Nutrients in mitigating the Covid-19 pathogenesis
Nutrition and nutrients play a vital role in enhancing immune response along with reduction of inflammation and oxidative stress 44–
46. Better nutritional status of CoVID-19 patients is associated with less adverse outcomes
18,
47–
52.
Vitamin D is involved in reducing respiratory infections, such as influenza, and a reduced plasma 25-hydroxyvitamin D (25(OH)D) concentration in SARS-CoV-2 patients has been observed
53. Moreover, people with vitamin D deficiency are at higher risk of getting infected with SARS-CoV-2
54,
55.
Co-supplementation of vitamin D along with glutathione precursor L-cysteine significantly increases serum 25(OH)D levels and augments vitamin D regulatory gene expression, which in turn reduces the oxidative stress and inflammatory responses in CoVID-19 patients 56. Vitamin D supplementation in SARS-CoV-2 infected patients attenuates the production of proinflammatory cytokines like Interferon (IFN)-γ, IL-6, IL-2 and TNF-α by inhibiting NF-κB and other pathways
57–
59. CoVID-19 associated inflammatory signalling pathways including NF-κB, Mitogen-Activated Protein Kinase (MAPK) and phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) and innate immune response pathways, such as Toll-like signalling and NOD-like signalling modulation and regulation can be mediated by the combination of curcumin, vitamin C, and glycyrrhizic acid
60.
Vitamin C has been known to improve the immune condition by enhancing differentiation and proliferation of B- and T-cells, but severe vitamin C deficiency is associated with pneumonia and respiratory tract infections 61. Intravenous administration of vitamin C can significantly decrease IL-6 levels
62,
63.
Glycyrrhizic acid and curcumin exhibits anti-viral, anti-inflammation, anti-cancer, and immune system benefits 60. The combination of
vitamin D/magnesium/vitamin B12 significantly reduced the subsequent need for oxygen therapy and/or intensive care support in older CoVID-19 patients 57.
Vitamin B12 is crucial in maintaining the healthy gut microbiome which plays a vital role in immune responses 57. Fat soluble vitamin E acts as an antioxidant that scavenges Reactive Oxygen species (ROS) and inhibits devastating effects of hyperinflammation 64. Moreover, the supplementation of vitamin E stimulates T cell function and confers protection against upper respiratory infections 65.
Selenium is one of the key micronutrients known to positively impact CoVID-19 patient recovery 66,
67. Selenium status regulates the expression of glutathione peroxidase 1 (GPX1), a cytosolic selenoenzyme known for its antioxidative properties. The antioxidant enzyme GPX1 mitigates the production of ROS and further leading to mutations in the viral genome
68. In addition, attenuating ROS also helps in the inhibition of proinflammatory NF-κB activation and further nuclear translocation
69. Severe endothelial injury and widespread pulmonary micro thromboses are accompanied with platelet activation and aggregation in patients with severe CoVID-19 manifestations.
The synthetic Rupatadine (histamine1 receptor antagonist) and natural flavonoids with anti-inflammatory properties are known to inhibit the platelet activating factor 70. E
lderly individuals with deficiency of nutrients, such as vitamin C, vitamin D, calcium, folate, and zinc are prone to increase severity of SARS-CoV-2 infection 71. Folic acid may inhibit furin protease and inactivates chymotrypsin-like protease (3CL pro)
72. Zinc (Zn 2+) deficiency contributes to impaired cell mediated immune response and increased susceptibility to various infections. However, increased intracellular levels of Zn 2+ disrupt viral RNA replication including SARS-CoV-2, where Zn 2+ inhibits RNA (Ribonucleic acid) dependent RNA polymerase (RdRp) elongation and template binding
73. Among CoVID-19 patients, iron deficiency is strongly associated with increased inflammation and longer stay in hospitals
74.
Health beneficial compounds, including minerals, antioxidants, phytochemicals, vitamins, and minerals present in fruits and vegetables, can exert antioxidative, anti-inflammatory and antiviral effects during various non-infectious and infectious disease
71.
Alliin, an S-allyl cysteine sulfoxide compound present in garlic has shown to have inhibitory action on 3CL pro, a protease that plays a vital role in SARS-CoV-2 replication 75. Salvianolic acid A and curcumin have the potential to bind to 3CL pro with greater affinity
76.
Resveratrol acts as an anti-inflammatory molecule that inhibits the NFκB pathway and thereby reduces circulatory cytokines, such as IL-6 and TNF-α levels, which are observed in severe SARS-CoV-2 infection
77.
Sea cucumber ( Stichopus japonicus) derived sulphated polysaccharide showed significant anti-viral activity against SARS-CoV-2 infection
78.
Omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid and docosahexaenoic acid have been shown to exhibit anti-inflammatory effects by downregulation of the NF-κB pathway 71,
79,
80. Free fatty acids such as oleic acid, arachidonic acid and linoleic acid have shown antiviral activity at micromolar concentrations
81. Dietary fibre intake alters the intestinal microflora and enhances relative proportion of SCFAs, which exhibit anti-inflammatory properties through fatty acid receptors like G-protein-coupled receptor (GPCR) 41 and 43
82–
84.
