Why so excited about IgA? Wanted to explain immunoglobulins (antibodies) a bit to explain why the real-world data is showing us that the #covid19 vaccines block transmission. There are 5 different types of immunoglobulins in human body: IgA, IgM, IgG, IgD, IgE. You hear a lot
about "antibodies" and neutralizing antibodies after #covid19 infection & #covid19 vax, which refers to IgG immunoglobulins. But function of IgA antibodies is to protect us at the surfaces that face the world, the "mucosa": nose, mouth, gut, genitals, etc nature.com/articles/nm1213
Obviously, 1st line of defense against respiratory pathogen like SARS-CoV-2 is where you encounter it (nose/mouth) so IgA responses there after vaccination would help you fight the virus the minute you are exposed and, importantly, limit viral replication so you can't pass it on
In movies (like Contagion where actors had vaccine administered intranasally) and also with #covid19, there is interest in nasal vaccine. But we knew from other systemic (given by shot) vaccines that IgA (line of defense in nose/mouth) is generated cvi.asm.org/content/23/6/4…
And now we have at least 3 papers (tell me if there are more!) showing us that IgA antibodies are induced by #covid19 vaccines: The first actually shows us that vaccines induce IgG antibodies that happily get into saliva to protect you there & IgA in most: biorxiv.org/content/10.110…
Tweeted 2nd paper last night but mRNA vaccines in pregnant and lactating women induced IgA (which is secreted in breastmilk by the way) and IgG. And then you know my favorite paper on this is where authors literally biopsied lymph nodes after vaccination medrxiv.org/content/10.110…
So no WONDER we are getting us all this accumulating data that the #covid19 vaccines reduce transmission with mucosal immunity being induced. Protects us the vaccinated from viral entry and protects others from us transmitting since viral replication inhibited at mucosal surface.
So, if you have a "positive PCR" after vaccination, would be important to know viral load in that swab (which you can quantify by knowing how many cycles the PCR machine has to go through to amplify that virus, CT threshold) to know if you could pass it on medrxiv.org/content/10.110…
Above paper & below would argue it will be hard for you to pass it on if you get exposed to #covid after vax with that effective mucosal immunity. So if you're not really re-infected & not infectious, isn't it like proverbial tree in forest falling medrxiv.org/content/10.110…
with no one around? Can it be heard? Mass asymptomatic testing after vaccination will not be indicated in my opinion. If symptomatic, test and even sequence thereafter if positive. And do know that vaccine failures will happen but will be RARE verywellhealth.com/second-cases-o…
TESTING AFTER VAX: Before anyone tells you there is a breakthrough infection, ask 1) was the person asymptomatic?; 2) what is CT value of the PCR test if PCR? If symptomatic & infectious by CT value, call it breakthrough; if not, immaterial (& why mass testing after vax problem)
Sorry, wanted to explain this more clearly. Looks like breakthrough after vaccine of getting COVID is very rare. If you don't have symptoms and you can't spread it, that is not a breakthrough but likely you being exposed and fighting it right away at the nose level
So, if you look at info in thread above, you can see that viral loads in your nose can be very low after you get tested after vaccine. Is that "infection" or is that you fighting the virus you were exposed to & stopping it in its tracks? And if you can't spread it & you don't
have symptoms, what is the point of testing and calling that a "breakthrough infection" (like perhaps that Israel case B.1.351 after vax -did the person have symptoms? What was the viral load in the nose & could they pass it on?). So, in my opinion, breakthroughs (true) =
1) person with symptoms + 2) person having a viral load high enough to spread (which can be told by looking at a certain value in your PCR test if they tell you or doing a rapid antigen). We will be calling a lot of specious breakthroughs if mass asymptomatic screening after vax
In my mind, this is a KEY point and why companies, counties, schools, etc. should reconsider this strategy of mass asymptomatic screening after vax. Asymptomatic person who can't spread it is not in any way a threat but will be called a breakthrough on the vaccine & upset people
1 more point: the virus starts to replicate in your nose and you block it off by your immunity if you are vaccinated (that is why I discussed IgA). But a PCR test can pick that up and say you are "positive" when you really were doing exactly what you were supposed to do: kill it
