Emerging trends in correlating SARS-CoV-2 binding and neutralizing antibody titers

[gardening-girl]

Most commercial antibody binding tests discussed on this site only measure antibody binding to the corona virus Spike protein. They do not test the ability of these antibodies to neutralize the virus. Neutralizing antibody tests are more difficult and expensive and are therefore usually only done in a research setting.

A recent MedPage article quotes a physician who has tested over 400 of his patients for both binding and neutralizing antibodies and has correlated neutralization assays with commercial antibody titers primarily using the LabCorp SARS-CoV-2 Semi-Quant Total Ab test that is being used in the LLS study.

In Dr. Segev’s experience "until you reach 250 units/mL, you have little evidence of neutralization". "When you get to 500 or 1,000, it rises in a linear fashion.” "So 2,000 gives you twice as much neutralizing capability as 1,000 on a LabCorp test."

For levels below 250 units/mL, "you have, at most, a modicum of protection," he noted. Those in the 250 to 500 range who are at low risk of exposure -- working from home, taking precautions -- should get a booster, "but there's no urgency." For those in the 500 to 1,000 range who have some risk of exposure or are more vulnerable to COVID, "then you're in the 'now-is-probably-a-good-time-to-get-boosted' range." "I suspect if you're over 1,000, and not at high risk, then you're probably good," he said.

He cautioned, however, that there's "not a cutoff at which you are protected or not protected."

What Do COVID Antibody Levels Really Mean?

medpagetoday.com/special-re...

In a recent opinion piece in the Hill, Dr. Segev writes the following:

“In a recent sub-study of the landmark Moderna trial, every 10-fold increase in antibodies meant an additional 34 percent lower risk of a clinical breakthrough infection. This means that across the “positive” range for antibody testing, some people have one-third the risk of a breakthrough infection compared to others.” * *

“Of course, antibodies are not the only component of the immune system. There are T-cells, memory B-cells and complex interactions between complex systems. However, antibodies are the mainstay of the immediate-early immune response, providing truly sterilizing immunity, so antibody levels determine how quickly you can react to the virus.”

“Antibody levels are critically important for two reasons: First, the faster you can react to the virus, the less time the virus has to replicate before your immune system kills it, so the less severe your infection will be. Second, and maybe even more important in the context of public health, the faster you can react to the virus, the less time you will be shedding virus asymptomatically and unknowingly putting others at risk.”

It's time to check antibodies and take the guesswork out of this pandemic.

thehill.com/opinion/healthc...

Given what we already know from experience as well as what we might have learned recently about the negative effect our CLL B-cells have on many aspects of our immune system , we CLLers know that even with high titers of binding antibodies we may still be susceptible to COVID-19, and therefore need to continue cautious behavior. And for those of us with low titer antibodies it reinforces the need for timely monoclonal antibody intervention.

gardening-girl

**Note: this study is still under peer review medrxiv.org/content/10.1101...

[kitchengardener2]

So after reading this, can it possible that because antibody tests for Covid show negative, it may still be possible to have antibodies for other things. Living in hope that we may eventually be able to resume living.

[gardening-girl in reply to kitchengardener2]

KG2, I'm not certain what you are asking. Unless you require regular IVIG infusions you are definitely making antibodies in response to all sorts of antigens in your environment. Testing negative to vaccination does not mean that you are not making any antibodies at all, you are just not making them at detectable levels in response to vaccination. Even those of us who rely in IVIG infusions are making antibodies, just a lower levels. Fingers crossed that your 3rd shot will do the trick for you!

[kitchengardener2 in reply to gardening-girl]

So I don’t have any infusion based treatment only tablets. However, I was given to understand that because I have a compromised immune system, I would be vulnerable to all infectious diseases. I do regular finger prick blood tests for a COVID 19 study in conjunction with the the National Office of Statistics and my result has always said negative for antibodies whilst my husband’s is positive. I took that to mean that I wasn’t making antibodies for anything. I will ask my consultant next week for her view. I was diagnosed with CLL in 2018 and have been having treatment with Acalabrutinib since early September this year. This whole pandemic time has scared me witless, I do go out but avoid people as much as possible. Our family live some distance away and we have seen very little of them. We won’t have a family Christmas again this year, the family all enjoy travelling and mixing and we just won’t risk it. They don’t seem to understand when we say that we don’t want to take chances and we feel that sometimes they think that I am making this whole thing up, because I am lucky enough to look and feel well.