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Probiotics: suppressors of respiratory tract infections and inflammation
Probiotics are living microorganisms that provide health benefits to the host upon administration at appropriate doses
85.
Probiotics exert a wide range of beneficial effects such as host microbiome balancing, stimulation of immune system, enhancement of intestinal barrier function or inhibiting pathogens by direct interactions 40,
46,
86,
87 (
Table 1). Several microorganisms belonging to the family of
Enterococcus species (
E. fecalis, E. faecium),
Bifidobacterium species (
B. bifidum, B. longum, B. lactis),
Lactobacillus species (
L. acidophilus, L. casei, L. rhamnosus), and
Saccharomyces (
S. boulardii, S. cerevisiae) are considered as probiotics
40.
Probiotic supplementation causes significant reduction in the incidence of oral and respiratory tract infections 88,
89. Dietary supplementation of cow’s milk and fermented rice with
L. paracasei CBA L74 helps in prevention of common infectious disease including upper respiratory tract infections in children
90. Daily intake of fermented milk containing probiotic
L. casei strain ‘Shirota’ has been shown to reduce the incidence and duration of respiratory tract infections in healthy middle aged office workers and young children via modulation of the immune system
91,
92.
Daily ingestion of the probiotic L. paracasei ST11 can reduce the degree of virus replication and dissemination thereby attenuating lung inflammation and subsequent death in mice infected with vaccinia virus
95.
L. gasseri SBT2055 exhibits antiviral activity against human respiratory syncytial virus (RSV) by silencing SWI2/SNF2-related cAMP Response Element-Binding Protein (CREB)-binding protein activator protein, which is involved in RSV replication.
L. gasseri SBT2055 reduced the expression of proinflammatory cytokines in lungs upon RSV infection
96. CC chemokine receptor 2 acts as a receptor for monocyte chemoattractant protein-1 (MCP-1), which induces increased lung inflammation and subsequently decreases survival associated with influenza virus infection. Prophylactic oral administration of heat-killed
E. faecalis can protect mice from influenza virus infection and subsequent lung inflammation by modulation of MCP-1 production. Alternatively, lipoteichoic acid of
E. faecalis binds to toll like receptor 2 and exerts antiviral and anti-inflammatory activity during influenza infection
97.
Oral administration of probiotics L. paracasei, L. gasseri, and B. longum improved immune response and reduced mortality in influenza infected mice 105 by reducing the inflammation and oxidative stress associated with it
106,
107.
Probiotics, in combination with enteral nutrition, given to post-operative gastric cancer patients aids in increased production of antibodies and reduction of inflammatory cytokines 108. Oral administration of
L. plantarum ameliorates intestinal inflammation and lipid metabolism disorders by modulating gut microbiota in turn producing more SCFAs in high-fat diet induced obese mice
100. This disrupted enterohepatic immunoregulation, which can be ameliorated by intervention of
Clostridium butyricum B1 via its metabolite butyric acid
99.
Probiotic mixture of Lactobacillus and Bifidobacterium prevents the non-alcoholic fatty liver disease by suppressing systemic adiposity and inflammation through butyric acid and its receptor GPR109A
98.
Treatment with probiotic strain L. acidophilus DDS-1 upsurges the abundance of beneficial bacteria such as Lactobacillus spp and Akkermansia spp and also the levels of butyrate, while downregulating the production of inflammatory cytokines IL-6, IL-1β, IL-1α, MCP-1, Macrophage Inflammatory Protein (MIP)-1α, MIP-1β, IL-12 and IFN-γ in aging mice
101.
L. paracasei KW3110 suppresses hyperinflammation via activation of M2 macrophages and exhibit anti-inflammatory effects via suppression of IL-β production and caspase 1 activation by promoting IL-10 production
103. Probiotic complex of
L. acidophilus, L. casei, L. fermentum, L. paracasei, Streptococcus thermophilus, Bifidobacterium longum, B. bifidum, B. breve, L. rhamnosus, L. plantarum, L. helveticus, and
L. salivarius in combination with zinc and coenzyme Q10
can improve autoimmune arthritis via downregulation of proinflammatory cytokines including IL-6, IL-17 and TNF-α and inhibition of T-helper cell 17 (Th17) cell differentiation 109–
111.
Oral administration of B. infantis suppresses allergic inflammation in lungs by significantly reducing serum levels of Immunoglobulin (Ig)E, IgG1, IL-4 and IL-13 102 . Daily administration of
L. plantarum DR7 for 12 weeks can prevent development of upper respiratory tract infections among young adults through various mechanisms including inhibition of respiratory infection causing bacteria such as
Staphylococcus aureus,
Streptococcus pneumoniae,
Streptococcus pyogenes and
Streptococcus mutans, stimulation of proinflammatory cytokine production such as IL-10 and IL-4, and enhancement of antioxidant potential of RBC membrane
93. Significant reduction in the number of
Bifidobacteria and Lactobacilli along with increased number of
Escherichia coli is observed in the gut of children with recurrent respiratory tract infections. Oral probiotic supplement containing
Bifidobacterium infantis, L. acidophilus, E. faecalis and Bacillus cereus restored the intestinal flora along with reduction in incidence of respiratory tract infections and use of antibiotics
23.
