Covid and Antihistamines
Sep. 22nd, 2025 02:55 pm![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
silvercat17These are not my words. This is a straight copying of Rahaeli's thread on bluesky: https://bsky.app/profile/rahaeli.bsky.social/post/3lzeskoaaks2j
The updated COVID/histamine link thread because people keep tagging me in to explain it and I keep intending to update the post from 2023 (synecdochic.dreamwidth.org/805203.html) and just not having the capacity because of my own health shit so here is a thread I can pin.
Covered in this thread:
1. The underlying science behind the link
2. Antihistamines as COVID prevention practical advice
3. Prophylactic antihistamines to make you not feel like shit after a COVID vaccine practical advice
4. Antihistamines during an active COVID infection to prevent long COVID
1. The underlying science behind the COVID/antihistamine link
There are two major connections between the SARS-CoV-2 virus and histamine. The first is that the virus uses histamine receptors as a method of cell entry/replication: https://journals.asm.org/doi/10.1128/mbio.01088-24 https://journals.asm.org/doi/10.1128/mbio.01697-24 This explains a number of early findings in studying how SARS-CoV-2 behaves such as https://www.nature.com/articles/s41586-020-2286-9
The second is that, once present in the body, the spike protein of SARS-CoV-2 is a potent mast cell degranulation trigger. Mast cells are a part of the immune system that perform multiple functions in fighting off infections, and mast cell dysfunctions are essentially autoimmune disorders. More on mast cells: en.m.wikipedia.org/wiki/Mast_cell
The link between mast cell degranulation and the SARS-CoV-2 virus (and all coronaviruses, in fact): https://journals.asm.org/doi/10.1128/jvi.00078-25
The non-science-words tl;dr: the COVID virus uses histamine receptors to infect your cells, and the spike protein of the virus temporarily freaks out an important part of your immune system and makes it too busy screaming about the virus to fight the virus as effectively.
This underlying science results in two easy practical things you can do to make your life easier when dealing with COVID. The first is:
2. Antihistamines for COVID prevention
It is VERY IMPORTANT that I start with: this is NOT a perfect preventative and should NOT be your only precaution. The best precaution against COVID is still wearing a well-fitting (K)N95 mask whenever you are around other people. If you've stopped masking, now is a great time to start again! There are other precautions you should be taking such as improved filtration (ie a portable HEPA filter) and a nasal barrier spray (Covixyl, Profi, Enovid, Flonase, even iota-carrageenan or plain saline spray/rinses).
Antihistamines should be part of a defense in depth strategy and not your only precaution. Did I mention you should be masking? Because you should be masking! That having been said: Because the virus uses the HRH1 receptors to enter cells, keeping those receptors busy reduces the attack vector.
The way to keep those receptors busy is H1 antihistamines. The important part, which I will get to in a second, is more frequent dosing and higher doses than recommended for allergic rhinitis ("allergies"). Any of the ones on this list will work: https://en.m.wikipedia.org/wiki/H1_antagonist
Cetirizine (Zyrtec in the US) is likely the one most people will do best with at higher doses and greater frequency because it has the best tolerability curve, but if you've tried it and it does you dirty, any H1 antihistamine you can tolerate should help. Diphenhydramine (Benadryl in the US) has some nasty side effects if you take it long-term at the doses you'd need (although those studies everyone likes to scaremonger about have some serious methodological flaws), but any of the second generation H1s are usually well tolerated at high doses.
The key to H1s for COVID prevention is emerging to be the timing and amount. The bottle says to take the second generation H1s every 24 hours: for COVID prevention, the key seems to be more frequent doses (every 12 hours, not every 24), and the highest dose you can tolerate. The guidance I have received from multiple doctors for my MCAS is that if you don't have pre-existing kidney problems or QT prolongation, it's okay to go up to 80mg/day cetirizine or loratidine (or combined in any split) a day without regular monitoring/supervision and well over that dose with. (My baseline is at 80mg/day, as 20mg cetirizine + 20mg loratidine every 12 hours, and I'm cleared to self-manage up to 160mg/day; I know people on higher doses. But for people without MCAS, stick to the hard limit of 80mg/day without a doctor's supervision.)
