The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19), led to an overwhelming strain on public health systems struggling to deal with the influx of cases to prevent viral transmission. As COVID-19 survivors gained immunity against SARS-CoV-2, thereby slowing the rate of transmission and reducing the overall severity of infection, post-COVID symptoms began to be recognized as evidence of persistent and sometimes disabling disease.
A new study published in The Lancet compares post-COVID manifestations caused by the SARS-CoV-2 wild-type, Alpha, and Delta variants among unvaccinated and vaccinated populations.
Study: Profiling post-COVID-19 condition across different variants of SARS-CoV-2: a prospective longitudinal study in unvaccinated wild-type, unvaccinated alpha-variant, and vaccinated delta-variant populations. Image Credit: Starshaker / Shutterstock.com
Long COVID is defined as symptoms lasting 28 days or more from the initial positive COVID-19 test. All symptoms persisting for 84 days or more from the first positive test are considered post-COVID.
Numerous studies have been conducted on long COVID symptoms as a result of their common occurrence and potential public health burden. The difficulty of recognizing symptoms as due to COVID-19 is compounded by the heterogeneous nature of the condition.
By June 2022, about two million people were estimated to have long COVID in the United Kingdom. About two-thirds of these individuals reported that their symptoms adversely affected their quality of life.
The current study used data from adults in the U.K. who reported symptoms using the COVID Symptom Study smartphone app from March 24, 2020, and December 8, 2021. All participants were physically healthy for at least one month before testing positive for COVID-19 and then reported long =COVID symptoms.
The researchers classified the participants by vaccination status and variant of infection. A prospective longitudinal design was used to identify any distinct patterns and disease profiles caused by different viral variants and vaccination status.
What did the study show?
The study included almost 10,000 people with long Covid. Of these, approximately 15% developed post-COVID symptoms. Importantly, neither a lower prevalence nor duration of post-COVID symptoms was observed between vaccinated and unvaccinated individuals.
For the unvaccinated wild-type population, four types of post-COVID conditions were observed. Comparatively, seven and five conditions were observed in the Alpha unvaccinated population and the vaccinated Delta cohort, respectively.
Irrespective of variant, long COVID symptoms could be classified into three different clusters. These comprised symptoms relating to cardiorespiratory organs, the central nervous system (CNS), and a multi-organ systemic inflammatory condition.
Cardiorespiratory symptoms were typically associated with severe breathlessness, particularly with the Alpha or Delta variants. CNS symptoms included loss or reduction of smell, brain fog, headache, and depression. These symptoms were not typically associated with other symptoms when caused by the Alpha or Delta variants.
While gut symptoms were reported, they occurred in two or less phenotypes for each variant.
In the unvaccinated wild-type population, most individuals presented with cardiorespiratory and CNS symptoms, followed by a cluster with symptoms relating to all phenotypes. Notably, the most severe symptoms occurred in this patient population.
The third cluster suffered mainly upper respiratory symptoms, including hoarseness and anosmia, with loss of appetite. The last cluster also had experienced CNS, upper respiratory, and gastrointestinal (GI) symptoms.
The second and fourth clusters had the most severe and chronic symptoms. However, they did not significantly differ from the others in terms of age, sex, or body mass index.
In the unvaccinated alpha population, the largest cluster of patients had CNS symptoms, whereas the smallest cluster of 13 individuals had widely varying symptoms.
Post-COVID after Delta infection was primarily associated with CNS symptoms in the largest cluster. The smallest cluster also experienced the most severe cardiorespiratory symptoms and some systemic and GI symptoms.
The wild-type second cluster was 75% more likely than all other clusters to consult a medical professional to help with their chronic symptoms. However, the third cluster was more likely to seek help for the post-COVID condition.
The second and fourth clusters were 20-30% more likely to report that the condition severely affected their daily life. Women were more at risk for severe impairment in daily life due to post-COVID and more likely to seek medical help.
What are the implications?
The current study demonstrated the value of digital apps in tracing and characterizing a large-scale pandemic. The researchers attempted a novel method of symptom profiling, the results of which yielded three symptom clusters across variants.
These findings corroborate earlier studies reporting differing degrees of functional impairment across people in the general population post-COVID. The same symptom clusters have been reported in post-COVID analysis in a COVID-hospitalized cohort.
CNS symptoms are frequently reported among long COVID patients and have been correlated with certain brain imaging phenotypes. Notably, SARS-CoV-2 appears to spread through degenerating olfactory neurons, thereby explaining the prominence of smell-related symptoms.
Cardiorespiratory symptoms are often related to lung damage. Thus, this cluster of long COVID patients should be closely monitored for the development of lung lesions.
The current study is the first to profile post-COVID-19 condition across different SARS-CoV-2 variants and in patients with varying vaccination status.”
Importantly, the study findings can be generalized, as this study was conducted in a large sample covering a wide spectrum of post-COVID symptoms.
Nevertheless, further studies that include a more representative range of the U.K. population are needed. Vaccination status should also be analyzed with greater granularity to better understand how different SARS-CoV-2 variants affect the risk of developing long COVID.
Our study suggests that future investigations into mechanisms underlying post-COVID-19 condition should consider dividing affected individuals into different subgroups, to identify distinct [underlying] processes.”
- Canas, L. S., Molteni, E., Deng, J., et al. (2023). Profiling post-COVID-19 condition across different variants of SARS-CoV-2: a prospective longitudinal study in unvaccinated wild-type, unvaccinated alpha-variant, and vaccinated delta-variant populations. The Lancet. doi:10.1016/S2589-7500(23)00056-0.