CF Carrier Prevalence May Factor in Variability in COVID-19 Outcomes
The prevalence of cystic fibrosis (CF), used as an indicator of the number of CF carriers, was correlated with rates of COVID-19 and related mortality during the pandemic’s early stages across 37 different countries, a study showed.
“This report suggests a possible contribution of the CFTR genetic profile of populations in understanding the country variability of COVID-19 spread and fatality,” the researchers wrote.
The study, “Geographical distribution of cystic fibrosis carriers as population genetic determinant of COVID-19 spread and fatality in 37 countries,” was published in the Journal of Infection.
The effects of the COVID-19 pandemic, including its spread and clinical impact, have varied widely by geographical region. While many factors, including socioeconomic and environmental ones, may partly explain this variability, it’s possible that underlying genetic factors also play a role.
CF is a recessive genetic condition, meaning that two mutated copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene must be inherited — one from each parent — for the disease to manifest. Those carrying one mutated copy, called CF carriers, do not develop CF, but are more susceptible to respiratory infections and can pass the mutation on to their children.
As part of the GEN-COVID study (NCT04549831) in Italy, researchers identified that CF carriers were more likely to have severe COVID-19 infection and had a higher risk of mortality compared with noncarriers.
Since CF prevalence varies significantly among different ethnicities, researchers hypothesized CF carrier status may be one genetic factor influencing the geographic variability in COVID-19’s impact.
The research team evaluated the prevalence of CF and COVID-19, as well as COVID-19-associated mortality in 37 countries during the pandemic’s “first wave,” ending on June 1, 2020. Since CF is inherited from CF carriers, CF prevalence is thought to also reflect the distribution of carriers.
CF’s prevalence was determined using officially registered cases available through the Cystic Fibrosis Foundation, the European Cystic Fibrosis Society, and Cystic Fibrosis Canada. The prevalence of COVID-19 was obtained through the World Health Organization.
In the 37 studied countries, COVID-19 prevalence was significantly correlated with CF prevalence. Ireland, the United Kingdom, and Belgium had the highest prevalence of both CF patients and COVID-19 cases.
To account for country-by-country differences including rates of diagnostic testing, population size, and other national pandemic responses (e.g. school closures, travel bans), an adjusted statistical analysis was performed. A significant correlation was still seen between COVID-19 and CF.
Similarly, COVID-19-associated mortality rates significantly correlated with CF prevalence, even after adjusting for other factors. Mortality rates also were also correlated with the percentage of the population older than 65 and total cancer prevalence.
Data suggest CF patients are not more susceptible to severe COVID-19 or are at an elevated risk for mortality, “raising the hypothesis that CF patients may have intrinsic protective factors,” the researchers wrote. Indeed, some lab evidence showed that CFTR defects may limit the replication and spread of SARS-CoV-2, the virus that causes COVID-19.
While the relationships reported can’t be established as causative, the findings “enlighten a possible contribution of CFTR in COVID-19 pathogenesis [disease process],” they wrote, noting that more detailed laboratory studies will be required to better understand this relationship.
The possibility that viral testing and data reporting practices may differ substantially between countries and that COVID-19 related deaths may have been underestimated during the early stages of the pandemic were noted as limitations of the study, the researchers said.