Coronavirus disease-2019 (COVID-19) disease can cause asymptomatic and mild flu-like symptoms as well as severe symptoms ranging from respiratory failure and death. Growth hormone (GH) is produced in the anterior pituitary and plays an important role in the immune system. COVID-19 is severe in the elderly, men, obese, diabetics, and people with immune deficiency.
The probability of GH deficiency is high in these patient groups. In this study, we aimed to investigate the relationship between the severity of COVID-19 infection and GH level.
- GH and IGF-1 levels of patients with lung involvement were lower than patients without lung involvement.
- Lung involvement and IGF-1 deficiency had a significant effect on COVID-19 infection, while age, gender and glucose had no effect.
Growth hormone (GH) is produced in the anterior pituitary and shows its effect through insulin-like growth factor-I (IGF-I) . GH and IGF1, the most important mediator of GH effects, apart their role in growth regulation during childhood, coordinate several processes throughout adult life . GH stimulates protein synthesis, increases lipolysis, and potentiates the action of insulin .
GH and IGF-1 have an important role in the immune system. Both GH and IGF-1 stimulate the development and survival of antigen-sensitive clones of B and T cells . GH has negative feedback effects on many pro-inflammatory cytokines .
Coronavirus disease-2019 (COVID-19) has been causing a rapidly spreading pandemic all over the world since December 2019. COVID-19 affects primarily the respiratory tract, but may also cause multi-organ dysfunction due to the widespread presence of angiotensin-converting enzyme-2 receptors, an entry point for the virus . COVID-19 affects many secondary endocrine organs (thyroid, pancreas, adrenals, and gonads) are reported to be affected .
COVID-19 can cause asymptomatic and flu-like mild symptoms as well as severe symptoms that progress to respiratory failure and death . It has a more severe course especially in the elderly, men, obese, diabetic individuals, and individuals with immune deficiency. The probability of GH deficiency is high in these patient groups. In this study, we aimed to investigate the relationship between the severity of COVID-19 infection and GH level.
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9677050/
In our study, we found that GH and IGF-1 levels in patients with lung involvement in COVID-19 were lower than those without lung involvement in COVID-19. In addition, we observed that COVID-19 infection was more severe in GH and IGF-1 deficiency, regardless of age and gender.
COVID-19 disease is a pandemic problem that started in Wuhan, China and spread rapidly all over the world. The COVID-19 pandemic is still spreading rapidly around the world, causing more than 250 million cases and more than five million deaths (worldometer data). It caused the health system to collapse in many countries. Quarantine methods applied to prevent the spread of the disease negatively affected the economies of the country.
Studies are ongoing in research centers around the world to create a suitable vaccine or effective medical treatment for the virus, but there is still no effective treatment for COVID-19 infection . COVID-19 infection is more severe in the elderly, men and chronic diseases , the possibility of GH deficiency is high in this patient group. GH replacement therapy may be a promising agent in the treatment of COVID-19 infection.
COVID-19 infection is more common and more severe in men.
According to Chinese data, mortality rates are 36% in female patients and 64% in male patients . According to European data, the rate of COVID-19 infection is 71% in male and 29% in female . In our study, 168 (37%) of the patients were female and 288 (63%) were male. When we compared female and male, the CRP value and the number of days of hospitalization were higher in male, and the difference was statistically significant (Table 3). Consistent with the literature, we can say that COVID-19 infection is more common and more severe course in male patients.
Although IGF-1 levels are similar in adult males and females, GH secretion is higher in adult females than males . Sex steroids in women increase GH secretion, GH receptor expression and IGF-1 synthesis in target tissue . While the normal for GH levels is 0.4–10 ng/ml for adult men, it is 1–14 ng/ml for adult women . Normal aging is associated with a gradual decline in serum GH and the decline is more rapid in men than in women . In our study, IGF-1 level was higher in females than males, but there was no statistically significant difference and GH levels were similar in males and females.
GH plays an important role in the immune system, it stimulates the development of T cells by stimulating the thymus gland [16, 17]. GH stimulates the proliferation of T and B lymphocytes, the production of immunoglobulin, the development of myeloid precursor cells and their response to cytokine . GH and IGF-1 stimulate the maturation of myeloid cells, stimulate phagocyte migration, increase phagocyte production of superoxide anions and cytokines, and may protect against bacterial infections.
GH has negative feedback effects on many proinflammatory cytokines. In adults with GH deficiency, CRP, Interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) levels increase and decrease after GH replacement . CRP level is low in patients with acromegaly, CRP increases with the treatment of acromegaly . GH suppresses serum cytokine levels directly and indirectly. Estrogen inhibits receptor signals of cytokines such as IL-6, leptin and prolactin. CRP, IL-6, and TNF-alpha levels increase in both GH and estrogen deficiency .
IL-6 level rises in severe COVID-19 patients and as IL 6 level increases, mortality rate increases in COVID-19 patients. In our study, patients who are followed up with a diagnosis of COVID-19 infection, mean GH: 0.262 ng/ml (0–3) and IGF-1: 66.33 ng/ml (51–187) were in the normal range when evaluated by age. Pulmonary involvement in COVID-19 disease is important in both diagnosis and follow-up, as the degree of lung involvement increases, the prognosis is negatively affected [8, 21].
In our study, we found that GH and IGF-1 levels of patients with lung involvement were lower than patients without lung involvement, the difference was statistically significant (Fig. 1, 2). Patients with lung involvement had higher CRP levels and had a longer hospital stay. In the multivariate regression analysis, we found that lung involvement and IGF-1 deficiency had a significant effect on COVID-19 infection, while age, gender, and glucose had no effect. In GH and IGF-1 deficiency, we can say that COVID-19 infection progresses more severely regardless of age and gender.
The severity and mortality of COVID-19 infection increase in patients with diabetes mellitus . In patients with poorly controlled diabetes, there is GH resistance in the liver due to portal insulin insufficiency. There is a decrease in the production of hepatic IGF-1 in GH resistance. Total and free IGF-1 levels decrease during insulin insufficiency .
In our study, although patients with poorly controlled diabetes were not included, fasting blood glucose and HbA1c values were higher in COVID-19 patients with pulmonary involvement compared to those without pulmonary involvement, but there was no statistical significance.
As a result, GH is important in the immune system, its deficiency can cause serious viral and bacterial infections. Although there are articles [10, 24–26] in the literature on GH and COVID-19 infection, our study is the first study to investigate the relationship between lung involvement and GH/IGF-1 in COVID 19 disease. In our study, we found GH and IGF-1 deficiency in COVID-19 infection with lung involvement.
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