The Second Booster is Under My Delt: Mixing and Matching, Side Effects, and Risk Calculations

Yesterday morning after much reading and discussion with colleagues and with considerable consternation the skeptical cardiologist received a second booster.

I reviewed my angst-ridden decision-making on the 4th jab in a previous post. Briefly, I am >65 years of age without other risk factors for severe COVID-19 (I have asthma and hypertension but don’t consider these risk enhancers). I received an initial set of Pfizer shots in January of 2021 as soon as they were authorized and I jumped the gun on getting a Pfizer booster in August of 2021. I have upcoming inpatient hospital duties beginning April 18.

Two days ago, the FDA and CDC authorized the Pfizer and Moderna vaccines for a second booster in adults >50 years of age.

The data from an Israeli study showing a marked reduction in hospitalizations and death during their intense Omicron COVID-19 surge with a second booster were convincing.

Deaths due to Covid-19 in the second-booster group were 22% of the first-booster group.

Mixing and Matching Vaccines

In the time I had before my 9 AM appointment at CVS to receive Moderna’s Spikevax as my second booster I tried to decide if I should be getting Moderna’s booster or Pfizer’s booster. Choosing all Pfizer would classify as homologous boosting, going with Moderna would be heterologous. The FDA says either approach is fine.

The FDA EUA authorizes a single (0.25 mL) booster dose of the Moderna COVID-19 Vaccine at least 5 months after completing a primary series of the Moderna COVID-19 Vaccine or SPIKEVAX.

Moderna’s Spikevax logo

The regular full dose of Moderna is 100 micrograms of nucleoside-modified messenger RNA (mRNA) compared to Pfizer’s full dose vaccine which is 30 micrograms. The Moderna booster dose is 1/2 of the full dose so you still get more mRNA (50 micrograms) than with Pfizer’s full dose booster.

Three pieces of information convinced me to switch to Moderna. If I had previously gotten all Moderna I would have switched to Pfizer:

  1. study published in JAMA in January using data prior to Omicron showed those receiving two Moderna shots had lower hospitalizations than those receiving two Pfizer.
  2. This article published in Cell showed that in macaques exposed to Omicron the Moderna vaccine (mRNA-1273) and an Omicron specific mRNA vaccine elicited comparable immunity and protection shortly after the boost.
  3. Finally, a study published on Tuesday showed differing cellular and humoral immune responses to the Pfizer and Moderna vaccines which suggested to me that switching between the two types makes sense to provide a broader immune response. Moderna provided increased levels of several antibodies compared to Pfizer:

differences emerged across epitope-specific responses, with higher concentrations of receptor binding domain (RBD)- and N-terminal domain-specific IgA observed in recipients of mRNA-1273 (Moderna). Antibodies eliciting neutrophil phagocytosis and natural killer cell activation were also increased in mRNA-1273 (Moderna) vaccine recipients as compared to BNT162b2 recipients. Antibodies eliciting neutrophil phagocytosis and natural killer cell activation were also increased in mRNA-1273 vaccine recipients as compared to BNT162b2 recipients

The Booster Experience

Scheduling (and rescheduling) this vaccination was easily done online with CVS. Whether I indicated I was immunocompromised or not the system let me schedule the appointment for the booster. I was never asked if this was a first or second booster.

One of the commenters on my previous post indicated CVS turned him away saying he was ineligible. Others have indicated that Rite-Aid did not deny them jab #4.

When I entered the CVS at 850 AM yesterday I checked in using a link I was texted. I was first in line and was asked my birthdate and for a copy of my vaccine card. I showed a digital image of my card with the first two injections. At no time was I asked if I was immunocompromised or if I had had a first booster.

The pharmacist near the front desk told me that I was lucky because this was the first dose from a brand new bottle. I said “excellent.”

After waiting about 15 minutes a lady came out and directed me to a chair and asked if a left arm injection was OK. I said yes and took off my outer shirt, leaving a long-sleeve T-shirt. She rattled off some instructions which included staying hydrated. I rolled up the sleeve and she told me that it might be more painful because the rolled up sleeve was affecting the injection site. I said “should I take off my T-shirt?” She said it wasn’t necessary. I said “I’d rather take it off and have less pain” and took off my T-shirt.

The injection (left deltoid) was fairly painless. Before she bustled back into the pharmacy I asked her why this particular pharmacy (which happened to be extremely close to my house) was administering Moderna. She told me that CVS sends Pfizer to some pharmacies and Moderna to others. They don’t send both in order “to reduce errors.”

Booster Side Effects

I had had little to no side effects from the first 3 Pfizer injections. Four hours after the first one I began feeling extremely tired. I took a nap for 45 minutes and felt totally normal thereafter. With the others all I felt was minor soreness at the injection site.

