Variance in the Variants: A Comparison of the Symptomatology of SARS‐CoV‐2 Variants in Wales, February 2020–July 2022

Comparisons of SARS-CoV-2 variants' severity in terms of outcomes such as hospitalisation are commonly reported. By contrast, despite the vital importance of understanding evolution of the SARS-CoV-2 symptom profile for public health surveillance, few comparative studies have investigated differences in variants' symptomatology. The aim of this comprehensive analysis was to investigate whether successive variants were indeed associated with distinct symptom patterns in a large Welsh sample covering a broad time period and multiple variant waves. Symptom and variant typing data were derived from contact tracing data and sequencing of positive SARS-CoV-2 PCR tests collected in Wales, respectively. Descriptive epidemiology and binary logistic regression modelling were then used to investigate differences in the symptom profile of N = 226 002 cases infected with Wild-Type, Alpha, Delta, or Omicron variants of SARS-CoV-2. The median number of symptoms and the proportion of cases reporting as symptomatic were lower for those infected with Omicron (BA.4) and Omicron (BA.5) compared to those infected with Wild-Type (B.1.612), Alpha (B.1.1.7), Delta (B.1.617.2 and descendent lineages, excluding AY.4.2), Delta (AY.4.2), Omicron (BA.1) and Omicron (BA.2). Indeed, the odds of being symptomatic when infected with the Omicron (BA.4) or Omicron (BA.5) variant were 83% and 84% lower, compared to those infected with Wild-Type. Anosmia in particular, was reported in non-Omicron variants at approximately three-to-five times the proportion of cases (range 20.23%-26.41%) compared to Omicron variants (range 4.18%-7.65%). Indeed, the odds of having anosmia when infected with an Omicron variant were 85%-91% lower than when infected with Wild-Type, versus 32%-43% lower for non-Omicron variants, relative to Wild-Type. We suggest, given these changes in symptomatology and the vast reduction in testing and sequencing, symptom surveillance should continue, to approximate burden of infection and facilitate rapid updating of clinical case definitions following any further evolution in the symptom profile. While disentangling the contribution of genomic, immunological and sampling changes to our findings remains challenging, symptom surveillance could also potentially aid emerging variant detection when used in combination with other surveillance approaches.