COVID-19 News: Decreased Growth Arrest-Specific 6 (Gas6) and sAxl Plasma Levels Linked To Hair Loss In Post COVID Individuals

COVID-19 News: A new study by researchers from Università del Piemonte Orientale (UPO)-Italy, A.O.U. Maggiore della Carità-Italy, Ospedale Alessandria-Italy and University of Trieste-Italy has found that decreased growth arrest-specific 6 (gas6) and sAxl plasma levels are associated with hair loss in COVID-19 survivors.


 
Post-acute symptoms following COVID-19 are quite common, but the exact causes behind these conditions remain unclear. In this forward-looking observational study, the Italian researchers aimed to examine the possible involvement of Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer).
 
Gas6 and its receptors, Axl and MerTK, play a significant role in promoting and sustaining inflammation. Gas6 is a 75 kDa soluble glycoprotein, a part of the vitamin-K-dependent protein family, and interacts with the TAM tyrosine kinase receptor family, which includes Tyro-3, Axl, and MerTK. Gas6 has a stronger affinity for Axl compared to Tyro-3 and MerTK. After protease cleavage, the transmembrane receptor's extracytoplasmic structure is released into the plasma as a soluble form (sAxl and sMer) that can still bind Gas6, likely exerting a modulatory function.
 
The Gas6/TAM signaling system is involved in various processes like cell survival, growth, aggregation, migration, angiogenesis, and controlling inflammatory responses. It also plays a role in chronic immunological diseases, with overactivation being linked to numerous neoplastic conditions.
 
Recently, the TAM system has been proposed as having a role in COVID-19. Several authors have suggested that the TAM receptor family is involved in SARS-CoV-2 infection, COVID-19 severity, and the development of clinical complications.
 
Higher baseline plasma Gas6 and sAxl levels have been associated with worsening clinical conditions and directly correlating with disease severity.
 
Additionally, TAM signaling has been implicated in coagulopathies related to abnormal inflammation and fibrosis development in COVID-19 patients.
 
Although Gas6/TAM signaling has been examined during the acute phase of COVID-19, its role in the development of long COVID syndrome remains unexplored. Therefore, the study aimed to investigate a possible association between circulating Gas6, sAxl, and sMer levels with long-term consequences in COVID-19 survivors.
 
The study team assessed 263 individuals one year after being discharged from the hospital for COVID-19, and they agreed to provide a blood sample to measure their circulating Gas6, sAxl, and sMer levels.
 
Out of the participants, 98 (37.3%) reported experiencing at least one lingering physical symptom a year after being discharged. In the univariate analysis, sAxl showed a slight association with residual symptoms, but only the lung's diffusing capacity for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96–0.99; p = 0.007) and being female (OR 2.49, CI 95%: 1.45–4.28; p = 0.001) were independently linked to long-lasting symptoms in the logistic regression analysis.
Hair loss was reported by 69 (26.2%) subjects. The univariate analysis found associations between Gas6, sAxl, DLCO, and female gender with hair loss development. The logistic regression analysis showed that Gas6 (OR 0.96, CI 95%: 0.92–0.99; p = 0.015), sAxl (OR 0.98, CI 95%; 0.97–1.0; p = 0.014), and female gender (OR 6.58, CI 95%: 3.39–12.78; p = 0.0001) were independent predictors of hair loss.
 
Reduced levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. For most patients, this hair loss resolved on its own, but 23.7% still reported persistent hair loss one year after being discharged from the hospital.
 
The study findings were published in the peer reviewed International Journal Of Molecular Sciences.
https://www.mdpi.com/1422-0067/24/7/6257
 
Recent research has suggested that Gas6/TAM signaling system plays a role in COVID-19 severity and complications, including coagulopathies and fibrosis. However, the role of Gas6/TAM signaling in long COVID syndrome remains unexplored.
 
This study investigated the association between circulating Gas6, sAxl, and sMer levels and long-term sequelae in COVID-19 survivors.
 
The study findings revealed that the Gas6/TAM system does not appear to be altered in patients with post-acute COVID symptoms, except for hair loss after SARS-CoV-2 infection.
 
Past COVID-19 News coverages have already reported that hair loss is common among COVID-19 survivors, with a prevalence of about 25%.
 
https://www.thailandmedical.news/news/new-british-study-shows-that-sexual-dysfunction-and-hair-loss-are-joining-fatigue-and-brain-fog-as-leading-long-covid-issues-
 
https://www.thailandmedical.news/news/breaking-covid-19-symptoms-study-by-indiana-university-and-covid-19-survivors-group-claims-of-sars-cov-2-associated-hair-loss
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262270/
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653091/
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653091/
 
The exact mechanisms behind this complication are unknown, but several risk factors have been suggested, including stress, treatments during the acute phase, and the psychological impact of the pandemic. Chronic stress can impact hair growth by keeping hair follicle stem cells in a quiescent state, leading to hair loss. Gas6 has been identified as a potential regulator of hair growth and is sensitive to stress.
 
In this study, patients with hair loss showed decreased levels of Gas6 and sAxl compared to others. While the findings are interesting, the study had some limitations, such as a relatively small population size, the lack of baseline Gas6 and sTAM measurements to understand their role in hair loss development, and the reliance on self-reported hair loss without a formal diagnosis. Despite these limitations, the study provides valuable insights that warrant further investigation into the Gas6/TAM system's involvement in hair loss.
 
The study also evaluated the potential association between Gas6 and its soluble receptors with long COVID, based on the observation that this condition may be related to persistent organ damage, lung fibrosis, and persistent low-grade inflammation. In the study population, the prevalence of persistent complaints was high (39.3%), consistent with previously published data on larger cohorts.
 
However, only sAxl levels were marginally decreased in long COVID patients, and this association was lost in a multivariate model, suggesting that the Gas6/TAM system may not play a significant role in long COVID.
In conclusion, the study confirms that hair loss is common among COVID-19 survivors and suggests that it may be associated with a derangement of the Gas6/TAM system. Although Gas6 and its soluble receptors' levels one year after the acute disease did not show significant associations with persistent organic symptoms, lower Gas6 and sAxl levels were associated with patients who experienced hair loss following COVID-19. Further research into the factors contributing to hair loss in COVID-19 survivors could provide novel insights into this common condition in the general population and potentially identify a new and relevant pathway.
 
For the latest COVID-19 News, keep on logging to Thailand Medical News.