It is now 24 hours since the Moderna jab. The left deltoid is moderately tender to touch and with certain shoulder motions I feel moderate pain, nothing that I would take an analgesic for.

Around the 4 hour mark afterwards I felt antsy with a slight tightness. After eating those symptoms resolved. At the 6 hour mark I went on a bike ride. I felt a little more winded than usual and my heart rate was higher but this was likely due to running out of nebivolol, a beta-blocker that slows the heart rate and lowers the blood pressure.

This morning I feel back to normal.


While I was searching Twitter prior to the injection, I came across a comment that said the booster would cost $800. This statement is manifestly inaccurate.

The federal government has mandated that you don’t have to pay anything for COVID-19 vaccinations. The CDC website states very clearly “Vaccines were paid for with taxpayer dollars and will be given free of charge to all people living in the United States, regardless of insurance or immigration status.”

CVS asks for insurance information when you register online for a vaccine but it is not necessary to give them this information.

Individual Risks Calculations and Other FactorsInfluencing the Decision

The decision to get this second booster was not easy. Although I’m over age 68 years my overall risk of getting seriously ill or dying from COVID-19 is very low given my vaccinated status.

You can plug your age and other factors in the 3 risk calculators at the British Heart Foundation to see where you stand.

You can also assess the risk of various COVID exposures at this Harvard site.

The fourth booster is definitely not needed for those under age 50 years with no other risk factors. For those over age 80 years or those who are immunocompromised it is highly recommended.

For the rest of us this becomes a highly individualized decision. As I indicated I would not have gotten it if I was not looking at potential high exposure situations. I would not have gotten it if I had had significant side effects from prior COVID vaccinations. One reader commented on experiencing frequent symptomatic PVCs after his third injection. That would have steered me away from a fourth.

Another reader wrote “My husband (67) and I (almost 69) got the initial 2 Moderna shots in Feb and March 2021. Got the booster precisely 6 months later. We have some health issues, so we continue to mask, lead a quiet life, etc. However, we will be traveling overseas in October. Should we get the 2nd booster now? Or wait until a little closer to our trip—perhaps August or September?”

Timing is important as studies clearly show waning of immunity over time. If you do decide to get it, it makes sense to get it about 2-3 weeks before a trip or an event at which you anticipate significant exposure

Prior COVID-19 infections: “natural immunity”

As one reader pointed out, if you have had a documented COVID-19, the calculus changes:

I have had double Pfizer’s, then was positive (probably for delta), and then got a booster because it was required for work. I would say that if you had one or more previous infections plus 1 booster, the benefit of a fourth jab would be infinitesimal. another strategy would be to wait until you got an infection and then take Paxlovid to give you that 90% protection from death and hospitalization

My concern about his proposed strategy (which I have also considered) is that I have concern for the availability of paxlovid and question whether just being >65 would qualify for its use.

Whether you decide to get the second booster or not, I hope you base your decision on good information.

Quadraboostingly Yours,


N.B. After posting this I note that MedPage Today has just published a good post with discussion on mixing and matching vaccine doses from various experts.


25 thoughts on “The Second Booster is Under My Delt: Mixing and Matching, Side Effects, and Risk Calculations”

  1. Retired 67 year old physician with no risk factors except controlled mild hypertension. I was double dosed early in 2019/20 with no untoward effects. A Red Cross donation showed I had developed antibodies. Last fall I decided to skip the booster since half of the people I asked were sick for a couple days afterwards. My PCP said it “kicked his
    ass.” So when he offered at that time I decided that I’d take my chances. Got COVID over New Years and was quite fatigued for 2-3 days with some incredible night sweats and a sore throat that persisted for a couple weeks. My dosed and boosted 34 year old son caught if from me and had a milder case as did my non boosted wife.

    Four months later my Red Cross donation showed I had antibodies at a high enough level to be used as convalescent plasma! Looking forward to next donation to see if the antibodies persist.

    I really cannot come up with a rationale to get boosted with any of the current doses available.
    BTW my Vit D level was 90 at the time so I’m skeptical that that had any effect.

