Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, found a study published on MedRxiv as a preprint. The journal Science describes the data as “ominous”.
It reports that South Africa has seen three massive COVID-19 waves already: one with the original SARS-CoV-2, one with the Beta variant—which never made much headway outside the country and has now disappeared—and one with Delta. Studies found that a previous infection offered imperfect but significant protection against Beta and Delta, and many had hoped that the population immunity built up in South Africa so far would help dampen further spread of SARS-CoV-2. But scientists worry Omicronʼs dozens of mutations might help it evade immunity.
An analysis of 35,670 reinfections among nearly 2,8m positive tests suggests their fears are warranted. The study does not indicate whether Omicron makes people sicker, nor was it able to look at the vaccination status of infected people. An earlier infection or vaccination might still offer some protection from severe disease.
Juliet Pulliam, an infectious disease epidemiologist at the South African Centre of Excellence in Epidemiological Modelling and Analysis, and her colleagues started investigating the rate of reinfections in January, after Beta had emerged. Beta seemed to evade immune responses from previously infected people in lab experiments, but the researchers wanted to better understand its real-world behaviour.
Taking advantage of South Africaʼs extensive records of tests for SARS- CoV-2, they analysed the number of reinfections, defined as a positive test more than 90 days after the same person had an initial infection. They found that a prior bout reduced peopleʼs risk of another one by about the same amount during both the Beta and Delta waves.
After Delta subsided, the researchers wrote a paper, which they posted as a preprint last month. But they continued to update their database. In October, Pulliam says, while overall rates of infection were quite low, they noticed something odd: the risk of first infections was decreasing— possibly due to a pickup in vaccinations—whereas the risk of reinfections seemed to increase sharply.
“I thought something was wrong with the data or the programming,” she said. “Then about two weeks ago, we started seeing other signals that SARS-CoV-2 was gaining ground again.
“Wastewater sampling started showing increases, labs started showing significant increases in positive cases, and other bells started going off. At that point it dawned on me that the pattern in the graphs could be related to an actual signal.” The team was not surprised when Omicron was identified, and they quickly updated their preprint.
Although there are a lot of uncertainties in the paper, it looks as though an earlier infection offers only half as much protection against Omicron as it does against Delta, said Natalie Dean, a biostatistician at Emory University. Pulliam agrees thatʼs a good estimate.
“The exact numbers are fraught with issues,” said William Hanage, an epidemiologist at the Harvard TH Chan School of Public Health. “But thatʼs not the point here,” he adds. “It is a first pass that provides a good enough comparison to show us that, as we might have expected, reinfections are a big deal with Omicron.”
All eyes are now on South African hospitals, which are starting to fill again with COVID-19 patients. Thatʼs where researchers hope to see clues as to whether vaccination or a previous infection reduces the severity of a new one.
Study details
Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa
Juliet Pulliam, Cari van Schalkwyk, Nevashan Govender, Anne von Gottberg, Cheryl Cohen, Michelle Groome, Jonathan Dushoff, Koleka Mlisana, Harry Moultrie.
Abstract
Objective
To examine whether SARS-CoV-2 reinfection risk has changed through time in South Africa, in the context of the emergence of the Beta, Delta, and Omicron variants
Design
Retrospective analysis of routine epidemiological surveillance data Setting Line list data on SARS-CoV-2 with specimen receipt dates between 4 March 2020 and 27 November 2021, collected through South Africa’s National Notifiable Medical Conditions Surveillance System
Participants
A total of 2,796,982 individuals with laboratory-confirmed SARS-CoV-2 who had a positive test result at least 90 days prior to 27 November 2021. Individuals having sequential positive tests at least 90 days apart were considered to have suspected reinfections.
Main outcome measures
Incidence of suspected reinfections through time; comparison of reinfection rates to the expectation under a null model (approach 1); empirical estimates of the time-varying hazards of infection and reinfection throughout the epidemic (approach 2)
Results
A total of 35,670 suspected reinfections were identified among 2,796,982 individuals with laboratory-confirmed SARS-CoV-2 who had a positive test result at least 90 days prior to 27 November 2021. The number of reinfections observed through the end of the third wave was consistent with the null model of no change in reinfection risk (approach 1). Although increases in the hazard of primary infection were observed following the introduction of both the Beta and Delta variants, no corresponding increase was observed in the reinfection hazard (approach 2). Contrary to expectation, the estimated hazard ratio for reinfection versus primary infection was lower during waves driven by the Beta and Delta variants than for the first wave (relative hazard ratio for wave 2 versus wave 1: 0.75 (CI95: 0.59–0.97); for wave 3 versus wave 1: 0.71 (CI95: 0.56–0.92)). In contrast, the recent spread of the Omicron variant has been associated with a decrease in the hazard coefficient for primary infection and an increase in reinfection hazard coefficient. The estimated hazard ratio for reinfection versus primary infection for the period from 1 November 2021 to 27 November 2021 versus wave 1 was 2.39 (CI95: 1.88–3.11).
Conclusion
Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection. In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. This finding has important implications for public health planning, particularly in countries like South Africa with high rates of immunity from prior infection. Urgent questions remain regarding whether Omicron is also able to evade vaccine-induced immunity and the potential implications of reduced immunity to infection on protection against severe disease and death.
See more from MedicalBrief archives:
So far, milder disease seen with Omicron, with shorter hospital stays — SA hospitals analysis
State of play with Omicron – The discovery, the spread, the politics, and the science
Triple shot of Pfizer vaccination ‘neutralises Omicron variant ‘