Even the second generation H1s can be sedating in people who don't regularly take them, so if you're starting them for COVID prevention, taper up. Go back down if you're still getting drowsiness after 2 weeks at the new dose. Some people also tolerate a mix of two H1s better than one single one. Fedofenadine (Allegra in the US) is a different dosage, as is levocetirizine, and the calculations are more complicated. If you're using one of those, start with "the dose on the bottle, taken every 12 hours instead of every 24".
There does seem to be some preventative effects in taking a H2 antihistamine as well as a H1 antihistamine, but that's more complicated. The only OTC H2 antihistamines on the market in the US are famotidine and cimetidine, and cimetidine is hard to find. (Nizatidine is prescription-only.) Many countries don't have famotidine or cimetidine available OTC and it needs a prescription. Note: proton pump inhibitors (another type of antacid) are NOT H2 antihistamines and won't work for COVID prevention.
Famotidine is the one I know best. It's usually sold in 20mg or 40mg pills and for this, you want to take it as 20mg twice daily, NOT 40mg once a day. Don't go over 40mg/day: that one genuinely does have some small increased risk over that dosage that's IMO not worth it for COVID prevention--especially since the science does point to the H1 being more important for prevention than the H2.
3. Prophylactic antihistamines for COVID vaccination
Remember up there ^^ where I said the spike protein of the virus is a potent mast cell destabilizer? When your mast cells freak out about something, they drop a lot of chemicals into your bloodstream that cause all kinds of symptoms. A lot of the post-vaccine "feeling like absolute shit" many people have that goes beyond the usual "post-vaccine slight malaise while your immune system learns what to do with the thing you just taught it" is a mast cell episode: the vaccine can cause them even in people without MCAS.
This advice is specific to the COVID vaccine: it will not work on other vaccines (unless you have subclinical or very mild MCAS and your reactions to those vaccines are also mast cell related).
Taking a "rescue dose" of antihistamines before you get the vaccine will reduce the severity of the mast cell reaction. In most people without mast cell diseases, it can completely prevent problems; in others it just makes them way more tolerable.
THIS DOES NOT AFFECT VACCINE EFFICACY IN THE SLIGHTEST. (In all caps because people always try to say that the severity of the reaction after is necessary for the immune response. It is not.) There are a million studies proving this but you can look them up yourself because I'm far enough into the thread composer that if I switch to another app I'll lose the entire thread. I'll try to remember to come back and add them later. (One study even found a slight, but not statistically significant, *increase* in vaccine efficacy with pre-medication, because again: mast cells are part of the immune system and the byproducts of mast cell degranulation interfere with immune response: preventing it improves immune response.)
The dosage and timing for pre-vaccination is EITHER:
- 50mg diphenhydramine (Benadryl) OR 50mg promethazine (Phenergan) 15 minutes before the shot OR
- 20mg cetirizine OR 20mg loratidine 2-3 hours before the shot
Only take one of those (ie, don't take Benadryl AND cetirizine).
If you are driving yourself to the appointment and you don't know if that dosage will knock you out (it does a lot of people), you can go right home after and take it ASAP: that timing is just geared for maximum effectiveness, but even taking it later will help.
If you forget to take the antihistamines until you feel like shit, you can still take them later. I strongly recommend the cetirizine, loratidine, or promethazine over the diphenhydramine if you're going to be taking more than one dose. (Again, this is not because of those severely methodologically flawed studies people like to wave around, it's because diphenhydramine has more nasty side effects and if you can avoid them, you should.) For diphenhydramine and promethazine, it's "25-50mg every 4-6 hours until you no longer feel like shit"; for cetirizine or loratidine it's "20mg every 12 hours until you no longer feel like shit".
If you're already taking antihistamines for COVID prevention, take the one extra dose before the shot, but don't keep taking more after, just stick to your normal preventative dose. This is all adapted from the pre-exposure prophylaxis that people with mast cell disorders need to use in order to be safely vaccinated at all, and if you want the papers on it, that's what you want to look up. (The usual MCAS prophylaxis also includes prednisone, but that's not indicated unless you absolutely require it for mast cell treatment because that one *is* an immunosuppressant.)
