Association Between S100b Levels and COVID-19 Pneumonia: A Case Control Study

Abstract

Background/Aim: Extracellular S100b effects are mediated by the receptor for advanced glycation end products (RAGE), which is the S100b membrane receptor. RAGE belongs to the immunoglobulin superfamily of cell surface molecules and serves as a multiligand receptor and is expressed in high abundance by alveolar type I (AT-I) cells in adult pulmonary tissue. This study aimed to provide an insight into the association between the severity of COVID-19 disease and serum S100b levels during admission to the emergency department (ED). Patients and Methods: A total of 64 patients (34 mild cases; 30 severe cases) were diagnosed with COVID-19 pneumonia and 30 healthy volunteers were admitted to study. Serum S100b levels were measured by using enzymle linked immunoassay method from blood serum samples. Results: Serum S100b levels showed a significantly higher mean value in mild and severe disease cohorts than in healthy controls (p=0.036 and p=0.028 respectively). Receiver operating characteristic (ROC) analysis indicated greater area under the curve (AUC) for serum S100b levels of the p=0.014). In addition, serum S100b concentration was measured as 151.7 ng/ml at 79.3% sensitivity and 51.7% specificity (p=0.014). Serum S100b protein levels can serve as a valuable clinical marker in establishing diagnosis of patients. Though not useful in identifying different stages of COVID-19 infection, serum S100b concentration along with other known markers can be utilized to reliably predict clinical severity along with other clinical parameters. Transmitted from human to human through droplets, Coronavirus disease-19 (COVID-19) infection can progress asymptomatically. Its clinical manifestations, however, have a wide spectrum in symptomatic patients, ranging from upper respiratory tract infections (URTI) to serious clinical conditions such as pneumonia, acute respiratory disease syndrome (ARDS), sepsis, and septic shock (1, 2).S100b protein is a cytosolic calcium binding biomarker with a molecular mass of 21 kDa. Despite its extra-cranial presence, S100b is mainly expressed in the central nervous system (CNS) (3). As a cytosolic calcium sensor, this protein acts on dynamics of cytoskeletal components, energy metabolism, protein phosphorylation, and calcium homeostasis. When released from damaged cells, extracellular signals could be activated by S100b. It is also structurally released by astrocytes in the brain and can function in an autocrine or paracrine manner (4).Accumulating data from in vitro experiments have revealed the impact of extracellular S100b on the biology of various cellular types other than the CNS. In vitro trials have provided clinical evidence that S100b, similar to other S100 family of proteins, stimulates inflammatory responses in lymphocytes, vascular smooth muscle cells, endothelial cells, macrophages, and cardiomyocytes (5,6).Inside and outside the CNS, S100b acts as a damaged molecular model (DAMP) protein, which is released from damaged cells and can activate cells of innate immune response, altering the ...

Plasma biomarkers of brain injury in COVID-19 patients with neurological symptoms

“…[ 24 ]. Similar to GFAP, increased plasma levels of S100B were reported in the acute phase of COVID-19 patients [ 5 , 17 , 28 ]. However, data is limited regarding the serum levels of both GFAP [ 29 ] and S100B [ 30 ] together in the context of neurological signs of CNS dysfunction in SARS-CoV-2 infected patients.…”

“…S100B is a calcium-binding protein localized in the astrocytic cytoplasm and, some in adipose tissue [ 24 , 25 ]. The raised plasma levels of S100B as an astrocytic injury marker have rarely been explored in relation to COVID-19 [ 5 , 17 , 28 ]. Mete et al showed significantly higher S100B levels in patients with COVID-19 pneumonia with severe disease than in the controls [ 28 ].…”

“…The raised plasma levels of S100B as an astrocytic injury marker have rarely been explored in relation to COVID-19 [ 5 , 17 , 28 ]. Mete et al showed significantly higher S100B levels in patients with COVID-19 pneumonia with severe disease than in the controls [ 28 ]. Similarly, Aceti et al found that serum S100B significantly correlated with clinical severity in COVID-19 patients, as in association with inflammatory markers of ferritin, C-reactive protein, procalcitonin, etc.…”

Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19

“…Levels of lymphocytes, procalcitonin, and creatinine were higher in COVID-19 stroke patients ( 94 ). S100B was higher in patients with mild and severe COVID-19 than in healthy controls, and may be a marker of disease severity ( 95 ). Antiphospholipid antibodies (i.e., anti-phosphatidylserine/prothrombin) were higher in COVID-19 patients, particularly those with neurological manifestations, than in controls.…”

Reply to: Utility of Serum S100B as a Marker in SLE Patients During and After the SARS-Cov-2 Pandemic

“…Moreover, several studies have shown that serum S100B, a marker for brain injury which can also be elevated in cases of COVID-19 infection, is considered to be a potential biomarker of cognitive impairment and SLE (particularly important in distinguishing NPSLE) ( 5 , 6 , 7 ). In addition to S100B, we also need to add the other specific molecular markers related to NPSLE itself and COVID-19 infection to confirm the possible sequences and interactions between them on neuropsychiatric manifestations.…”