Adjusting the immune system is still a blind spot Five years of covid. Lessons (not) learned for the next pandemic

13 January 2025

Five years after the start of the Covid pandemic, many lessons have already been learned in preparation for the next pandemic that will undoubtedly come. But some lessons have been learned better than others, argue researchers from Radboudumc and the University of Athens in JAMA. Research into adjusting an immune system disrupted by infection is still a blind spot. 

 

'We have learned many lessons from COVID-19, but how to get vaccines to low- and middle-income countries effectively isn’t one of them', the editors of Nature Biotechnology wrote recently. It is not the only criticism scientists have of the lessons we could have learned from the Covid pandemic. Referring to the saying “never waste a good crisis,” Helen Branswell argues in STAT that it is critical for public health to learn from disease outbreaks and environmental disasters. ‘figuring out what worked and what didn’t is fundamental to emergency response planning for the next time.'

 

Interaction guest and host

Apparently, five years after the start of the Covid pandemic, we are not quite there yet. In the article Host-Directed Therapy in Pandemic Preparedness, published in JAMA, Mihai Netea, Frank van de Veerdonk and Evangelos Giamarellos-Bourboulis point out a blind spot in the preparation for another pandemic. Too little research is being done on ways to adjust the immune system of sick people. According to the authors, there are clearly two pillars missing in the rigging of our pandemic preparedness. First is the study of microbe-host interactions in the early stages of a pandemic. How does our immune system respond to the new pathogen and in what way can that response be individually adjusted? This is immediately the second point: too little research into effective therapies with which the immune system of patients can be adjusted and brought back into balance. In short: more attention to what happens in a pandemic with the host's own immune system.

 

Dysregulated immune system

Netea explains why this aspect is so important: “There is a high probability that a future pandemic will be caused by a respiratory virus. After all, all pandemics of the past century were caused by a respiratory virus, with the exception of HIV. The disease process of such severe viral infections is primarily caused by a dysregulated immune response. This dysregulated systemic inflammatory response is the cause of death in most patients with influenza, not the excessive growth of the virus in the body. Even in patients with Covid, the dysregulated inflammatory response is the main cause of pneumonia and respiratory problems. For this very reason, during the Covid pandemic, new immune-regulating therapies were an important part of treatment and were also more effective than antiviral drugs.”

 

Adjusting defenses

Thus, according to the authors, the current pandemic preparedness programs should invest more in research into disrupted immune responses caused by severe viral infections. More attention is needed for the development of new immune-modulating therapies, identification of biomarkers and effective investment strategies. In short, more focus on host-targeted treatments with immunotherapeutic agents is essential, they state in their paper in JAMA.

 

Rapid evolution

In Science, Jon Cohen's article Learning from a pandemic many are forgetting calls attention to an issue closely related to the development of new immune-modulating therapies, namely the extraordinary speed at which the Covid virus is evolving. If the virus changes rapidly, the host's immune system has to anticipate quickly. These are two sides of the same coin. With the high speed of virus evolution, antibody and vaccine treatments are likely to lose their effectiveness quickly. Then more knowledge about how the virus will evolve is very useful, both for the timely development and production of vaccines, antibodies and means to readjust the dysregulated immuunsystem.

 

Covid is still here

It is estimated that more than 20 million people died from the Covid pandemic, the costs ran to $16 trillion and about 130 million people ended up in poverty, Cohen writes in Science. To add that Covid is still striking: “In October 2024, at least 1000 people died from COVID-19 each week.”

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Paper in JAMA: Host-Directed Therapy in Pandemic Preparedness - Mihai G. Netea, Frank L. van de Veerdonk, Evangelos J. Giamarellos-Bourboulis

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