[Annie1920 in reply to kitchengardener2]

I was told that after having negative spike and neucleocapsid test that I have very little chance of mounting a resistance to a Covid attack.. Also since CLL affects B cells all infections are likely to be 1.worse and 2.more likely.. So we haven't see children or g children for 18+ months now sadly.. I feel as if life has paused in limbo

[kitchengardener2 in reply to Annie1920]

Poor you not seeing children and grandchildren. We just have siblings, no children so a little easier but we still miss them. We are blessed with some good caring friends and have virtually lived in a bubble with them. Agree though, life is in limbo with all our plans on hold. You take care. x

[gardening-girl in reply to kitchengardener2]

KG2, I'd agree that because you have a compromised immune system, that you would be more vulnerable to infectious diseases than the general population. Do you have your IgG level checked when you have blood work done? If so, that would give you a general idea about your overall antibody levels since IgG = antibodies. I think that the normal range for IgG is ~600-1600 mg/dL, and supplemental IVIG isn't usually administered until levels drop to <300 mg/dL and there have been significant infections.

[kitchengardener2 in reply to gardening-girl]

Not sure if IgG is checked but will look at printout. Thanks

[bennevisplace in reply to kitchengardener2]

I'm hopeful. See my comment below.

[teakbank12]

My NHS antibody test came back as zero reading last Friday.Hence having had three primary doses and getting this result is pretty upsetting to hear.

Dave

[gardening-girl in reply to teakbank12]

I agree, it is a disconcerting result. Just keep a lookout for early COVID symptoms and go for the monoclonal intervention at first sign.

[Annie1920 in reply to teakbank12]

Mine too but I was expecting a poor result.. Hey ho even more hiding away sadly

[Pin57]

Great information g-g, thanks for sharing! Glad to see additional research on spike antibodies is happening and interesting to read what “the scores” provide guide-wise.

Basically (my crude layman’s takeaway), is that much more spike antibodies is much more better for that critical first line of defense versus covid…. But …another takeaway for us CLLers is to continue to practice safe protocols no matter what ones “scores” may be. Got it.

[bennevisplace]

Thanks for this g-g.

Very interesting and not entirely discouraging for those of us who tested negative for spike antibodies after two or three doses of vaccine. If I read that part right, the authors calculated vaccine efficacy at day 57 to be 45-60 percent even when the antibody titre was unmeasurably low. That's some protection against symptomatic disease, and one would suppose a higher level of protection against severe illness. Please correct me if I'm wrong.

In this study the vaccine was Moderna. Here is an earlier study of correlates of protection by the Astrazeneca vaccine nature.com/articles/s41591-...

[gardening-girl in reply to bennevisplace]

I agree that the authors seem to be reporting that the vaccine efficiency at day 57 is between 45-60% even when the antibody titer is below the detectable level. However, the number of persons in that category is very small. They do make the following statement in an attempt to explain that level of protection in individuals with undetectable antibody levels: "In addition to markers measuring distinct immunological functions, markers not measured fully in serum (e.g., mucosal markers) and/or anamnestic responses not fully represented by a single time point measurement may be needed to fully explain vaccine efficacy."

It remains as a medRxiv. article, not yet published. I wonder who has agreed to wade through all of the statistical jargon and manipulation to review it!

Speaking of which, I see from the link that you provided to the AZD1222 vaccine "Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection" paper that it now has gone through peer review. That's encouraging. When I referred to it in an earlier post, it had not yet been peer reviewed.

healthunlocked.com/cllsuppo... ?responses=146586198

[bennevisplace in reply to gardening-girl]

Yes indeed. I had forgotten about the pre-print you linked to circa 3 months ago. How quickly we forget things - correction, I forget things. I'm saving this post!

BTW did you see this one? researchgate.net/publicatio... Maybe it's old hat by now...

[gardening-girl in reply to bennevisplace]

Thanks for the link to the "A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation" paper. PubMed lists 83 citations for it, many of which also report methods. I haven't seen any test sites in the US that make a neutralizing antibody available to the general public, although LabCorp back in June 2020 announced that they were selling kits to researchers.

[country76]

It seems that a lot of us, including myself, Have tested negative and less than .4 antibodies. I wish the experts would figure this out.