Question about paper 10 January: Cross-reactive memory....SARS-CoV-2....

[Vrbic]

TL;DR

Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts, summary for

Hello everyone,

I'm a physicist so I'm not an expert in immunology etc., but I'm interested in this topic. I read the abstract of this paper (Discussion was very scholarly for me) but still, I'm not sure if I understand it correctly. So I have some questions:
1) Is there exist some possibility that exposure to "ordinary" coronaviruses gives someone some kind of immunity?
2) They wrote they observe "higher frequencies of cross-reactive (p=0.0139)". What does that say? That some immunity is active in about 1.39% of tested people who has negative test?
3) If a person has "higher frequencies..." does it mean the Coronavirus is not inside his bode? Is such a person infectious?
4) What do their results say generally? How many people (in per cent) may have "natural" immunity against Covid?
5) Is there anything else interesting for ordinary people?

Thank you all who will respond.

 

[TeethWhitener]

Link to paper in question:
https://www.nature.com/articles/s41467-021-27674-x

 

[Vrbic]

Link to paper in question:
https://www.nature.com/articles/s41467-021-27674-x

Hi, thank you for your post, but the problem is I'm not much familiar with terminology etc. and I'm not able to extract all these informations or be sure I'm correct. I have a link on this paper and I read it at least parts.

 

[DaveE]

I don't recall if they discussed this paper, but this podcast has a great discussion of memory T cells.
https://www.microbe.tv/twiv/twiv-855/

 

[TeethWhitener]

Hi, thank you for your post, but the problem is I'm not much familiar with terminology etc. and I'm not able to extract all these informations or be sure I'm correct. I have a link on this paper and I read it at least parts.

The link wasn’t for you; it was for everyone else. If you’re referencing a paper on these forums, make sure to provide a link so that people can go read firsthand what you’re talking about.

 

[Vrbic]

The link wasn’t for you; it was for everyone else. If you’re referencing a paper on these forums, make sure to provide a link so that people can go read firsthand what you’re talking about.

I'm sorry. I was so thinking about questions I forgot to include a link.

 

[jim mcnamara]

Terms in Biology tend toward many syllables, so names are abbreviated: example - SomeLongName2 -> SL-2. They are usually defined for the reader like this: SomeLongName(SL) 2. SL is the abbreviation. Sometimes they assume you know ones like IgM which makes it harder. So if you use text search from the beginning of the paper, look for "SL", and most of the time you can decode it. Which may not help much anyway.

(p=.0001) is the result of statistics where p<.05 is considered significant. So, p=.00013 passes with very good significance.

Epitopes are the "unique signature" of an amino acid sequence on viral surfaces somewhere. The immune system uses this sequence of amino acids like police might use a license plate to find bad guys driving on a road. It remembers the epitope. The most commonly remembered epitopes are ones that are located in places on the virus that are "easy to read". Less steric hindrance, for example.

Cross-reactivity refers to virus B being flagged as a bad guy by an immune cell (let's not go there now) that "should" not know about it. Because the immune system is "naive" about Virus B.

The false but sometimes helpful identification of Virus B as bad is based on an epitope from virus A. So we may have an immune response across usually closely related pathogens.

The down side of this may be a root cause of some allergies, the good side is that the immune system can zap bad guys that is has not seen before. And vaccines stimulate this future possible cross-reactivity by making a Bcell create "memories" of epitopes it has never seen before. This is probably why mRNA vaccines, which force immune cells to remember a variety of easily accessed epitopes (on the receptor binding domain of Covid virions), are able to work against multiple variants. Like Δ and Ω. The memory may not be super-duper good, but it often can stop the person from getting really sick or symptomatic by giving the immune system a head start on the virus.

The paper says that some part of the population that has never been exposed to Covid (testing blood samples from way before the epidemic) does respond immunologically to Covid. Probably due to other closely related Coronavirus infections in the recent past.

One other issue. Virology and immunology understanding has grown explosively in the past two years. So if a friend has an old copy of a textbook in that area, it will not be all that helpful.

 

[Ygggdrasil]

1) Is there exist some possibility that exposure to "ordinary" coronaviruses gives someone some kind of immunity?

Yes. The protection is nowhere near the level provided by vaccination or prior infection by SARS-CoV-2, but it is possible that prior infection by some of the "ordinary" coronaviruses could offer some level of protection against severe disease.

For more information, see this previous Physics Forum thread here: https://www.physicsforums.com/threa...om-exposure-to-endemic-coronaviruses.1005206/

2) They wrote they observe "higher frequencies of cross-reactive (p=0.0139)". What does that say? That some immunity is active in about 1.39% of tested people who has negative test?

As @jim mcnamara mentioned, these figures are p-values, which are calculations from statistical tests. For that particular experiment (reported in Fig 2C of the paper, shown below), they measured the relative concentration of certain immune cells from 52 individuals who were in close contact with a COVID-19 case, then tracked which ones became infected (PCR-positive, red) or not (PCR-negative, blue):

The plot on the right shows that the PCR-negative cohort had a higher amount of the cross-reactive T-cells than the PCR positive group. The p-value says how likely that difference would occur by chance (e.g. just through random sampling one might see a difference between the two groups). The p-value says that if you just randomly sampled the population, you would get a difference as large as the difference observed here only 1.39% of the time. Thus, the results are not likely due to a fluke in sampling a small number of patients but instead likely represent some real correlation (but note that correlation does not necessarily imply causation).

3) If a person has "higher frequencies..." does it mean the Coronavirus is not inside his bode? Is such a person infectious?

The study was measuring specific immune cells (T-cell) in the body that are capable of recognizing portions of SARS-CoV-2. These immune cells were likely generated from prior infection by an "ordinary" coronavirus, but these cells stay in the body after the "ordinary" Coronavirus is eliminated.

4) What do their results say generally? How many people (in per cent) may have "natural" immunity against Covid?

The study does not measure this. From their data, around 7 of the 52 people measured showed appreciable amounts of cross-reactive T-cells, but the population of patients in which they measured the T-cell were not randomly sampled from the general population, so it is unclear whether these numbers would generalize to a wider population.

 

[Vrbic]

Terms in Biology tend toward many syllables, ...

Thank you for the comprehensive answer, it helped me to understand the issue.

 

[Vrbic]

Yes. The protection is nowhere near the level provided by vaccination ...

Thank you also to you! I'm now almost expert :-D At least in understanding this selected paper :-)