"Our observations could also explain why older COVID-19 patients are much more vulnerable to the disease," says senior author Shane Crotty, Ph.D., who co-led the study with Alessandro Sette, Dr. Biol.Sci., both professors in LJI's Center for Infectious Disease and Vaccine Research. "With increasing age, the reservoir of T cells that can be activated against a specific virus declines and the body's immune response becomes less coordinated, which looks to be one factor making older people drastically more susceptible to severe or fatal COVID-19."
Adds Sette, "What we didn't see was any evidence that T cells contribute to a cytokine storm, which is more likely mediated by the innate immune system." ...snip...
The effect was magnified when the researchers broke down the dataset by age. "People over the age of 65 were much more likely to have poor T cell responses, and a poorly coordinated immune response, and thus have much more severe or fatal COVID-19," says Crotty. "Thus, part of the massive susceptibility of the elderly to COVID-19 appears to be a weak adaptive immune response, which may be because of fewer naïve T cells in the elderly."
Naïve T cells are inexperienced T cells that have not met their viral match yet and are waiting to be called up. As we age, the immune system's supply of deployable naïve T cells dwindles and fewer cells are available to be activated to respond to a new virus. "This could either lead to a delayed adaptive immune response that is unable to control a virus until it is too late to limit disease severity or the magnitude of the response is insufficient," says Moderbacher.
In line with what other research teams had found before, antibodies don't seem to play an important role in controlling acute COVID-19. Instead, T cells and helper T cells in particular are associated with protective immune responses. "This was perplexing to many people," says Crotty, "but controlling a primary infection is not the same as vaccine-induced immunity, where the adaptive immune system is ready to pounce at time zero."
