The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities

Abstract

In December 2019, a novel human-infecting coronavirus, named SARS-CoV-2, has been recognized to cause a pneumonia epidemic outbreak with different degree of severity in Wuhan, Hubei Province in China. Since then this epidemic spread worldwide in Europe, and Italy also have been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82% of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poor-known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analyzed: 1) the structure of SARS-CoV-2 and SARS-CoV; 2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the Cytokine Release Syndrome; 3) the modification of the cell microRNome and of the immune response in patients with SARS infection; 4) the possible role of some liposoluble compounds (such as vitamin A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

Sars-CoV-2: Lessons from Both the History of Medicine and from the Biological Behavior of Other Well-Known Viruses

“…The production of VD stimulated by sun radiation seems very effective in reducing viral infectivity and in preventing the development of more severe forms of viral-related infections. Therefore, its use has been proposed several months ago with a therapeutic or preventive role in patients at a higher risk of severe clinical manifestations of SARS-CoV-2-related infection, such as aged people or for the treatment of these individual [17,22,[210][211][212]. Whether solar radiation can be effective for viruses inactivation and for VD production, air pollution could severely prevent such beneficial effects, because airborne particles shield solar radiation up to significant levels [213].…”

“…It may reach the neurons of the brain, the heart, the spleen, the lymph nodes and other lymphoid tissues [15]. In particular, the SARS-CoV-2 infects the host's lymphocytes and macrophages, causing both their death through apoptosis and subsequent severe lymphopenia and, afterward, making them very efficacious carriers for its spreading [16,17]. Therefore, this virus reaches the mucosa-associated lymphoid tissue, bronchus-associated lymphoid tissue and nasopharynx-associated lymphoid tissue.…”

“…Studies 'in vivo' have suggested the potential proinflammatory role of some of them in the pathogenesis of SARS-CoV-2. Particular regions in nucleocapsid (N) and spike (S) proteins of this pathogen can directly bind several specific DNA sequences, detectable in the promoter region of a wide series of interleukins and cytokines, promoting the production and the release of these mediators [17,22,36,37]. SARS-CoV-2-induced disease with severe clinical courses and with a fatal outcome is characterized by a massive release of a wide spectrum of cytokines.…”

“…This event is defined as 'cytokine storm' and leads to the life-threatening condition, known as 'cytokine release syndrome' [38]. The cells (macrophages, monocytes, lymphocytes and DCs), the mediators, costimulatory-, inhibitory-molecules and the mechanisms involved in this complex process have been widely described in recent studies [17,22,39].…”

Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis

“…The lipid-soluble vitamin D needs magnesium to assume its active form (1,25[OH]2D)[ 45 ]. More and more studies have shown a link between low levels of vitamin D and increased susceptibility to contracting the SARS-CoV-2 infection, and in the severity of the clinical course[ 46 , 47 ]. In a recent meta-analysis, which included six studies[ 31 , 48 - 52 ] with a total of 5884 hospitalized COVID-19 patients, Hariyanto et al [ 53 ] showed how the use of PPIs was significantly associated with an increased risk of severity and mortality in COVID-19 cases.…”