Thursday, May 21, 2020

A Political Assault on Antibody Tests

If a positive test doesn’t indicate immunity, how in the world did patients ever recover from infection?

By Manish Butte and Andrew Bogan. Dr. Butte is an associate professor and chief of pediatric allergy, immunology and rheumatology at UCLA’s David Geffen School of Medicine. Mr. Bogan, a molecular biologist, is managing member of Bogan Associates LLC. Excerpts:

"some physicians are advising their patients—that antibodies may not provide immunity. This assertion defies generations of immunology research"

"Here’s how the immune system works: On viral infection, it reacts with two surges, “innate” and “adaptive” immunity. The innate response comes within minutes to hours and triggers alarms that result in effects across the body such as fever. Tissues and cells produce “interferons,” molecules that incapacitate many viruses and recruit white blood cells.

For mild infections, innate responses are sufficient to defeat the foe. But some viral infections require a second wave of response, and adaptive immune responses arrive four or five days after infection. Molecular bits of the offending pathogen, known as antigens, are brought to the lymph nodes, where white blood cells called T and B lymphocytes respond. These lymphocytes head out to the front lines—the infected tissues, such as the lung for Covid-19. The wave of T cells that arrive at the battlefront deploy the principal weapon in their arsenal, the release of cytotoxins, to kill virally infected cells. The over-aggressive immune response causes much of the devastation in severe cases of the disease.

Meanwhile, B cells pump out antibodies that over several weeks adapt to the pathogen. After the war is over, a few T and B cells linger in the lymph nodes and in the mucosa of the airways, forming an “immunological memory” that is programmed to fight faster and stronger the next time that pathogen shows up. Such cell memory provides “protective immunity,” which Thucydides first hypothesized in 430 B.C.

There is not a straightforward test to pick up the T-cell response during infection, nor for the presence of memory afterward. But the presence of antibodies can be detected from a blood sample using a serologic assay. For decades, these tests have been used as proof of immune response, a proxy for a vanquished invader, arising from either infection or vaccination."

"the lateral flow kit, which works like home pregnancy tests and can be used at a doctor’s office for rapid results."

"in a survey looking for antibodies as evidence of past infection in hundreds or thousands of people, the test is reliable enough to yield information about the progression of the pandemic, the infection rate in a population, and the fatality rate.

The laboratory-based tests authorized by the Food and Drug Administration for emergency use—those from Abbott, Ortho Clinical Diagnostics, Roche and others—are excellent."

"If these antibodies aren’t protective, then global efforts to develop a vaccine are pointless. Vaccines try to arm T and B cells so they fight quickly when exposed to the virus. If antibodies detected in a person who has recovered don’t confer immunity, then neither would antibodies developed in response to a vaccine."

"antibody levels fall over time. But that is observed in every response to infection or vaccination. The memory of B cells means the body can produce antibodies when needed in the future. If levels of protective antibodies didn’t wane rapidly after infections, the blood would become thick with antibodies over a typical winter season."

"antibody testing is the only way to identify convalescent serum donors for treatment of severely ill patients, and it is also required to qualify for some vaccine trials."

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