tetano
Editor, Senior Moderator
Ann Transl Med
. 2022 Jun;10(11):624.
doi: 10.21037/atm-21-6612.
Identification of novel drug targets for the risk and prognosis of COVID-19
Yi-Han Gan[SUP] #[/SUP][SUP] 1 [/SUP], Ya-Nan Ou[SUP] #[/SUP][SUP] 2 [/SUP], Yu-Xiang Yang[SUP] 1 [/SUP], Yue-Ting Deng[SUP] 1 [/SUP], Yi Liu[SUP] 2 [/SUP], Lan Tan[SUP] 2 [/SUP], Jin-Tai Yu[SUP] 1 [/SUP]
Affiliations
Abstract
Background: Since the epidemic continues, there is a pressing need to improve our understanding of coronavirus disease 2019 (COVID-19). Mendelian randomization (MR) studies provide us with a method to explore the causality between circulating proteins and COVID-19 susceptibility and severity. We aim to find new perspectives on the pathological mechanism of the disease and possible drug targets for treatment based on this study.
Methods: We conducted a phenome-wide MR study to prioritize circulating proteins causally associated with COVID-19 susceptibility, which was defined as "patients tested positive for COVID-19 vs. population controls", and severity, which was defined as "patients hospitalized with COVID-19 vs. population controls". And we repeated the analysis for different definition of COVID-19 susceptibility, severity and control groups.
Results: Association of three circulating proteins with COVID-19 susceptibility and severity were demonstrated via our study. C-C motif chemokine 4 (OR =1.887, 95% CI: 1.608-2.165, P=8.04×10[SUP]-6[/SUP]) and 2'-5'-oligoadenylate synthase 1 (OR =0.511, 95% CI: 0.266-0.757, P=8.51×10[SUP]-8[/SUP]) were found respectively positively and negatively correlated with increased COVID-19 severity. Tissue factor, contrary to previous studies, was found associated with decreased COVID-19 susceptibility (OR =0.667, 95% CI: 0.484-0.850, P=1.47×10[SUP]-5[/SUP]) and decreased COVID-19 severity (OR =0.459, 95% CI: 0.132-0.786, P=3.01×10[SUP]-6[/SUP]).
Conclusions: Genetic evidence supports C-C motif chemokine 4 as a risk factor for COVID-19 severity, and 2'-5'-oligoadenylate synthase 1 as a protective factor for COVID-19 severity. The causal association between tissue factor and COVID-19 is contrary to the previous studies, needing further analyses. Further research is warranted to assess the viability of C-C motif chemokine 4 and 2'-5'-oligoadenylate synthase 1 as well as their downstream pathways as drug targets for anti-inflammatory and anti-virus treatment in severe cases.
Keywords: Mendelian randomization (MR); coronavirus disease 2019 (COVID-19); proteomics.
. 2022 Jun;10(11):624.
doi: 10.21037/atm-21-6612.
Identification of novel drug targets for the risk and prognosis of COVID-19
Yi-Han Gan[SUP] #[/SUP][SUP] 1 [/SUP], Ya-Nan Ou[SUP] #[/SUP][SUP] 2 [/SUP], Yu-Xiang Yang[SUP] 1 [/SUP], Yue-Ting Deng[SUP] 1 [/SUP], Yi Liu[SUP] 2 [/SUP], Lan Tan[SUP] 2 [/SUP], Jin-Tai Yu[SUP] 1 [/SUP]
Affiliations
- PMID: 35813330
- PMCID: PMC9263786
- DOI: 10.21037/atm-21-6612
Abstract
Background: Since the epidemic continues, there is a pressing need to improve our understanding of coronavirus disease 2019 (COVID-19). Mendelian randomization (MR) studies provide us with a method to explore the causality between circulating proteins and COVID-19 susceptibility and severity. We aim to find new perspectives on the pathological mechanism of the disease and possible drug targets for treatment based on this study.
Methods: We conducted a phenome-wide MR study to prioritize circulating proteins causally associated with COVID-19 susceptibility, which was defined as "patients tested positive for COVID-19 vs. population controls", and severity, which was defined as "patients hospitalized with COVID-19 vs. population controls". And we repeated the analysis for different definition of COVID-19 susceptibility, severity and control groups.
Results: Association of three circulating proteins with COVID-19 susceptibility and severity were demonstrated via our study. C-C motif chemokine 4 (OR =1.887, 95% CI: 1.608-2.165, P=8.04×10[SUP]-6[/SUP]) and 2'-5'-oligoadenylate synthase 1 (OR =0.511, 95% CI: 0.266-0.757, P=8.51×10[SUP]-8[/SUP]) were found respectively positively and negatively correlated with increased COVID-19 severity. Tissue factor, contrary to previous studies, was found associated with decreased COVID-19 susceptibility (OR =0.667, 95% CI: 0.484-0.850, P=1.47×10[SUP]-5[/SUP]) and decreased COVID-19 severity (OR =0.459, 95% CI: 0.132-0.786, P=3.01×10[SUP]-6[/SUP]).
Conclusions: Genetic evidence supports C-C motif chemokine 4 as a risk factor for COVID-19 severity, and 2'-5'-oligoadenylate synthase 1 as a protective factor for COVID-19 severity. The causal association between tissue factor and COVID-19 is contrary to the previous studies, needing further analyses. Further research is warranted to assess the viability of C-C motif chemokine 4 and 2'-5'-oligoadenylate synthase 1 as well as their downstream pathways as drug targets for anti-inflammatory and anti-virus treatment in severe cases.
Keywords: Mendelian randomization (MR); coronavirus disease 2019 (COVID-19); proteomics.