  2. Dr. Pearson,
    The timing of this article is perfect for me as I am now contemplating my 1st boost. I’ve been aware of the mix n match protocol as I’m a TWIV (This Week in Virology) regular. I held out on the vax until Sept. of 21 until after seeing a paper on T cell response by Shane Crotty and Allesandro Sette @ La Jolla. The Moderna was a fairly clear winner in their paper (not that they were looking for one).
    I am a very healthy 67 yo cyclist with paroxysmal afib….after the 1st Moderna within 4-6 days it became a 2week 24/7 bout of afib….with my usually more benign symptoms MUCH MORE bothersome…and my mild tachycardia elevating to over 100…which was rare to never for me…..
    I WAITED 11 weeks for my 2nd shot as the longer timeframe allowed for a more broad B &T cell response according to their paper… and I had my nurse aspirate my 2nd injection….as that was a discussion taking place at the time as being a possible link to the cardiac “issues” being seen…(the lack of aspirating the shot)
    I luckily had no adverse effects AT ALL after the 2nd shot… and have NO way of knowing if my “issues” were even related to the vaccine…a majority of the hc workers that I know and have spoken to, feel it WAS likely the jab…..I’m not convinced.
    BUTTTTTTT…..My afib is occurring more often than not now, since the vax event… and I take metoprolol as a pill in the pocket…as a temporary prophylactic ….until I see an electro cardiologist on April 15 To talk shop and see what approach to take …..I’m going to wait on the boost until after that.
    But THANK YOU for this post!
    You have no way of knowing how the simple kind act of sharing GOOD PERSONAL EMPIRICAL evidence can have such a profound effect on us lay people, that usually have such a difficult time trying to separate the wheat from the chaff when health issues force us into becoming researchers and our own advocates.
    Many Thanks, and I continue to devour your afib content….you are my north star re: that…..

  3. Thank-You for the update Dr.. Your columns and website are always thoughtful and useful. My only thought right now is when will this all end? I’m about your age and I had to talk myself into getting this vaccine 3 times now and here I am again wondering if getting yet another booster is the smart thing to do. I’m not anti -vaccine, I am very healthy and I still wear a mask in public (while the vast majority of folks around me no longer do)but I do worry that the repeated jabs will, at some point ,have a negative consequences on our health that we just don’t know about yet. Reassurances aside by experts, the truth is we really don’t know .

    • Tony,
      You are correct. We have no long term safety data on the 4th jab. That is one reason I approached my jab with consternation.
      Dr. P

  4. Our current situation with various vaccines competing for deltoids for the same basic disease seems unique. OK, there are the two mRNAs at the top of the list. Still, how often does that happen?
    The question: how often has alternating of competing brands been shown to have a stronger immune effect than staying with one. There are plenty of childhood and adult vaccines that require repeated jabs, right?

  5. Thanks Dr Pearson for this information. Really help me to decide more easily on taking the 4 booster. We need this this medical support for more doctors like you. Could you please give us more information about treatment for high blood pressure, monotherapy vs combination , new drugs schemes and side effects.

    • Bexy,
      Glad my words helped.
      On high BP, I assume you have been to my ultimate guide page on BP?
      Not a whole lot new and significant since I last updated that but I should probably add a few things.
      I favor reduced dosage combo therapy with home monitoring of BP as it is more effective with less side effects.
      Dr P

    • JS,
      From everything I’ve read this would be totally unhelpful.
      If you had serial antibody titers and knew that there had been a significant drop (what constitutes significant is unclear because the immunity is also derived from T and B cells responses) then you might use that to help you decide if you were truly on the fence.
      However, zero data to support this approach and no one is advising it.
      dr P

  6. I got my 2nd booster yesterday at Walgreens. Just took a chance and walked in and they took my info including Medicare card. Fifteen minutes and I was done. Fourth Pfizer shot. Only after effect is a bit of a stiff neck which I had after the first jab also but not second or third. Strange. I was 6 months out from the first booster so it was probably time.

    • Warren,
      I have a power dislike of waiting in lines (really waiting anywhere) thus I fear the walk-in visit.
      Dr P

  7. Thanks much for this. I’m immunocompromised with lupus & several other autoimmune diseases & I’m on infliximab which affects antibody production. It took me 3 doses just to make antibodies. I just saw my immunologist who told me to go get the booster because he’s concerned about Ba.2. The immunologist is also very concerned about availability of Paxlovid now that the Administration is touting a new treatment plan. I’m in the DC suburbs & my immunologist consults with Biden Administration.

    I wanted to thank you for your recent blogs on testing & CVD risk, I found it very helpful for discussing my potential heart disease risks & testing given my lifelong inflammatory conditions. My new Johns Hopkins cardiologist was on board with all your recommendations.

    • sally,
      I’m glad my words were helpful and that your Hopkins cardiologist was on board with them. When I get the League of Skeptical Cardiologists launched I shall have to invite him.
      Dr P

  8. I got it and am still a little conflicted about whether it was/is a good idea. Age 53, t2 diabetes documented as remission (a1c 4.5-5.1 for past three years), obese, but bmi is 30.5. No other health issues. Previously had J&J and Pfizer. Was infected soon after the booster. Probably omicron – symptoms were extremely mild. Was conflicted about which 2nd booster to get. Went with Pfizer out of an irrational anxiety about getting all three types. I used to be better-informed on topics related to this virus. Lately I’ve just grown tired of reading about it.