To save me the tedious complaining I've been getting for four years from people who aren't familiar with the science, and out of an abundance of caution that almost certainly will not apply to anyone reading this because if you already know you feel like shit after a vaccine it means you've HAD ONE: Prophylactic antihistamines have an infinitesimal chance of suppressing an anaphylactic reaction to a vaccine until you are no longer in the place you were vaccinated, which is equipped to treat the reaction. If you have safely had a dose of the vaccine before, the chances drop to almost zero. If you have never had a dose of vaccine before, either don't take the antihistamines until 6 hours after vaccination, or immediately seek medical care at the slightest hint of difficulty breathing, throat swelling, or severe hives. The chances of this happening are almost nonexistent, but every time I don't include this warning a lot of tedious people show up to yell at me, so there, I have now included it.
Finally, 3. Antihistamines during an active COVID infection to protect against long COVID. The papers for this are mostly linked in that 2023 review I linked at the threadstarter, and again I'm very deep in the composer and don't want to lose what I've written, so go look there for the citations. This is, again, not a perfect preventative; studies seem to consistently show about a 40-60% risk reduction in long COVID. This is probably because MCAS is a sensitizing disorder and a lot of long COVID behaves almost identically to MCAS: the likelihood is the people with the MCAS-like long COVID had a predilection to it before and enough exposures to mast cell sensitizers was enough to activate the disease.
Stabilizing the mast cell reaction during the active COVID infection phase can prevent or reduce the sensitization and lower your risk of it lingering. In this phase, it does seem the H2 antihistamine (famotidine) is more effective than the H1, but they're both still important. The doses are the same. When you test positive for COVID, start taking:
-20 mg cetirizine or loratidine
-20 mg famotidine
-Every 12 hours
-Until you are completely recovered
(And rest! Rest as long as you can! Be a potato! Do absolutely nothing you do not have to! The more and longer you rest, the better your chances are for a full recovery!)
If you're in one of the countries where you can't get a H2 antihistamine without a prescription and you don't have a doctor who will write you one, taking just the H1 will still help. (If you're using a different H1, the principle is the same as above: twice the frequency, twice the dose as on the bottle. I always use cetirizine and loratidine because they're the easiest to communicate and the most widely available.)
If you are prescribed Paxlovid, it has a moderate interaction with cetirizine/loratidine: it can slow the metabolism of the drug and increase the amount of it in your blood. Start with 10mg every 12 hours instead of 20mg every 12 hours and see if you tolerate it; increase it if you do. (The other reason I usually recommend cetirizine is because it's the most well studied H1 at higher doses and blood serum concentration, we know its safety curve, and there is SO MUCH data that it's perfectly safe at higher concentrations.)
The updated COVID/histamine link thread because people keep tagging me in to explain it and I keep intending to update the post from 2023 (synecdochic.dreamwidth.org/805203.html) and just not having the capacity because of my own health shit so here is a thread I can pin.
Covered in this thread:
1. The underlying science behind the link
2. Antihistamines as COVID prevention practical advice
3. Prophylactic antihistamines to make you not feel like shit after a COVID vaccine practical advice
4. Antihistamines during an active COVID infection to prevent long COVID
1. The underlying science behind the COVID/antihistamine link
There are two major connections between the SARS-CoV-2 virus and histamine. The first is that the virus uses histamine receptors as a method of cell entry/replication: https://journals.asm.org/doi/10.1128/mbio.01088-24 https://journals.asm.org/doi/10.1128/mbio.01697-24 This explains a number of early findings in studying how SARS-CoV-2 behaves such as https://www.nature.com/articles/s41586-020-2286-9
The second is that, once present in the body, the spike protein of SARS-CoV-2 is a potent mast cell degranulation trigger. Mast cells are a part of the immune system that perform multiple functions in fighting off infections, and mast cell dysfunctions are essentially autoimmune disorders. More on mast cells: en.m.wikipedia.org/wiki/Mast_cell
The link between mast cell degranulation and the SARS-CoV-2 virus (and all coronaviruses, in fact): https://journals.asm.org/doi/10.1128/jvi.00078-25
The non-science-words tl;dr: the COVID virus uses histamine receptors to infect your cells, and the spike protein of the virus temporarily freaks out an important part of your immune system and makes it too busy screaming about the virus to fight the virus as effectively.
