SARS-CoV-2 neurovascular invasion supported by Mendelian randomization

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to affect vessels and nerves and can be easily visualized in the retina. However, the effect of SARS-CoV-2 on retinal morphology remains controversial. In the present research, we applied Mendelian randomization (MR) analysis to estimate the association between SARS-CoV-2 and changes in the thickness of the inner retina.

Two-sample MR analysis was conducted using summary-level data from 3 open genome-wide association study databases concerning COVID-19 infection (2,942,817 participants) and COVID-19 hospitalization (2,401,372 participants); moreover, the dataset of inner retina thickness, including the macular retinal nerve fiber layer (mRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL), included 31,434 optical coherence tomography (OCT) images derived from healthy UK Biobank participants. All the participants were of European ancestry. The inverse variance weighted (IVW) meta-analysis was used as our primary method. Various complementary MR approaches were established to provide robust causal estimates under different assumptions.

According to our MR analysis, genetically predicted COVID-19 infection was associated with an increased risk of mRNFL and mGCIPL thickness (OR = 1.74, 95% CI 1.20-2.52, P = 3.58 × 10^-3; OR = 2.43, 95% CI 1.49-3.96, P = 3.6 × 10^-4). The other MR methods produced consistent results. However, genetically predicted COVID-19 hospitalization did not affect the thickness of the inner retina (OR = 1.11, 95% CI 0.90-1.37, P = 0.32; OR = 1.28, 95% CI 0.88-1.85, P = 0.19).

This work provides the first genetically predictive causal evidence between COVID-19 infection and inner retinal thickness in a European population. These findings will contribute to further understanding of the pathogenesis of COVID-19 and stimulate improvements in treatment modalities.