Table 2.

Ongoing clinical studies of probiotic intervention in COVID-19.

Country	ClinicalTrials.gov ID	Study type	Study subjects	Age group	Sample size	Intervention	Dose	Duration	Primary outcome
Spain	NCT04390477	Open label RCT	COVID-19 patients requiring hospitalization	≥18 years	40	Dietary Supplement: Probiotic vs No intervention	1 × 10∧9 CFU/day	30 days	Cases with discharge to ICU
Spain	NCT04366180	Double-blind RCT	Healthcare workers without COVID-19	≥20 years	314	Probiotic (Lactobacillus) vs Control (Maltodextrin)	3 × 10∧9 CFU/day	8 weeks	Incidence of SARS-CoV-2 infection in healthcare workers
Italy	NCT04366089	Single-blind RCT	COVID-19 patients requiring hospitalization	≥18 years	152	Standard of care (Azithromycin and hydroxychloroquine) vs Oxygen-ozone therapy and probiotic (SivoMixx 200 billion: Streptococcus thermophiles, 2 Bifidobacterium strains, 5 Lactobacillus strains)	1.2 × 10∧12 CFU/day	21 days	Delta in the number of patients requiring orotracheal intubation despite treatment
Austria	NCT04420676	Double-blind RCT	COVID-19 patients with diarrhea	≥18 years	108	Synbiotic (Omnibiotic AAD: 2 Bifidobacterium strains, Enterococcus, 7 Lactobacillus strains) vs Placebo	Not mentioned	30 days	Duration of diarrhea
United States	NCT04399252	Double-blind RCT	People with household contact of COVID-19 patient	≥1 year	1000	Probiotic (Lactobaciltus rhamnosus GG) vs Placebo	2 capsules per day	28 days	Changes in Shannon bacteria diversity
Canada	NCT04334980	Double-blind RCT	Healthy subjects without COVID-19	19–45 years old	84	bacTRL-Spike (Bifidobacterium engineered to deliver plasmids encoding spike protein from SARS-CoV-2) vs Placebo	1 × 10∧9, 3 × 10∧9 or 1 × 10∧10	12 months	Frequency of adverse events (specifically including incidence of gastrointestinal-associated events)
Italy	NCT04368351	Retrospective Case-Control	COVID-19 patients requiring hospitalization	≥18 years	70	Standard of care (Azithromycin and hydroxychloroquine) vs Bacteriotherapy (SivoMixx: Streptococcus thermophiles, 2 Bifidobacterium strains, 5 Lactobacillus strains; Azithromycin and Hydroxychloroquine)	Not mentioned	21 days	Delta of time of disappearance of acute diarrhea
Mexico	NCT04517422	RCT	COVID-19 patients requiring hospitalization	18–60 year old	300	Combination of Lactobacillus plantarum CECT7481, Lactobacillus plantarum CECT 7484, Lactobacillus plantarum CECT 7485, and Pediococcus acidilactici CECT 7483 vs Placebo	Not mentioned	30 days	Severity progression of COVID-19, Stay at ICU, Mortality ratio.
Hong Kong	aApproved by CUHK-NTEC CREC: CRE-2020.407	Pilot study	COVID-19 Patients requiring hospitalization	≥18 years	50	Synbiotic (CUHK-Synbiotic vs Standard care)	2 × 10∧11 CFU/day	28 days	Composite outcome of symptom score improvement within 4 weeks.
Hong Kong	aApproved by CUHK-NTEC CREC: CRE-2020.400	A single-arm, open-labelled interventional study	Recovered/Discharged COVID-19 patients	≥18 years	20	Synbiotic (CUHK-Synbiotic)	2 × 10∧11 CFU/day	28 days	Changes in gut microbiome (bacteria, virome and fungome) at week 5 compared to baseline.

^aThe Joint Chinese University of Hong Kong – New Territories East Cluster Clinical Research Ethics Committee: CUHK-NTEC CREC.