Background: Lipid metabolism plays an important role in viral infections. We aimed to assess the causal effect of lipid-lowering drugs (HMGCR inhibitiors, PCSK9 inhibitiors, and NPC1L1 inhibitior) on COVID-19 outcomes using two-sample Mendelian randomization (MR) study.Methods: We used two kinds of genetic instruments to proxy the exposure of lipid-lowering drugs, including expression quantitative trait loci of drugs target genes, and genetic variants within or nearby drugs target genes associated with low-density lipoprotein (LDL cholesterol from genome-wide association study). Summary-data-based MR (SMR) and inverse-variance-weighted MR (IVW-MR) were used to calculate the effect estimates.Results: SMR analysis found that a higher expression of HMGCR was associated with a higher risk of COVID-19 hospitalization (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.06–1.81). Similarly, IVW-MR analysis observed a positive association between HMGCR-mediated LDL cholesterol and COVID-19 hospitalization (OR = 1.32, 95% CI = 1.00–1.74). No consistent evidence from both analyses was found for other associations.Conclusions: This two-sample MR study suggested a potential causal relationship between HMGCR inhibition and the reduced risk of COVID-19 hospitalization.Funding: Start-up Fund for high-level talents of Fujian Medical University.

Background: To identify whether RET is a potential target for NSCLC treatment, we examined the status of the RET gene in 631 early and mid stage NSCLC cases from south central China.Methods: RET expression was identified by Western blot. RET‐positive expression samples were verified by immunohistochemistry. RET gene mutation, copy number variation, and rearrangement were analyzed by DNA Sanger sequencing, TaqMan copy number assays, and reverse transcription‐PCR. ALK and ROS1 expression levels were tested by Western blot and EGFR mutation using Sanger sequencing.Results: The RET‐positive rate was 2.5% (16/631). RET‐positive expression was related to poorer tumor differentiation (P < 0.05). In the 16 RET‐positive samples, only two samples of moderately and poorly differentiated lung adenocarcinomas displayed RET rearrangement, both in RET‐KIF5B fusion partners. Neither ALK nor ROS1 translocation was found. The EGFR mutation rate in RET‐positive samples was significantly lower than in RET‐negative samples (P < 0.05).Conclusion: RET‐positive expression in early and mid stage NSCLC cases from south central China is relatively low and is related to poorer tumor differentiation. RET gene alterations (copy number gain and rearrangement) exist in all RET‐positive samples. RET‐positive expression is a relatively independent factor in NSCLC patients, which indicates that the RET gene may be a novel target site for personalized treatment of NSCLC.

Even though abdominal aortic aneurysm (AAA) and coronary heart disease (CHD) are both related to atherosclerosis, there could be important differences in risk factors. Based on Malmö Diet and Cancer Cohort, the incidence of AAA and CHD was followed prospectively. Cox regression was used to calculate the association of each factor with AAA and CHD and hazards ratio were compared using a modified Lunn-McNeil method; 447 participants developed AAA and 3129 developed CHD. After multivariate adjustments, smoking, antihypertensive medications, lipid-lowing medications, systolic and diastolic blood pressures, apolipoprotein (Apo) A1 (inversely), ApoB, ApoB/ApoA1 ratio, total leukocyte count, neutrophil count, and neutrophil to lymphocyte ratio were associated with the risks of both AAA and CHD. When comparing risk factor profiles for the 2 diseases, smoking, diastolic blood pressure, ApoA1, and ApoB/ApoA1 ratio had stronger associations with risk of AAA than with risk of CHD, while diabetes and unmarried status showed increased risk of CHD, but not of AAA (all P values for equal association <.01). The results from this big population study confirm that the risk factor profiles for AAA and CHD show not only many similarities but also several important differences.