Ghrelin: The Unexpected COVID-19 Hero?

COVID-19 Research: Scientists from Wrocław Medical University, Poland, suggests that a hormone known as ghrelin could play a critical role in the human body's response to COVID-19. The study found that ghrelin levels were significantly higher in individuals six months after a mild course of SARS-CoV2 infection. This breakthrough discovery may have profound implications for the treatment of COVID-19 patients and understanding the disease's long-term effects.


 
The SARS-CoV2 virus has the potential to trigger a severe inflammatory response, known as a cytokine storm, particularly in individuals with obesity. Cytokines are proteins released by cells that play a crucial role in cell signaling and interaction. During a cytokine storm, the body's immune system goes into overdrive, resulting in widespread inflammation that can lead to multiorgan failure.
 
Enter ghrelin, a hormone best known for regulating appetite but also appears to play a key role in the immune response. In the study, the researchers noted a significant increase in ghrelin concentration in the COVID-19 group, especially in females.
 
These findings suggest that ghrelin may have a protective role in the inflammatory process triggered by SARS-CoV2.
 
However, the study also showed no significant changes in leptin concentration, another hormone secreted mainly by white adipose tissue. Leptin, which also acts as a pro-inflammatory cytokine, has been linked to obesity-related health complications and adverse COVID-19 outcomes. Despite the observed increase in ghrelin, leptin levels remained the same, thus underlining the uniqueness of ghrelin's role.
 
The study findings are significant given that ghrelin can act in various parts of the body to regulate essential biological functions. For example, it influences glucose homeostasis, hormone secretion, cell proliferation, and survival. Importantly, ghrelin plays a pivotal role in regulating immune function and inflammation, potentially dampening the damaging effects of a cytokine storm.

Moreover, previous studies indicate that ghrelin has protective effects in acute lung injury models, suggesting it could help mitigate the respiratory distress associated with severe COVID-19 cases. For instance, treatment with ghrelin improved lung damage and reduced serum pro-inflammatory cytokine levels in a pancreatitis-induced acute lung injury model.
 
The question then arises: Could ghrelin help alleviate the severe symptoms that lead to the dreaded cytokine storm syndrome in COVID-19 patients? So far, no such therapy has been attempted, but these findings certainly open the door for further investigation.
 
In analyzing a group of middle-aged patients six months after contracting a mild form of SARS-CoV2, the study revealed significantly higher ghrelin levels in the COVID-19 group compared to a healthy control group of the same age and body mass index (BMI). This increased ghrelin level during and after COVID-19 infection could indicate a relationship between ghrelin and the immune system, underlining its potential as a mitigating agent in the COVID-19 battle.
 
The COVID-19 Research findings also revealed a negative correlation between ghrelin and testosterone levels, hinting at the possibility that gender might impact ghrelin concentration and thus the course of COVID-19. The complexity of these hormonal interactions underlines the need for further research to fully understand their implications in the disease's course and recovery process.
 
In addition to ghrelin, the study also explored leptin's role. Although leptin has been linked with worse outcomes in SARS-CoV2 infection due to its pro-inflammatory properties, the study found no significant differences in leptin levels between COVID-19 patients and the control group, despite its known role as an inflammatory cytokine produced by visceral adipose tissue. It was previously hypothesized that leptin, alongside other cytokines such as IL-6, IL-11, and IL-12, could amplify systemic inflammation in COVID-19 patients, especially those with obesity.
 
Other studies have associated elevated leptin levels with a more severe course of SARS-CoV2 infection. A prominent marker of adipose tissue dysfunction, the adiponectin to leptin ratio, was found to be reduced in COVID-19 patients, indicating a potential link to worsened outcomes. Notably, those with cardiometabolic disturbances exhibited the lowest ratios. Moreover, it was observed that patients requiring mechanical ventilation and those with a high BMI had significantly higher leptin levels, which correlated with increased inflammatory mediators and disease severity.
 
However, the present study found no such correlation. The leptin levels in the patient group that recovered from a mild form of COVID-19 six months prior and the healthy control group showed no significant difference. This could likely be attributed to the patients having only slightly elevated body mass and BMI values, a departure from the usual demographics where obesity or severe overweight is common. The patient group and control group were also deliberately matched by BMI, which might further explain the similar leptin levels.
 
The study revealed that leptin was significantly positively correlated with factors such as body mass, BMI, fat mass, insulin, HOMA value, LDL cholesterol, triglycerides, and alanine transaminase, suggesting a potential connection between leptin and an adverse metabolic profile. However, considering the mild course of SARS-CoV2 infection and only slightly elevated BMI values in the patient group, it seems leptin levels might not significantly impact COVID-19 outcomes in such populations.
 
Nonetheless, the research had its limitations. The study's main limitation was its small sample size, making the results preliminary and warranting further investigation. Also, the study did not assess ghrelin concentration in patients with severe forms of COVID-19. However, the study is valuable as it is only the second one concerning ghrelin levels in patients with SARS-CoV2 infection. The higher levels of ghrelin in patients who had mild SARS-CoV2 infection compared to the healthy group provide a promising lead for further research.
 
To summarize, this study from Wrocław Medical University offers promising insights into the role of ghrelin and leptin in the body's response to SARS-CoV2 infection. Elevated ghrelin levels in patients, even six months after mild SARS-CoV2 infection, suggest that this hormone could play a key role in the immune response and potentially the recovery process. On the other hand, leptin, despite its known pro-inflammatory effects, did not show significant variation between the patient and control group, suggesting its role in COVID-19 outcomes may be context-dependent. These insights present opportunities for additional research, especially in exploring the hormonal and immune interplay during and post-SARS-CoV2 infection. A better understanding of these processes could open the door to innovative therapeutic approaches for COVID-19.
 
The study findings were published in the peer reviewed Journal of Clinical Medicine.
https://www.mdpi.com/2077-0383/12/10/3551
 
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