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.