**5. Interventions with Antiviral Bacteria**

Gut microbiota control could have distal protective effects on antiviral responses. There is evidence of the role of inflammasome activation in immune defence against influenza virus infection [111,112].

The commensal respiratory bacteria, *Corynebacterium pseudodiphtheriticum* modulates the TLR3 antiviral response against respiratory syncytial virus, enhancing the production of TNFα, IL-6, IFNγ and IFNβ by increasing the T cell subpopulations that produce these cytokines [113]. The protective role of commensal bacteria, mainly probiotics, is now well established. Specific probiotics such as lactic bacteria, are actually considered friendly bacteria, and secrete antiviral substances during their growth [113,114]. A dialogue is established between the intestinal microbiota and that of the airways through the intestinelung axis and it could explain how gut bacteria are able to enhance antiviral immunity as gut microbial metabolites could stimulate immune cells that, in turn, could move distally and mediate an antiviral response [112,114].

*Lactobacillus paracasei* and *L. plantarum* were able to reduce the inflammatory response in the lungs by increasing IL-10, and thus controlling the antiviral response [115,116]. Studies have shown the action of *L. gasseri* in various viral infections, including respiratory infections. Recent reports indicate *L. gasseri* SBT2055 is a promising probiotic useful for the prevention of human respiratory syncytial virus [117]. Finally, other nutritional interventions for coronavirus infection control have also been suggested, such as reducing the consumption of purine food sources [118], as it has been suggested that coronaviruses use purine nucleotides to promote synthesis of RNA [119].

Some possible mechanisms of antiviral activity mediated by bacteria could be the following: (i) bacteria could prevent the adsorption and cellular internalization of the virus by trapping it; (ii) bacteria could establish a link with cells to organize antiviral protection; (iii) microbial metabolites could have a direct antiviral effect.

Interestingly, some probiotic strains show antiviral activity against some coronaviruses [120]. Selective probiotic strains are able to control the levels of type I interferons, increase the number and activity of antigen presenting cells, NK cells, T lymphocytes, specific antibody levels in the lungs [119]. Specific probiotic strains are also capable of modifying the dynamic balance between proinflammatory and immunoregulatory cytokines that allow viral clearance while minimizing lung damage mediated by the immune response. *Bifidobacterium longum SP 07/3, L. gasseri* PA 16/8, and *Bifidobacterium bifidum* MF 20/5 contribute to reducing the duration of common cold episodes but also days with fever [121]. This could be especially important in preventing COVID-19 complications. A randomized clinical trial with *L. plantarum* DR7 showed suppression of plasma proinflammatory cytokines, such as IFN-γ, TNF-α in adult patients and potentiation of anti-inflammatory cytokines in young adults, along with a reduction in oxidative stress levels [122].

Strategies could be developed to alter the gut microbiome in order to manage the gastrointestinal effects of the virus in elderly COVID-19 patients and also to control the lung microbiota.
