Chronic low-grade inflammation transformed to acute life-threatening inflammation?

In COVID-19, a severe cytokine storm can occur with high levels of IL-6, which often leads to acute respiratory distress syndrome (ARDS), organ failure and death[3]. It is intriguing to consider that this involvement of high IL-6 and other inflammatory markers might suggest that the excessive immune response of the cytokine storm that occurs in severe COVID-19 might be at least partly related to the elevated inflammatory markers in the comorbid conditions discussed above.
It is interesting to consider the hypothesis mentioned above that abnormal microbiota are causing low-grade infection or dysbiosis, and chronically stimulating an immune response against them and, consequently, elevating IL-6 and CRP. Then, when the acute increase in the innate immune response occurs during the COVID-19 infection, the immune system reacts against the dysbiotic microbes as well as SARS-CoV-2. And the overall immune activation leads to antibodies against the coronavirus, but also higher levels of antibodies to some of the microbes of the dysbiotic microbiome.
Thus, the immune response targeting at least some microbial strains in the microbiome might be at least part of what leads to the excessive, dysregulated immune response in those with severe COVID-19. At least some of these dysbiotic microbes are likely to not be amenable to being eliminated by the immune system for various reasons discussed elsewhere, such as heterologous infection and immunodominance[12]. Thus, the increased immune response against these dysbiotic microbes during COVID-19 may not always be reversible and instead may lead to prolonged intense inflammation culminating in organ failure.
Severe COVID-19 disease in younger people could be at least partly explained by dysbiotic microbiomes occurring earlier than usual due to a variety of chemical and microbial exposures, inherited microbiomes, air pollution, occupational exposures, diet and lifestyle factors, as well as previous antibiotic use, which might also lead to elevated IL-6 and CRP. The ability of some healthy elderly patients to recover from infection with COVID-19 could be due to a more balanced or “healthy” microbiome with little, if any, of the more pathogenic/dysbiotic species or strains, as has been indicated in association with healthy aging[104].
Other factors are also likely to be involved; however, it is possible that the microbiome present prior to the viral infection could play an important role in the outcome of COVID-19.