Thread by @ChecchiaPaul

1/ Quick update and then a few points to clarify:
Update: RSV has started to turn the corner. Hospitalizations are starting to come down. Unfortunately, COVID is now replacing them, but at least one is running its expected course.

2/ Some small positive news to report. (dshs.texas.gov/.../2020-21-RS…...)
Points to make:
1. Boosters are not failures and therefore should not be feared.
2. Vaccines are not antibiotics, vitamins, or therapies.
3. Our immune system is incredible.

3/ Lots of stuff, so I’m going to try to tackle them with data.
Will we all need a booster? No idea. I will start this post with a very clear caveat that I am not an ID physician, nor am I a vaccine virologist, immunologist, or molecular biologist.

4/ I work at the “sharp end of the spear” in an ICU, so all I care about is that the vaccines keep you out of my world. From that perspective, I see absolutely no data to support the need for a booster. I am willing to admit I am very biased from that point of view.

5/ I’m also willing to admit my view means I do not have all the information necessary to answer the question about boosters fully, but I will try.
We most likely will need a booster AT SOME POINT, but that should in no way cause fear or be seen as a failure.

6/ When you cut your hand or foot and you go to get sutured, they ask if you can remember the date of your last tetanus shot and give you a booster when you can’t name the date. That is not a failure nor is it something you even think twice about; that is a vaccine.

7/ That is waning immunity. That is ongoing protection. That is medicine at work.

8/ As I reviewed a few weeks ago, the need for vaccine booster doses has been reported as early as the 1940s. (pubmed.ncbi.nlm.nih.gov/20275867/)

9/ The timing for boosters has been based on either a drop in measured antibody responses or it has been triggered by the resurgence of the disease.

10/ These links outline how physicians found the need for a booster against two devastating, and now rare, childhood diseases of pertussis (whooping cough) and Haemophilus influenzae Type b (Hib).( journals.lww.com/.../Duration_o…... ) (academic.oup.com/cid/article/58… )

11/ The need for a booster for COVID will be slightly different because we have such an advanced understanding of the immune system that we didn’t have even 20 years ago.

12/ We can either measure the immune system with a blood test, or we can wait for significant outbreaks, such as those described in the links above to tell us that our immune system needs to be re-energized. Cautionary note, be careful interpreting “significant outbreak”.

13/ For some diseases it might be the hint of an infection in a few people (think ebola level), for others it could be whole populations who get moderately sick (think pertussis).

14/ Take pause, that really isn’t known for COVID at this point and therefore the strategy to gauge the need for boosters is also unclear. That is not a shortcoming; it is knowledge-gaining.
Many people are looking solely at neutralizing antibody titers.

15/ Let’s dive into those antibodies a bit for clarity. First, the antibody response in our blood must drop. If you kept high antibody levels for every single virus you’ve ever been exposed to you in your blood it would basically become a solid substance of antibodies.

16/ The body knows better than that. It keeps a couple at the ready that will carry the code and ramp up when needed.

17/ As this old reference points out, the biggest drop and then potential need for boosters come from pathogens that the body doesn’t see all that often. (pnas.org/content/97/24/…)

18/ Tetanus and diptheria, for example, aren’t running around in the community (thanks vaccines) so our immune systems need to be reminded. This is not going to be the case for COVID for a very long time. Our immune system will be primed for the foreseeable future.

19/ Second, remember that is just one part of the immune response. The complexity of our immune response is no longer understood to be determined solely by measuring antibodies. We know so much more now about the way our system marshals T cells, etc. in fighting off disease.

20/ Measuring antibodies in a test tube, lab-only experiment is far from our human experience. We must be very cautious of looking at only those types of experiments to judge long term vaccine efficacy.

21/ Finally, we know that the immune response generated from previous infection is good, but emerging evidence clearly states that there is safety and improved efficacy in the vaccine induced response. (nature.com/articles/s4158…)

22/ The most recent report shows that there is a 2.5X increased risk of a breakthrough infection if you only are relying on previous infection to protect you vs. full vaccination. (cdc.gov/mmwr/volumes/7…... )

23/ Interestingly, there was no statistical difference if you got one shot following a previous infection. This contradicts one non-peer reviewed report from the Cleveland Clinic that found similar protection between vaccinated and previously infected.
(medrxiv.org/con.../10.1101…

24/ )
[Side note, I have no idea why this is a question people are interested in pursuing other than resource distribution.

