'Now everyone's an immunologist': How COVID-19 helps improve understanding of immunology
Click Here to Manage Email Alerts
SCOTTSDALE, Ariz — The study of COVID-19 may in turn improve the understanding of immunology by demonstrating that the immune system is “highly alive,” said a speaker at the Basic and Clinical Immunology for the Busy Clinician symposium.
“The whole job of the immune system is to protect the body from danger but not to harm us,” Leonard Calabrese, DO, RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic, and chief medical editor of Healio Rheumatology, told attendees at the hybrid meeting. “I am going to use COVID-19 as a model of how this actually works.”
To begin, Calabrese reviewed a few familiar data points regarding the pathogenesis of COVID-19 infection, from acquisition and the initial innate immune response to viral proliferation.
“Within 5 to 7 days, adaptive immunity kicks in,” he said. “Within 10 days, all antibodies are formed.”
Calabrese added that almost everyone will develop a CD4 response while most will demonstrate a CD8 response.
At this point, most patients will improve. However, those who progress to a third stage of infection may require hospitalization or die due to a heightened immune inflammatory response.
According to Calabrese, this intersection — at the understanding of the immune system and the advent of COVID-19 — may push knowledge of immunology forward.
“Stage 3 is still a very important, enigmatic and instructional phase of this disease,” he said.
Regarding the myriad known immune response triggers, Calabrese noted infection, but also foreign antigens and other dangers to the body.
“It is far more refined than we had given it credit for,” he said of the immune system.
In particular, the definition of what could be considered a “danger” to the body has evolved, according to Calabrese.
“These dangers may be in much different forms than we knew of even 10 or 20 years ago,” he said. “Our immune system can be triggered by what we call neuro-psycho-immunologic triggers.”
Changes in atmosphere could cause this, along with climate change, social determinants of health and exposure to pollution.
“Our brains are intimately tied to our immune system,” Calabrese said. “There is a two-way street between the brain and the immune system.”
All of this is relevant to COVID-19, according to Calabrese, as, in addition to the virus itself, the disruption and stress of the pandemic may be a trigger of certain immune responses and compound the viral infection.
These effects may work in concert with the immunological impacts of the virus that implicate the key players in the immune response. For example, when the virus penetrates the cell, it “engages multiple toll-like receptors (TLR), particularly those that recognize RNA,” Calabrese said.
The virus then disrupts the homeostasis of the immune system and activates the inflammasome. Interleukin-1 is implicated, while proteins react to other TLR, including TLR-3.
“All of this can generate interferon response and inflammation,” Calabrese said. “The choreography of the inflammation is so important to how we exist.”
COVID-19 can disrupt that choreography. Although the amount of research on SARS-CoV-2 can be overwhelming to comprehend, Calabrese suggested that understanding the role of interferon in the creation of autoantibodies could hold an important clue to understanding not only the pathogenesis of the virus, but of the immune response to any infection or assault.
“Are interferons driving severe COVID?” he said. “Are they just passengers in the car? We still don’t know.”
However, there are a few certainties that may serve as building blocks to answer these questions.
“Interferon is your friend when it is functioning as an antiviral,” Calabrese said. “It is a foe when it is causing inflammation.”
To that point, he offered a tip for managing patients with the virus.
“Early on you want to bolster the defenses, later on you want to use the anti-inflammatory,” Calabrese said. “COVID has shown us that the immune system is highly alive.”
He added that the heightened focus on the immune system will be a positive for the medical and scientific communities overall.
“A few years ago, if I was at a cocktail party and said I worked in immunology, no one cared,” Calabrese said. “Now everyone’s an immunologist.”
Collapse
Calabrese L. Advances in Immunology for the Non-Immunologist: The human immune response at 30,000 feet – History and COVID-19 as the model. Presented at Basic and Clinical Immunology for the Busy Clinician, Feb. 25-26, 2023; Scottsdale, Arizona (hybrid meeting).
Click Here to Manage Email Alerts