Vitamin C (VC), also known as ascorbic acid, is known for its antioxidant properties. This characteristic of VC appears to play an essential role in modulating elevated levels of oxidative stress like infections and cancers. Infections lead to an activation of our immune system, which releases various oxidizing agents grouped as Reactive Oxygen Species (ROS). Though these ROS are useful to deactivate the microorganisms, they prove to be detrimental to the host cells [15]. The duration of mechanical ventilation is reduced by 14% in a recent trial among 685 patients with the use of VC. Another multi-centric study confirmed the reduction in ventilation time by 25% with the dosage of 1-6g/day of VC in patients treated in critical care [16-18]. With a pandemic like COVID-19, additional safe, cost-effective, and immune-supportive strategies, such as VC, may be warranted to protect individuals and populations against developing a severe disease [19]. Thus, VC can be a potential prophylactic and therapeutic target for severe ARDS in COVID-19 patients [20]. Fowler et al. [21] and Wang et al. [22] suggested that VC has a therapeutic role in critically ill patients. Studies conducted by Hemilä et al. [23] and Messina et al. [24] point towards the promising nature of VC in effectively improving the morbidity and mortality of patients in regard to COVID-19. With the rise of epidemics like COVID-19, additional safe, cost-effective, and immune-supportive strategies, such as VC, may be warranted to protect individuals and populations against developing a severe disease [21-26]. Furthermore, previous evidences of VC to reduce the ICU stay and morbidity of patients in critical care with conditions like ARDS, sepsis, burns, trauma and respiratory failure, give an opportunity to investigate the role of VC in similar situations related to COVID-19 [27-35]. Though the studies differ in doses used in the treatment of critical patients with the coronavirus, VC definitely seems to improve the outcomes (Table 1).

The role of Vitamin D (VD) in providing immunity is unclear. The potential mechanisms include antiviral immunomodulation, induction of autophagy and apoptosis, and genetic or epigenetic regulation. Furthermore, the risk of viral infections can be reduced by VD. In addition, it has been observed in COVID-19 patients, that it works by enhancing the release of cytokines (pro-inflammatory) by the T helper type 2 cells, which will cause a diminution (anti-inflammatory) of the functioning of the T helper type 1 cells during various bacterial and viral crises [36, 37]. The high prevalence and outbreak of COVID during the winters raise the suspicion that there could be a relationship between VD deficiency and the infection leading to the high mortality rates in the elderly populations, who are known to produce lower amounts of VD, as compared to younger individuals when regularly exposed to sunlight [38]. Various studies have suggested that there exists a relationship between VD deficiency and COVID-19, thus suggesting it might act as an aid to decrease the fatal nature of the virus. Nair et al. and Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention interpret age as a risk factor for VD deficiency, which, if appropriately supplemented with VD, will improve COVID-19 outcomes. Similar studies report the association of low VD levels and positive blood cultures that might impact the severity of the condition [39-44]. More studies need to define VD deficiency and groups prone to the deficit in relation to the coronavirus in order to prevent and cure it (Table 2).

Vitamin A (VA) is a fat-soluble compound, which plays an essential role in many physiological functions like embryonic development, vision, immunity, cellular differentiation, and proliferation [45, 46]. WHO stated in an article that VA supplementation improved the outcome of respiratory infections in nutritionally challenged children [47]. It is a fact that VA improves the clinical results in patients affected by measles associated pneumonia. However, some studies show that low doses of VA are associated with a low risk of respiratory infection [48]. Though these results have not been consistent, VA still does not have an established role in epidemics like COVID-19. VA seems to have an effective role in improving the morbidity of COVID-19 cases by alleviating the functions of neutrophils, natural killer cells, monocytes or macrophages, T cells, and B cells [49]. Therefore, the role of VA in COVID-19 treatment remains inconclusive.

The European Micronutrients recommendations network of excellence (EURRECCA) has stated that selenium plays a crucial role in five significant functions like cognition individuals aged >50 years, viral load and onset of Acute Respiratory Distress Syndrome (AIDS) in Human Immunodeficiency Virus (HIV) positive patients, immune functions, male fertility, and cancer (particularly for persons at risk of prostate cancer) [50]. Supplementing a moderate dose of selenium can strengthen cellular immunity, humoral immunity, and nonspecific immunity. Thus, its deficiency can impair immunity and is a potential form of protection for the prevention and therapies of infections of the respiratory system [51]. Selenium is known for its remarkable redox biology when it comes to neutralizing the release of the reactive oxygen species in the reaction to infections in the body. Numerous studies indicated the implication of its deficiencies with the evolution of various infections, cancers, neurodegenerative diseases, and cardiovascular diseases [50]. With the rise of infections like COVID-19, it is possible to say that selenium can have a protective and therapeutic role in improving morbidity rates. Selenium had improved effects after an influenza vaccine challenge [52].

