COVID: mRNA vaccine anaphylaxis -- ?overblown

 Anaphylaxis is a rare event after the mRNA vaccines, apparently more common with the Pfizer one (see covid mRNA vaccine anaphylaxis jama2021 in dropbox, or doi:10.1016/j.vaccine.2015.07.035) 

Details: 

-- this is an updated report of anaphylaxis from both the Pfizer and Moderna vaccines, after the initial reports finding the Pfizer vaccine had 11.1 cases per million doses and the Moderna vaccine 2.5 per million doses. 

-- the current report is based on the Vaccine Adverse Event Reporting System (VAERS) for anaphylaxis at levels 1, 2, or 3, after 9,943,247 doses of the Pfizer vaccine and 7,581,429 doses of Moderna were administered 

    -- Brighton Collaboration anaphylaxis level: level 1 occurred in 50%, level 2 in 45% and level 3 in 5% (level 1 is the worst)

        --for the Brighton Collaboration anaphylaxis criteria, see https://www.spsu.ch/en/docs/media/273d46e0-5363-49c4-aec8-a2d190b75acf/4692a94e94a54deabc8acf1136815161

-- for those having anaphylaxis (total of 66 people: 47 after Pfizer and 19 after Moderna): median age 40,  96% female, 10 minutes to symptom onset (80% <15 minutes; 89% within 30 minutes), 80% had allergies or allergic reactions, 30% history prior anaphylaxis

-- anaphylaxis by dose: 54 cases after the first dose (37 cases with Pfizer and 17 cases with Moderna), 5 after second dose (4 Pfizer and 1 Moderna), with 6 Pfizer and 1 Moderna unclear which dose

 

Results: 

-- Pfizer vaccine: 47 cases, 4.7/million doses administered 

-- Moderna vaccine: 19 cases, 2.5/million doses administered 

    --these numbers were as of January 18, 2021 

-- cases were from multiple lots of vaccine (i.e. it wasn’t just a couple of bad lots) 

-- all cases were treated in healthcare settings, with 18 in intensive care, 7 of whom required endotracheal intubation
-- 21 (32%) of the 66 anaphylaxis cases were in people with a prior of anaphylaxis exposures, including anaphylaxis to vaccines, contrast media, meds, latex, foods. 

     -- all anaphylaxis cases were treated in healthcare settings 

-- of the 7 intubated patients, median time to symptom onset was 6 minutes (range <1 to 45 minutes), and all but one was within 11 minutes 

    --facial, tongue or laryngeal angioedema were present in 4 patients 

    --hospitalization ranged from 1-3 days 

-- treatment included epinephrine, steroids, antihistamines 

-- no deaths reported 

Commentary:  

-- when anaphylaxis was first noted by the CDC, almost all anaphylaxis cases were within 15 minutes. They suggested that there be a post-vaccination observation period of 15 minutes in general, but a 30-minute period for those with a history of severe allergic reactions to catch the few outliers (89% in above study were still within 30 minutes)

--almost all cases were in women (63 of the 66 cases) or had history of allergies/prior anaphylaxis

--and there was only a total of 5 cases after the second dose (though 7 were “unknown” for which dose) 

--but there have currently been 481,000 deaths in the US from Covid  

    --so far in February, we are averaging >3000 Covid deaths per day. and, so far, no deaths from anaphylaxis since the first vaccine given (though some may have been prevented by the requisite observation period)

        --the bar is certainly in favor of preventing an adverse outcome: we do not want to create bad outcomes, esp in people who might never get the virus. but having no deaths in many months from the vaccine is a tad lower than the perhaps 150K range of Covid deaths since jan 1.

    --as we have accumulated huge numbers of mRNA vaccine doses administered, it appears that the incidence of severe anaphylaxis requiring intubation is quite small, with 7 patients in 17,524,676 receiving either mRNA vaccine; and, all but 1 patient had a severe reaction within 11 minutes  

--at least in some settings, the requirement to have people wait 15 minutes (or 30 minutes with prior allergies) post-vaccination does significantly limit the number of people who can get the vaccine 

Limitations: 

--these numbers are based on the voluntary reporting of health care providers of adverse events; these may not be complete. 

    --and given the remarkably few reports in those with level 3 (least severe) anaphylaxis, decreased reporting seems to be very likely at least for these milder cases

--it would be great to have more granular data. Who were the people who had more anaphylaxis, and especially those with more severe reactions? Were there clear predictors other than the history of allergy/anaphylaxis? Did the relatively few men have severe enough reactions to worry about? Did the very few who had reactions after the second dose have mild or severe reactions? Was there an age group that had the severe reactions (maybe more in younger people with more robust immune systems??, and the average age in this study was only 40). i would think this data should be available and decipherable

 

so, maybe the following makes sense: 

--in those settings where there is not enough room or staff to monitor people for 15-30 minutes after vaccination, maybe we should immunize as many people as possible as quickly as possible, since we do now know that the mortality rate of the virus far exceeds the potential mortality rate from anaphylaxis. when there are constraints on space or staff:

    --It may make sense to have those with history of anaphylaxis be observed; but at least from this data, 11% were beyond 30 minutes, and 1 of the intubated ones had symptom onset at 45 minutes (the other 6 had symptoms within 6 minutes). so, unclear what optimal waiting time should be to prevent serious, life-threatening anaphylaxis, or what number of deaths from severe reactions needs to be prevented to justify the appropriate waiting time.

    --the number of cases after the second vaccine dose was minimal. Assuming that these few people did not have severe reactions, maybe we can get by without their waiting at all? (and anyone waiting in a room for 15-30 minutes may in fact expose themselves to others getting the vaccine, prior to their developing immunity)

    --and, maybe other criteria (age, sex) could also prune down the numbers needing to wait at all???  maybe only younger women with a history of severe allergies for the first dose only????

 

Of course, these decisions need to be made by the state or local public health organizations with the state leaders, though guidance from the CDC would be beneficial. but these data seem to be pretty compelling 

geoff

 

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