A Thoughtful Way To End The Covid-19 Pandemic (Part 16)

There are many lessons we can take away from the ways in which SARS-CoV-2 works to suppress and evade the innate immune system. The more we understand how and why this virus targets certain components of our immune defenses, the more effective and focused our efforts to strengthen our vulnerabilities can become, in particular for older adults and other populations at high risk for Covid-19.

The first lesson is that when we talk about innate immunity, we tend to conflate two arms of the immune system that warrant clear distinction. One is the pathway that stimulates interferon and interferon-stimulated genes. The other is the pathway that triggers inflammation through proinflammatory cytokines like tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8). Evidence suggests that while the interferon pathway has a protective function that weakens as we age, the inflammatory pathway only grows in potency, which can in fact have adverse and even lethal consequences for older adults.

The second lesson we’ve learned is that more components of innate immunity are essential to its general functioning than we initially thought. Only in recent years have researchers begun to unpack the full efficacy of innate immunity—as compared to adaptive immunity—as a line of defense against pathogens. Studies of SARS-CoV-2 add to this existing body of work by documenting the various mechanisms viruses can develop to target innate immunity with greater precision. It appears that suppression of innate immunity allows SARS-CoV-2 to replicate to higher titers more efficiently, peaking before symptoms begin to show.

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Originally published on Forbes (November 1, 2021)

© William A. Haseltine, PhD. All Rights Reserved.