Tommy Nyberg and colleagues1
- Nyberg T
- Ferguson NM
- Nash SG
- et al.
Comparative analysis of the risks of hospitalization and death associated with omicron (B.1.1.529) and delta (B.1.617.2) variants of SARS-CoV-2 in England: a cohort study. Use an unvaccinated cohort to show differences between the intrinsic severity of omicron (B.1.1.529) and delta (B.1.617.2) variants of SARS-CoV-2 without confounding by preexisting immunity. They report an 80% reduction in omicron severity compared to the delta variant, suggesting the possibility of living through the COVID-19 pandemic without social and economic disruption. However, reliance on SARS-CoV-2 test positivity to identify cases of COVID-19 and on hospitalizations and all-cause deaths as outcomes could have introduced misclassification bias and residual confounding. Up to one in three SARS-CoV-2 infections are asymptomatic. ,2
- Already P
- Fitzpatrick MC
- Room CF
- et al.
Asymptomatic SARS-CoV-2 infection: a systematic review and meta-analysis. and this proportion was even greater during the omicron wave.3
- Garrett N
- Tapley A
- Andriesen J
- et al.
High rate of asymptomatic carriage associated with the omicron variant strain. Studies that use test positivity exclusively as a case definition may report inflated hospitalization and mortality rates. Misclassification is exacerbated by higher prevalence of infection due to more transmissible variants and by increased proportions of non-severe and severe cases, potentially attenuating differences in severity between variants. In the Appendix, we show the potential effects of three SARS-CoV-2 case phenotypes on the apparent hospitalization and mortality rates of SARS-CoV-2 infection with the delta and omicron variants. Misclassification may also differ by age, vaccination status, and comorbidities that influence susceptibility to infection and disease.4
- Woodruff RC
- Campbell AP
- Taylor CA
- et al.
Risk factors for severe COVID-19 in children.5
- A C
- Warner S
- Wiltz JL
- et al.
Risk factors for severe COVID-19 outcomes among persons ≥ 18 years of age who completed a primary series of COVID-19 vaccinations: 465 healthcare facilities, United States, December 2020 to October 2021.Using other data streams can help populate large data sets when clinical data is sparse or absent. For example, administrative coding could be used to identify reasons for hospital admission that are likely related (eg, pneumonia) or unrelated (eg, trauma) to COVID-19,4.
- Woodruff RC
- Campbell AP
- Taylor CA
- et al.
Risk factors for severe COVID-19 in children. and identify comorbid conditions to include as covariates in comparative analyses.4
- Woodruff RC
- Campbell AP
- Taylor CA
- et al.
Risk factors for severe COVID-19 in children.5
- A C
- Warner S
- Wiltz JL
- et al.
Risk factors for severe COVID-19 outcomes among persons ≥ 18 years of age who completed a primary series of COVID-19 vaccinations: 465 healthcare facilities, United States, December 2020 to October 2021. Delivery of therapeutics used specifically or more frequently for COVID-19 (eg, remdesivir and dexamethasone) could enrich those hospitalized with the disease. Ultimately, applying a probabilistic approach to case definition could allow estimates of confidence in identifying cases and associating outcomes.
After correcting for misclassification bias, the intrinsic severity of the omicron variant of SARS-CoV-2 might be even lower than suggested by Nyberg and colleagues.
We declare no competing interests.
Supplementary material
References
- 1.
- Nyberg T
- Ferguson NM
- Nash SG
- et al.
Comparative analysis of the risks of hospitalization and death associated with omicron (B.1.1.529) and delta (B.1.617.2) variants of SARS-CoV-2 in England: a cohort study.
Lancet. 2022; 399: 1303-1312
- 2.
- Already P
- Fitzpatrick MC
- Room CF
- et al.
Asymptomatic SARS-CoV-2 infection: a systematic review and meta-analysis.
Proc Natl Acad Sci USA 2021; 118e2109229118
- 3.
- Garrett N
- Tapley A
- Andriesen J
- et al.
High rate of asymptomatic carriage associated with the omicron variant strain.
medRxiv. 2022; ()
- 4.
- Woodruff RC
- Campbell AP
- Taylor CA
- et al.
Risk factors for severe COVID-19 in children.
Pediatrics 2021; 149e2021053418
- 5.
- A C
- Warner S
- Wiltz JL
- et al.
Risk factors for severe COVID-19 outcomes among persons ≥ 18 years of age who completed a primary series of COVID-19 vaccinations: 465 healthcare facilities, United States, December 2020 to October 2021.
MMWR Mortality Wkly Rep. 2022; 71: 19-25
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Publication history
Published: September 10, 2022
Identification
DOI: https://doi.org/10.1016/S0140-6736(22)01469-6
Copyright
Published by Elsevier Ltd.
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