Probiotics in Prevention and Treatment of COVID-19: Review of Latest Evidence
The novel coronavirus pandemic of 2019 (COVID-19) continues to evolve and threaten the world beyond the first wave with emerging infections caused by multiple strains of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The infection is estimated to have spread to about 216 countries, with a catastrophic impact on global health and the economy. Most COVID-19 cases are mild to moderate with self-limiting respiratory illness. Geriatric patients and individuals with hypertension, diabetes, cardiovascular and pulmonary diseases, and malignancies are more vulnerable to severe COVID-19 and its complications. Considering the immunomodulatory, anti-inflammatory, antioxidant, and antiviral potential of probiotics, the rationale and evidence for its clinical application as a preventive and therapeutic adjuvant option for COVID-19 is reviewed.
Gut Dysbiosis correlated with COVID-19 infections and its Severity
Five studies directly connect microbiota with COVID- 19, supporting the presumptive role of probiotics in both prevention and treatment of COVID-19. A study sequencing faecal samples of patients reported that COVID-19 infections significantly modified faecal microbiomes marked by a decline in beneficial commensals and enrichment of opportunistic pathogens. The baseline abundance of Coprobacillus and few Clostridium species have correlated with the severity of COVID-19. The abundance of Faecalibacterium prausnitzii, an anti-inflammatory bacterium, inversely correlated to COVID-19 severity, demonstrating the influence of SARS-CoV-2 on gut microbiome. Along similar lines, Yeoh YK, et al, reported significant alterations in the gut microbiome and dysbiosis in COVID 19 patients, associated with disease severity and inflammatory markers. The continuously evolving evidence supports the potential role of microbiota in the susceptibility, progression, and severity of COVID-19.
Immunomodulatory Activity of Probiotics: Beyond the Gut
Although the mechanism of action of probiotics profoundly focuses on the GIT, the effect of probiotics is not confined to the initial infection site. They can act on the entire body via immune modulation. Probiotics and their antigenic metabolites are phagocytosed by microfold cells to form endosomes in gut-associated lymphoid tissues. These antigens are suddenly released and taken in by dendritic cells (DCs), which can transport them to local lymph nodes and consequently activate naive T and B cells to differentiate into diverse effector subpopulations. This cascade subsequently, initiates the release of relevant cytokines and various immune responses
Probiotics such as Lactobacillus have the ability to restore host health by eliminating pathogens and regulating immune responses in intestinal epithelial cells. Probiotics stimulate the immune system, thus increase immunoglobulins (Igs) generation, enhance macrophage and lymphocyte activity, and interferon (IFN)- ɤ stimulation. Probiotics may also attenuate exaggerated immune responses, primarily through their anti-inflammatory activities.
Rationale for consideration of probiotics in the management of COVID-19
Dysbiosis predisposes an individual to abnormal inflammatory status and increases the susceptibility to disease. Probiotic supplementation helps to maintain symbiosis in the GIT and thereby modulate the immune system. The symbiotic state helps to control the severity of COVID-19 via the gut-lung and gut-brain axes. Probiotics can modulate innate and adaptive immune responses, control the synthesis of immunoglobulins, inhibit various cytokines and chemokines, express several virus defence genes and regulate T helper (Th1, Th2, Treg) cells.
Up to 71% of COVID-19 patients are administered antibiotics as reported in some countries, and diarrhoea was reported in up to 36% of them. Reinforcement of colonic microflora using probiotics diminishes secondary infection and diarrhoea in patients receiving antibiotics.
Probiotics in Respiratory Infections and COVID-19: Review of Evidence
A scientific report from Asia showed that COVID-19 patients suffer microbial dysbiosis with depleted Lactobacillus and Bifidobacterium in their gut, and about 60% of these patients express gastrointestinal symptoms such as diarrhoea, nausea, and vomiting. The gastrointestinal symptoms also imply greater severity of COVID-19 infection. A meta-analysis published by Kang EJ, et al. revealed that probiotics such as Lactobacillus and Bifidobacterium led to a decrease in respiratory symptoms, which are invariably, also a symptom of SARS-CoV-2 infection. A meta-analysis of RCTs suggests that probiotics decreased ventilator-associated pneumonia (VAP)  and reduced the duration of antibiotic use for VAP thus bringing out their therapeutic opportunity for their consideration to improve clinical outcomes in COVID-19.
Evidence supports the role of probiotics in regulating the immune system, suggesting a definitive role for probiotics in viral infections. Probiotics supplementation could reduce the severity of COVID-19 morbidity and mortality. They may be able to inhibit cytokine storm by simultaneously boosting innate immunity and evading the exaggeration of adaptive immunity, which is often challenged to respond rapidly and aggressively to the viral onslaught. Probiotics-induced suppression of inflammatory cytokine response may prevent both the severity and the occurrence of Acute Respiratory Distress Syndrome (ARDS), making probiotics an attractive adjunct.
Rediscovering and repurposing effective therapies could help to positively impact the course of the pandemic, clinical outcomes of COVID-19, and the lives of the affected population across the globe. Considering utilisation of probiotics in high risk and severely ill patients and frontline health workers might be a noteworthy therapeutic option to limit the infection and may help flatten the COVID-19 curve.
 World Health Organization. Rolling updates on coronavirus disease (COVID-19). Available from:
https:// www.who.int/ emergencies/ diseases/ novel- coronavirus- 2019/events- as- they- happen
 Zuo T, Zhang F, Lui GCY, et al. Alterations in gut microbiota of patients with COVID-19 during the time of hospitalization. Gastroenterology 2020;159:944–955 e8. doi: 10.1053/j.gastro.2020.05.048
 Yeoh YK, Zuo T, Lui GC, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 2021;0:1–9.
 Gu S, Chen Y, Wu Z, et al. Alterations of the gut microbiota in patients with COVID-19 or H1N1 influenza. Clin Infect Dis 2020;71:2669–2678. doi: 10.1093/ cid/ ciaa709
 Zeng W, Shen J, Bo T, et al. Cutting edge: probiotics and fecal microbiota transplantation in immunomodulation. J Immunol Res 2019;2019:1603758
 Azad MAK , Sarker M , Wan D . Immunomodulatory effects of probiotics on cytokine profiles. Biomed Res Int 2018;2018: 8063647.
 Kurian et al., Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects, Archives of Medical Research, https:// doi.org/ 10.1016/ j.arcmed.2021.03.002
 Xu K, Cai H, Shen Y, et al. Management of coronavirus disease-19 (COVID-19): the Zhejiang experience. Zhejiang Da Xue Bao Yi Xue Ban 2020;49:147–157. doi: 10.3785/j.issn.1008-9292.2020. 02.02.
 Kang EJ, Kim SY, Hwang IH, et al. The effect of probiotics on prevention of common cold: a meta-analysis of randomized controlled trial studies. Korean J Fam Med 2013;34:2–10.
 Su M, Jia Y, Li Y, et al. Probiotics for the prevention of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials. Respir Care 2020;65:673–685
Disclaimer: The views expressed in the above article are solely those of the author/agency in his/her private capacity and DO NOT represent the views of Medical Dialogues.
Read website full disclaimer here