25/ I don’t ask to check if I was previously infected with measles, mumps, tetanus, or even the flu prior to agreeing to receive an incredibly safe and effective vaccine.]

26/ Third, there are groups trying to further define some reliable test that can correlate with vaccine effectiveness. (medrxiv.org/.../2021.06.21…) *not peer reviewed

27/ If you want to read some fantastic stuff about the inner workings of the immune system and how Tcell responses live up to the challenge follow @sailorrooscout and @MonicaGandhi9. I could never compete with the way they describe the response.

28/ We do need something to follow to see if the vaccine response stays protective. As I said, the choices are either to measure something in the blood or wait to see new outbreaks and dose accordingly.

29/ Honestly, either is a viable strategy if you don’t have a disease that kills quickly. (see links above) As I understand it, neutralizing antibodies can be viewed as a potential marker, similar to cardiac troponin or any lab test. Let me explain.

30/ If you measure cardiac troponin in the blood, it definitely means a heart muscle cell has been damaged in some way. It’s a signal that something is going on to be looked at; but it is far from the full story.

31/ (see discussion about myocarditis) It doesn’t always mean you are having a myocardial infarction. It has to be put in the context of the situation.

32/ No lab (let me repeat that) NO LAB TEST gives you the whole picture as an isolated result; it must be interpreted by knowledgeable clinicians.

33/ If you have measured troponin and you have changes on your ECG, you are having chest pain, and you are 68 years old and obese; well that makes the picture clear.

34/ Similarly, if you are healthy, exposed to COVID, have been vaccinated, and are not sick at all, I don’t really care what your antibody levels are; I know you are being protected.

35/ We must all practice as a zentensivist and minimize our response to jump at only one lab test. (atsjournals.org/.../ats-schola…)

36/ Of course, any lab can be the proverbial "canary In a coal mine" to give us a trending, leading signal; but we just don't know yet how to rely only on antibody levels In this situation.

37/ This will be where we need a real understanding of “breakthrough” cases rather than getting all worked up over individual cases. The public health apparatus must regain the trust of society by clear messaging around what is important.

38/ When they start to see a real signal, they will test and evaluate, and then determine the need for a booster.

39/ Based on the grand rounds given by the head of vaccine development at Pfizer that I had the pleasure of listening to, even the vaccine manufacturers don’t really know how to gauge if their vaccines are maintaining effectiveness.

40/ They are using antibody responses, but they are rather forthright that they don’t currently know how to gauge when boosters will be needed. Don’t be afraid of that fact. They are constantly examining, measuring, and preparing.

41/ There is a signal in some elderly and immunocompromised individuals. They have prepared for that and are ready to go with a third shot. If (big if) more data comes in that starts to paint the picture of a need for a booster in the rest of us; they will be ready to go.

42/ Other than that, they still don’t know. Again, I will repeat that we should avoid being cynical about this fact and let the scientists be the scientists. Let them figure this one out without staring over their shoulders second guessing every step.

43/ One final point, I have heard of people sneaking around to get a third dose. I am an EXTREME proponent of the safety of these vaccines, but I am not willing to experiment on myself outside of a clinical trial. Do I think this will cause major harm?

44/ Probably not, but please remember that vaccines are not antibiotics. Sometimes we need a higher blood level of a particular antibiotic to fight a bacterial infection. This is not the case with immunizations. Vaccines are not therapy.

45/ Giving somebody antibodies (monoclonal or polyclonal) can be that therapy, but simply giving more vaccines is just not the same thing. That isn’t the way they work. I would strongly recommend against sneaking a third dose unless you sign up for a true clinical trial.

46/ Additionally, we can’t even get the world vaccinated with even one dose right now, let alone two; are you really going to take a third without even knowing if you need it? If you have read this far, you will see that I’m contradicting myself.

47/ I just said I would still get the vaccine after infection, why would this be different? Honestly, I’m confused because the data are unclear and incomplete.

48/ I get that this is all confusing, but I’m going with: 1. unvaccinated>get something (PLEASE), 2. previously infected>at least get one dose, but it’s safe and probably better to get 2, 3. fully vaccinated and vulnerable (extremely elderly or immunocompromised, not those…

49/ …with co-morbidities but real suppression such as chemo or transplant)>watch for approval of the 3rd, 4. all other fully vaccinated individuals>be patient and be without fear.