This underlying science results in two easy practical things you can do to make your life easier when dealing with COVID. The first is:
2. Antihistamines for COVID prevention
It is VERY IMPORTANT that I start with: this is NOT a perfect preventative and should NOT be your only precaution. The best precaution against COVID is still wearing a well-fitting (K)N95 mask whenever you are around other people. If you've stopped masking, now is a great time to start again! There are other precautions you should be taking such as improved filtration (ie a portable HEPA filter) and a nasal barrier spray (Covixyl, Profi, Enovid, Flonase, even iota-carrageenan or plain saline spray/rinses).
Antihistamines should be part of a defense in depth strategy and not your only precaution. Did I mention you should be masking? Because you should be masking! That having been said: Because the virus uses the HRH1 receptors to enter cells, keeping those receptors busy reduces the attack vector.
The way to keep those receptors busy is H1 antihistamines. The important part, which I will get to in a second, is more frequent dosing and higher doses than recommended for allergic rhinitis ("allergies"). Any of the ones on this list will work: https://en.m.wikipedia.org/wiki/H1_antagonist
Cetirizine (Zyrtec in the US) is likely the one most people will do best with at higher doses and greater frequency because it has the best tolerability curve, but if you've tried it and it does you dirty, any H1 antihistamine you can tolerate should help. Diphenhydramine (Benadryl in the US) has some nasty side effects if you take it long-term at the doses you'd need (although those studies everyone likes to scaremonger about have some serious methodological flaws), but any of the second generation H1s are usually well tolerated at high doses.
The key to H1s for COVID prevention is emerging to be the timing and amount. The bottle says to take the second generation H1s every 24 hours: for COVID prevention, the key seems to be more frequent doses (every 12 hours, not every 24), and the highest dose you can tolerate. The guidance I have received from multiple doctors for my MCAS is that if you don't have pre-existing kidney problems or QT prolongation, it's okay to go up to 80mg/day cetirizine or loratidine (or combined in any split) a day without regular monitoring/supervision and well over that dose with. (My baseline is at 80mg/day, as 20mg cetirizine + 20mg loratidine every 12 hours, and I'm cleared to self-manage up to 160mg/day; I know people on higher doses. But for people without MCAS, stick to the hard limit of 80mg/day without a doctor's supervision.)
Even the second generation H1s can be sedating in people who don't regularly take them, so if you're starting them for COVID prevention, taper up. Go back down if you're still getting drowsiness after 2 weeks at the new dose. Some people also tolerate a mix of two H1s better than one single one. Fedofenadine (Allegra in the US) is a different dosage, as is levocetirizine, and the calculations are more complicated. If you're using one of those, start with "the dose on the bottle, taken every 12 hours instead of every 24".
There does seem to be some preventative effects in taking a H2 antihistamine as well as a H1 antihistamine, but that's more complicated. The only OTC H2 antihistamines on the market in the US are famotidine and cimetidine, and cimetidine is hard to find. (Nizatidine is prescription-only.) Many countries don't have famotidine or cimetidine available OTC and it needs a prescription. Note: proton pump inhibitors (another type of antacid) are NOT H2 antihistamines and won't work for COVID prevention.
Famotidine is the one I know best. It's usually sold in 20mg or 40mg pills and for this, you want to take it as 20mg twice daily, NOT 40mg once a day. Don't go over 40mg/day: that one genuinely does have some small increased risk over that dosage that's IMO not worth it for COVID prevention--especially since the science does point to the H1 being more important for prevention than the H2.
3. Prophylactic antihistamines for COVID vaccination
Remember up there ^^ where I said the spike protein of the virus is a potent mast cell destabilizer? When your mast cells freak out about something, they drop a lot of chemicals into your bloodstream that cause all kinds of symptoms. A lot of the post-vaccine "feeling like absolute shit" many people have that goes beyond the usual "post-vaccine slight malaise while your immune system learns what to do with the thing you just taught it" is a mast cell episode: the vaccine can cause them even in people without MCAS.
