous outbreaks, like severe acute respiratory syndrome and Middle East respiratory syndrome, suggest this might be the case.
Having a serologic test may provide the opportunity to tell, for example, whether health care workers have developed immunity. Although such health care workers would still be required to wear personal protective equipment, they would be at lower risk for getting re-infected, compared to health care workers who do not have this immunity.
A serologic test also might be used to determine the levels of COVID-19-related antibodies in a person's blood ― information that may be useful in the experimental treatment known as convalescent plasma therapy. Plasma is the component of the blood with no blood cells. The idea behind this treatment, which involves giving patients an infusion of antibody-rich plasma from those who have recently recovered, is that COVID-19 antibodies might neutralize the virus or jump-start a patient's own immune response. Researchers studying COVID-19 in China have suggested in two small case studies of patients that this pre-antibiotic era approach to treating infectious diseases might be a useful tactic in the pandemic. But studies of previous coronaviruses suggest that donors need to have high levels of antibodies in their blood for the therapy to work.
While the blood test is not used for intial diagnosis, on a large scale, serology also can provide essential information in tracking where the disease has been and forecasting future hot spots. The virus may no longer be detectable in some people, but confirming whether a population has been exposed can reveal which geographic areas are vulnerable and which are not.
Recognizing the importance of serology and how much it can contribute to fighting the pandemic, companies and medical research centers across the world are eagerly developing antibody tests. One new test, based on a widely used approach for detecting specific proteins, called ELISA, appears to be capable of reliably detecting SARS-CoV2 antibodies. ELISA stands for enzyme-linked immunosorbent assay. Mayo Clinic evaluated multiple different commercially available serologic tests and recently selected one that shows excellent clinical sensitivity and specificity to be used as part of clinical trials for convalescent plasma donors and patient testing in the coming weeks.
"ELISA tests are high-throughput assays used throughout laboratory medicine," says Elitza Theel, Ph.D., director of Mayo Clinic's Infectious Diseases Serology Laboratory. "In the realm of testing for infectious diseases, they are used to detect antibodies against, or proteins released from, various different infectious pathogens.
For COVID-19, a specific protein from the SARS-CoV-2 virus is used as the target antigen in the ELISA to detect any antibodies in patient serum that can recognize that specific viral protein.
"We look for a specific level of 'signal' from the test," says Dr. Theel. "If the patient sample has a signal level above the threshold, the result is considered as positive, indicative of the presence of antibodies against SARS-CoV-2."
What's clear is that serology will contribute to wide-ranging areas of COVID-19 diagnosis, treatment and research. Researchers will want to use serology to learn more about timing. For instance, how soon after infection do patients with COVID-19 develop antibodies? This information may help track the progress of the disease. How long do COVID-19 antibodies last in the body? The answer will be helpful in the development and scheduling of an eventual vaccine. Ultimately, serology will provide a crucial tool to track and address the pandemic.
Mayo's test will launch in early April, but it will not be widely available for some time due to limited availability of components.