The elderly population and people with comorbidities are categorized as major risk groups against COVID-19 infection. Dementia is the major cause of disability in the elderly population and accounting 70% of the elderly population [6, 11, 12]. On the other hand, several studies have revealed that people with dementia have severe symptoms and an increased risk of mortality compared to the patients infected by COVID-19 without dementia [7]. In our study, we compared serum and blood biomarkers of deceased and survived dementia patients infected by COVID-19.
COVD-19 induces thrombosis, coagulopathy, and cytokine storm that lead to severe symptoms and are associated with higher mortality risk [13]. Additionally, the COVID-19 virus triggers microglia activation, chronic neuroinflammation, and neurodegeneration in the central nervous system (CNS) and the virus shares molecular similarities with CNS protein epitopes leading to the autoimmune state triggering cytokine storm [14]. Therefore COVID-19 may severe the symptoms in patients with neurological disorders.
Several biomarkers have been associated with aging, for instance, leukocytosis, lymphocytopenia, neutrophilia, anemia, and severe inflammatory state were observed in the elderly patients characterized by enhanced levels of CRP, fibrinogen, ferritin, d-dimers according to the literature. Additionally, renal and hepatic function is impaired in elderly patients characterized by elevated levels of BUN, creatinine, AST, and PT [15]. Among those biomarkers, fibrinogen, d-dimer, and C-reactive protein (CRP) level indicating increased risk for thrombosis and mortality significantly increased in the deceased dementia patients compared to the survived ones according to our clinical data (Figure 1) [16].
Minerals such as magnesium (Mg), calcium (Ca), phosphate (P), and sodium (Na) play a vital role in the various biological functions including cell signaling, nervous system, reproductive metabolism, and detoxification system [17–20]. Additionally, impairment in the electrolyte levels has been reported in the patients infected by COVID-19 [21]. Ca is involved in the pumps and exchangers at the plasma membrane responsible for the signal transduction. Decreased levels of Ca levels have been reported in acute pulmonary infections, pulmonary disease, and viral infections including COVID-19 [22–24]. Ca is utilized by viruses for the internalization and regulation as key factors for viral replication in the host [25]. Deceased patients have lower Ca levels compared to the survived patients according to the clinical data (Figure 2). On the other hand, Mg is involved in the anti-oxidant metabolism, blood pressure homeostasis, muscle metabolism, neuronal system, and protein synthesis [21]. Several studies have been reported that serum Mg levels increased in the COVID-19 patients that correlate with our data (Figure 2).
Moreover, our clinical data have revealed that serum biochemistry biomarkers including glucose, BUN, creatinine, ALT, AST, troponin, lactate, and procalcitonin levels increased in the deceased dementia patients infected by COVID-19 compared to the survived ones (Figure 3). Increased level of blood glucose is tightly associated with COVID-19 progression and mortality risk [26]. On the other hand, increased levels of creatinine are associated with muscle loss and creatinine levels increased in the deceased dementia patients indicating excessive muscle loss compared to the survived dementia patients (Figure 3) [3]. Additionally ALT and AST levels increased in the patients with COVID-19 infections as indicators of liver damage, inflammation, hepatic ischemia, drug-induced liver damage, and muscle loss [27]. Additionally, renal and hepatic function is impaired in elderly patients characterized by elevated levels of BUN, creatinine, AST, and PT [15]. Our clinical data showed increased ALS, AST, direct bilirubin, indirect bilirubin, and BUN levels indicating enhanced impairment in the liver and kidney function in the deceased dementia patients compared to the survived ones (Figure 3, 4). Moreover, an increased level of troponin is an indicator of myocardial dysfunction and respiratory infection. Increased troponin levels in COVID-19 have been associated with increased inflammation-causing elevated levels of oxidative stress, myocarditis, myocardial infarction, and microangiopathy [28]. Troponin levels increased in the deceased patients compared to the survived ones indicating impaired myocardial function (Figure 3). On the other hand, increased procalcitonin levels are reported as bacterial co-infection in COVID-19 patients as we reported in our clinical study (Figure 3) [29]. Albumin is the most abundant protein in the serum and associated with increased inflammation in the body [3] and tightly associated with mortality risk and disease progression in patients with COVID-19 [30]. We have found decreased albumin levels in deceased patients compared to the survived ones as a possible biomarker of increased inflammation and reduced anti-oxidant defense (Figure 4).
Anemia is associated with poor prognosis and increased risk of mortality in the patients infected by COVID-19. Increased RBC, decreased Hb, PDW, and HCT levels have been associated with anemia as we observed in the deceased dementia patients infected by COVID-19 compared to the survived patients (Figure 5) [30]. Moreover, our clinical data have revealed that increased NEU, decreased LYM, MONO, EOS, MPV, PCT, BASO, and INR levels in the deceased dementia patients infected by COVID-19 compared to the survived ones (Figure 6). Indicated changes in the blood biomarkers are tightly associated with a higher risk of mortality and disease progression [31]. Also with aging, leukocytosis, lymphocytopenia, neutrophilia, anemia, and severe inflammatory state were observed that are overlap with the COVID-19 pathology which may severe symptoms in the elderly patients [17].
In conclusion, elderly patients are in the risk group for COVID-19 infection, thus the prediction of disease severity and mortality risk should be tightly controlled in those patients. Blood and serum biomarkers could be used to predict disease severity in dementia patients and treatment options could be determined and applied for those patients.