ABSTRACT
Coronavirus disease 2019 (COVID-19) caused by the recently uncovered human coronavirus SARS-CoV-2 [1] presents a clinical spectrum that ranges from an asymptomatic condition to critical illness [2]. Patients with critical illness present respiratory failure, septic shock and/ or multi-organ failure induced by the so-defined cytokines storm [3]. Hepcidin modulates cellular iron export to plasma and extracellular fluid through ferroportin, which acts as hepcidin receptor and cellular iron exporter in vertebrates. Hepcidin is not routinely measured in COVID-19 patients, but some preliminary studies showed that high levels of hepcidin are associated with the severity of disease [4] as well as low levels of serum iron are correlated with the severity and mortality of disease and severe hypoxemia in intensive care unit (ICU) patients [5]. The aim of this study was to analyze retrospectively the levels of hepcidin in a group of COVID-19 patients admitted to the intensive care unit (ICU) of the Policlinico Tor Vergata of Rome, Italy. Thirty-eight patients from November 2020 to May 2021 because of pneumonia caused by SARS-CoV-2 were enrolled in the study. Based on the clinical outcome, the patients were assigned to two groups: survivors and non-survivors. A series of laboratory parameters were monitored during the stay of the patients in the ICU and their levels correlated to the clinical outcome. The Hepcidin was determined with Intrinsic Hepcidin IDxTM ELISA kit (Intrinsic Lifesciences, San Diego, CA, USA) that is a competitive immunoenzymatic assay based on a monoclonal antibody (mAb) with high affinity to the Nterminus of hepcidin-25. Of the parameters measured, significant statistical differences in the level of hepcidin, IL-6, LDH, leucocyte count, LNR, NLR, neutrophils level, CRP, and TNF-alpha were observed between the survivors and non-survivors groups. Specifically, a higher level of hepcidin, IL-6, LDH, leucocyte count, LNR, NLR, neutrophils, CRP and TNF-alpha were measured in the non-survivor group compared to the survivor group. In conclusion, Hepcidin can be prognostic of the clinical outcome, moreover, it could be used together with other markers in a predictive algorithm of disease severity.
ABSTRACT
Currently, the COVID-19 pandemic, caused by the novel SARS-CoV-2 coronavirus, represents the greatest global health threat. Most people infected by the virus present mild to moderate respiratory symptoms and recover with supportive treatments. However, certain susceptible hosts develop an acute respiratory distress syndrome (ARDS), associated with an inflammatory "cytokine storm", leading to lung damage. Despite the current availability of different COVID-19 vaccines, the new emerging SARS-CoV-2 genetic variants represent a major concern worldwide, due to their increased transmissibility and rapid spread. Indeed, it seems that some mutations or combinations of mutations might confer selective advantages to the virus, such as the ability to evade the host immune responses elicited by COVID-19 vaccines. Several therapeutic approaches have been investigated but, to date, a unique and fully effective therapeutic protocol has not yet been achieved. In addition, steroid-based therapies, aimed to reduce inflammation in patients with severe COVID-19 disease, may increase the risk of opportunistic infections, increasing the hospitalization time and mortality rate of these patients. Hence, there is an unmet need to develop more effective therapeutic options. Here, we discuss the potential use of natural immunomodulators such as Thymosin α1 (Tα1), all-trans retinoic acid (ATRA), and lactoferrin (LF), as adjunctive or preventive treatment of severe COVID-19 disease. These agents are considered to be multifunctional molecules because of their ability to enhance antiviral host immunity and restore the immune balance, depending on the host immune status. Furthermore, they are able to exert a broad-spectrum antimicrobial activity by means of direct interactions with cellular or molecular targets of pathogens or indirectly by increasing the host immune response. Thus, due to the aforementioned properties, these agents might have a great potential in a clinical setting, not only to counteract SARS-CoV-2 infection, but also to prevent opportunistic infections in critically ill COVID-19 patients.