Predicting the risk of severe COVID-19 outcomes in primary care: development and validation of a vulnerability index for equitable allocation of effective vaccines

ABSTRACT

Background

General practitioners (GPs) need a valid, user-friendly tool to identify patients most vulnerable to COVID-19, especially in the hypothesis of a booster vaccine dose. The aim of this study was to develop and validate a GP-friendly prognostic index able to forecast severe COVID-19 outcomes in primary care. Indeed, no such prognostic score is as yet available in Italy.

Research Design and Methods

In this retrospective cohort study, a representative sample of 47,868 Italian adults were followed up for 129,000 person–months. The study outcome was COVID-19-related hospitalization and/or death. Candidate predictors were chosen on the basis of systematic evidence and current recommendations. The model was calibrated by using Cox regression. Both internal and external validations were performed.

Results

Age, sex and several clinical characteristics were significantly associated with severe outcomes. The final multivariable model explained 60% (95%CI 58–63%) of variance for COVID-19-related hospitalizations and/or deaths. The area under the receiver-operator curve (AUC) was 84% (95% CI: 83–85%). On applying the index to an external cohort, the AUC was 94% (95% CI: 93–95%).

Conclusions

This index is a reliable prognostic tool that can help GPs to prioritize their patients for preventive and therapeutic interventions.

KEYWORDS:

• COVID-19
• primary health care
• prognostic model
• vaccination
• hospitalization
• death

Acknowledgments

The authors sincerely thank all General Practitioners contributing to the Health Search and Mille in Rete databases. The authors thank Dr Bernard Patrick (University of Genoa) for his linguistic review of the manuscript.

Author contributions

All persons that contributed to this manuscript met the criteria for authorship and are listed as authors. Francesco Lapi, Alexander Domnich, Iacopo Cricelli and Ettore Marconi were responsible for conceptualization, methodology, analysis, writing and editing of the manuscript. Alessandro Rossi, Ignazio Grattagliano, Gerardo Medea, Aurelio Sessa, Erik Lagolio, Giancarlo Icardi and Claudio Cricelli were responsible for the critical review of the manuscript for important intellectual content. Francesco Lapi and Claudio Cricelli were responsible for validation of the manuscript.

Declaration of interest

F Lapi, E Marconi and I Circelli provided consultancies in protocol preparation for epidemiological studies and data analyses for AstraZeneca and Pfizer. C Cricelli, A Rossi, I Grattagliano, G Medea and A Sessa provided clinical consultancies for AstraZeneca and Pfizer. G Icardi provided consultancies and/or received grants for conducting experimental and/or observational studies for GSK, Sanofi Pasteur, MSD, and Pfizer. A Domnich was a permanent employee of Seqirus, a pharmaceutical company who manufacture and commercialize influenza vaccines. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Ethical standards: approval and informed consent

The study protocol was approved by the Scientific Committee of the Italian College of General Practitioners and Primary Care. This study followed the principles of the Declaration of Helsinki and compliant with the TRIPOD Statements (https://www.tripod-statement.org/resources/).

Supplementary material

Supplemental data for this article can be accessed here