Plasma Proteome-Wide Mendelian Randomization Analysis Reveals Biomarkers and Therapeutic Targets for Different Stages of COVID-19

Background. The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in a global health crisis with significant morbidity and mortality. While effective vaccinations have been developed, drug treatments for the disease are still required, particularly for different stages of the disease and to combat evolving variants. Identifying reliable biomarkers and potential therapeutic targets for the different stages of COVID-19 is crucial. Methods. Mendelian randomization using the largest publicly available datasets was conducted to identify potential causal plasma proteins for severe COVID-19, hospitalized COVID-19, and SARS-CoV-2 infection. Independent, and strongly associated cis- or pan-pQTLs were used as instrumental variables for each protein. The FDR q-value was used to correct for multiple testing followed by sensitivity analyses, reverse MR and genetic colocalization to ensure the robustness of the results. Results. We identified proteins with strong evidence of causal association with different stages of COVID-19. Some of these proteins were identified previously, such as BGAT and BCAT2, but we also identified the novel proteins, such as KLC1, MRVI1, CACO2, and PCNP. Conclusion. These proteins provide valuable insights into the underlying mechanisms of COVID-19. The identification of these proteins offers new opportunities for developing potential therapeutic targets or biomarkers for the treatment and prevention of COVID-19.