# Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

## TL;DR

This paper improves the accuracy of predicting COVID-19 severity by incorporating host genetics and organ-specific weights using a new method inspired by quantum mechanics.

## Contribution

The novel approach introduces 'Boolean quantum features' and integrates organ-specific weights to enhance polygenic scores for predicting disease severity.

## Key findings

- The new IPGSph scores achieved 84–86% accuracy in predicting severity when combined with age.
- The method improved accuracy by 10% compared to previous models using only genetic features.
- Boolean quantum features and organ weights were integrated using a genetic algorithm.

## Abstract

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (
IPGSph1
and
IPGSph2
). By applying a logistic regression with both IPGS, (
IPGSph2
(or indifferently
IPGSph1
) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%.