Background: Recently specific interactions and crosslinks between the gut microbiota and the lungs have been recognized, particularly with regard to respiratory immune and anti-microbial reactions. This is often known as the “gut-lung axis” or “a common mucosal immunological system”. Objective: The aim of the current systematic review was to evaluate evidence, from published clinical trials and cohort studies, if probiotics may have an effect in improving and managing COVID-19 symptoms. Materials and methods: The available studies were searched through a comprehensive search of electronic databases that included PubMed, Science Direct, Scirus, ISI Web of Knowledge, Google Scholar and CENTRAL (Cochrane Central Register of Controlled Trials), using a combination of the following keywords: “COVID-19" OR "SARS-CoV-2" AND "Microbiota" OR "Probiotics” OR “Gut Lung Axis”. The literature was reviewed until August 31, 2022. Results: Only 3 studies were included. One of them evaluated the efficacy of probiotics in COVID-19 patients to obtain complete remission of all signs and symptoms. The clinical trial proves that probiotics have a significant effect on complete remission of all signs and symptoms of COVID-19 patients with statistical significant difference. Only one clinical trial out of the 3 included studies had evaluated the need for O2 therapy during the study between the probiotics and control groups, but without statistical significant difference. No statistical significant difference between the probiotics group and placebo group was observed regarding fatal prognosis during the only clinical trial that measured death as an outcome. Conclusion: We couldn’t judge on these results as they are insufficient data for pooling and meta-analysis. However, what we can say is “Most probably Probiotics have no role in treatment of COVID-19 infection”.

Probiotics, prebiotics, and synbiotics modify various aspects of local and systemic immune function in multiple experimental models. However, their impact and mechanisms of action are not known across all products or noticed in every population studied, and impacts on in vitro, ex vivo, or other measures of immune function do not necessarily result in an impact on infection and illness in vivo. Studies have discussed that intestinal microbiota has an essential role in enhancing the immune system against viruses. The regulatory impact of the intestinal microbiota on viral infection is connected with local and systemic immune responses and plays a part in congenital and adaptive immune responses. The microbiota composition critically modulates the production of virus-specific CD4 and CD8 T cells and antibody responses following influenza virus infection. The intestinal microbiota has an important role in the stabilizing of immune homeostasis by augmenting the integrity of the barrier functions of the gut mucosa, which is a crucial aspect of systemic immunity. In conclusion, the intestinal microbiota can influence organismal immunity locally and systemically, proximally, and distally. Studying the possible mechanism by which the intestinal microbiota maintains host immunity can provide a clearer understanding of the occurrence and development of diseases.

CoV-2 disease 2019 (COVID-19) pandemic has exerted a great burden on the health and economic systems worldwide. One of the most important factors that affect the severity and prognosis of COVID-19 is the occurrence of hyperstimulation of the immune system resulting in “cytokine storm”. Similar to SARS-CoV, an intracellular complex called nod like receptor family pyrin domain containing 3 (NLRP3) inflammasome was found to be activated by SARS-CoV-2, then in turn stimulates several interleukins and initiates the inflammatory cascade. In addition, other inflammatory mediators such as interferons e.g., IFN-α, and IFN-γ, interleukins e.g., IL-1β, IL-12, IL-18, tumor necrosis factor-α (TNF- α), and chemokines e.g., CCL2, CXCL10 have been reported in severely ill patients. These mediators represent the corner stone in developing cytokine storm that results in uncontrolled systemic inflammatory reaction with subsequent acute respiratory distress syndrome (ARDS), multiple organ failure and eventually death. Based on its anti-inflammatory effects, colchicine has also gained attention to be utilized in the management of COVID-19 patient. Colchicine exerts its anti-inflammatory effect through inhibition of formation of microtubules which is considered an essential step in several cellular processes such as division, signalling, and migration. Also, colchicine affects the cytokine cascade by inhibiting IL-1β leading to reduction in neutrophils recruitment, free radicles production and inflammasome stimulation. This raises the concerns about the effectiveness of colchicine in COVID-19 treatment and the possibility of providing an improvement of the clinical course of the disease.