403 - Association of surfactant protein genetic variants with risk of hospitalization in COVID-19 positive children

COVID-19 has affected over 15 million children in the US since March 2020. The clinical presentation varies from asymptomatic/mild upper respiratory tract infection to potentially life-threatening lower respiratory disease requiring hospitalization. The complex interaction between environmental and genetic factors may explain the heterogeneity of clinical presentations of COVID-19. Surfactant proteins (SP) play role in the lung innate host defense (SP-A and SP-D) and normal lung function (SP-B and C).  Therefore, we hypothesized that single nucleotide polymorphisms (SNPs) of SPs are associated with COVID-19 hospitalization risk.

Objective:

To study associations between SP genetic variants and hospitalization risk in COVID-19-positive children.

Design/Methods:

We prospectively enrolled 288 COVID-19-infected children. Those who did not require hospitalization for COVID-19-related symptoms or required hospitalization for reasons other than COVID-19 served as controls. Those who needed hospitalization for COVID-19-related symptoms served as cases. We collected clinical and demographic data. DNA was extracted from collected blood. Using a multiplexed PCR workflow, SP genes were targeted and genotypes were assigned. The association of SP genes SNPs with hospitalization risk was tested by multivariate logistic regression models adjusting for significant covariates (age, sex, ancestry, co-viral and bacterial infections) using the PLINK (v2.0) software. We applied Bonferroni correction for the number of tests performed.

Results:

Those who required COVID-19-related hospitalizations were younger, lower in weight, had higher incidences of congenital anomalies, were exposed to household smoking, and required higher rates of emergency room visits and intensive care unit admissions, Table 1. Hospitalized children had a higher risk of co-infections with bacteria or viruses, required higher respiratory support and were exposed to higher rates of antibiotics and other medications including systemic steroids, bronchodilators, remdesivir, vasopressors, and doxycycline. Based on the odds ratio, rs8192327 and rs8192340 of the SFTPC were associated with decreased risk of hospitalization, whereas, rs3024795 of the SFTPB was associated with an increased risk of COVID-related hospitalization, Table 2. However, none of those associations remained significant after the Bonferroni correction. None of the SFTPA and SFTPD SNPs were associated with hospitalization risk in children.

Conclusion(s):

SP genes, particularly involved in normal lung function (SFTPB, SFTPC), are likely modifiers of hospitalization risk in COVID-19 infections.