Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality?
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Abstract
Background: The link between coagulation system disorders and COVID-19 has not yet been fully elucidated.
Aim: Evaluating the association of non-previously reported coagulation proteins with COVID-19 severity and mortality.
Design: Cross-sectional study of 134 COVID-19 patients recruited at admission and classified according to the highest COVID-19 severity reached (asymptomatic/mild, moderate, or severe) and 16 healthy control individuals.
Methods: Coagulation proteins levels (antithrombin, prothrombin, factor_XI, factor_XII, and factor_XIII) and CRP were measured in plasma by the ProcartaPlex Panel (Invitrogen) multiplex immunoassay upon diagnosis.
Results: We found higher levels of antithrombin, prothrombin, factor XI, factor XII, and factor XIII in asymptomatic/mild and moderate COVID-19 patients compared to healthy individuals. Interestingly, decreased levels of antithrombin and factors XI, XII, and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death.
Conclusion: COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might “paradoxically” imply a higher risk of progression to severe disease and COVID-19-related mortality.
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SciScore for 10.1101/2021.04.19.21255747: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study protocol was approved by the Ethics Committee of the Institute of Health Carlos III (PI 33_2020-v3) and the Ethics Committee of each hospital. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Clinical data and samples: Epidemiological, clinical, disease evolution data, as well as laboratory parameters such as PT, international normalized ratio (INR) and APTT were collected from clinical records using an electronic case report form (eCRF) which was built using REDCap ( REDCapsuggested: (REDCap, RRID:SCR_003445)Results from OddPub: We did not detect open …
SciScore for 10.1101/2021.04.19.21255747: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study protocol was approved by the Ethics Committee of the Institute of Health Carlos III (PI 33_2020-v3) and the Ethics Committee of each hospital. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Clinical data and samples: Epidemiological, clinical, disease evolution data, as well as laboratory parameters such as PT, international normalized ratio (INR) and APTT were collected from clinical records using an electronic case report form (eCRF) which was built using REDCap ( REDCapsuggested: (REDCap, RRID:SCR_003445)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Several limitations should be considered. First one is the limited sample size, of healthy and asymptomatic cases, which could have limited the possibility to find statistical significance differences in some comparisons. Second one is that we have analysed five coagulation protein; as coagulation cascade is extremely complex, further studies should consider additional factors to fully describe the COVID-19 effects over the entire coagulation cascade. However, these additional factors have been extensively studied, and we analysed those that were not previously addressed. In conclusion, our results indicate that: 1) COVID-19 causes an early increase of some specific coagulation proteins such as antithrombin, prothrombin, contact factors and factor XIII in most patients, even in those who won’t suffer from clinically significant disease, suggesting that commonly elevated D-dimer levels are driven by an initial enhanced procoagulant state and not just by hyperfibrinolysis; 2) Although not reflected in routine tests such as PT and APTT, and despite common initial hyperfibrinogenemia, patients who will eventually advance to severe disease show early decreased levels of these anticoagulant and procoagulant markers, suggesting factor consumption, an these levels were associated with higher COVID-19 related mortality. Evolving investigations will allow us to better clarify the crosstalk between the immune and clotting systems in this pandemic disease.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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