A correlation between low selenium levels and an increased risk of COVID-19 related mortality has been found in China, leading to worse outcomes [53]. Thus, blinded randomized controlled trials are needed to explore the correlation between COVID-19 and selenium.

Dietary zinc deficiency in developing countries is widespread and often exacerbated by acute and chronic infections. It is a necessary component of numerous metalloproteins, including those critical for DNA replication and cell division, and is crucial for maintaining immunological integrity, predominantly cellular immunity and antioxidant activity. It is also associated with growth, impaired immunity, learning disabilities, and anorexia [54]. Studies show that children with Zinc deficiency are at an increased risk of respiratory tract infections. Many mechanisms have been implicated in the role of zinc deficiency in causing an increased susceptibility to Acute Respiratory Infections (ARI’s). Zinc plays a vital barrier role in the cohesiveness of respiratory epithelial cells and controls the secretion of pro-inflammatory cytokines. Improved immunity has been confirmed with high dose Zinc supplementation for Torque Teno Virus (TTV) [55].

It is reported that Zinc supplementation could play a key role in preventing ARI in developing countries. It is supposed to lower the duration of respiratory tract infections, the number of episodes, the severity of bronchiolitis, and pneumonia [56]. But, this effect was minimal when other cases specific filters were applied [57]. Hence, the role of zinc in pandemics like COVID is unclear.

“Probiotics” are live microorganisms that are supposed to be beneficial to the health and well-being of an individual when ingested or applied to the body. The Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) have described probiotics as “live microorganisms which confer a health benefit on the host when administered in adequate amounts” [58]. The most commonly used probiotics are Lactobacilli and Bifidobacteria strains, and the yeast Saccharomyces boulardii. Some reports contemplate the use of probiotics in COVID-19. In a recent study, Trompette et al. stated that improving the diet quality in a susceptible COVID-19 individual could mitigate the risk of significant infection and complications [59]. Morrow et al. [60] conducted randomized controlled trials and reported that critically ill patients on mechanical ventilation if given probiotics (i.e., live Bacillus subtilis, Lactobacillus rhamnosus GG, and Enterococcus faecalis) developed significantly less ventilator-associated pneumonia compared with the patients who were on placebo [60]. There is also an indication that probiotic strains maintain equilibrium between pro-inflammatory and immunoregulatory cytokines, which aid in viral clearance while reducing immune response-mediated lung damage, which might be of particular interest in preventing ARDS, a significant complication of COVID-19. An RCT with Lactobacillus Plantarum DR7 diminished plasma pro-inflammatory cytokines (IFN-π, TNF-α) in middle-aged adults (30 to 60 years of age) and boosted anti-inflammatory cytokines (IL-4, IL-10) in young adults (30 years of age), supplemented by reduction of plasma peroxidation and oxidative stress compared with placebo [61]. This finding might be helpful, as it shows to inhibit the cytokine storm occurring in COVID-19 patients. Lactobacillus acidophilus and Bacillus clausii in the animal study did not show any reduction in the expression of coronavirus receptors in the murine small intestine when compared with the control and the post-Salmonella infection models. Feng et al. conducted animal studies and found that coronaviruses receptors could increase in the presence of both invasive bacteria and their counterpart, probiotics (Lactobacillus acidophilus and Bacillus clausii) in the murine small intestine with control and post-salmonella infection models [62]. Due to a lack of substantial data, further clinical trials are warranted to understand the effect of probiotics in COVID-19.

