Thread by @enn_nafnlaus

Really concerning paper. I really want to know the biological mechanism behind this.

nature.com/articles/s4159…

Summary:

(a) COVID patients (community-enrolled), whether with Long COVID (LC) or not (MC), have dramatically elevated interferon levels persisting 4 months after...

..infection - something not seen in uninfected controls (UHC) or people who caught "cold" coronaviruses (HCoV). As a reminder, interferons are cytokines sound the alarm call to viral infection and form a complex regulatory network of pro- and anti-inflammatory signals. Elevated..

...levels of pro-inflammatory interferons - as observed - promote aggressive T-cell responses; symptoms can range from asymptomatic to feeling ill to serious pathological states.

(b) While in non-Long COVID patients most IFN levels have significantly declined by 8 months, in...

... Long COVID patients most experience little to no decline in a number of interferons.

(c) Plasma ACE2 activity remains significantly elevated at 4 months in both categories of COVID patients but not in uninfected patients or those infected by cold coronaviruses. Levels...

...declined significantly in both groups by 8 months. ACE2, normally a surface protein that triggers reduction in blood pressure, can change into a soluble form (sACE2) during viral entry (and some non-pathogenic conditions) detectable in blood plasma.

(d) The pro-inflammatory..

...IFN-β cytokines proved the most diagnostic for Long COVID. They did best-fit measures for diagnosing Long COVID with variations of 2, 3 or 4 measured parameters, and IFN-β was in 89%, 93%, and 94% of the best-performing fits.

5) They then measured levels of various classes...

... of immune cells. They plotted out measurements using TriGraph to cluster cells of similar types near each other. A remarkable lack of certain groupings of T cells are almost entirely absent in Long COVID patients. (1) is a grouping of naive Cd8+ (killer) T-cells; (2) is a...

... grouping of mature Cd8+ (killer) T-cells; (3) is a grouping of Cd4+ (helper) T-cells; (4) a grouping of innate T-like cells which may include natural killer (NK) cells that attack cells that (like SARS-CoV-2 causes) try to hide from T-cells by downregulating MHC-I; and ...

(5) a grouping of naive B (antibody-producing) cells.

In general, naive T and B cells were heavily suppressed. These are immune cells with a potentially new novel variable region for targeting pathogens which can become activated if a matching antigen is encountered.

Naive immune cells provide a potential reservoir of defense against new pathogens without actively causing pathology.

(6) A number of other markers of T-cell activation and T-cell exhaustion were dramatically elevated in either all post-COVID patients, only Long-COVID...

... patients, or a mix of the two.

In total: just like the sudden acute respiratory symptom that characterizes severe acute COVID-19 is associated with high levels of inflammatory cytokines and a generally dysregulated immune system, this also characterizes post-infection...

... states as well, with a particularly slow to absent recovery in Long COVID patients.

The mechanism remains unclear. "Possibilities include persistence of antigen, autoimmunity driven by antigenic cross-reactivity or a reflection of damage repair"

** ED: Not just T-cell groupings, but also B- and innate immune cells.