UK study | Risk of long-term symptoms of COVID-19 associated with delta and Omicron variants

The Lancet publishes a peer-reviewed newsletter assessing the risk of long-term symptoms of COVID-19 associated with delta and omicron variants of SARS-CoV-2. The study found that the Omicron variant had a lower chance of developing long-term symptoms of COVID-19 than the delta variant, based on age and time since vaccination. However, the absolute number of people with long-term symptoms of COVID-19 at a given time depends on the shape and magnitude of the pandemic curve.

The Omicron variant of SARS-CoV-2 (PANGO B.1.1.529), which was first detected in November 2021, has spread rapidly around the world and rapidly replaced the previous variant. The COVID-19 database on the Our World in Data website shows that the number of confirmed cases reported in Europe between December 2021 and March 2022 (the peak Omicron) has exceeded all previously reported cases. Compared with several previous variants, Omicron caused a lower severity of acute illness, at least in the vaccinated population. However, the potential for long-term symptoms in large numbers of patients is a major future concern, and health and workforce planners urgently need relevant information to rationally allocate resources.

In this observational case-control study, we aimed to determine the occurrence of long-term COVID-19 symptoms (long COVID) during peak and delta peaks in Omicron, UK (according to the National Institute for Health and Care Excellence). ] guidelines, defined as the relative odds of the onset of new symptoms or the persistence of symptoms 4 weeks or more after the onset of acute COVID-19. We used self-reported data from the COVID Symptom Study application [1] (King's College London Research Ethics Management Application System No. 18210, ref LRS-19/20 -18210). Data were extracted and preprocessed using ExeTera13 (version 0.5.5).

Inclusion criteria for both variant groups were positive post-vaccination real-time PCR or lateral flow SARS-CoV-2 antigen testing; weekly documentation in the app for at least 28 days after positive testing [2]; and vaccine Not infected with SARS-CoV-2 prior to vaccination.

We identified 56,003 UK adult patients who tested positive for the first time between 20 December 2021 and 9 March 2022 and met inclusion criteria. It is estimated that more than 70% of the UK cases during this period can be attributed to the Omicron variant, so the above cases are hereinafter referred to as Omicron cases. Using the same selection criteria, we identified 41,361 UK adult cases, known as delta cases, who tested positive for the first time between 1 June 2021 and 27 November 2021. The study included both symptomatic and asymptomatic infections, and for peak Omicron, only participants who tested positive before February 10, 2022, to ensure all participants had at least 28 days after testing positive time to report symptoms.

In both variant groups, there were more female participants than male participants (55% in Omicron cases and 59% in Delta cases). Delta and Omicron cases were similar in age (mean age 53 years) and comorbidity prevalence was similar (about 19%). The Multiple Deprivation Index (IMD) can be used to estimate relative deprivation in a given area on a scale of 1 to 10, with 1 being the most deprived and 10 the least deprived. For localized IMD, the Omicron case distribution was slightly less deprived than the delta cases (IMD 1-3, 16.7% vs 17.5%). To assess the association between long-term symptoms of COVID-19 (outcome) and duration of infection (exposure), we used a univariate logistic regression model and adjusted the relationship between gender, IMD, age, comorbidity, and vaccination status (1-dose, 2-dose) or 3 doses) and body mass index, all of which were associated with risk of long-term symptoms of COVID-19. [3]

Considering the potential for a gradual decline in immunity acquired through vaccination, we performed a stratified analysis based on the length of time between infection and the most recent vaccination, including three groups: 3 months, 3-6 months, and 6 months above.

Among Omicron cases, 4.5% (2,501/56,003) had long-term symptoms of Covid-19, while among Delta cases, 10.8% (4,469/41,361) had long-term symptoms of Covid-19. Omicron cases were less likely to develop long-term symptoms of COVID-19 in terms of timing of vaccination, with ORs ranging from 0.24 (0.20-0.32) to 0.50 (0.43-0.59). The above results were also confirmed in different age groups (Figure).

We believe this is the first peer-reviewed study to report long-term symptoms of COVID-19 associated with Omicron variant infection, highlighting that health monitoring using a smartphone app can yield rapid insights that we have consistently shown are accurate and is repeatable [1]. One of the main strengths of our study of long-term symptoms of COVID-19 is the prospective documentation of various symptoms. Limitations of self-reported data include the lack of direct detection of patient-infected variants (assuming here from national data) and the lack of objective measurement of disease duration. Although the sample could not be fully generalized to the UK population due to reasons such as gender and socioeconomic bias, the characterization data for the two variant groups were similar and comparable. Our data are insufficient to estimate the odds of developing long-term symptoms of COVID-19 in unvaccinated individuals, nor the impact on children. Finally, to enable rapid reporting, the Omicron case was evaluated for a slightly shorter period than the delta variant, and longer-lasting COVID-19 symptoms (eg, >12 weeks) could not be evaluated.

Overall, we found that the Omicron variant had a reduced chance of developing long-term symptoms of COVID-19 compared with the delta variant based on age and time since vaccination (OR range, 0.24–0.50). However, the absolute number of people with long-term symptoms of COVID-19 at a given time depends on the shape and magnitude of the pandemic curve. For example, given the high number of patients infected with Omicron in the UK between December 2021 and February 2022, our data are consistent with data from the UK Office for National Statistics, which estimates that a prolonged period of Covid-19 The number of symptomatic patients actually increased from 1.3 million in January 2022 to 1.7 million in March 2022 [4]. During the peak period in Omicron, UK, there were more than 350,000 new symptomatic COVID-19 cases per day, 4% of which had long-term symptoms of COVID-19, according to estimates made by the ZOE app modelling on 26 March 2022 . In view of this, the number of patients with long-term symptoms of the new crown will inevitably rise in the future. END

Author introduction and statement

Michela Antonelli, Joan Capdevila Pujol, Tim D Spector, Sebastien Ourselin, *Claire J Steves [email protected]

SO and CJS contributed equally. TDS is a co-founder and shareholder of ZOE. JCP is an employee at ZOE. SO and CS have consulted for ZOE. MA declares no competing interests. This work is supported by the UK Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award to Guy's & St Thomas’ and King's College Hospital NHS Foundation Trusts and King's College London, and via a grant to ZOE from the UK Health Security Agency. This work is also supported by the Chronic Disease Research Foundation and the Wellcome Engineering and Physical Sciences Research Council Centre for Medical Engineering at King's College London.

School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK (MA, SO); Department of Twin Research and Genetic Epidemiology, King’s College London, London SE1 7EH, UK (TDS, CJS); ZOE, London, UK (JCP); Department of Ageing and Health, Guys and St Thomas’ NHS Foundation Trust, London, UK (CJS)

Reference：

[1]. Varsavsky T, Graham MS, Canas LS, et al. Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study. Lancet Public Health 2021; 6: e21–29.

[2]. Sudre CH, Murray B, Varsavsky T, et al. Attributes and predictors of long COVID. Nat Med 2021; 27: 626–31.

[3]. Antonelli M, Penfold RS, Merino J, et al. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet Infect Dis 2022; 22: 43–55.

[4]. Office for National Statistics. Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK: 3 March 2022.

https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/3march2022(accessed March 15, 2022).

[5] For Our World In Data COVID-19 data see

?https://ourworldindata.org/coronavirus