{rfName}
Gr

License and use

Icono OpenAccess

Altmetrics

Grant support

This research was funded by MINISTERIO DE CIENCIA E INNOVACION (Project#RTI2018-095672-B-I00), Instituto de Salud Carlos III, Fondo de Investigacion Sanitaria (grant numbers PI15/00531, PI19/01410), Fundacio La Marato TV3 (grant numbers 20153030 and 20153031), and was co-funded by EUROPEAN UNION (ERDF A way to make Europe), Consejo Superior de Investigaciones Cientificas (CSIC-COV19-016/202020E155), Proyectos COVID-19 de la Junta de Castilla y Leon (07.04.467B04.74011.0), AGAUR (2017_SGR_177), and CERCA Programme/Generalitat de Catalunya.

Analysis of institutional authors

Ortiz Perez, Jose TomasAuthorMari Ayala, MartaAuthorMorales AAuthorCristóbal HAuthorMari MAuthorTutusaus AAuthorGarcia De Frutos PCorresponding Author

Share

Publications
>
Article

Growth Arrest-Specific Factor 6 (GAS6) Is Increased in COVID-19 Patients and Predicts Clinical Outcome

Publicated to:Biomedicines. 9 (4): 335- - 2021-04-01 9(4), DOI: 10.3390/biomedicines9040335

Authors: Morales, Albert; Rojo Rello, Silvia; Cristobal, Helena; Fiz-Lopez, Aida; Arribas, Elisa; Mari, Montserrat; Tutusaus, Anna; de la Cal-Sabater, Paloma; Nicolaes, Gerry A F; Ortiz-Perez, Jose T; Bernardo, David; Garcia de Frutos, Pablo

Affiliations

Abstract

Background: Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. Methods: Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. Results: GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. Conclusions: Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.

Keywords

axlgas6immune responseimmunothrombosismertkviral infectionvitamin kAxlCovid-19Gas6Immune responseImmunothrombosisMertkViral infectionVitamin k

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Biomedicines due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous).

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.86. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.71 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 11.67 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-08, the following number of citations:

  • WoS: 28
  • Scopus: 30
  • Europe PMC: 22
  • OpenCitations: 28

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-08:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 50.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 50 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Netherlands.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Morales Muñoz, Albert) and Last Author (García de Frutos, Pablo).

the author responsible for correspondence tasks has been García de Frutos, Pablo.