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Development and validation of a clinical and genetic model for predicting risk of severe COVID-19

Gillian S Dite1, Nicholas M Murphy1, Richard Allman1

  • 1Genetic Technologies Ltd, Fitzroy, Victoria, Australia.

Epidemiology and Infection
|July 2, 2021
PubMed

Insights

A new clinical and genetic model accurately predicts severe coronavirus disease 2019 (COVID-19) risk. This tool is vital for personalized risk assessment, especially where vaccination is limited or refused.

Area of Science:

  • Genetics
  • Epidemiology
  • Biostatistics

Background:

  • Clinical and genetic risk factors for severe coronavirus disease 2019 (COVID-19) are often analyzed separately.
  • Understanding the combined effect of these factors is crucial for accurate risk prediction.
  • Existing models may not fully capture the complex interplay of clinical and genetic predispositions to severe COVID-19.

Purpose of the Study:

  • To develop and validate a combined clinical and genetic model for predicting severe COVID-19 risk.
  • To assess the predictive performance of the new model compared to existing tools.
  • To provide a tool for individual risk stratification in diverse populations.

Main Methods:

  • Utilized multivariable logistic regression on a large dataset of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) positive participants from the UK Biobank.
  • A 70% training dataset was used for model development, with the remaining 30% reserved for validation.
  • Model performance was evaluated using discrimination (Area Under the Receiver Operating Characteristic Curve) and calibration metrics.

Main Results:

  • The developed clinical and genetic model demonstrated significant association with severe COVID-19 in the validation dataset (OR=1.77 per quintile).
  • The model achieved acceptable discrimination with an Area Under the ROC Curve of 0.732.
  • Calibration analysis confirmed no significant over- or under-estimation or dispersion of predicted risk.

Conclusions:

  • Accurate prediction of individual risk for severe COVID-19 is achievable through integrated clinical and genetic modeling.
  • This predictive tool holds significant importance in areas with limited vaccine availability or vaccine hesitancy.
  • The model's utility is underscored by ongoing concerns regarding vaccine effectiveness against new variants and transmission dynamics.

Keywords:
Risk factorsrisk predictionsevere COVID-19single-nucleotide polymorphism

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