Evaluation of the effect of kefir supplementation on inflammatory markers and clinical and hematological indices in COVID-19 patients; a randomized double-blined clinical trial

In December 2019, a pneumonia outbreak occurred in Wuhan, China, which its origin was not known at first, but later after the isolation of a new respiratory virus related to SARS-CoV, it was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. This disease has infected more than 600 million people and killed more than 6,470,000 people worldwide, until August 2022 [2]. Although a continuous effort has been made to find effective medication therapies and vaccines for the treatment and prevention of this disease, which is still ongoing, nutritional strategies to strengthen the immune system for better prevention and treatment and to reduce the complications of this disease are of particular importance [3], [4]. The human immune system is the first line of defense against viruses and diseases, and several immune response mechanisms are involved in the body's defense when pathogens attack, and nutrition has a great effect on strengthening these immune response mechanisms against pathogens [5]. It has been shown that the risk of mortality and adverse inpatient events in adults with COVID-19 is significantly higher in patients who have nutritional problems or are malnourished [6]. Malnutrition or the risk of malnutrition is also associated with excessive inflammation and immunosuppression in COVID-19 patients and may contribute to the progression of the disease and exacerbation of its complications [7]. Therefore, nutrients that can potentially increase immunity against the coronavirus (COVID-19) and reduce the risk of contracting the disease or the speed of the factors that cause it, are of great importance in the prevention and treatment of infected patients [8], [9], [10]. The nutritional status and diet have a great impact on the process of the COVID-19 disease, which is mainly due to the bidirectional relation between the gut microbiota and the lung, or the gut-brain axis, which may aggravate clinical outcomes in viral respiratory infections [11]. In the infection caused by COVID-19, the integrity of the gut microbiome is lost, and the extent of which is related to the severity of the disease, and in people with underlying diseases in which the intestinal permeability is increased and the diversity of the intestinal microbiome is reduced, a poor prognosis has been observed [12]. Also, the immune function of the human body is highly dependent on specific nutrients in the diet and bioactive compounds in the foods [13]. Despite the contradictory and limited studies, in general, probiotic fermented dairy products can have preventive and ameliorating effects on various pathophysiological disorders in the body [14]. Modulation of the gut/lung microbiome due to the immunomodulatory properties of probiotics and prebiotics could be helpful as an adjunct to the prevention/treatment of COVID-19 patients [15]. Fermented foods, which have been recommended in studies as nutrients to strengthen the immune system against contracting the disease of COVID-19, in addition to having nutritious properties, by helping to digest other foods and also increasing antioxidant activity, help strengthen the immune system [16]. Studies have shown that certain fermented foods and probiotics can provide vital microbes with the ability to enhance gut immunity, while prebiotics can improve gut immunity by selectively stimulating normal gut flora microbes [3]. It is also said that the probiotic-enriched foods market, including fermented dairy products, has expanded progressively during the pandemic period due to their potential immune-boosting properties [17]. Studies have shown that regular consumption of fermented dairy products, including kefir, is likely to be effective in improving immune defenses in the gut [18]. Kefir is a fermented drink that can be prepared at home cheaply and can improve the host's immunity and reduce the possibility of viral infections [19], [20]. This product is one of the widely used traditional fermented dairy products, which has many complex probiotic and nutritional compounds. Kefir grains contain casein and other milk solids along with yeasts and lactobacilli, which are the characteristic factors of kefir fermentation and can act as a starter to induce fermentation when combined with fresh milk [21]. Available research data show a strong relationship between regular consumption of kefir and its effects on improving health, especially its effect on improving the immune system and its antiviral effects due to its probiotic strains and bio-functional metabolites [22]. As an anti-inflammatory agent, kefir can reduce the expression of IL-6, IL-1, TNF-α, and interferon-γ, therefore, kefir may be an important inhibitor of the "cytokine storm" to prevent complications of severe COVID-19 [23].

To the best of our knowledge, no study has assessed the effects of kefir supplementation as a probiotic product on clinical outcomes and inflammatory markers in COVID-19 patients. Given the limited data, we aimed to investigate the effect of kefir consumption compared with non-kefir on the inflammatory and clinical indicators and also hematological indices among COVID-19 patients.

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