Increased angiotensin-converting enzyme 2, sRAGE and immune activation, but lowered calcium and magnesium in COVID-19: association with chest CT abnormalities and lowered peripheral oxygen saturation

Abstract

Background. The characterization of new biomarkers of COVID-19 is extremely important. Few studies measured the soluble receptor for advanced glycation end product (sRAGE), angiotensin-converting enzyme 2 (ACE2), calcium and magnesium in COVID-19. Aims: To measure sRAGE, ACE2, interleukin (IL)-6, IL-10, CRP, calcium, magnesium, and albumin in COVID-19 patients in association with peripheral oxygen saturation (SpO2) and chest CT scan abnormalities (CCTA) including ground glass opacities. Methods. This study measured sRAGE, ACE2, IL-6, IL-10, CRP using ELISA techniques, and calcium, magnesium, and albumin using a spectrophotometric method in 60 COVID-19 patients and 30 healthy controls. Results. COVID-19 is characterized by significantly increased IL-6, CRP, IL-10, sRAGE, ACE2, and lowered levels of SpO2, albumin, magnesium and calcium. Neural networks showed that a combination of calcium, IL-6, CRP, and sRAGE yielded an accuracy of 100% in detecting COVID-19 patients with calcium being the most important predictor followed by IL-6, and CRP. COVID-19 patients with CCTAs showed lower SpO2 and albumin levels than those without CCTAs. SpO2 was significantly and inversely correlated with IL-6, IL-10, CRP, sRAGE, and ACE2, and positively with albumin, magnesium and calcium. Patients with positive IgG results showed a significant elevation in the serum level of IL-6, sRAGE, and ACE2 compared to the negatively IgG patient subgroup. Conclusion. The results show that immune-inflammatory and RAGE pathway biomarkers may be used as external validating criterion for the diagnosis COVID-19. Those pathways coupled with lowered SpO2, calcium and magnesium are drug targets that may help to reduce the consequences of COVID-19.

Increased serum thromboxane A2 and prostacyclin but lower complement C3 and C4 levels in COVID-19: associations with chest CT-scan anomalies and lowered peripheral oxygen saturation

“…In agreement with Al-Hakeim et al (2020) and other studies reviewed in the latter paper [31], this study found that serum albumin, and total calcium and magnesium were significantly lowered in COVID-19. Hypoalbuminemia may be explained by the acute phase responses in COVID-19 with increased breakdown of albumin and increased production of positive acute phase proteins [71], and by enhanced capillary permeability leading to the leaking of albumin to the interstitial space [72].…”

“…Recently, we published that chest CT abnormalities (CCTAs) (comprising ground-glass opacities (GGOs), pulmonary densification areas consistent with residual lesions, pneumonic consolidation, and crazy-paving patterns), could be observed in 78.3% of RT-PCR test–proven COVID-19 cases and that the presence of CCTAs was characterized by significantly lowered peripheral oxygen saturation (SpO2) and serum levels of albumin [31]. The latter is a negative acute phase protein which is lowered in response to the systemic inflammatory response in COVID□19 [1, 31-33]. Moreover, lowered SpO2 values were significantly associated with signs of immune activation, and positively with albumin, magnesium, and calcium [31].…”

“…The latter is a negative acute phase protein which is lowered in response to the systemic inflammatory response in COVID□19 [1, 31-33]. Moreover, lowered SpO2 values were significantly associated with signs of immune activation, and positively with albumin, magnesium, and calcium [31]. In addition, the latter study found that lowered serum calcium was the single best biomarker of acute COVID-19 and was more important than inflammatory biomarkers including interleukin-6 (IL-6) and C-reactive protein (CRP) in discriminating COVID-19 patients from healthy controls.…”

Intersections between Pneumonia, Lowered Oxygen Saturation Percentage and Immune Activation Mediate Depression, Anxiety and Chronic Fatigue Syndrome-like Symptoms due to COVID-19: A Nomothetic Network Approach

“…Chest imaging, especially computed tomography scan (CT-scan), is critical for the diagnosis, management, and follow-up of COVID-19 infection (Fang Y, 2020;Zhang et al, 2020a). CT scan anomalies (CCTAs), including ground-glass opacities (GGOs), pulmonary densification areas consistent with residual lesions, pneumonic consolidation, and crazy-paving trends are observed in 78.3% of RT-PCR test-proven COVID-19 patients and are associated with lower peripheral oxygen saturation (SpO2) (Al-Hakeim et al, 2021).…”

“…COVID-19 and increased CCTAs are accompanied by increased serum IL-6, CRP, and IL-10, and lowered albumin and oxygen saturation percentage (SpO2) . Moreover, we detected increased levels of sRAGE (soluble receptor for advanced glycation end-products) and angiotensin converting enzyme 2 (ACE2) in COVID-19 patients (Al-Hakeim et al, 2021). sRAGEs are generated through proteolysis of the extracellular domain of RAGE or through alternative RNA splicing (Sterenczak et al, 2009;Zhang et al, 2008).…”