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HOW LONG DOES IMMUNITY LAST? To COVID vaccines or infection? We do not really know but there have been some really nice papers lately that give us more information. Please remember immunity divided into antibodies (which can come down & not work as well against variants)
IgA is one in the nose & mouth ("mucosa") that is raised by shots (vaccines) to certain extent but rise higher after natural infection; IgG is the one that is "humoral" or in the bloodstream. Many threads on here about cellular-mediated immunity: B & T cells cover all variants
This recent preprint is really important and summarized by @florian_krammer below in depth. Main take-aways: Breakthrough infections induce IgA (we knew) but protection from vaccine long-lasting even against former variants to severe disease/mortality
RSV VACCINE FOR OLDER ADULTS: Respiratory syncytial virus (RSV) respiratory virus (most common after flu pre-COVID). 2 subtypes, A&B (1 dominates/season). Droplet; Recurrent infections. Most severe in neonates & adults >65; FDA approves 1st RSV vax today msn.com/en-us/news/us/…
RSV vaccine 3 trials of new RSV vaccine, all published in the @NEJM recently so just to keep them straight- here is the vaccine which just got approved May 3 by the FDA for older adults. Remember our T/B cells so protection against severe disease higher! nejm.org/doi/full/10.10…
A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented RSV-related severe respiratory illness by 94% in adults>=60 years (71% against RSV infection, likely to fall with time as antibodies fall but severe disease protection will remain)
NASAL VACCINES: To explain nasal vaccines, we have to explain the immune system first.
IgA is an antibody that helps attack the pathogen and exists in mucosal surfaces (like nose/mouth)
IgG is an antibody that is in the bloodstream bbc.com/news/world-asi…
Cellular immunity is fantastic, redundant (so even if one cell line down in immunocompromised, have other), generated by either vaccine or infection; Comprised of
T cells- so in breadth from vax - works even across spike protein with its mutations
And the 2nd type of cell produced by vaccines or infection -B cell- amazing thing about B cells is that - if see omicron or one of its subvariants in future- they make antibodies adapted to that variant or subvariant (aided by T cells); adaptive immunity
PUBLIC HEALTH POLICY: Seem to be at reckoning phase of COVID response- what worked, what didn't. Which interventions will be used in future pandemic responses? Interventions asked of public need good medical evidence for them (e.g. RCTs preferably, systematic reviews) to impose
In our field, Cochrane reviews represent best way to sum up the medical evidence to date by performing meta-analyses or systemic reviews of currently-available data; here is Cochrane on masks & other interventions for respiratory viruses including COVID cochranelibrary.com/cdsr/doi/10.10…
Many asked past 3 years how CDC developed policies on masks (& age to mask), distancing (feet), ventilation, schools-> all non-pharmaceutical interventions. Originally theory-based. Now 3 years in, have data (RCTs highest level) to form policies from both US and other countries
VACCINE DISCRIMINATION: We need to stop vaccine requirements for US entry like almost every other country. Am finishing COVID chapter for our ID "bible" & vaccines prevented transmission early on with alpha, but not enough now with current variants to justify such discrimination
Moreover, shame, stigma, blame (remember COVIDiots?), coercion, discrimination not good public health tools. When used for HIV, public health & ID physicians decried them but tactics used a lot in COVID. This book tries to explore & correct that for future barnesandnoble.com/w/endemic-moni…
Concept of #harmreduction in pandemic responses means watching carefully if vulnerable people (like students, older people, low-income populations, migrants, sex workers, prisoners, those with disabilities, refugees, minorities) harmed more by response nature.com/articles/s4146…
FEAR: Some media & public health officials concerned Americans aren't fearful of COVID now. But the vaccines & therapeutics DO WORK. If we can't celebrate biomedical advances & imbibe their effectiveness (we have better tools for COVID than flu), what is point of developing?
In HIV medicine, when therapies came out, we didn't say to people- stay fearful; make this the controlling principle of your life. The book #Endemic I wrote (coming out July 11, 2023) hails these biomedical advances & the age we are in to fight pandemics to reassure the world
This is a rather brilliant summary of the issue from @benryanwriter