ABSTRACT
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.
ABSTRACT
RATIONALE: Since the first known US case of COVID-19 (Coronavirus Disease 2019) was reported in early 2020, little was known about the prevalence in the cystic fibrosis (CF) population. CF is a genetic disorder caused by more than 1700 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in a wide spectrum of disease phenotypes. As the majority of individuals with CF have chronic lung disease, this population is considered to be high risk for severe disease if infected with any virus, especially that of SARS-CoV 2 (severe acute respiratory syndrome coronavirus 2). As the number of cases in the US nears 18 million and the number of deaths in the US is currently reported at greater than 318,000, the prevalence of COVID-19 in the CF population remains largely unknown although the clinical course for those infected is becoming more clear. To date, the Cystic Fibrosis Foundation reported 344 cases of COVID-19 in the US and 3 people who have died, giving a case fatality rate of 0.9%. METHODS: Early in the course of the pandemic, we began studying the exposures, and symptoms of people with CF to evaluate the prevalence of COVID-19 IgG antibody in patients who receive care at the MN CF Center. Individuals >/= 12 years of age completed a brief, online survey detailing possible exposures, symptoms of COVID-19, and behavioral data (e.g. social distancing practices). We extracted additional data through the electronic medical record (EMR) to identify risk factors for COVID-19 IgG development including age, BMI, sex, FEV1 (forced expiratory volume in 1 second), CFTR modulator use, diabetes. Participants were evaluated for COVID-19 IgG at the time of enrollment (0 months) and the natural history of COVID-19 IgG will be further elucidated with additional Ab testing at 6 months and 12 months post-enrollment. RESULTS: Early data includes 75 enrollees with an average age of 35 years. 51% of participants are female. Of those tested, 9.5% had a positive COVID IgG test. 83% of those individuals tested positive for COVID with PCR analysis. CONCLUSION: SARS-CoV-2 is becoming more prevalent in the state of MN and the prevalence of COVID-19 IgG in individuals with cystic fibrosis suggest similar exposure as the general community. Additional data collection at 6 months and 12 months will identify the natural progression of IgG immunity in in CF patients in response to COVID-19.