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People with chronic obstructive pulmonary disease (COPD) constitute one of COVID-19 risk groups for poor prognosis upon infection. Variability in predisposition and clinical response to COVID-19 exist but our understanding of these factors in the COPD population is limited. This study explored the genetic background as a possible answer to COVID-19 infection response heterogeneity, either for the poor prognosis in people with COPD or across healthy worldwide populations. Significant SNPs (susceptibility: rs286914/rs123297601–3; severity: rs657152/rs113859424) were selected from the literature and their allelic frequencies5,6 used to calculate the probability of having multiple risk alleles in both our COPD cohort and each worldwide population. A polygenic risk analysis was conducted in the COPD cohort for the two mentioned phenotypes, and for hospitalization and survival to COVID-19 infection. No differences in genetic risk for COVID-19 susceptibility, hospitalization, severity or survival were found between people with COPD and the control group (all p-values>0.01), either considering risk alleles individually, allelic combinations or polygenic risk scores. Alternatively, all populations, even those with European ancestry (Portuguese/Spanish/Italian), showed significant differences from the European population in genetic risk for COVID-19 susceptibility and severity (all p-values

People with chronic obstructive pulmonary disease (COPD) constitute one of COVID-19 risk groups. Variability in predisposition and clinical response to COVID-19 exist but our understanding of these factors in the COPD population is limited. This study explored the genetic background as a possible answer to COVID-19 infection response heterogeneity, either for the poor prognosis in people with COPD or across worldwide populations. Our cohort comprises 255 people with COPD (66±9 years; 72% male; FEV1 53.01±20.31% predicted) and 243 controls (67±10 years; 80% male; FEV1 100.46±19.19% predicted) clinically characterized and genotyped using saliva samples. COVID-19 associated SNPs (susceptibility: rs286914 and rs12329760; and severity: rs657152 and rs11385942) were assessed in our cohort and in the major world populations. Allelic frequencies were used to calculate the probability of having multiple risk alleles. Polygenic risk analysis was also conducted, in our cohort, for the two mentioned phenotypes (susceptibility and severity). No differences in genetic risk for COVID-19 susceptibility or severity were found between people with COPD and the control group (all p-values>0.01), either considering risk alleles individually, allelic combinations or polygenic risk scores. All populations, even those sharing European ancestry (Portuguese, Spanish and Italian), showed significant differences from the European (all p-values

People with chronic obstructive pulmonary disease (COPD) constitute one of COVID-19 risk groups for poor prognosis upon infection. Variability in predisposition and clinical response to COVID-19 exist but our understanding of these factors in the COPD population is limited. This study explored the genetic background as a possible answer to COVID-19 infection response heterogeneity, either for the poor prognosis in people with COPD or across healthy worldwide populations. Significant SNPs (susceptibility: rs286914 and rs12329760; severity: rs657152 and rs11385942) were selected from the literature and their allelic frequencies used to calculate the probability of having multiple risk alleles in both our COPD cohort and each worldwide population. A polygenic risk analysis was conducted in the COPD cohort for the two mentioned phenotypes, but also for hospitalization and survival to COVID-19 infection. No differences in genetic risk for COVID-19 susceptibility, hospitalization, severity or survival were found between people with COPD and the control group (all p-values > 0.01), either considering risk alleles individually, allelic combinations or polygenic risk scores. Alternatively, all populations, even those with European ancestry (Portuguese, Spanish and Italian), showed significant differences from the European population in genetic risk for COVID-19 susceptibility and severity (all p-values < 0.0001). Our results indicated a low genetic contribution for COVID-19 infection predisposition or worse outcomes in people with COPD. Also, our study unveiled a high genetic heterogeneity across major world populations for the same alleles, even within European subpopulations. published