Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa
Date
2022-08-19
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Abstract
South Africa was among the first countries to detect the SARS-CoV-2 Omicron
variant. Propelled by increased transmissibility and immune escape properties, Omicron displaced
other globally circulating variants within 3 months of its emergence. Due to limited testing,
Omicron’s attenuated clinical severity, and an increased risk of reinfection, the size of the Omicron
BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood in South Africa and in many
other countries. Using South African data from urban and rural cohorts closely monitored since
the beginning of the pandemic, we analyzed sequential serum samples collected before, during,
and after the Omicron BA.1/2 wave to infer infection rates and monitor changes in the immune
histories of participants over time. Omicron BA.1/2 infection attack rates reached 65% (95% CI,
60% – 69%) in the rural cohort and 58% (95% CI, 61% – 74%) in the urban cohort, with repeat
infections and vaccine breakthroughs accounting for >60% of all infections at both sites.
Combined with previously collected data on pre-Omicron variant infections within the same
cohorts, we identified 14 distinct categories of SARS-CoV-2 antigen exposure histories in the
aftermath of the Omicron BA.1/2 wave, indicating a particularly fragmented immunologic
landscape. Few individuals (<6%) remained naïve to SARS-CoV-2 and no exposure history
category represented over 25% of the population at either cohort site. Further, cohort participants
were more than twice as likely to get infected during the Omicron BA.1/2 wave, compared to the
Delta wave. Prior infection with the ancestral strain (with D614G mutation), Beta, and Delta
variants provided 13% (95% CI, -21% – 37%) , 34% (95% CI, 17% – 48%), and 51% (95% CI,
39% – 60%) protection against Omicron BA.1/2 infection, respectively. Hybrid immunity (prior
infection and vaccination) and repeated prior infections (without vaccination) reduced the risks of
Omicron BA.1/2 infection by 60% (95% CI, 42% – 72%) and 85% (95% CI, 76% – 92%)
respectively. Reinfections and vaccine breakthroughs had 41% (95% CI, 26% – 53%) lower risk
of onward transmission than primary infections. Our study sheds light on a rapidly shifting
landscape of population immunity, along with the changing characteristics of SARS-CoV-2, and
how these factors interact to shape the success of emerging variants. Our findings are especially
relevant to populations similar to South Africa with low SARS-CoV-2 vaccine coverage and a
dominant contribution of immunity from prior infection. Looking forward, the study provides
context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer naïve
to the virus.