Deciphering COPD as a risk group for COVID-19: can we blame genetics?

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<0.0001). Our results indicated a low genetic contribution for COVID-19 infection predisposition or worse outcomes in people with COPD. We quantified also the high genetic heterogeneity across major world populations for the same alleles, even within European subpopulations.

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