Response to comment on ‘SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung’

Mast, Alan E.; Gailani, David; Garvin, Michael R.; Alvarez, Christiane; Miller, J Izaak; Jones, Piet; Aronow, Bruce J.; Jacobson, Daniel

doi:10.7554/elife.74951

Cited by 1 publication

(2 citation statements)

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“…As SERPING1 is one of the proteins with the highest connectivity in the SARS-CoV-1 and SARS-CoV-2 interactomes, it was proposed that SARS-CoV-2 infection directly causes deficiency in C1 esterase inhibitor ( Thomson et al, 2020 ). Recently, clinical samples of COVID-19 patients revealed C1-Inhibitor as one of the most prominently downregulated genes with 80-fold decreased expression ( Mast et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, induction of CAS along with downregulation of KKS inhibitor SERPING1 and des-Arg-Kinin inactivator ACE2 may lead to local excess of DAK, resulting in constitutive activation and induction of its receptor B1R ( Figure 1B ). Indeed, clinical samples from COVID-19 patients revealed that B1R was one of the most prominently upregulated genes with a 260-fold expression increase ( Mast et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

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Whole patient knowledge modeling of COVID-19 symptomatology reveals common molecular mechanisms

Brock¹,

Jackson²,

Soldatos

et al. 2023

Front. Mol. Med

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Infection with SARS-CoV-2 coronavirus causes systemic, multi-faceted COVID-19 disease. However, knowledge connecting its intricate clinical manifestations with molecular mechanisms remains fragmented. Deciphering the molecular basis of COVID-19 at the whole-patient level is paramount to the development of effective therapeutic approaches. With this goal in mind, we followed an iterative, expert-driven process to compile data published prior to and during the early stages of the pandemic into a comprehensive COVID-19 knowledge model. Recent updates to this model have also validated multiple earlier predictions, suggesting the importance of such knowledge frameworks in hypothesis generation and testing. Overall, our findings suggest that SARS-CoV-2 perturbs several specific mechanisms, unleashing a pathogenesis spectrum, ranging from “a perfect storm” triggered by acute hyper-inflammation, to accelerated aging in protracted “long COVID-19” syndromes. In this work, we shortly report on these findings that we share with the community via 1) a synopsis of key evidence associating COVID-19 symptoms and plausible mechanisms, with details presented within 2) the accompanying “COVID-19 Explorer” webserver, developed specifically for this purpose (found at https://covid19.molecularhealth.com). We anticipate that our model will continue to facilitate clinico-molecular insights across organ systems together with hypothesis generation for the testing of potential repurposing drug candidates, new pharmacological targets and clinically relevant biomarkers. Our work suggests that whole patient knowledge models of human disease can potentially expedite the development of new therapeutic strategies and support evidence-driven clinical hypothesis generation and decision making.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%