relative hazard ratio for the period of Omicron
emergence (1 November 2021 to the start of
the fourth wave) versus wave 1 was 1.75 (95%
CI: 1.48 to 2.10), and for wave 4 versus wave 1,
itwas1.70(95%CI:1.44to2.04).Discussion and limitations
Our analyses suggest that the cumulative
number of reinfections observed through the
end of wave 3 was consistent with the null
model of no change in reinfection risk through
time. Furthermore, our findings suggest that
the relative hazard of reinfection versus pri-
mary infection decreased with each subsequent
wave of infections through September 2021,
as would be expected if the risk of primary
infection increased without a corresponding
increase in reinfection risk. Thus, our analy-
ses show no population-level evidence of im-
mune escape associated with emergence of
the Beta or Delta variants. By contrast, in
November 2021, the number of daily new
reinfections spiked and exceeded the 95%
projection interval from the null model, and
this was accompanied by a notable increase in
the hazard ratio for reinfection versus primary
infection. The timing of these changes strongly
suggests that they were driven by the emer-
gence of the Omicron variant. This finding has
now been supported by analyses of reinfec-
tion with Omicron in the United Kingdom
and Qatar ( 14 Ð 16 ).
Differences in the time-varying force of in-
fection, original and subsequent circulating
lineages, testing strategies, and vaccine cov-
erage limit the usefulness of direct compar-
isons of rates of reinfections across countries
or studies. However, pre-Omicron reinfection
does appear to be relatively uncommon. The
PCR-confirmed reinfection rate ranged from
0 to 1.1% across 11 studies included in a system-
atic review ( 17 ). Although none of the studies
included in the systematic review reported an
increasing risk of reinfection over time, the du-
ration of follow-up was less than a year and
most studies were completed before the iden-
tification of VOCs. Furthermore, all studies
predated the emergence of Omicron. Our find-
ings for the period before the emergence of
Omicron are consistent with results from the
PHIRST-C community cohort study conducted
in two locations in South Africa, which found
that infection before the second wave provided
84% protection against reinfection during the
second (Beta) wave ( 18 ), which is comparable
to estimates of the level of protection against
reinfection for wild-type virus from the SIREN
study in the United Kingdom ( 19 ).
A preliminary analysis of reinfection trends
in the United Kingdom suggested that the
Delta variant may have a higher risk of re-
infection compared with the Alpha variant
( 20 ); however, this analysis did not take into
account the temporal trend in the populationPulliamet al.,Science 376 , eabn4947 (2022) 6 May 2022 3of8
Fig. 2. Time between consecutive infections based on the time between successive positive tests.
Note that the time since the previous positive test must be at least 90 days to be considered a reinfection.
(A) Time in days between the last positive test of the putative first infection and the first positive test
of the suspected second infection. (B) Time in days between the last positive test of the putative second
infection and the first positive tests of the suspected third infection. Colors represent suspected reinfections
diagnosed on or after 1 November 2021. In both panels, bars for these individuals are colored by the
wave during which the previous infection occurred (purple indicates wave 1; pink, wave 2; orange, wave 3; and
light gray, interwave).
Fig. 3. Timing of infections for individuals with multiple suspected reinfections.Circles represent the
first positive test of the first detected infection; triangles represent the first positive test of the suspected
second infection; squares represent the first positive test of the suspected third infection; and crosses
represent the first positive test of the suspected fourth infection. Colored bands represent wave periods,
defined as the period for which the 7-day moving average of cases was at least 15% of the corresponding
wave peak (purple indicates wave 1; pink, wave 2; orange, wave 3; and turquoise, wave 4).
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