This advice is specific to the COVID vaccine: it will not work on other vaccines (unless you have subclinical or very mild MCAS and your reactions to those vaccines are also mast cell related).
Taking a "rescue dose" of antihistamines before you get the vaccine will reduce the severity of the mast cell reaction. In most people without mast cell diseases, it can completely prevent problems; in others it just makes them way more tolerable.
THIS DOES NOT AFFECT VACCINE EFFICACY IN THE SLIGHTEST. (In all caps because people always try to say that the severity of the reaction after is necessary for the immune response. It is not.) There are a million studies proving this but you can look them up yourself because I'm far enough into the thread composer that if I switch to another app I'll lose the entire thread. I'll try to remember to come back and add them later. (One study even found a slight, but not statistically significant, *increase* in vaccine efficacy with pre-medication, because again: mast cells are part of the immune system and the byproducts of mast cell degranulation interfere with immune response: preventing it improves immune response.)
The dosage and timing for pre-vaccination is EITHER:
- 50mg diphenhydramine (Benadryl) OR 50mg promethazine (Phenergan) 15 minutes before the shot OR
- 20mg cetirizine OR 20mg loratidine 2-3 hours before the shot
Only take one of those (ie, don't take Benadryl AND cetirizine).
If you are driving yourself to the appointment and you don't know if that dosage will knock you out (it does a lot of people), you can go right home after and take it ASAP: that timing is just geared for maximum effectiveness, but even taking it later will help.
If you forget to take the antihistamines until you feel like shit, you can still take them later. I strongly recommend the cetirizine, loratidine, or promethazine over the diphenhydramine if you're going to be taking more than one dose. (Again, this is not because of those severely methodologically flawed studies people like to wave around, it's because diphenhydramine has more nasty side effects and if you can avoid them, you should.) For diphenhydramine and promethazine, it's "25-50mg every 4-6 hours until you no longer feel like shit"; for cetirizine or loratidine it's "20mg every 12 hours until you no longer feel like shit".
If you're already taking antihistamines for COVID prevention, take the one extra dose before the shot, but don't keep taking more after, just stick to your normal preventative dose. This is all adapted from the pre-exposure prophylaxis that people with mast cell disorders need to use in order to be safely vaccinated at all, and if you want the papers on it, that's what you want to look up. (The usual MCAS prophylaxis also includes prednisone, but that's not indicated unless you absolutely require it for mast cell treatment because that one *is* an immunosuppressant.)
To save me the tedious complaining I've been getting for four years from people who aren't familiar with the science, and out of an abundance of caution that almost certainly will not apply to anyone reading this because if you already know you feel like shit after a vaccine it means you've HAD ONE: Prophylactic antihistamines have an infinitesimal chance of suppressing an anaphylactic reaction to a vaccine until you are no longer in the place you were vaccinated, which is equipped to treat the reaction. If you have safely had a dose of the vaccine before, the chances drop to almost zero. If you have never had a dose of vaccine before, either don't take the antihistamines until 6 hours after vaccination, or immediately seek medical care at the slightest hint of difficulty breathing, throat swelling, or severe hives. The chances of this happening are almost nonexistent, but every time I don't include this warning a lot of tedious people show up to yell at me, so there, I have now included it.
Finally, 3. Antihistamines during an active COVID infection to protect against long COVID. The papers for this are mostly linked in that 2023 review I linked at the threadstarter, and again I'm very deep in the composer and don't want to lose what I've written, so go look there for the citations. This is, again, not a perfect preventative; studies seem to consistently show about a 40-60% risk reduction in long COVID. This is probably because MCAS is a sensitizing disorder and a lot of long COVID behaves almost identically to MCAS: the likelihood is the people with the MCAS-like long COVID had a predilection to it before and enough exposures to mast cell sensitizers was enough to activate the disease.
Stabilizing the mast cell reaction during the active COVID infection phase can prevent or reduce the sensitization and lower your risk of it lingering. In this phase, it does seem the H2 antihistamine (famotidine) is more effective than the H1, but they're both still important. The doses are the same. When you test positive for COVID, start taking:
-20 mg cetirizine or loratidine
-20 mg famotidine
-Every 12 hours
-Until you are completely recovered
(And rest! Rest as long as you can! Be a potato! Do absolutely nothing you do not have to! The more and longer you rest, the better your chances are for a full recovery!)
