Long COVID Half as Likely After Omicron Infection vs Delta, Say UK Investigators

The Omicron variant of the SARS-CoV-2 virus poses approximately half the risk of leading to long COVID compared with the Delta variant, according to an analysis by researchers from King’s College London.

The study, published in mid-June in The Lancet found that, depending on age and time since vaccination, the odds of experiencing long COVID were between 20-50% less during the Omicron period versus the Delta period.

The study is the first peer-reviewed analysis to report on risk for long COVID and infection with the Omicron variant, the authors state.

Looking at data from the European ZOE COVID Symptom study app database, investigators led by Dr Claire Steves, clinical senior lecturer at Kings College London, found that the number of confirmed cases of infection with Omicron between December 2021 and March 2022 (Omicron period) exceeded all previous case counts. Although this variant is associated with less severe acute illness than previous virus variants, the potential for significant numbers of people to experience long-term sequelae, the authors warn, is real and requires that health care systems have adequate information in order to respond.

The UK Office of National Statistics estimated the numbers of people with long COVID actually increased from 1.3 million in January 2022 to 2 million as of 1st May 2022.

Stevens et al thus set out to identify the relative odds of long-COVID in the UK during the Omicron period compared with similar odds during the period when the Delta variant was predominant. For purposes of the study, investigators used the definition of long-COVID from the UK National Institute for Health and Care Excellence guidelines, ie, having new or ongoing symptoms 4 weeks or more after the start of acute COVID-19.

Inclusion criteria for the case-control observational study were the same for both variant-dominated periods—positive real-time PCR or lateral flow antigen test for SARS-CoV-2 after vaccination, at least 1 log per week in the study app for at least 28 days after testing positive, and no previous SARS-CoV-2 infections before vaccination.

The investigators report identifying 56 003 UK adults who were infected with Omicron between December 20, 2021, and March 9, 2022, and, using the same selection criteria, 41 361 adults who tested positive for the Delta variant between June 1, 1021, and November 27, 2021. They considered both symptomatic and asymptomatic infections.

When they reviewed characteristics of both cohorts, Steves et al found participation among women was higher during both periods than among men (55% Omicron, 59% Delta cases). Age was similar across the cohorts (mean age 53 years) as was prevalence of comorbidities (~19%), they state. They also considered for both groups the local area Index of Multiple Deprivation (IMD), a score ranging from 1 (most deprived) to 10 (least deprived) and found that Omicron cases were distributed in areas of slightly lower deprivation than Delta cases (16.7% vs 17.5% for IMD 1–3).

For the assessment of association between reporting of long COVID and Delta vs Omicron infection period, they used univariate logistic regression modelling adjusted for sex, IMD, age, comorbidities, vaccination status (1, 2, or 3 doses) and body-mass index, all variables that have been associated with the risk for long COVID.

To allow for potential waning of immunity after vaccination, investigators stratified the analysis according to time between infection and most recent vaccination: 3 months, 3-6 months, and >6 months.

The final analysis showed that among 56 003 cases of omicron infection, 2501 (4.5%) experienced long COVID. Among the 41 361 cases of infection with the delta variant, 4469, or 10.8%, experienced long COVID.

Long COVID was less likely among Omicron cases for the 3 vaccine time periods with an odds ratio that ranged from 0.24 (0.20 - 0.32) to 0.50 (0.43-0.59). The results remained consistent, the researchers point out, when they stratified the analysis by age group.

But the lower risk doesn’t mean people shouldn’t worry about long COVID, Dr Steves cautioned in an interview with NPR:

“The caveat is that the Omicron variant has spread very rapidly through our populations, and therefore a very much larger number of people have been affected,” she said. “So, the overall absolute number of people who are set to go on to get long COVID, sadly, is set to rise.”

Reference: Antonelli M, Pujol JC, Spector TD, Ourselin S, Steves CJ. [Correspondence] Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. The Lancet. 2022:399:P2263-2264. Published June 19, 2022. DOI: https://doi.org/10.1016/S0140-6736(22)00941-2