Acute respiratory tract infections (ARTI) place an enormous impact on patients and primary healthcare system due to their extraordinary incidence. In 2019, the world prevalence of ARTI reached 17.2 billion and accounted for 43.8% of all causes of the global disease burden [1]. Respiratory infections are the most common reason for seeking medical attention, with personal recurrence rates ranging from 2 to 6 times per year [2]. Although usually mild and self-limiting, ARTIs significantly affect work productivity and quality of life [3].

Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) brought a new challenge, being both common and severe, affecting upper and lower airways with considerable constitutional symptoms. As with other respiratory infections, the management of outpatients with mild COVID-19 without risk of progressing to severe disease, remains supportive and include close observation for early recognition of the life-threatening symptoms, reduction the risk of further SARS-CoV-2 transmission, advising on when to seek an in-person evaluation [4]. Absence of the effective specific measures in most COVID-19 cases serves a rationale for exploration of a new complementary approaches, one of which may be the use of probiotics.

Indirect evidence shows that patients with COVID-19 and diarrhea have more severe disease, increased concentration of inflammatory cytokines, markers of tissue damage, suggesting the intestinal cells can serve an additional entry and reservoir for SARS-CoV-2 [5, 6]. As with type II alveolar cells, intestinal and colonic enterocytes express angiotensin I converting enzyme 2 (ACE2), a receptor though which SARS-CoV-2 inoculates the body [7]. Bifidobacteria and lactobacilli adhering to enterocytes can hypothetically interfere with infection process and disease manifestation [8,9,10]. Interestingly that bacteria may potentially downregulate amide and peptide metabolism in the gut including angiotensin-converting enzyme 2 (ACE2) [11, 12]. It may explain the reason that cell cultures exposed to probiotics yielded lesser amount of transmissible gastroenteritis coronaviruses [13]. Additionally, the beneficial effects of probiotics in respiratory infections can be realized via several non-specific mechanisms discussed within the gut-lung axis paradigm [14], including enhancement of innate antiviral immune defense [15]. A recent systematic review of 23 randomized clinical trials involving a total of 6950 participants with ARTI, demonstrated fewer cases, shorter case duration, and reduced antibiotic prescription rates in patients taking probiotics [16].

The objective of this study was to assess the role of short-term ingestion of probiotics in mild symptomatic COVID-19, post-disease symptoms, and humoral immune response to SARS-CoV-2 in outpatients.