Plasma S-Adenosylmethionine Is Associated with Lung Injury in COVID-19

Abstract

Objective. S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are indicators of global transmethylation and may play an important role as markers of severity of COVID-19. Methods. The levels of plasma SAM and SAH were determined in patients admitted with COVID-19 ( n = 56 , mean age = 61 ). Lung injury was identified by computed tomography (CT) in accordance with the CT0-4 classification. Results. SAM was found to be a potential marker of lung damage risk in COVID-19 patients ( SAM > 80 nM ; CT3,4 vs. CT 0-2: relative ratio (RR) was 3.0; p = 0.0029 ). SAM / SAH > 6.0 was also found to be a marker of lung injury (CT2-4 vs. CT0,1: RR = 3.47 , p = 0.0004 ). There was a negative association between SAM and glutathione level ( ρ = − 0.343 , p = 0.011 ). Interleukin-6 (IL-6) levels were associated with SAM ( ρ = 0.44 , p = 0.01 ) and SAH ( ρ = 0.534 , p = 0.001 ) levels. Conclusions. A high SAM level and high methylation index are associated with the risk of lung injury in patients with COVID-19. The association of SAM with IL-6 and glutathione indicates an important role of transmethylation in the development of cytokine imbalance and oxidative stress in patients with COVID-19.

COVID-19 and One-Carbon Metabolism

“…In addition, a negative correlation between rGSH and advance oxidation protein products in patients with high lung damage was observed [29]. A similar study involving fifty-six COVID-19 patients admitted to the hospital between September and December 2020 in Moscow, Russia [18], found lower GSH concentration in patients with a higher degree of lung damage (>50% of lobar involvement) as compared to patients with a lower degree of lung injury (<25% of lobar involvement). There also has been a significant increase in SAM level and SAM/GSH ratios, and a tendency to higher Hcy levels in subjects with more injured lungs [18] (Table 2).…”

“…volvement) as compared to patients with a lower degree of lung injury (<25% of lobar involvement). There also has been a significant increase in SAM level and SAM/GSH ratios, and a tendency to higher Hcy levels in subjects with more injured lungs [18] (Table 2). Another study involving sixty COVID-19 patients hospitalized in Houston, TX and twenty-four uninfected controls, found that total and reduced red blood cells GSH were significantly lower in COVID-19 patients then in controls.…”

“…The glutathione hypothesis of COVID-19 appears to be supported by available data (Table S1). Indeed, GSH levels are consistently decreased in COVID-19 patients [17,18,28,29]. For example, a study on fifty-nine COVID-19 patients admitted to the hospital between August and November 2020 in Moscow, Russia [29], found that the levels of total GSH (tGSH) were significantly lower in moderate and severe COVID-19 patients compared with mildly affected subjects, while reduced CysGly (rCG) was significantly decreased in patients with higher degrees of lung damage based on percentage of lobar involvement (>26%) as compared to subjects with a lower degree of lung damage (0-25% of lobar involvement) (Table 2).…”

“…However, although SAM has not been quantified in long COVID-19, this hypothesis doesn't seem to hold much water because several studies showed significant increases or no changes in plasma SAM levels in COVID-19 cases (Table S1). Moreover, SAH levels are either elevated [15,16], attenuated [17] or do not change in COVID-19 [18]. For example, a study on fifty-six COVID-19 patients admitted to the hospital between September and December 2020 in Moscow, Russia, has shown that an elevated SAM level and SAM/SAH and SAM/glutathione ratios have been associated with an increased risk of severe lung injury.…”

“…For example, a study on fifty-six COVID-19 patients admitted to the hospital between September and December 2020 in Moscow, Russia, has shown that an elevated SAM level and SAM/SAH and SAM/glutathione ratios have been associated with an increased risk of severe lung injury. Furthermore, an elevated SAM concentration and SAM/SAH and SAM/GSF ratios have been associated with an increased risk of lung damage [18]. Metabolomic analyses have revealed that SAM was significantly elevated in critical cases of COVID-19 [15] and those with a fatal outcome [19] as compared to control, mild and moderate cases of COVID-19 [15] (Table S1).…”