Various acute respiratory tract infections caused by viruses, including respiratory syncytial virus, enterovirus, pneumonia-causing viruses, adenovirus and influenza virus, are the main causes of debility and death worldwide [1]. The main causative agent for these respiratory tract infections (RTIs) are DNA/RNA viruses. However, the RTIs associated with RNA viruses are more virulent in comparison to those that are caused by DNA viruses [2]. Specifically, coronaviruses belong to a highly significant re-emerging RNA virus family, causing serious life-threatening respiratory infections [3]. Ever since the onset of the infectious coronavirus disease (popularly known as COVID-19) in Wuhan city of China, the pandemic has increased rapidly in 57 countries, with over 276 million COVID-19 cases and over 5.37 million deaths reported as of 27 December 2021. Additionally, imposing several socio-economic, proper feedback strategies and rigid public health measures globally, involving social distancing, mask wearing, personal hygiene, quarantines, and lockdowns, the number of infections and death due to SARS-CoV-2 virus are constantly rising [4].

Given the continuous evolution of the virus that leads towards SARS-CoV-2, WHO, in collaboration with researchers, national authorities, institutions and expert networks, monitored the emergence of variants that posed an increased risk to global public health and prompted the characterization as Variants of Interest (VOIs) and Variants of Concern (VOCs). Currently, using comparative assessment strategies, WHO labeled five variants as VOCs Alpha (United Kingdom, September-2020), Beta (South Africa, May-2020), Gamma (Brazil, November-2020), Delta (India, October-2020)and Omicron (Multiple countries, November-2021), while Lambda (Peru, December-2020) and Mu (Colombia, January-2021) were labeled as VOIs.

With the continuous boost from WHO, current ongoing research trends and developmental attempts are completely focused on developing effective therapy to counter the novel virus [5]. In this direction, anticoagulants, convalescent plasma, Hydroxychloroquine, Remdesivir, Vasodilators, non-steroidal anti-inflammatory drugs, monoclonal antibodies and Lopinavir/Ritonavir are in distinct phases of trials, research, or approvals. However, none of the above treatments are completely effective against the virus ^[6][7][8][6,7,8]. In the absence of potent and efficacious vaccines and medicines, the virus is severely transforming and exhibits symptomatic, pre-symptomatic and asymptomatic forms in the affected population. Both asymptomatic and pre-symptomatic exemplifications are certainly one of the principal reasons for the pandemic [9]. Moreover, WHO released an assessment that this novel disease might persist in staying with the global population for a prolonged period. Therefore, proper investment and constant preparedness in public health and other resources are required for supervising the spread and morbidity caused by SARS-CoV-2.

The novel COVID-19 exhibits wide diversity in disease severity, spanning from minor and ill-defined common cold-like symptoms to pneumonia, and then can lead to life-threatening complications such as acute respiratory distress syndrome (ARDS) and multiple organ failure [10]. The proliferation and transmission of SARS-CoV-2 are caused through respiratory droplets; however, Ng et al. reported that the gut could also play a major role in the pathogenesis of COVID-19 [11]. Moreover, it was also reported that some coronaviruses, including the present SARS-CoV-2, could infect enterocytes, thus plating as a potential reservoir for virus proliferation [12]. Altogether, few clinical reports have revealed that gastrointestinal symptoms are conventional in COVID-19-infected patients, and in few cases, it leads to disease severity ^[13][14][13,14]. In addition, current pandemic control measures and practices to manage pandemics implement long-term effects on the human microbiome across the world, given the imposition of fleeing endemic areas, physical distancing, scapegoating of certain groups, mask-wearing, personal hygiene, quarantines, and lockdowns that influence overall microbial loss and inability for reinoculation. Rapid depletion and reduction of microbes over generations may lead to the extinction of microbial species ancestrally associated with humans; species may be permanently lost from the microbial pool unless reinoculation from other sources occurs ^[15][16][15,16]. In this context, various reports have suggested probiotic strains as promising therapeutics to enhance human immunity, thus inhibiting pathogens colonization and further minimizing the incidence and intensity of the infections. Moreover, little clinical evidence also illustrated the significance of probiotics in preventing viral and bacterial infections, including RTIs, sepsis, and gastroenteritis [17].

Keeping in view the enormous health and economic burden, repurposing the usage of natural compounds such as probiotics and prebiotics can be an effectual therapeutic approach in blocking and/or reducing SARS-CoV-2 severity. In this review, we describe the existing curative and preventive trial studies focused on the usage of probiotics and prebiotics to combat viral infections. Moreover, the possible application of probiotics bacteria as a prophylactic approach against COVID-19 is also outlined in the present study.