Misclassification bias in estimating clinical severity of SARS-CoV-2 variants – Authors' reply

Citing modelling results that indicated a declining infection detection rate in the USA during the transition period between the dominance of the delta (B.1.617.2) and omicron (B.1.1.529) variants, possibly driven by increasing proportions of undetected infections in people with non-severe disease, Yek and colleagues hypothesise a mechanism for differential detection rates: the omicron cases for which a positive test result was recorded might have included a relatively higher proportion of infected people who were prone to severe disease than the analogous delta cases—for example, because a higher proportion of people infected with the omicron variant who sought testing had comorbidity. [...]available data do not suggest a change in the proportion of infections being detected in England by community PCR testing during the study period (although the extent of community testing was reduced later2). [...]recent studies in other European countries with comorbidity data available reported only minor differences in comorbidity between delta and omicron cases, and provided comorbidity-adjusted relative risks consistent with those from our study.4–6 One of these studies explored the effect of adjusting versus not adjusting for comorbidity and found only marginal differences.5 Taken together, we believe the available data indicate that it is unlikely that the proposed mechanisms have strongly biased the results of our analysis.