If you're in one of the countries where you can't get a H2 antihistamine without a prescription and you don't have a doctor who will write you one, taking just the H1 will still help. (If you're using a different H1, the principle is the same as above: twice the frequency, twice the dose as on the bottle. I always use cetirizine and loratidine because they're the easiest to communicate and the most widely available.)
If you are prescribed Paxlovid, it has a moderate interaction with cetirizine/loratidine: it can slow the metabolism of the drug and increase the amount of it in your blood. Start with 10mg every 12 hours instead of 20mg every 12 hours and see if you tolerate it; increase it if you do. (The other reason I usually recommend cetirizine is because it's the most well studied H1 at higher doses and blood serum concentration, we know its safety curve, and there is SO MUCH data that it's perfectly safe at higher concentrations.)
no subject
Date: 2025-09-22 10:18 pm (UTC)https://bsky.app/profile/rahaeli.bsky.social/post/3lzfsapv5us22
Unless the bottle specifically says "low dose Zyrtec", Zyrtec is 10mg. They do also have a 5mg product but it is prominently labeled as "low dose". But yeah, you can mix two different H1s (Zyrtec in the morning, Claritin in the evening, etc) and get the same results. The important thing for prophylaxis is the increased frequency, because it keeps the receptors that the virus uses to enter your cells occupied. As I said several times in the thread, when using it for prophylaxis, titrate up to the highest dose you can tolerate, up to 80mg/day. The vast majority of people are capable of acclimating to higher doses of at least *one* of the second generation H1 antihistamines over time!
We don't actually know what the proper dosage is for prophylaxis yet, because there's plenty of evidence that it helps but no systemic attempt to determine dose. My best guess is 40mg/day as 20mg q12h will be the sweet spot for most people. But if all you can tolerate is 10mg q12h, then that's still a useful part of a defense in depth strategy. It's the "every 12 hours" that's the important part, because of the metabolism curve and the goal of keeping the histamine receptors occupied with the preferential binder.
no subject
Date: 2025-09-22 10:22 pm (UTC)https://bsky.app/profile/rahaeli.bsky.social/post/3lzffhxzjm222
Right?! I have MCAS (not postviral; it came as a BOGO with my Ehlers Danlos) and early on in that first terrible wave of OG COVID, Sinai found H1+H2 antihistamine use was correlated with better outcomes in their systemic medication review, which made my ears perk up given the symptoms. Then some studies failed to replicate it and while others did replicate and it seemed to be dose-dependent and I went "hmm", and a lot of how people described their long COVID symptoms sounded REALLY familiar and I went "hmmmmmmmm", and then I got my first dose of mRNA vaccine--and got kicked into one of the worst MCAS flares I've ever had and it was identical to how other people were describing their really bad reactions and I said "hmmmmmmm" and recommended a few friends with subclinical MCAS symptoms who got hit really badly try the prophylactic diphenhydramine and it worked, and then the papers started coming out showing that treating long COVID like it's MCAS helps in a huge number of cases, and and and, so by late 2023 I was reasonably convinced there was SOME kind of mast cell involvement.
The smoking-gun papers that have been coming out in the last 18 months or so have been very vindicating! Like, I totally get why I got so much pushback when hypothesizing out loud before, even though I tried as hard as I could to supply citations and scientific grounding --so I didn't sound like I was suggesting that people eat horse paste and all, but at this point even my doctor (who's with the Hopkins system) says the Hopkins LC clinic is recommending Hopkins GPs start their suspected LC and high-risk patients on the MCAS antihistamine protocol
The histamine receptor/mast cell theory doesn't explain *everything* weird about COVID but it explains *so much*, and the intervention is so low risk, that I really do think most people should be taking prophylactic antihistamines at this point, knowing what we do about the long term effects! Like, living with MCAS is fucking miserable and I wouldn't wish it on my worst enemy, and my case is just edging into "straight up moderate" from my prior "mild to moderate". If people can avoid it, I heartily recommend doing so!