This study showed that dietary fiber intake in COVID-19-infected patients was significantly lower than in the non-COVID-19 group. It was also demonstrated that dietary intake of starch and total sugar was significantly associated with increased odds of COVID-19. On the other hand, fiber intake was significantly associated with decreased odds of COVID-19-related hospitalization. The results of the dynamical system analysis also revealed that participants who consumed cholesterol, total sugar, and PUFA above the calculated cut-off had a greater chance of future risk of COVID-19. At the same time, fiber intake above the cut-off showed a protective role.

Based on our results, dietary intake of total sugar was associated with increased odds of COVID-19. Carbohydrates with high glycemic index and subsequent acute insulin response lead to an overload of mitochondrial capacity and increased production of free radicals. Also, the consumption of simple carbohydrates causes an immediate increase in inflammatory cytokines and C-reactive protein [13]. Increased inflammatory responses and oxidative stress promote dysregulation in the innate immune system, resulting in an increased risk of infections [14].

According to the study results, dietary intake of fiber was significantly lower in COVID-19 patients, and each unit increase in dietary intake of fiber was associated with 1% decrease in the odds of hospitalization due to COVID-19. Dietary fibers are important factors regarding immunomodulation and decrease inflammation. A significant decrease in hs-CRP concentration has been reported with increasing fiber consumption [15]. Dietary fiber can also have a prebiotic effect by stimulating the growth of beneficial microbes such as Lactobacillus sp. and Bifidobacterium sp. and inhibiting pathogens such as Clostridium sp. [16]. In a study conducted by Hegazy et al. [17] on 200 patients with COVID-19, daily consumption of foods containing prebiotics, less sugar, regular exercise, adequate sleep and fewer antibiotic prescriptions led to a milder disease and faster clearance of the virus. Fiber sources and prebiotics indirectly affect the immune system by changing the composition and population of the gut microbiota [18]. In addition to changes in gut microbiota composition, prebiotics and most fibers can cause significant changes in the immune system by raising the expression of anti-inflammatory cytokines while decreasing the expression of pro-inflammatory cytokines [19, 20]. In an interventional study, Zhang et al. [21] investigated the effect of a new formula of bifidobacteria strains, galacto-oligosaccharides, xylo-oligosaccharides, and resistant dextrin (SIM01) in patients with COVID-19. They observed that patients receiving SIM01 developed significantly more SARS-CoV-2 IgG antibodies by day 16 than controls, and at week 5, plasma levels of IL-6, monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), TNF-α, and IL-1RA significantly decreased in SIM01 but not in the control group.

The beneficial effects of prebiotics are believed to be mainly induced by increasing short-chain fatty acids (SCFA) production and strengthening the immune system of the gastrointestinal tract. It has also been found that prebiotics such as wheat bran, fructo-oligosaccharides, and galactosaccharides are known to raise butyrate levels, thereby decreasing inflammation and improving asthma and cystic fibrosis conditions [22, 23]. It is evident that dietary fiber-mediated modulation of gut microbiota and even lung microbiota can affect immunity and decrease the severity of viral infection in both the gastrointestinal and respiratory tracts [24]. Since fibers and prebiotics are generally safe, this microbiome therapy may improve and accelerate the recovery of patients with COVID-19, with less need for hospitalization.

Considering the dynamic system results, cholesterol consumption above the daily cut-off of 180 mg was associated with an increased risk of COVID-19. Cholesterol-rich food, often provided by unhealthy diets, affects the inflammatory markers and lipoprotein metabolism, modulating the lipoprotein profile. Based on animal and human studies, a high-cholesterol diet may increase the risk of pulmonary bacterial infections. Dietary cholesterol may also aggravate viral infections [25]. Our results also showed that patients who consume PUFAs above the cut-off are more susceptible to COVID-19. Among nutrients, omega-3 PUFAs are known to resolve inflammatory responses and support the immune system. In vivo and in vitro studies support the beneficial role of omega-3 PUFAs in lessening COVID-19 complications [26]. Conversely, eicosanoids from omega-6 (ω-6) PUFAs increase inflammatory responses [27]. Generally, it should be considered that excessive intake of PUFAs may be associated with dyslipidemia, dysregulation of glucose homeostasis, and immunosuppression [26].

This study had some limitations. First, we determined the COVID-19-positive patients based on PCR-positive results performed in all related clinical sites in Mashhad. We considered all other patients without a PCR-positive result as COVID-19-negative. It should be considered that some patients affected by SARS-COV2 are asymptomatic or may not perform a PCR test. Besides, our study has not considered the frequent infections with SARS-COV2 in individuals. Besides, although 24-h dietary recall can be used to assess dietary intakes of the population, it is not the ideal instrument to investigate the association of diet as an independent variable with health outcomes. Another limitation was that we excluded subjects with dietary missing data, which may affect the generalizability of our results. It should also be noted that some medical conditions such as diabetes or impaired glucose tolerance can be related to the risk of COVID-19 and its severity that have not been included in our analytical models.

During the COVID-19 pandemic, plenty of studies have been published on dietary changes due to COVID-19 and mechanistically or clinically reviewing the importance of nutrition in preventing or managing COVID-19. There are few studies concerning the effect of nutritional intake on COVID-19 susceptibility and severity. In this study, we evaluated the impact of previous dietary intakes on COVID-19 infection during the pandemic period. Another strength point of this study was that we applied advanced dynamical system analysis methods to predict the risk of COVID-19 in the future. Although COVID-19 is now subsiding in our region, the results of this study may help prevent and better manage the future new emerging infectious disease crisis such as COVID-19.