The New England Journal of Medicine has published online Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections. The study by the Cornell Medicine–Qatar group of investigators has received some attention in the lay press and has even been interpreted as showing that under certain circumstances that vaccination increases the likelihood of contracting the infection. It doesn’t. But there’s a lot less and more to the work than first meets the eye.
What was done was “a national, matched, test-negative, case–control study in Qatar from December 23, 2021, through February 21, 2022, to evaluate the effectiveness of vaccination with BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna), natural immunity due to previous infection with variants other than omicron, and hybrid immunity (previous infection and vaccination) against symptomatic omicron infection and against severe, critical, or fatal coronavirus disease 2019 (Covid-19).” For simplicity and as an aid to comprehension I’ll call the first vaccine Pfizer and the other Moderna.
The investigators examined a database in Qatar from December 23, 2021, through February 21, 2022. This period was during a high incidence of COVID infection from the Omicron variant of the virus. Both the BA.1 and BA.2 variants were examined. The reader must consider that Qatar has a population which is 91% under age 50. A test-negative, case–control design, in which effectiveness estimates were derived by comparing the odds of previous infection or vaccination or both among case participants (persons with a positive PCR test) with that among controls (PCR-negative persons). Five groups were compared with the group that had no previous infection and no vaccination.
The authors conclude that no discernable differences in protection against symptomatic BA.1 and BA.2 infection were seen with previous infection, vaccination, and hybrid immunity. Vaccination enhanced protection among persons who had had a previous infection. Hybrid immunity resulting from previous infection and recent booster vaccination conferred protection a little higher than from infection alone (data not shown). The essential findings of the the study are shown in the figure below.
The top panel has the Pfizer data while those from the Moderna vaccine are in the bottom. As is readily apparent the best protection was observed in subjects that were 4-6 months post infection. The effectiveness of vaccination alone was essentially nonexistent in the two dose regimen, but was more robust when three doses of either vaccine were administered. What caught the eye of the lay press was the -10.3 effectiveness of the Moderna two dose regimen at more than 6 months. What the study shows is that vaccination alone has a transitory efficacy that is completely gone at 6 months. The three dose course was more effective than the two, but its duration is not apparent from this study.
The likelihood of a booster vaccination combined with prior infection conveying superior protection against symptomatic disease is suggested by this study, but the data are of insufficient duration to allow such a conclusion. Note that prior infection conveys much longer protection than does vaccination given to subjects who had not been infected prior to vaccination. Also the study population was young and relatively healthy. Whether results in a population older and with significant comorbidity would be similar to those of this study is not known. The effectiveness, side effects, frequency of dose, and applicability of COVID vaccination needs more study.