Trained Immunity and COVID-19

Priming the innate immune system could prepare our immune system for a future viral attack by SARS-CoV-2, the cause of COVID-19, and prevent infection and even clear the infection faster. A viral infection can induce memory T cells in humans, influencing the severity of disease after reinfection.

The term "trained immunity" refers to the long-term functional reprogramming of innate immune cells. Cells of the innate immune system can remember earlier encounters with pathogens. It is now well established that macrophages, monocytes, and natural killer cells show enhanced responsiveness when reencountering a pathogen.

A host's immune responses are divided into innate immune responses and adaptive immune responses. The innate immune system reacts rapidly, whereas the adaptive immune system is slower but developing a more specific immunological memory. Observations from specific mammalian models of vaccination showed that protection from reinfection could occur independently of T and B lymphocytes. Hence, innate immunity can display adaptive characteristics after challenged with a pathogen or their products. This type of immunological memory is known as "trained immunity" or "innate immune memory."

Recently, Kolodny et al. suggested that the innate immune system's priming could be a way to prepare a human's immune system for future viral attacks such as the infection by SARS-CoV-2, the cause of COVID-19.

How can this be achieved?  The administration of a standard vaccine or any reagent that elicits a broad anti-viral innate immune response could do the job.

Several points will need to be considered when selecting this approach:

  • Ensure that the priming does not evoke an autoimmune response.
  • Select and test priming agents that do not trigger adverse effects.
  • Select agents that reduce the likelihood of immune system dysregulation and hyper-inflammation.

However, to achieve this, carefully designed clinical trials may be needed to determine this approach's risks and opportunities.


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Kolodny O, Berger M, Feldman MW, Ram Y. A new perspective for mitigation of SARS-CoV-2 infection: priming the innate immune system for viral attack. Open Biol. (2020) 10:200138.

Mihai G. Netea, Leo A. B. Joosten, Eicke Latz, Kingston H. G. Mills, Gioacchino Natoli,Hendrik G. Stunnenberg, Luke A. J. O’Neill, Ramnik J. Xavier; Trained immunity: A program of innate immune memory in health and disease Science  22 Apr 2016: Vol. 352, Issue 6284, aaf1098. [sciencemag] [Figures and Table]