Thread by @mahesh_shenai

1a/jamanetwork.com/journals/jama/… Interesting paper recently pub by JAMA. re: prior C19 in mRNA vaxed persons. This D/N compare V+PI vs. PI alone, but V+PI vs. Vax alone (a different ?). PI + Vax significantly reduced infection risk compared to mRNA Vax alone. Fascinating result in🧵👇

1b/ SPOILER: Vaxed persons with a PI had a much lower rate of infection, in both Pfizer (0.18x) and Mdrna (0.35x). But MORE INTERESTING: Those Vaxed >6m after PI did better than Vax<6 months, by a lot!
(fyi, PI= prev. inf, nPI= not PI).

2/ Some may misinterpret the meaning of the study here. So to be clear: THIS DOES NOT ANSWER the ?? of whether vax significantly reduces infection risk in PI persons. Instead, it asks the converse: does PI reduce risk in vaxed persons?

3/ The study draws from a national Qatari database, of more than 1.5M persons who were vaccinated between 12/20 and 9/21, with follow-up starting 14 days after 2nd dose. They used a “matched cohort” design.

4a/ Briefly, for study looked at Pfizer and Moderna vaccinees separately. Authors matched all PI persons within each group 3:1 with nPI persons, according to age, sex, nationality, and vax dose month. Then looked at infection rates.

4b) The methodology looks sound, and the matching process appears to have been done properly, minimizing noisy adjustments.

5/ The results demonstrated significant risk reduction for vaccinees in PI. Adjusted HR (aHRs) below:
Pfizer: 0.18 (Vax/PI << Vax/nPI)
Mdrna: 0.35 (Vax/PI <<Vax/nPI)
KM Curves below:

6/ Additionally, authors note aHRs decreasing by month, suggesting accelerated vax waning in nPI>PI persons with time. This effect was more dramatic with Moderna vaccine. PI persons appeared protected from vax waning.

7/ Perhaps, most interestingly – authors also looked at timing of vax after PI, on infection rate. And they found: Vax >6 months after PI had significantly LOWER re-infection rates then Vax<6mos. aHRs:
Pfizer: 0.62
Moderna: 0.40
(!!!)

8/ The authors d/n postulate reasons for this result, but it implies that those with longer PI-vax interval have BETTER post-vax protection. Could earlier vax after PI impair natural immunity process, or later vax more effective? Both possibilities must be strongly considered!

9/ BUT, the question to VAX is still up in the AIR. Because, in this study, we do not know what the rate of reinfection is prior to Vax, and the length of time a pre-vaxed PI person may be at elevated risk reinfection risk.

10/ Based on this study, however, the marginal risk a PI person takes in waiting to get vax, may be countered by the additional protection gained by waiting to get vax. If a PI person gets vaxed, TIMING IS IMPORTANT.

11a/ And of course, study limitations are important. PI was determined by PCR, so asymptomatics could be misclassified. Also PI persons may “select” for healthier persons due to mortality (which was very low in Qatar).

11b/ Also Qatar is a very young population, and its demographics may not be particularly generalizable to other national populations.

12/ HOWEVER, our current policies (wrongly) do not consider PI at all, let alone timing after PI. This study suggests that there may be trade-offs between early and late vax after PI, and maybe an optimal “window”.

13a/ Moreover, there may be millions of people who have had asymptomatic infections, and seroconverted recently and quietly. If this study is true, rush to vax without knowing “immune” status may mute level of protection!

13b/ Its complicated! The proper time for vaccination in PI persons (if any) should be determined by person, their physician, and relevant immunological testing. Not MANDATES!

14/ MANDATES are inefficient. In scenarios where the risk-benefit calculations can become complex, persons are forced into vax only for socioeconomic reasons – not clinically optimal reasons. This is particularly true in the previously infected and 5-11yos.

15/ Knowing this will fall on deaf ears, I still call on the CDC to consider more nuance in their vaccination guidance for PI persons. Health and professional livelihoods depend on it !!!

Thank you for reading. As always, open to discussion comments/corrections/concerns.