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Implementation of the User-Friendly Odds Ratio Calculator for Unvaccinated Individuals in a Country with a High COVID-19 Death Toll

2022; RELX Group (Netherlands); Linguagem: Inglês

10.2139/ssrn.4099428

1556-5068

Mirosław Kwaśniewski, Urszula Korotko, Karolina Chwiałkowska, Magdalena Niemira, Jerzy Jaroszewicz, Barbara Sobala‐Szczygieł, Beata Puzanowska, Anna Moniuszko‐Malinowska, Sławomir Pancewicz, Anna Parfieniuk‐Kowerda, Diana Martonik, Dorota Zarębska‐Michaluk, Krzysztof Simon, Monika Pazgan‐Simon, Iwona Mozer‐Lisewska, Maciej Bura, Agnieszka Adamek, Krzysztof Tomasiewicz, Małgorzata Pawlowska, Anna Piekarska, Aleksandra Berkan‐Kawińska, Andrzej Horban, Justyna D. Kowalska, Regina Podlasin, Piotr Wasilewski, Arsalin Azzadin, Mirosław Czuczwar, Michał Borys, Paweł Piwowarczyk, Sławomir Lech Czaban, Jacek Bogocz, Magdalena Ochab, Anna Kruk, Sandra Uszok, Agnieszka Bielska, Anna Szałkowska, Justyna Raczkowska, Gabriela Sokołowska, Joanna Chorostowska‐Wynimko, Aleksandra Jezela‐Stanek, Adroana Rozy, Urszula Lechowicz, Urszula Połowianiuk, Agnieszka Tycińska, Kamil Grubczak, Aleksandra Starosz, Wiktoria Izdebska, Tadeusz F. Krzemiński, Jean Bousquet, Milena Sokołowska, Genoveffa Franchini, Jennifer Hadlock, Adam Krętowski, Andrzej Eljaszewicz, Robert Flisiak, Marcin Moniuszko,

Influenza Virus Research Studies

Background: In certain countries including Poland, many individuals have remained unwilling to be vaccinated despite high COVID-19 death tolls. Hesitancy towards vaccination is often linked with a low level of community knowledge on the prevalence and impact of personal risk factors for severe COVID-19. To date, several cross-ancestry studies identified a number of genetic loci that are associated with the severity of COVID-19, but it is not sufficiently understood whether these genetic factors are similarly relevant to different populations and what is their significance in comparison to other known risk factors such as age, sex and body mass index (BMI). Here we attempted not only to assess but rather quantify to what extent genomic, phenotypic, and comorbid factors impact the severity of COVID-19. Methods: To this end, we jointly analyzed whole exome sequencing (WES) and detailed clinical data from 1186 unvaccinated COVID-19 patients of Polish origin. Findings: The genome wide association study (GWAS) revealed that in our cohort, only variants in the 3p21.31 peak were significantly associated with the severity of COVID-19. We found that the presence of the 3p21.31 risk allele has doubled the odds ratio for developing a severe course of COVID-19. Interestingly, however, in our predictive model, the clinical significance of this risk allele was largely exceeded by age, then male sex, and elevated BMI, but not by the existence of comorbidities. Given these results, we designed a user-friendly odds ratio calculator based on our model and developed an online application providing individual quantitative assessment of odds ratio of development of severe COVID-19 for both carriers and non-carriers of the risk allele. Notably, in the light of relatively high COVID-19 death rates in Poland and vaccination rate of as low as 59%, our on-line application has been incorporated into a state-run main public patient e-platform. Our solution has become available as a boost nation-wide educational campaign aimed at increasing the awareness of COVID-19 - related risks in vaccine-hesitant citizens. Interpretation: Altogether, we demonstrate here unprecedented in Poland example of task-specific intense ad hoc collaboration of clinicians, geneticists and bioinformaticians resulting in creating a valuable patient-oriented informational tool that has successfully been adopted by the public healthcare system.Funding: AAll authors from Poland report a grant from Polish Medical Research Agency (ABM) during the conduct of the study (No 2020/ABM/COVID19/0001); JBog, and AKru report personal fees from IMAGENE.ME SA outside the submitted work; AJ-S reports personal fees from IMAGENE.ME SA outside the submitted work; JB reports personal fees and other supportfrom Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi-Aventis, Takeda, Teva, and Uriach and other support from KYomed INNOV outside the submitted work; AE and MM received grants from the National Science Centre and the National Research and Development Centre; TFK and MM are the members of the Council of the Medical Research Agency with no right to decide on any grant applications and they received no remuneration for the work done in this study; MS received research grant from the Swiss National Science Foundation and from the GSK outside the submitted work; GF is the employee of the National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services; MM reports lecture fees from Berlin-Chemie/Menarini, Astra Zeneca, Novartis, Chiesi, GlaxoSmithKline, Takeda, Teva, Lek-AM outside the submitted work.Declaration of Interest: Authors declared no conflict of interest with relation to this work.Ethical Approval: The study has been reviewed and approved by the Ethics Committee of MedicalUniversity of Bialystok (APK.002.155.2020).