Polyunsaturated Fatty Acids (PUFA) are classified into two classes, the Omega-6 (N-6) family of PUFA (e.g., linoleic acid, arachidonic acid) and the Omega-3 (N-3) family (e.g., alpha-linolenic acid, Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA). Such distinct groups of fatty acids have been extensively studied to understand their effects on cardiovascular and metabolic health, and cancer [63]. It is recognized that ω-3 PUFAs have anti-inflammatory properties and play an essential role in the body’s inflammation resolution [64]. In several lung infections, the administration of PUFA can improve the patient’s outcome in acute pneumonia. Sharma et al. reported in their study that the dietary supplementation of ω-3 PUFA supplementation exerts an overall beneficial effect against acute experimental pneumonia. This mechanism is operative through the up-regulation of nonspecific and specific host immune defenses [65]. Jones et al. concluded the susceptibility of poxvirus infection of mice was not affected by dietary fats utilization [66]. Dushianthan et al. [67] examined the effects of omega-3 fatty acids and antioxidants in adults with ARDS (a significant complication in COVID-19). The study showed an ambiguity in regards to the consumption of omega-3 and other antioxidants and their benefits towards the improvement of ICU length of stay and duration of ventilator days. They further concluded that the intervention of omega-3 usage produced a minuscule or no difference in all-cause mortality [67]. Considering the scarcity of data on hand, we have to rely on the results of ongoing trials to establish the role of ω-3 supplementation in ARDS and COVID-19.

Polyphenols are natural plant compounds and are generally involved in the defense against ultraviolet radiation or pathogenic aggression. Over the last decade, the possible health benefits of dietary plant polyphenols as an antioxidant have been of great interest. The main classes of polyphenols are phenolic acids, flavonoids, lignans, and stilbenes. Out of these, one of the most prominent phenols is the class flavonoids. The benefit of continuing the use of polyphenols against cancer growth, cardiovascular disorders, diabetes, osteoporosis, and neurodegenerative diseases was implied in recent epidemiological studies. Their key role in being anti-inflammatory, anti-mutagenic, antioxidant, and anti-carcinogenic is diverse [68]. The summary of the use of flavonoids and polyphenols in COVID-19 is exhibited in Table 3. Bhowmick et al. [69], and Adem et al. [70] reported the binding of flavonoids and polyphenols to the receptors of SARS-CoV-2, subsequently inhibiting it at a molecular level. They also proposed the affinity of flavonoids towards the ACE-2 receptor [69, 70]. Ang et al. [71] reported the use of Armeniacae semen, which was the most frequently used herbal supplement reducing the hyper-responsiveness on the airways for the treatment of pediatric COVID-19 in the Chinese population [71].

Bhatia et al. [72] suggested the use of “Black Tea,” a theaflavin, in the routine diet as it is an inexpensive and easily accessible source of polyphenols. Polyphenols in black tea could potentially stop the replication and transmission of viruses and could be useful in the current health emergency state. The study suggested that patients quarantining at home with mild symptoms of COVID-19 can include these polyphenols in their diets. This dietary supplement could augment their physiological response against COVID-19. In-vitro testing should be conducted to assess the effectiveness of these polyphenols in the supportive treatment of COVID-19 [72].

Curcumin is a chemical with potent anti-inflammatory and antioxidant properties, popularly found in turmeric. These novel compounds have been proposed as an adjunctive therapy on social media. Jena et al. depicted the role of curcumin and catechin in binding to the S-protein at the location where host cell binding is known to occur. Similarly, they documented the attachment of these molecules to ACE2 sites that served as a viral entry medium. The study concluded that curcumin has the potential to block the entry of viral protein by inhibiting the host cell receptor and virus binding [73].

On 14^th April 2020, MGC pharmaceuticals announced the approval from the Human Research Ethics Committee ('Ethics Committee') of Nazareth Hospital EMMS in Israel to implement a Phase II placebo-controlled clinical trial to determine the safety and efficacy of a natural anti-infective formulation ('ArtemiC' or 'Product') in patients infected with COVID-19 [74].

Colloidal silver is composed of small silver particles in a liquid marketed as a dietary supplement claiming to have antiviral properties. There is, however, a shortage of evidence to support arguments related to its benefits. In reality, colloidal silver can be hazardous to one's health. Zachar et al. [75] concluded that successful Minimum Inhibitory Concentration (MIC) was achieved in both the bronchial tree and the alveoli after investigating its effect in specific locations of the respiratory system during viral and bacterial infections. They concluded that successful MIC was achieved in both the bronchial tree and the alveoli. This approach was proposed as a first-line treatment to suppress the progression of the SARS-COV-2 infection in the respiratory system [75]. Further studies are needed to support this hypothesis.