The presence of antibodies to SARS-CoV-2, the virus that causes COVID-19, in a person's blood means the person has been exposed to the virus, but what that actually means in terms of immunity requires different research altogether, experts said. Widespread testing, including antibody testing in some cases, is considered a cornerstone of any plan to "reopen America" and is considered particularly important for healthcare workers. Last week, the New York Times reported data from the state of New York indicating that one out of every five New York City residents had been exposed to SARS-CoV-2, based on random testing of 3,000 people. The FDA has authorized a number of COVID-19 antibody tests under emergency use authorization, but as experts from the Infectious Diseases Society of America (IDSA) pointed out, all these tests can do is detect exposure to the virus. Recently, IDSA released its COVID-19 Antibody Testing Primer, and at a press briefing, experts cautioned that detection of antibodies does not yet equate to immunity to the virus. In fact, their recommendation was to assume people who have been exposed are still at risk of infection; people with antibodies should not change their risk-avoiding behaviors in any way. The World Health Organization also warned against the idea of "immunity passports" allowing people with antibodies against COVID-19 to travel and return to work because they would be protected against reinfection. But the organization said there is "no evidence that people who have recovered from COVID-19 and have antibodies are protected from a second infection." Determining immunity to SARS-CoV-2 requires a different approach, IDSA spokesperson Mary Hayden, MD, of Rush University Medical Center in Chicago, told MedPage Today separately. For example, monitoring individuals with SARS-CoV-2 antibodies in their blood for a year compared with individuals without these antibodies and comparing incidence of COVID-19 infection. "If antibodies were protective, fewer patients in the antibody group would develop infection," she said. Laboratory methods may also be used, where the virus is grown in cell culture and antibodies are added. Hayden noted, "If the virus dies, the antibodies are said to be 'neutralizing' and would be predicted to protect a person from infection." (Still, in vitro evidence like this would not constitute proof.) SARS-CoV, the virus that caused SARS, is the closest "analogy" to SARS-CoV-2, Warner Greene, MD, PhD, of the University of California San Francisco and director of the Center for HIV Cure Research at Gladstone Institutes in San Francisco, told MedPage Today. What seemed important for SARS was "the formation of antibodies that blocked binding of the spike protein" to the ACE2 receptor, but that the T cell response was also important, he added. "Both the antibody side and the T cell side combined to create potent immunity against SARS," he said. "Though it's not been proven in SARS-CoV-2, we anticipate people who launch an immune response will be protected." People infected with SARS continued to have a good immune response for 6 years, though Greene said immunity "waned over time," and likely would have required a vaccine had SARS come back. He also pointed out SARS-CoV-2 is obviously a "different subtype" of virus than SARS. Immunity can also be documented through human challenge studies, where people with and without antibodies would be deliberately exposed to the virus and development of active infection then compared. Hayden noted that this would not be ethical for COVID-19, given its potential lethality and lack of effective treatment. The common cold coronavirus could serve as a viral "surrogate" for immunity studies, Hayden said, and a few small human challenge studies have been performed with it. "My take on these studies overall is that they indicate that many humans exposed to these common cold coronaviruses develop infection," Hayden said. "When challenged again with the same virus, they either don't develop infection or they develop a milder form of the infection." In these cases, Hayden said, antibody detection correlates with protection from future infection, but "the concentration of antibodies in the blood wanes over a few years." At the IDSA briefing, experts emphasized that more research is needed about what the results of antibody testing mean and how can they be used to control the COVID-19 pandemic. IDSA spokesperson Liise-anne Pirofski, MD, of Albert Einstein College of Medicine in New York City, warned of potential cross-reactivity from other coronaviruses in antibody testing, and suggested the idea of a "confirmatory test," similar to HIV, with the ability to "validate certain proteins of the virus as markers of a good antibody response." "The virus has not been around long enough for us to draw conclusions about antibodies," she said. "We just don't know yet." Source
