In a recent study published in The nature of communication journal, researchers tracked the changing symptom profiles associated with different variants of severe acute respiratory syndrome CoV-2 (SARS-CoV-2), particularly the Omicron BA.1 and BA.2 subvariants.
Study: Variant-specific symptoms of COVID-19 in a study of 1,542,510 adults in England. Image credit: NIAID
Previous community studies have shown that symptom profiles differ among different SARS-CoV-2 variants. So they used variable selection and classification techniques to identify symptoms that were predictive of the causal variant. They also assessed how much symptom data could predict reverse transcription-polymerase chain reaction (RT-PCR) positivity for SARS-CoV-2.
Identification of individuals more likely to be infected and infectious based on symptom profiles is of great clinical value. As many countries have already lifted restrictions, mandatory isolation measures and routine testing, such monitoring will become increasingly important.
The REACT-1 (Real-time Assessment of Community Transmission-1) study monitored the spread and clinical manifestation of SARS-CoV-2 in the population in England on a monthly basis from 1 May 2020 to 31 March 2022.
In this study, researchers used regression and variable selection models to examine data from the REACT-1 study of more than 1.5 million people randomly selected from the population of England. They further predicted the symptom profiles of each variant of SARS-CoV-2 that was dominant in England and around the world during this period. These variants were the wild type (wt) parent strain, Alpha, Delta and Omicron BA.1 and BA.2. More importantly, for each variant, they identified 26 symptoms that best predict high viral load, indicating higher infectivity and the ability to transmit COVID-19 more quickly.
Variant prevalence data in the bottom panel are from GISAID.
The study population included 1,542,510 adults aged 18 years and older, including 17,448 individuals positive for SARS-CoV-2. Of these, 2971, 2275, 1493, and 10,709 individuals tested positive for wt, Alpha, Delta, and Omicron variants, respectively. In a multivariate analysis, the team used logistic regression penalized by the Least Absolute Shrinkage and Selection Operator (LASSO) to identify all symptoms positively predictive of COVID-19 positivity for each variant. This method accounted for differences in symptoms by variant type. In addition, he considered cold-like symptoms such as runny nose and sneezing for Omicron BA.1 and BA.2.
Researchers have observed distinct underlying pathophysiology associated with different SARS-CoV-2 variants. Against the backdrop of differential infection- and vaccine-induced population immunity, there were differences in the symptoms of coronavirus disease 2019 (COVID-19) caused by Omicron compared to previous variants and within Omicron (BA.2 vs. BA.1). Individuals infected with Omicron BA.2 reported the most of all 26 symptoms (75.9%), followed by BA.1 (70%), Delta (63.8%), Alpha (54.7%), and wt (45%).
Loss of smell and taste and cold-like symptoms were less and more predictive of smear positivity for Omicron than for other variants. Specifically, Omicron infections were not as strongly associated with anosmia as the previous variants. Changes in viral gene sequences that regulate host responses in Omicron-infected individuals likely reduced the downregulation of olfactory receptor expression, causing anosmia after COVID-19. However, comprehensive transcriptomic studies in animals and humans could identify and clarify the mechanisms involved in this phenomenon.
In addition, the researchers noted that while Omicron BA.2 infections were more symptomatic, with cold or flu symptoms, they were 54% more likely to have symptoms “a lot” affecting daily activities and an average of one additional symptom, compared to BA.1 . The higher symptom burden and severity associated with BA.2 may also have a higher social and economic impact.
The inherent severity of SARS-CoV-2 variants is multifaceted due to different levels of population immunity due to prior SARS-CoV-2 infection or vaccination. However, the rapid replacement of BA.1 by BA.2 in England and the high PCR positivity allowed a comparison of the symptom burden and symptom severity of the two variants in a population with similar characteristics.
After adjusting for vaccine booster status and time since last vaccine dose, symptom burden and severity-related findings were robust for Omicron BA.2 with BA.1. They also support previous findings that Omicron BA.2 has higher transmissibility in a highly vaccinated population.
Ultimately, the study results revealed that Omicron infections caused symptoms such as fever, chills, sore throat, muscle aches, runny nose, sneezing, and headache that were associated with the lowest set cycle (CT) thresholds. It further supports that Omicron showed higher viral load and infectivity than previous variants.
Overall, based on the symptom profiles reported during the two years of the COVID-19 epidemic in England, the Omicron BA.2 subvariant caused more symptoms and disruption of daily activities in infected individuals than its predecessors. As a result, from 1 April 2022, the English government switched to a “living with COVID-19” policy. While many countries, including England, have stopped or restricted free or routine SARS-CoV-2 testing programs, new variants of the virus continue to emerge. Understanding symptom profiles can help identify high-risk individuals.
Link to journal:
- Variant-specific symptoms of COVID-19 in a study of 1,542,510 adults in England, Matthew Whitaker, Joshua Elliott, Barbara Bodinier, Wendy Barclay, Helen Ward, Graham Cooke, Christl A. Donnelly, Marc Chadeau-Hyam, Paul Elliott, Nature Communications 2022, DOI: https://doi.org/10.1038/s41467-022-34244-2, https://www.nature.com/articles/s41467-022-34244-2#Sec7
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