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3 reasons why seroprevalence studies underestimate proportion of population with some form of immunity to COVID

1) False negative: lower titer antibodies, or antibodies not targeted by assay
2) Cross immunity from prior corona virus infection
3) T cell only response to COVID
1) We have data that almost half the persons with PCR positive COVID who are asymptomatic or found by screening studies can become sero negative. Becoming sero negative doesn’t automatically mean they are not immune.
First this @NatureMedicine study: nature.com/articles/s4159…
Second is this screening study from Germany. medrxiv.org/content/10.110…
2) & 3) Several studies now suggest possible cross immunity from prior corona virus infections, or T cell only responses to COVID exposure.
See thread by @PSampathkumarMD for list of studies.
See also excellent thread by @Rfonsi1
And observations from trends in hotspots that provide support to this idea of a larger % or relatively immune population than seroprevalence studies suggest.
Updated thread by @Rfonsi1 with more details and references.
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Vincent Rajkumar
@VincentRK
@LouRaguse @nooktacular When we vaccinate we make B lymphocytes divide & make small clones of cells that make antibodies targeting the offending virus. These cells retain memory of the virus. Later if a real infection occurs they will mount a antibody response that’s more vigorous than with the vaccine
@LouRaguse @nooktacular The antibodies that the 1st exposure generates can be thought of as a biomarker that indicates generation of these B lymphocytes that target the virus. But the fact they disappear doesn’t mean that the B cells that were generated died. They seldom do. They live on as memory cells
@LouRaguse @nooktacular With some vaccines we use 2-3 doses & subsequent boosters to keep training the immune system about the virus. Everytime you do that you solidify generation of memory cells. Antibodies are a biomarker. The level measured in the blood won’t be enough to fight a big viral infection
Read 5 tweets
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Vincent Rajkumar
@VincentRK
@rajrealestate 1) We mount B & T cell responses to infections. Seroprevalence studies look for antibodies made by B cells. They don’t measure T cell response. They probably also miss low level exposure that didn’t generate enough antibody titer to meet whatever cut-off they picked for positive
@rajrealestate 2) Many studies now show that T cells reactive to SARS CoV-2 are present in blood collected way before pandemic. So there is likely some cross reactive immunity from prior corona virus infections. Corona viruses are very common. SARS CoV-2 is one type, but related.
@rajrealestate 3) T cells reactive to SARS CoV-2 have also been found much more often in close contacts of COVID patients who have no antibodies by serology. This suggests antibodies are not generated in all people who are exposed COVID.
Read 6 tweets
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Vincent Rajkumar
@VincentRK
I’m convinced that seroprevalence studies greatly underestimate the true level of immunity of a given population to COVID.
Take Sweden: point is not whether they did the right thing. I think they didn’t & lost a lots of lives. The point is given the low seroprevalence & continued lack of lockdown etc how did their COVID rates plummet? Is their seroprevalence capturing the true % of immune population
By immune I don’t mean immune from not having COVID PCR positive if you go checking for it. But immune from having symptomatic COVID. @Rfonsi1
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