In this study, we investigated the levels of circulating S100B in serum of patients affected by SARS-CoV-2 virus at various stages of the disease. S100B serum concentrations resulted correlated with the severity of the disease, as indicated by clinical/laboratory parameters. The major part of data at present available on the S100B protein as a biomarker and pathogenic factor deals with disorders primarily related to the nervous system whereas disorders primarily related to other systems having been essentially disregarded : thus, present results appear to enlarge the field of investigation on this protein and its potentials in Covid-19 and, more in general, infectious diseases. Indeed, the discrete distribution of S100B in definite extra-neural cell types offers the basis for a functional/pathogenic role of the protein in extra-neural tissues, which at present has not been exhaustively investigated.
This study was performed during the epidemic peak, with the advantage of collecting homogeneous data from the same outbreak but with all the restrictions present while managing the emergency, including the limits in sample size and in the number of additional clinical or laboratory parameters to be assessed. However, the acquired data were stressed by an accurate statistical analysis, strongly reporting a role for S100B in Covid-19.
The increased levels of S100B are reasonably related to inflammatory processes, as also supported by its significant correlation with CRP, which is known to be a recognized inflammatory hallmark . S100B is known to participate in inflammatory processes [25,26] which are also known to be raised during SARS-CoV-2 disease [19,21]. Interestingly, in this respect we observed that S100B levels are correlated with indicators of distress involving non-neural districts, such as ALT, d-Dimer, PCT, suggesting, in this case, a wider and systemic valence for S100B as a putative biomarker.
The source of increased serum S100B in SARS-CoV-2 patients remains to be identified. Since information indicating a prevalent involvement of the nervous system in pathogenic processes of SARS-CoV-2 at present is lacking , it seems unlikely that in this case the protein is primarily released from this tissue, which at present is regarded to be the natural source of the protein in biological fluids in the major part of pathological conditions already known. Among the cell types which are known to express and putatively release the protein, adipocytes, dendritic and lymphoid cell types [28-31] appear to be putative sources for serum S100B in this disease. Adipocytes are known to secrete inflammatory cytokines which play a recognized role in crosstalk with the immune system, which at present are known to be especially relevant in processes leading to obesity [32,33]. Since the role(s) of molecules secreted by this intriguing cell type, including S100B, is at present largely unknown, this finding might add a novel element deserving interest. In the case of dendritic and lymphoid cell types, their role in inflammatory processes is widely known [34,35], so that the mechanistic involvement of S100B in their function would merely increase the breadth of knowledge in this respect. It is interesting to note that, under pulmonary inflammation, S100B has been reported to be upregulated in bronchiolar epithelial cells and airway dendritic cells [36,37]. Moreover, as shown in alveolar cell types, S100B can stimulate the secretion of pro-inflammatory cytokines, that are commonly involved in lung inflammation, following a similar process suspected to be present also in Covid-19 [19-22,36,37].
Additional studies will be needed in order to define the source of serum S100B in patients affected by SARS-CoV-2, but the finding of increased serum levels of the protein, correlated with the gravity of the disease and inflammatory processes, offers a novel biomarker potentially useful to monitor the disease. In addition, in the light of growing evidence candidating S100B as an active factor in inflammatory processes , the present findings may even propose the protein as a therapeutic target to counteract the potent inflammatory processes characterizing this infectious disease.
In conclusion, increased serum levels of S100B correlate with the severity of Covid-19 and inflammatory processes, offering a novel biomarker potentially beneficial in monitoring the disease course and prognosis. In the light of growing evidence candidating S100B as an active factor in inflammatory processes driven by DAMP and RAGE, the present findings propose this protein as a severity marker and its cellular pathways as candidate targets to unravel pathogenetic mechanisms and counteract the potent inflammatory processes characterizing SARS-CoV-2 infection.