Coronavirus disease 2019 (COVID-19) - an international public health emergency declared by the World Health Organization [1], has massively spread across 210 countries & territories around the globe [2]. Several generations have been exposed to COVID-19 at different stages of life. [3]
COVID & Digestive Symptoms – Eyes will see what the mind knows !!
Although COVID-19 most commonly presents with respiratory symptoms, such as cough and shortness of breath, there is evidence that the illness can also present with non-respiratory symptoms, most notably digestive symptoms such as diarrhoea, diminished appetite, and nausea [4]
Expression of SARS-CoV-2 virus in the Digestive Tract
The digestive symptoms of COVID-19 likely manifest because the virus enters the target cells through angiotensin-converting enzyme 2 [5], a receptor found in the gastrointestinal tract - both the upper and lower, where it is expressed at nearly 100-fold higher levels than in respiratory organs [6]. Viral nucleic acid was reported to have detected in feces in over half of the patients infected with COVID-19 virus 4 and in almost one-fourth of cases' stool samples test positive when respiratory samples are negative [7]
The relevance of GI Symptoms in the Diagnosis of COVID
Most of the emerging COVID-19 literature has emphasized on severe or critically ill patients, yet over 80% of patients have only mild disease [8]. It is important to describe the clinical characteristics of low severity infection patients to provide information for early clinical recognition of COVID so as to facilitate rapid self-quarantine for people with presumed symptoms who are not sick enough to warrant hospitalization.
Moreover, mild symptomatic patients can be mediators of rapid dissemination of COVID-19 by unwittingly spreading the virus in the outpatient setting; making this group to be seemingly a major driver of the pandemic [9] Because COVID-19 testing has largely focused on patients with respiratory symptoms—not digestive symptoms—it is possible that there is a large cohort of undiagnosed patients with low severity illness but with digestive symptoms, such as diarrhea, who could be unknowingly spreading the virus
Mild COVID with More Digestive Symptoms - Silent Spreaders
In a study conducted in 206 patients with low severity, COVID-19 found notable results indicating the presence of a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to possess a longer delay before viral clearance, and to experience a delay in diagnosis compared to patients who had only respiratory symptoms [10]
Potential Role of Probiotics in COVID-19
There are studies which indicate that COVID-19 might be associated with intestinal dysbiosis causing inflammation and poorer response to pathogens [11] thus making a case for probiotic strains that restore gut homeostasis [12]. The gut microbiome has a critical impact on systemic immune responses, and immune responses at distant mucosal sites, including the lungs [13]
Potential benefits of Lactobacillus in Respiratory Infections
There is certainly acceptable scientific data with the use of various Lactobacillus strains in improving outcomes in respiratory infections. Studies have indicated that Lactobacillus based species helps to reduce the incidence of laboratory-confirmed respiratory viral infections in elderly individuals [14]. In another study conducted in 742 children, Lactobacillus administration led to a reduction in the risk for nosocomial gastrointestinal and respiratory tract infections in paediatric facilities.[15]
The potential of Lactobacillus through a more severe spectrum of respiratory illness is substantiated through a study conducted in mechanically ventilated patients indicating the use of Lactobacillus was associated with a lower incidence of development of ventilator-associated pneumonia, thus reflecting potential clinical utility for prophylaxis of ventilator-associated pneumonia(VAP) in a high-risk ICU population [16]
In summary, orally administered probiotic strains can reduce the incidence and severity of viral respiratory tract infections (RTIs). At a time when doctors are using drugs with little anti- COVID-19 data, probiotic strains documented for anti-viral and respiratory activities could become part of the armamentarium to reduce the burden and severity of this pandemic [17]
References:
[1] Li Q, Guan X,WuP, et al. Early Transmission Dynamics in Wuhan,China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med 2020;382:1199–207.
[2] Saber-Ayad M, Saleh MA, Abu-Gharbieh E. The Rationale for Potential Pharmacotherapy of COVID-19. Pharmaceuticals (Basel). 2020;13(5):96. Published 2020 May 14. doi:10.3390/ph13050096
[3] Saghazadeh A, Rezaei N. Towards treatment planning of COVID-19: Rationale and hypothesis for the use of multiple immunosuppressive agents: Anti-antibodies, immunoglobulins, and corticosteroids. Int Immunopharmacol. 2020;84:106560. doi:10.1016/j.intimp.2020.106560
[4] Xiao F, Tang M, Zheng X, et al. Evidence for gastrointestinal infection of SARS-CoV-2.Gastroenterology 2020. Epub ahead of print march 3, 2020.
[5] Zhou P, Yang XL, Wang XG, et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579(7798):270–3
[6] ACE2 angiotensin I converting enzyme 2 [Homo sapiens (human)]. Gene ID: 59272. (https://www.ncbi.nlm.nih.gov/gene/59272)
[7] Gu J,Han B,Wang J. COVID-19: Gastrointestinal manifestations and potential fecal-oral transmission.Gastroenterology2020.[EpubaheadofprintMarch 3,2020.]
[8] Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507–1
[9] Li R, Pei S. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2). 2020. [Epub ahead of printMarch 16, 2020.]
[10] Han C, Duan C, Zhang S, et al. Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes. Am J Gastroenterol. 2020;115(6):916-923. doi:10.14309/ajg.0000000000000664
[11] Gao QY, Chen YX, Fang JY. 2019 Novel coronavirus infection and gastrointestinal tract. J Dig Dis. (2020) 12:3. doi: 10.1111/1751-2980.12851. [Epub ahead of print].
[12] Di Pierro F. A possible probiotic (S. salivarius K12) approach to improve oral and lung microbiotas and raise defenses against SARS-CoV-2. Minerva Med. (2020). doi: 10.23736/S0026-4806.20.06570-2. [Epub ahead of print].
[13] Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, Sonnenberg GF, et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity. (2012) 37:158–70. doi: 10.1016/j.immuni.2012.04.011
[14] Wang B, Hylwka T, Smieja M, Surrette M, Bowdish DME, Loeb M. Probiotics to Prevent Respiratory Infections in Nursing Homes: A Pilot Randomized Controlled Trial. J Am Geriatr Soc. 2018;66(7):1346-1352. doi:10.1111/jgs.15396
[15] Hojsak I, Abdović S, Szajewska H, Milosević M, Krznarić Z, Kolacek S. Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections. Pediatrics. 2010;125(5):e1171-e1177. doi:10.1542/peds.2009-2568
[16] Morrow LE, Kollef MH, Casale TB. Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial. Am J Respir Crit Care Med. 2010;182(8):1058-1064. doi:10.1164/rccm.200912-1853OC
[17] Baud D, Dimopoulou Agri V, Gibson GR, Reid G, Giannoni E. Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic. Front Public Health. 2020;8:186. Published 2020 May 8. doi:10.3389/fpubh.2020.00186