In a recent study posted to Preprints with The Lancet*, researchers demonstrated that coronavirus disease 2019 (COVID-19) symptoms varied between cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and Delta variants of concern (VOCs).
Although similar studies have previously characterized the differences between Omicron breakthrough infections from those of the Delta variant infections, the current study, being conducted on a larger scale, reported results generalizable at the population scale. Additionally, as the study participants were matched 1:1 with respect to age, gender, and the number of vaccine doses, those factors did not confound the study observations.
About the study
In the present study, researchers compared the prevalence of as many as 32 COVID-19 related symptoms, their duration, and the severity of the acute SARS-CoV-2 infection between Omicron and Delta cases.
They enrolled 62,002 COVID-19-positive, vaccinated individuals from the ZOE COVID App in the UK. The app-enabled capturing of self-reported daily updates on COVID-19 symptoms, test results, vaccination information of participants, including their baseline demographic. If the participants were self-quarantining or seeking health care, the app data revealed the level of intervention and related outcomes at the time of enrollment to the current study.
Through a Euclidean distance-based algorithm, the participants with Omicron infection were matched 1:1 on age, sex, and the number of vaccine doses (two or three doses) with subjects having Delta variant infection.
The researchers collected data from June 1 to November 27, 2021, and from December 22, 2021, to January 17, 2022. During the first-time phase, more than 70% of infections were due to the Delta variant; in the latter, Omicron replaced Delta to become the dominant variant in the UK, resulting in more than 70% COVID-19 cases.
The researchers employed multivariable logistic regressions to investigate the odds of developing symptoms and having severe outcomes (hospitalization) in Omicron vis-à-vis Delta infected individuals within seven days from/to the positive COVID-19 test date. They also compared the odds of developing specific symptoms lasting for more than seven days and less than seven days.
Lastly, they conducted sensitivity analyses to minimize the influence of confounding by vaccination status in the clinical presentation of the two SARS-CoV-2 variants.
Of all the study subjects, 33,785 users tested positive when Delta VOC was dominant, while 29,217 when Omicron was dominant. After 1:1 matching, there were only 4,990 participants with both Omicron and Delta infections.
Of all the 32 COVID-19 symptoms assessed, seven were significantly less prevalent among Omicron than among Delta cases in both vaccination groups, and 12 symptoms were significantly less prevalent overall. All the individuals infected during the Omicron-dominated period did not display at least one out of the three most common COVID-19 symptoms, including fever, loss of smell, and persistent cough. Strikingly, loss of sense of smell, symbolic of the clinical presentation of COVID-19, was present in under 20% of Omicron cases. Likewise, brain fog, eye burning, dizziness, fever, and headaches were significantly less prevalent in Omicron cases.
Regarding COVID-19 severity observed in Omicron cases, as observed in several previous studies, hospital admission was significantly lower among Omicron cases. Also, the duration of acute symptoms was two days shorter in Omicron cases than that of Delta. Furthermore, a third vaccine dose reduced symptom duration in those infected during the Omicron period, compared to the Delta period.
Among double vaccinated and boosted individuals, the risk of hospitalization was lower following an Omicron infection than with Delta. Regarding recovering from illness, with an odds ratio (OR) of 2.49, Omicron infections were twice as likely to recover within one week of the onset of symptoms than Delta infections.
The genomic sequence analysis has shown over 30 mutations in Omicron compared to the original SARS-CoV-2 strain, although the effects of most of these Omicron mutations are not known. The current study characterized the differences in the clinical presentation of infection by Omicron versus Delta. To summarize, among vaccinated individuals, the clinical symptoms associated with an infection by the SARS-CoV-2 Omicron variant were different, milder, and shorter duration than those presented by the Delta VOC.
The study findings will inform public health clinicians about what symptoms to look for while devising COVID-19 mitigation strategies and help in understanding the potential effects of future SARS-CoV-2 VOCs.
Preprints with The Lancet publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.