Abstract
Populations seem to respond differently to the global pandemic of severe acute respiratory syndrome coronavirus 2. Recent studies show individual variability in both susceptibility and clinical response to COVID-19 infection. People with chronic obstructive pulmonary disease (COPD) constitute one of COVID-19 risk groups, being already associated with a poor prognosis upon infection. This study aims contributing to unveil the underlying reasons for such prognosis in people with COPD and the variability in the response observed across worldwide populations, by looking at the genetic background as a possible answer to COVID-19 infection response heterogeneity. SNPs already associated with susceptibility to COVID-19 infection (rs286914 and rs12329760) and severe COVID-19 with respiratory failure (rs657152 and rs11385942) were assessed and their allelic frequencies used to calculate the probability of having multiple risk alleles. This was performed on a Portuguese case-control COPD cohort, previously clinically characterized and genotyped from saliva samples, and also on worldwide populations (European, Spanish, Italian, African, American and Asian), using publicly available frequencies data. A polygenic risk analysis was also conducted on the Portuguese COPD cohort for the two mentioned phenotypes, and 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. All populations, even those with European ancestry (Portuguese, Spanish and Italian), showed significant differences from the European population in genetic risk for both COVID-19 susceptibility and severity (all p-values < 0.0001). Our results indicate a low genetic contribution for COVID-19 infection predisposition or worse outcomes observed in people with COPD. Also, our study unveiled a high genetic heterogeneity across major world populations for the same alleles, even within European sub-populations, demonstrating the need to build a higher resolution European genetic map, so that differences in the distribution of relevant alleles can be easily accessed and used to better manage diseases, ultimately, safeguarding populations with higher genetic predisposition to such diseases.
Highlights
There is increasing evidence about both individual and populational variability in the susceptibility and disease behaviour of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from asymptomatic to severe respiratory failure and need for prolonged mechanical ventilation [1]
SNPs already associated with susceptibility to COVID-19 infection and severe COVID-19 with respiratory failure were assessed and their allelic frequencies used to calculate the probability of having multiple risk alleles
Our results indicate a low genetic contribution for COVID-19 infection predisposition or worse outcomes observed in people with chronic obstructive pulmonary disease (COPD)
Summary
There is increasing evidence about both individual and populational variability in the susceptibility and disease behaviour of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from asymptomatic to severe respiratory failure and need for prolonged mechanical ventilation [1]. The human genetics community came together and launched the COVID-19 Host Genetics Initiative [2], an unprecedent worldwide collaboration whose mission is to generate, share and identify genetic variants associated with COVID-19 susceptibility, severity and other clinically relevant outcomes. Three independent studies, aimed at finding if patients’ genetic background could be responsible for the differences in susceptibility to COVID-19 infection [4,5,6], identified 3 genetic variants associated with COVID-19 positive testing: rs286914 at locus 11p13, rs12329760 at locus 21q22.3 and rs41303171 at locus Xp22.2. This study aims contributing to unveil the underlying reasons for such prognosis in people with COPD and the variability in the response observed across worldwide populations, by looking at the genetic background as a possible answer to COVID-19 infection response heterogeneity
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