CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Editor: Deborah Sesok-Pizzini, MD, MBA, chief medical officer, Labcorp Diagnostics, Burlington, NC, and adjunct professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Genetic link between risk for Alzheimer disease and severe COVID-19 outcomes
December 2021—Alzheimer disease is characterized by extracellular amyloid-β deposits, tau tangles, neuronal death, and extensive neuroinflammatory changes. Genetic studies have revealed the importance of gene variants that increase the risk for developing the disease. Genetic sequencing data and RNA-sequencing and single-cell RNA-sequencing data have shown changes in microglial activity as Alzheimer disease progresses. Activated microglia, or interferon-response microglia (IRM), increase during the normal aging process and increase even further in response to amyloid pathology. This mechanism of action of IRM is not well understood. Stimulating interferon receptors leads to expression of interferon-stimulated genes, including oligoadenylate synthase 1 (OAS1). Recent reports link the OAS1 gene to increased risk of Alzheimer disease due to enrichment of the gene in transcriptional networks expressed by microglia. However, the exact function of OAS1 within the microglia is not known. Interferon receptors are also associated with antiviral responses. Several gene variants in OAS1 have been shown to contribute to the genetic risk associated with critical outcomes of COVID-19 and the requirement for intensive care. Many patients hospitalized with COVID-19 also display neurological symptoms, including encephalopathy. The authors conducted a study to confirm that a single-nucleotide polymorphism (SNP) within OAS1 is significantly associated with Alzheimer disease and severe COVID-19. They took 2,547 DNA samples from six research institutes in the United Kingdom that are part of the Alzheimer’s Research UK (ARUK) network. The ARUK network consisted of confirmed or probable Alzheimer disease diagnosis (n = 1,313) and controls (n = 1,234). Since all demographic variables differed between cases and controls, they were included in the analysis as covariats. SNPs were identified in the gene locus of OAS1 associated with Alzheimer disease and COVID-19. Allele-dependent expression of OAS1 at the four SNPs of interest (rs1131454[A] and rs4766676[T] associated with Alzheimer disease and rs10735079[A] and rs6489867[T] associated with critical illness with COVID-19) was studied by mining data from whole blood, frontal cortex, and lung through the Genotype-Tissue Expression (GTEx) project via the GTEx portal. By analyzing single-cell RNA-sequencing data of myeloid cells from Alzheimer disease and COVID-19 patients, the authors showed that interferon-responsive genes, including OAS1, were upregulated with age, amyloid plaques, and severe COVID-19. They found that rs1131454 within OAS1 is associated with Alzheimer disease and critical illness due to COVID-19. The authors concluded that the data from this study support a link between genetic risk for Alzheimer disease and susceptibility to critical illness with COVID-19 related to the OAS1 gene. They noted that this may impact future treatments for Alzheimer disease and COVID-19, including the development of biomarkers to track disease progression and long-term COVID-19 sequelae.
Magusali N, Graham AC, Piers TM, et al. A genetic link between risk for Alzheimer’s disease and severe COVID-19 outcomes via the OAS1 gene. Brain. 2021. https://doi.org/10.1093/brain/awab337
Correspondence: Dr. Dervis A. Salih at dervis.salih@ucl.ac.uk
Impact of COVID-19 on academic productivity of female physicians and researchers in one specialty
Many studies have analyzed disparities in gender equity inherent in various medical specialties. The COVID-19 pandemic has emphasized gender inequities due to an increase in household demands for child care duties at the same time that the pandemic has increased professional demands. During the pandemic, fewer women than men have published in various medical specialties. The authors of this study looked at the impact of the pandemic on the academic productivity of female physicians and researchers in the specialty of transfusion medicine. They collected data to determine if women in transfusion medicine published less in 2020 than in 2019 using the number and quality of published manuscripts as a measure of academic productivity. The authors compared articles in four transfusion medical journals published from Jan. 1 through July 31, 2019 against those published during the same period in 2020. The journals were Transfusion, Transfusion Medicine, Transfusion Medicine Reviews, and Vox Sanguinis. The authors assessed 1,024 articles from the journals to determine whether they included women as first or senior authors. The results showed that women were first authors in 45.9 percent of the articles and senior authors in 35 percent for 2019 and 2020 combined. However, they showed a statistically significant decrease in the percentage of women as first authors between 2019 (49.1 percent) and 2020 (42.7 percent). Yet there was no significant difference in the percentage of women as senior authors between 2019 (35.4 percent) and 2020 (35.5 percent). The authors concluded that fewer women were first authors on articles in transfusion journals in 2020 than in 2019. The data are consistent with findings from other medical specialties. The authors suggested that the academic productivity of female first authors was impacted by the pandemic more than that of senior authors because the former tend to more often be junior faculty, potentially with younger children.