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

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Nyberg, Erik Tommy 
Ferguson, Neil 
Blake, Joshua 
Hinsley, Wes 
Bhatt, Samir 


As Yek and colleagues note, test-positive cases generally have more severe disease than untested infectees. This may lead to overestimation of absolute risks, but relative risks (RRs) are not necessarily biased unless the proportion of detected severe cases differs systematically between variants. Citing modelling results that indicated a declining infection detection rate in the USA during the delta-to-omicron transition, possibly driven by increasing proportions of undetected infectees with non-severe disease, Yek and colleagues hypothesise a mechanism for differential detection rates: the test-positive omicron cases may have included a relatively higher proportion of infectees prone to severe disease than test-positive delta cases, e.g. because a higher proportion among omicron infectees who sought testing had comorbidity.



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The Lancet

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MRC (unknown)
MRC (MC_PC 19074)
National Institute for Health Research (NIHR) (via University of Bristol) (200877 2020 - 245)
UKRI MRC (MR/R015600/1; Unit Programme number MC/UU/00002/11); UKRI MRC/DHSC NIHR COVID-19 rapid response call (MC/PC/19074; MR/V038109/1); NIHR Health Protection Units in: Modelling and Health Economics (NIHR200908), Behavioural Science and Evaluation; philanthropic funding from Community Jameel. The funders played no direct role in the research. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.