    • Matilda,
      I share your COVID fatigue. I was hoping I wouldn’t have to keep delving deeply into the darn thing. But as I was grappling with a decision that I knew many shared I dove in again.
      Dr P

  9. A question for this scenario which I and my wife followed. Me, 77, wife 75. Both same time for all shots. 2 shots of Modera (full strength 1/14/21 and 2/11/21). Then a 3rd full strength shot of Moderna on 8/31/21. Our 3rd shot, full strength, was based on discussions with our PCP, who has now retired. Side effects for the 3rd shot for both of us were not horrible but more noticeable than for shot 2. Our PCP said (months ago before he retired) OK for you two to get a 4th shot. We waited knowing our 3rd shot was full strength and not the booster strength. So, what we are now considering is a 4th booster strength shot, of Pfizer not Moderna (per your nicely present article above). Just wondering what your thoughts are on when to time the jab, given our jab scenario?

  10. Thanks very much for this feedback. Dr. Pearson. It is extremely helpful. I’m 78 and had the booster 4 months ago; all Moderna, with only minor side-effects, so when the timing is right, I think I’ll go with Moderna again, simply because I’m nervous about any new side-effects if I switch to Pfizer, and since the “FDA says either approach is fine.”

    • Bill,
      I think that is a reasonable approach. I would hold off for now , await more good information.
      That study I quoted has been cited as justification for both Moderna to pfizer switch as well as pfizer to Moderna.
      We will have to see if any additional data emerge that support that conclusion
      Dr P

  11. Interesting. Your comments and research further emphasize that it should be an “individual” decision and not mandatory for anyone, regardless of profession. I have had covid and did fine with it. No jabs for me due to a stroke (AFib), and I know the stats are not huge, but I know two people who had strokes after getting the jab (one had had covid also). It’s a tough decision. I appreciate your input

    • Can you provide specific details on the research supporting only voluntarily receiving a Covid vaccine regardless of profession? Although I am generally against government mandates, as a healthcare worker (albeit in IT), I am fully supportive of healthcare organizations requiring Covid vaccines. Also, the risk of stroke is much higher in individuals that have contracted Covid vs. the vaccine ( Correlation is not causation..

      • Hi Doug – I think we disagree about mandatory vaccines, which is okay. I respect your opinion but still do not believe they should be forced on anyone, regardless of their job status. I’m prior military and many are being forced out due to the mandates. I am not against vaccines in general, and as being retired from the military have obviously had vaccines. I just think we live in an age where an unproven vaccine should not be forced. And I say unproven, because it does not prevent the virus. As far as the stroke comment, one person I know that had a stroke had had both Covid and the vaccines, the other only the vaccine. Everything comes with risk, I realize that. But as a free society we should not be forced by the government. And as a byline, I also know many health care workers who are going to lose their job without the jab. Regardless of weather they have had covid or not. Shame when we have such a shortage of medical personnel. Thanks for your input.

      • Doug,
        Thanks for your comments. The major issue with stroke post COVID19 appeared to be a rare syndrome of cerebral venous sinus thrombosis.(CVST) which was mostly seen in women <60 years of age who received Astra-Zeneca vaccine.
        A large Mayo clinic study found that patients were as likely to get this in the 30 days before the vaccine as in the 30 days after.
        Among patients receiving any COVID-19 vaccine, there were 10 cases of CVST observed (0.0019%) in the 30 days following vaccine administration, and 10 cases of CVST were observed in the 30 days prior to administration. 3 of the 10 post-vaccination CVST cases were from individuals receiving the “Pfizer/BioNTech vaccine, but there were also 3 cases among this same cohort in the 30-day pre-vaccination window, suggesting that these events were likely not caused by the vaccine (RR: 1.0, 95% CI: [0.23, 4.40] (Table 1). To date, no cases of CVST have been documented within 30 days before or after any doses of the Moderna or Janssen vaccines at the Mayo Clinic (Table 1). The relative risk of CVST in the 30 days following any COVID-19 vaccination was not statistically significant (RR: 1.50, 95% CI: [0.28, 7.10], see Table 1).”

        As to whether health care workers should be mandated to get vaccinated, I find it complicated without a simple answer. At my prior employer, we were all mandated to get the flu vaccine and although I bristled at being forced to get it I understood the logic. Some of that has to do with transmitting flu to other HCW or to patients, some to improving health and attendance of the workforce . The same considerations are in play with COVID vaccines but i think the risks of the vaccine have been overemphasized and the whole issue politicized thus it has become controversial.
        Dr. P

  12. Excellent, relevant, and thoughtful post. Very helpful and I particularly appreciate the pros and cons for different situations and demographics. Thank you.


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