Pathogenesis of COVID-19

Coronavirus disease 19 (COVID-19/2019-nCoV) caused due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The increasing spread and transmission through the contact of aerosol droplets from infected persons have put the whole scientific and medical community on alarm. Covid -19 has very complex pathogenesis. CoVs are positive-stranded RNA viruses with nucleocapsid and envelope. The nucleocapsid (N) protein holds the RNA genome, and the S, E, and M proteins together create the viral envelope. The viral RNA hijacks the host cell’s machinery to initiate the viral genome replication and polypeptides chain synthesis and form the replication-transcription complex (RCT) needed to synthesize the sub-genomic RNAs as well as structural proteins (envelope and nucleocapsid) The viral envelope has a crucial role in the viral assembly, release, and promoting viral pathogenesis .^1,2 COVID-19  infection is associated with reduces the antiviral and innate immunity of the host, induces oxidative stress which disturbs body’s homeostasis and redox balance which triggers the stress-dependent kinases induction causing inflammation and damage to various organs causing the acute lung injury, tissue fibrosis, and pneumonia. ³

Presently, various vaccines, drugs are being evaluated and undergoing preclinical and clinical studies to identify and develop an exact medicine to combat the COVID-19 pandemic. In this context, different natural products including, health drinks, food supplements, energy drinks have proved to be beneficial in enhancing immunity and acting as antioxidant, anti-inflammatory, antiviral and antibacterial supplements have also gained interest throughout the world. Most of these include vitamin A, B, C, D, curcumin, selenium, quercetin, etc. which may help as immunity boosters, prevent virus spread, preclude the disease progression to the severe stage providing both prophylactic and therapeutic support against COVID-19.

Vitamin C helps in various functions of the immune cells and enhances protection against any infection. Studies have shown that Health drinks containing vitamins decrease the duration and severity of upper respiratory infections (mostly viral infections), including the common cold. The total recommended daily allowance (RDA) for VC is 60 mg. Various spices, herbs, fruits, and vegetables like turmeric, Centella, amla, orange, mango are loaded with Vitamin C . Vitamin C acts as a potent antioxidant and helps to maintain the redox homeostasis inside the cell prevents lipid peroxidation, and protein alkylation and prevent damage of cells due to ROS or RNS during the oxidative burst. Studies also have revealed that administration of VC in combination with quercetin provides synergistic antiviral, antioxidant and immunomodulatory effects.^4,5 Some clinical studies have shown overall recovery in high risk and mildly symptomatic patients when 250-500mg quercetin and 500mg Vit C when administered orally twice a day for 7 days and 500 mg quercetin and 3 g of vitamin C twice a day for 7 days in ARDS patients (assisted ventilation/intubation) improves the overall recovery in SARS-CoV-2 subjects.⁶  Hence food supplements, health drinks having Vitamin C may help to boost the immunity and also  anti-inflammatory, antioxidant effect against SARS-CoV-2 infection .⁷

Curcumin exhibits a wide series of pharmacological activities ranging from, antibacterial, antiviral, antifungal, antioxidant and anti-inflammatory activities. Animal models disclosed that curcumin supplementation may help in interrupting various respiratory diseases, more specifically, acute respiratory distress syndrome (ARDS), acute lung injury, pneumonia, pulmonary fibrosis, and sepsis by modulating inflammation and oxidative stress. ⁸ It is active against both RNA and DNA viruses.⁹ Recent studies reveal that curcumin has the potential to inhibit ACE2, modulates characteristics of the lipid bilayer, as well as viral S protein inhibiting the entry of the virus into cells, inhibits the viral protease, stimulates host interferon production to activate the host innate immunity, etc.¹⁰

Quercetin, also found in Amla has potent antioxidants with anti-inflammatory and antiviral activity. It was reported to inhibit TNF-α production in LPS-induced macrophages, 11   inhibit IL-8 production in lung A549 cells 12, and also reduce the mRNA levels of TNF-α and IL-1α in glial cells 13. Animal studies have shown that quercetin decreases the production of cyclooxygenase (COX) and lipoxygenase (LOX) enzymes in rat liver epithelial cells 14. Studies have revealed the antiviral effects on both RNA and DNA viruses by inhibiting the virus entry and viral-cell fusion15 and reduces the expression of pro-inflammatory cytokines and lung inflammation induced by rhinovirus in mice¹⁶.

Vitamin A is essential for providing the intestinal immune response. It may play a vital role fighting against viral diseases, including COVID-19 owing to its pulmonary, immunomodulatory, and antimicrobial roles of Vitamin A has been implicated in modulating the pathogenesis of ARDS, influencing the production of IL1-β and IL-1 receptor antagonist by alveolar macrophages, and the subsequent pulmonary infiltration of neutrophils. An animal study using Vitamin A with Simvastatin showed increased pulmonary regeneration. Vitamin A is effective as an antioxidant and antivirals. ¹⁷

Vitamin B complex and folic acid both play important and complementary roles in both innate and adaptive immune responses. Vitamin B6 helps in the formation and migration of lymphocytes into the intestine and enhances the cytotoxic effects of natural killer cells NK cells) and restricting the spread of any infection. Vitamin B12 facilitates the One-carbon (1C) metabolism and supports many physiological processes together with the folate cofactor. Together with folic acid It helps in the formation of red blood cells and white blood cells and helps in limiting any infection and enhancing immunity. Folic acid is also essential for antibody production and metabolism. Fimognari et al. reported lower levels of folate and vitamin B12 in chronic obstructive pulmonary disease (COPD) patients. ^{17, 18}

Vitamin D is also essential for maintaining immunity. Animal models showed that that vitamin D decreased microbial ALI and ARDS by modulating the expression of the renin-angiotensin system (RAS), including ACE 1 and 2. A meta-analysis study showed of vitamin D supplementation and the risk of acute (bacterial and viral) respiratory tract infection showed a 12% overall protective effect of vitamin D supplementation. This increased to 19% with a daily or weekly consumption and further increased to 70% protective effect was observed when deficiency was corrected.¹⁷ Thus, maintaining a diet containing a balance of vitamins obtained from natural sources may help to boost the innate immunity, provide antioxidant and anti-inflammatory to better fight the covid-19 pandemic.

References:

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