key: cord-0875381-p18w87iu
authors: Yu, Yihua Bruce; Briggs, Katharine T.; Taraban, Marc B.
title: Why some people tolerate the second dose of a vaccine but not the first dose
date: 2022-03-29
journal: Ann Allergy Asthma Immunol
DOI: 10.1016/j.anai.2022.01.033
sha: d59f9d2c1242de509eaabea7479cf901288968d4
doc_id: 875381
cord_uid: p18w87iu

nan

In response to "...Why a College?" I thank Dr Blaiss for the recent perspective article entitled "The Future of the American College of Allergy, Asthma, and Immunology: Why a College?," which sheds insight into our history and provides an important roadmap forward. 1 I could not agree with you more that the College is poised and will be nimble in navigating future challenges and opportunities to provide critical clinical information and specialty-specific advocacy for its members. Furthermore, I appreciate your acknowledgment of the shifting demographics of our future workforce, with an increasing number of female applicants to fellowship programs, a trend which those of us involved in fellow-intraining education also observe. A future specialty consisting of wellqualified practitioners whose demographics are also representative of the greater population would be an ideal outcome. Having all areas of medicine be representative of the general population is a laudable goal for medical education, and it is hoped that we might see this occur in our lifetimes. In the end, I believe this will best serve our patients.

Finally, allow me to clarify some historical points, having personally known all the female presidents of the College, and with these women elected within the span of my career. The late Dr Diane Schuller became our first female president from 1994 to 1995, followed by Dr Betty Wray as our second female president from 1996 to 1997. There was a gap after their leadership until Dr Dana Wallace's presidency in 2010, then another gap until the recent presidency of Dr Luz Fonacier. Thus, we have had 4 female presidents of the American College of Allergy, Asthma, and Immunology to date in our history. I hope to become the fifth later this year. That said, I will not be the last, nor do I anticipate a lapse of time until we see our next female leader. There are numerous, well-qualified female allergist colleagues in the College committee and council activities, increasingly represented in leadership roles. I am honored to know and work alongside them, with the special privilege of mentoring a few of these women. Their (and thus, our) future is bright! The proverbial "glass ceiling" may be permanently shattered.

Kathleen R. May, MD, FACAAI Allergy, Immunology, and Pediatric Rheumatology Medical College of Georgia Augusta University Medical Center Augusta, Georgia kamay@augusta.edu Why some people tolerate the second dose of a vaccine but not the first dose

Vaccine adverse reaction investigations typically rest on the premise that every dose of a vaccine has the potential to cause adverse reactions in sensitive populations. In the case of an anaphylaxis reaction to messenger RNA (mRNA) vaccines against coronavirus disease 2019 (COVID-19) , the investigation quickly focused on polyethylene glycol, which is present in every dose of these vaccines. 1 To date, no definitive conclusion has been reached. On the contrary, a recent study published in this journal suggests that the polyethylene glycol skin test has little use in assessing allergic reactions to these vaccines. 2 It is perhaps time to consider factors other than vaccine ingredients, such as the quality of individual vaccine doses. 3 There are now multiple reports on people who developed adverse reactions, including anaphylaxis, to the first dose of mRNA COVID-19 vaccines but tolerated the second dose. [4] [5] [6] [7] For example, 1 retrospective study reported that 159 people who developed immediate reactions to the first dose of mRNA COVID-19 vaccines, including 19 cases of first-dose anaphylaxis, all tolerated the second dose. 4 At least 5 people who developed first-dose anaphylaxis tolerated the second dose without premedication.

One possible explanation for this observation is some adverse reactions were caused by defective doses of vaccines. Here, a defective dose means its critical quality attributes are outside the acceptable range. When the product defect rate is low, it is unlikely that the same person will receive 2 bad doses. This may be the reason why some people tolerate the second dose of a vaccine but not the first dose, and vice versa.

As of January 18, 2021, the anaphylaxis rate for Pfizer and Moderna mRNA COVID-19 vaccines in the United States was 4.7 cases/ million doses administered and 2.5 cases/million doses administered, respectively. 8 Unless the defect rate of these 2 vaccines at vaccination sites is known to be much lower than the anaphylaxis rate, the possibility that some anaphylaxis cases were caused by defective doses cannot be excluded. It is unrealistic to expect any pharmaceutical product to have a zero defect rate by the time they are administered. Pharmaceutical product defects may occur during manufacturing, which is not very precise, 9 or during distribution, in which mishandling such as cold chain breaches may happen. 10 Whereas adverse reactions caused by defective doses may occur to any pharmaceutical product, the 2-dose regimen of mRNA COVID-19 vaccines offers an opportunity to test these two possibilities more readily. If anaphylaxis is primarily caused by good-quality vaccine doses (most in a batch), then the probability of 1 person experiencing anaphylaxis twice would be on the order of 4.7/10 6 and 2.5/10 6 doses for the 2 mRNA COVID-19 vaccines-that is, a few per million. However, if anaphylaxis is primarily caused by bad-quality vaccine doses (few in a batch), then the probability of 1 person experiencing anaphylaxis twice would be on the order of (4.7/10 6 ) 2 and (2.5/10 6 ) 2 for the 2 mRNA COVID-19 vaccines-that is, a few per trillion. When data become available, these 2 possibilities may be distinguished by the number of vaccinees who experienced anaphylaxis twice divided by the total number of vaccinees who received 2 doses.

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