One of the most important recent studies on post-COVID biology delivers a concerning message.
SARS-CoV-2 doesn’t just affect immune cells.
It can leave long-lasting changes directly in the immune proteins circulating in our blood.🧵
SARS-CoV-2 doesn’t just affect immune cells.
It can leave long-lasting changes directly in the immune proteins circulating in our blood.🧵
https://twitter.com/harryspoelstra/status/2023714217740640700
Think of the immune system in three layers.
immune cells (T, B, NK…)
signaling molecules
effector proteins - antibodies and complement
This study shows persistent changes in the deepest layer - the effector proteins themselves.
immune cells (T, B, NK…)
signaling molecules
effector proteins - antibodies and complement
This study shows persistent changes in the deepest layer - the effector proteins themselves.
Researchers analyzed blood samples from more than 400 people after COVID-19.
They identified hundreds of chemical alterations in proteins - called ncAA modifications.
It’s about proteins becoming chemically different.
They identified hundreds of chemical alterations in proteins - called ncAA modifications.
It’s about proteins becoming chemically different.
The most striking finding?
Some of these changes did not disappear after recovery.
They were still detectable up to 12 months after infection.
This suggests COVID can leave a long-lasting/persistent molecular imprint on the immune system.
Some of these changes did not disappear after recovery.
They were still detectable up to 12 months after infection.
This suggests COVID can leave a long-lasting/persistent molecular imprint on the immune system.
The most affected systems were two core pillars of immunity.
Antibodies and the complement system.
These are the main drivers of inflammation and tissue damage during immune responses.
Antibodies and the complement system.
These are the main drivers of inflammation and tissue damage during immune responses.
In antibodies, modifications appeared in the most critical regions.
The antigen-binding sites,
the Fc regions that activate immune cells and complement
In other words -
Even if antibodies recognize targets correctly, their effector strength may be altered.
The antigen-binding sites,
the Fc regions that activate immune cells and complement
In other words -
Even if antibodies recognize targets correctly, their effector strength may be altered.
The strongest signal was seen in the complement system.
Unlike coagulation changes - which mostly normalized -
many complement protein modifications persisted.
This raises concern about sustained inflammatory activation.
Unlike coagulation changes - which mostly normalized -
many complement protein modifications persisted.
This raises concern about sustained inflammatory activation.
The study highlights one particularly important mechanism - deamidation of amino acids!
This modification is
irreversible (!)
alters protein charge
can change protein function
may create new autoantigenic epitopes
In essence, it can act as a molecular memory of inflammatory stress.
This modification is
irreversible (!)
alters protein charge
can change protein function
may create new autoantigenic epitopes
In essence, it can act as a molecular memory of inflammatory stress.
The authors describe this phenomenon as structural immune imprinting.
The immune system may not only remember pathogens.
It may also carry long-lasting chemical alterations of its own proteins.
The immune system may not only remember pathogens.
It may also carry long-lasting chemical alterations of its own proteins.
So it is a strong biological signal that COVID-19 can leave a deep, long-lasting molecular reprogramming of immune effector systems.
These findings align with broader observations in post-COVID research
chronic low-grade inflammation
thrombo-inflammatory states
persistent immune dysregulation
chronic low-grade inflammation
thrombo-inflammatory states
persistent immune dysregulation
Sum:
COVID-19 may leave a lasting chemical imprint on key immune proteins - particularly antibodies and complement - potentially keeping the immune system in a chronically altered state.
Further research is urgently needed to understand the clinical impact!
COVID-19 may leave a lasting chemical imprint on key immune proteins - particularly antibodies and complement - potentially keeping the immune system in a chronically altered state.
Further research is urgently needed to understand the clinical impact!
Liu at al., Widespread ncaas Imprints in the Serum Proteome of COVID-19 Convalescents Uncovering Immune System Sequelae. mcponline.org/article/S1535-…
Ignoring these persistent immune alterations is a major public-health failure. The long-term population burden of chronic inflammation, immune dysregulation, and post-COVID illness may ultimately rival - or exceed - the acute waves of 2020–2021. @szupraha @ZdravkoOnline @adamvojtech86 @adamkova_vera
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