Thread by @jeffgilchrist

Reinfection, immune evasion, and protection of residents in LTC

This thread looks at multiple studies that help reveal why #SARS2 can #reinfect hosts and evade #immune response, #vaccine waning, and what protects residents in Ontario #longtermcare and #retirement homes. 🧵1/

An unrolled one-page web view for this long thread that may be easier to read or share can be found here (

https://twitter.com/jeffgilchrist/status/1644660799263080449

). 2/

The 1st study looks at the protection of residents in Nursing (LTC) and Retirement homes in Ontario ( jamda.com/article/S1525-… ). Their results add to accumulating knowledge that recent vaccination is important to maintain protective immunity in older adults. H/T: @MsMacrophage 3/

The study found that risk of Omicron infection was not different by age or sex. Infection risk decreased 47% with 3 vaccine doses of Moderna compared to Pfizer which they believe is likely due to the higher dose given with Moderna. 4/

They also found that risk was reduced by 81% with a 4th dose of any mRNA vaccine which suggests that vaccine-elicited immunity from a third dose wanes within several months. 5/

How does "hybrid immunity" hold up for LTC residents that had a COVID-19 infection in the past 3 months? It only reduced the risk of infection by 48%, similar to getting a 3rd dose of vaccine but much less than getting a 4th dose of vaccine. 6/

Getting infected on purpose is not something that is worth doing considering it provides less protection than a recent vaccine dose and exposes you to potential Long COVID even in mild cases. 7/

Author Dr. Bowdish believes this helps understand why hospitalization in older adults and outbreaks in LTC now occur approximately every 3 months during the Omicron era (

https://twitter.com/MsMacrophage/status/1642862895129083905

). 8/

Dr. Bowdish points out the take home message from the study is that hybrid immunity (vaccination + infection) provides minimal duration of protection in the LTC population but having had a recent vaccine works. 9/

So why is it that Omicron infection provides not very durable protection of immunity and why does vaccine protection wane after 4 months? For one, Omicron is an umbrella term for a family of variants where many mutations and additional immune evasion have occurred over time. 10/

The more community transmission there is, the more mutations happen. Let's also take a look with a few studies. 11/

A study found that many different individuals from geographically diverse locations will mount antibody responses against the same precise viral epitopes (regions of the virus that antibodies from the immune system will recognise) and not randomly ( science.org/doi/10.1126/sc…). 12/

Humans have the ability to create a range of antibodies to target viruses but we seem to create antibodies that target the same viral regions again and again ( medicalxpress.com/news/2023-04-r… ). H/T: @Drferremd 13/

The authors of the study refer to these as "public epitopes" and the study mapped 376 immunodominant public epitopes from 51 viral species to single-amino-acid resolution. 14/

That means a virus may be able to mutate a single component (amino acid) and be able to reinfect an entire population of previously immune hosts. "We find an underlying architecture in the immune system that causes people... " 15/

"...no matter where in the world they live, to make essentially the same antibodies that give the virus a very small number of targets to evade in order to reinfect people and continue to expand and further evolve," said lead author Ellen L. Shrock, Ph.D., of the Elledge lab. 16/

They also found that mice produce antibodies for many of the same "public epitopes" although it does not overlap exactly with humans. 17/

While it is more likely that a person will produce antibodies against a public epitope, some people do produce antibodies against other epitopes which may be more effective at protecting them against reinfection. 18/

"The more unique antibodies may be a lot harder to evade, which is important to consider as we think about the design of better therapies and vaccines," said Elledge. 19/

The next study looked at antibody kinetics after COVID-19 vaccination ( mdpi.com/2076-393X/11/4… ). H/T: @madistod 20/

Their findings suggest that viral evolution will decrease effectiveness of vaccine protection against severe disease, especially for individuals with less durable immune response. 21/

They also found that using an antibody binding test (which is more accessible than a neutralization level test) is reasonably predictive and may help identify individuals who need more frequent vaccine boosting than average. 22/

While countries are moving towards a once a year boosting strategy for COVID-19 like the Flu, researchers are finding that the ideal boosting frequency for the average person is 3-4 times per year ( medrxiv.org/content/10.110…). 23/

Even then, about 20% of the population remains at risk with that more frequent schedule of 3-4 doses/year due to poor antibody persistence. 24/

Additionally, the COVID-19 virus has ways to actively suppress and evade your immune system, making it invisible to some parts of the immune system long enough for it to have a chance to replicate to the level that people become infectious (

https://twitter.com/jeffgilchrist/status/1611333222419566594

). 25/

If that wasn't enough, COVID-19 can also reprogram white blood cells to reduce how well some parts of the immune system work and evade the mucus layer in our nose that is supposed to help prevent infection (

https://twitter.com/jeffgilchrist/status/1612066649934290946

). 26/

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