Something weird is going on with white blood cell (WBC) counts, but I’m currently leaning towards believing something else is causing it.
Specifically, they’re seeing T-cell lymphopenia & neutrophilia during acute infection (too few lymphocytes, too many neutrophils), along with blood-clot markers (high D-dimer, a thrombosis indicator, presages death).
T-cells seem to be the worst-hit WBC (hyper-activated, decreased numbers), and I’d have expected them to be close to immune to Fc-based ADE once mature; they only express the receptor while young.
This points to some other factor being at play, and leans me against ADE being a major determinant of individual disease severity. I still expect vaccine development to be challenging, and to come with risks of bad reactions if there is not extensive animal testing (since SARS-1 and MERS vaccines repeatedly ran into issues, including for a vaccine against N-protein that shouldn’t trigger ADE in-vitro).
A few theories I’ve seen floating around for the blood results (I’m sure there’s more out there):
This old (2008) SARS-1 paper posits that glucocorticoid reaction (too much cortisol) could be an upstream cause of the lymphopenia + neutrophilia reaction seen in SARS, RSV, Ebola.
Something is causing/reacting to the cytokine storm
Both severe COVID19 disease and bad vaccine reactions steer towards Th-2 type immune responses (vaguely allergy-like responses)
I haven’t deep-dived this.
If I want to follow up on this, from a paper-skim it seems to be a Th2-type cytokine reaction. Confused about IL-10 results.
Some sort of immune-cell suppression effects, either infecting or indirectly impacting cells at an earlier stage of blood cell development/differentiation.
Something weird is going on with white blood cell (WBC) counts, but I’m currently leaning towards believing something else is causing it.
Specifically, they’re seeing T-cell lymphopenia & neutrophilia during acute infection (too few lymphocytes, too many neutrophils), along with blood-clot markers (high D-dimer, a thrombosis indicator, presages death).
T-cells seem to be the worst-hit WBC (hyper-activated, decreased numbers), and I’d have expected them to be close to immune to Fc-based ADE once mature; they only express the receptor while young.
This points to some other factor being at play, and leans me against ADE being a major determinant of individual disease severity. I still expect vaccine development to be challenging, and to come with risks of bad reactions if there is not extensive animal testing (since SARS-1 and MERS vaccines repeatedly ran into issues, including for a vaccine against N-protein that shouldn’t trigger ADE in-vitro).
A few theories I’ve seen floating around for the blood results (I’m sure there’s more out there):
This old (2008) SARS-1 paper posits that glucocorticoid reaction (too much cortisol) could be an upstream cause of the lymphopenia + neutrophilia reaction seen in SARS, RSV, Ebola.
Something is causing/reacting to the cytokine storm
Both severe COVID19 disease and bad vaccine reactions steer towards Th-2 type immune responses (vaguely allergy-like responses)
I haven’t deep-dived this.
If I want to follow up on this, from a paper-skim it seems to be a Th2-type cytokine reaction. Confused about IL-10 results.
Some sort of immune-cell suppression effects, either infecting or indirectly impacting cells at an earlier stage of blood cell development/differentiation.
We’ve found some additional receptor-binding affinities for SARS-CoV-2, so it’s not just ACE2-binding. But by far the most productively-infected tissues seem to be the lungs and bowels.
I have the impression that it’s not productively replicating in white blood cells, but also feel that doesn’t totally rule out interference with them.