This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Research article
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Severe corona virus disease 19 (COVID-19) is challenging to treat as it presents with thrombotic as well as inflammatory features. Specifically, endothelial cells are thought to be damaged in COVID-19. Here we assessed whether key druggable targets related to endothelial function, i.e., nitric oxide and platelets, are affected specifically in severe COVID-19, using a Mendelian randomization study.
Methods: We compared genetically predicted circulating nitric oxide, proxied by three relevant NOS3 functional variants (rs2070744, rs1799983 and rs3918226), and genetically predicted platelets, proxied by a functional variant related to platelet reactivity from GRK5 (rs10886430) and by platelet count (based on 243 variants), because they share a phenotype, in people with severe COVID-19 with the general population (cases=536, non-cases=329,391) largely based on studies from Northern Europe. We made a similar comparison for any COVID-19.
Results: Nitric oxide was inversely associated with severe COVID-19 (odds ratio (OR) 0.84 per raising allele, 95% confidence interval (CI) 0.75 to 0.95), but was not associated with any COVID-19. Associations of both platelet reactivity and platelet count with severe COVID-19 were in a harmful direction (OR 1.20, 95% CI 0.95 to 1.50 and OR 1.23, 95% CI 0.97 to 1.56 respectively) with combined OR 1.21, 95% CI 1.03 to 1.42, but associations with any COVID-19 were null.
Conclusions: Genetic validation of the role of nitric oxide and possibly of platelets in specifically severe COVID-19 suggests they could be targets of intervention for which well-established treatments exist.
Keywords
COVID-19, nitric oxide, platelets, endothelial, Mendelian randomization
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 21 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Epigenetics & Genomics
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 21 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Epigenetics & Genomics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Severe corona virus disease 19 (COVID-19) is challenging to treat as it presents with thrombotic as well as inflammatory features. Specifically, endothelial cells are thought to be damaged in COVID-19. Here we assessed whether key druggable targets related to endothelial function, i.e., nitric oxide and platelets, are affected specifically in severe COVID-19, using a Mendelian randomization study.
Methods: We compared genetically predicted circulating nitric oxide, proxied by three relevant NOS3 functional variants (rs2070744, rs1799983 and rs3918226), and genetically predicted platelets, proxied by a functional variant related to platelet reactivity from GRK5 (rs10886430) and by platelet count (based on 243 variants), because they share a phenotype, in people with severe COVID-19 with the general population (cases=536, non-cases=329,391) largely based on studies from Northern Europe. We made a similar comparison for any COVID-19.
Results: Nitric oxide was inversely associated with severe COVID-19 (odds ratio (OR) 0.84 per raising allele, 95% confidence interval (CI) 0.75 to 0.95), but was not associated with any COVID-19. Associations of both platelet reactivity and platelet count with severe COVID-19 were in a harmful direction (OR 1.20, 95% CI 0.95 to 1.50 and OR 1.23, 95% CI 0.97 to 1.56 respectively) with combined OR 1.21, 95% CI 1.03 to 1.42, but associations with any COVID-19 were null.
Conclusions: Genetic validation of the role of nitric oxide and possibly of platelets in specifically severe COVID-19 suggests they could be targets of intervention for which well-established treatments exist.
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
Loading...