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
COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve out- come in severe cases
Sorin Draghici
Wayne State University
Corresponding Author
Gil Mor
Wayne State University
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Current management efforts of COVID-19 include: early diagnosis, use of antivirals, and immune modulation. After the initial viral phase of the illness, identification of the patients developing cytokine storm syndrome is critical.1, 2 Treatment of hyper- inflammation in these patients using existing, approved therapies with proven safety profiles could address the immediate need to reduce the rising mortality.3 The identification of existing drugs that could modulate the immune response is an immediate need. Here we show that an analysis of the changes in the gene expression, path- ways and putative mechanisms between SARS-CoV2, influenza A, and respiratory syncytial virus can be used to identify FDA-approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. An important finding is that drugs in the same class may not achieve similar effects. An independent clinical study evaluated 213 subjects, 81 (38%) and 132 (62%) in pre-and post-methylprednisolone groups, respectively. Thirty-day all-cause mortality occurred at a significantly lower rate in the post-methylprednisolone group compared to pre-methylprednisolone group (29.6% vs. 16.6%, p=0.027). Clinical results con- firmed the in silico prediction that methylprednisolone could improve outcomes in severe cases of COVID-19. These findings are important for any future pandemic regardless of the virus.
Keywords
SARS-CoV2, influenza A, respiratory syncytial virus, hyper-inflammation, drug repurposing, methylprednisolone, gene expression
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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 15 May, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Drug Discovery, Design, & Development
Learn more about our company.
This is a preprint. It has not completed peer review.
Research Article
COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve out- come in severe cases
Sorin Draghici
Wayne State University
Corresponding Author
Gil Mor
Wayne State University
Corresponding Author
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 15 May, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Drug Discovery, Design, & Development
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Current management efforts of COVID-19 include: early diagnosis, use of antivirals, and immune modulation. After the initial viral phase of the illness, identification of the patients developing cytokine storm syndrome is critical.1, 2 Treatment of hyper- inflammation in these patients using existing, approved therapies with proven safety profiles could address the immediate need to reduce the rising mortality.3 The identification of existing drugs that could modulate the immune response is an immediate need. Here we show that an analysis of the changes in the gene expression, path- ways and putative mechanisms between SARS-CoV2, influenza A, and respiratory syncytial virus can be used to identify FDA-approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. An important finding is that drugs in the same class may not achieve similar effects. An independent clinical study evaluated 213 subjects, 81 (38%) and 132 (62%) in pre-and post-methylprednisolone groups, respectively. Thirty-day all-cause mortality occurred at a significantly lower rate in the post-methylprednisolone group compared to pre-methylprednisolone group (29.6% vs. 16.6%, p=0.027). Clinical results con- firmed the in silico prediction that methylprednisolone could improve outcomes in severe cases of COVID-19. These findings are important for any future pandemic regardless of the virus.
Figure 1
Figure 2
Figure 3
Figure 4