TABLE 3.

Several clinical studies of microecological intervention in COVID-19.

Identifier	Recruiting status	Study subjects	Age	Country	Sample size	Supplement	Intervention	Primary outcome	Access link
NCT04390477	Completed	Patients with a confirmed diagnosis of SARS-CoV-2 and require admission to the hospitalization	≥18 years	Spain	41	Probiotic	1 pill containing probiotic 1 × 10∧9 CFU or Placebo. 1 oral capsule per day for 30 days.	Percentage of patients with discharge to ICU	https://clinicaltrials.gov/ct2/show/NCT04390477
NCT04458519	Completed	COVID-19 patients not requiring hospitalization	18−59 years	Canada	23	Probiotic	Nasal irrigations with Probiorinse 2.4 Billion CFU (Colony-Forming Units) of Lactococcus Lactis W136 or saline (NeilMed Sinus Rinse). Twice-daily for a period of 14 days	Change in severity of COVID-19 infection	https://clinicaltrials.gov/ct2/show/NCT04458519
NCT04507867	Completed	Stage III positive COVID-19 patients with comorbidities (type 2 DM, SAH, overweight/obesity with BMI < 35)	30−75 years	Mexico	80	Synbiotic	Combination of three B vitamins (B1, B6, and B12) “Neurobion” 10 mg solution for IM injection, One every 24 h for the first 5 days. Probiotics Saccharomyces boulardii CNCM I-745 “Floratil.” One morning and one evening 250 mg capsule during the first 6 days. One envelope of NSS-1 in the morning and one envelope in the afternoon mixed with 400 ml of water each, contain nutritional support system or placebo	Overall mortality at day 40 and overall survival	https://clinicaltrials.gov/ct2/show/study/NCT04507867
NCT04517422	Completed	Mild COVID-19 patients, cough, fever, dyspnoea, or headache, onset < = 7 days	18−60 years	Mexico	200	Probiotic	Probiotics (Lactiplantibacillus plantarum CECT30292, Lactiplantibacillus plantarum CECT 7484, Lactiplantibacillus plantarum CECT 7485, and Pediococcus acidilactici CECT 7483) or Placebo (maltodextrin). Oral for 30 days	Severity of COVID-19 progression; stay of patients at ICU and mortality ratio	https://clinicaltrials.gov/ct2/show/NCT04517422
NCT04621071	Completed	COVID-19 patients	≥18 years	Canada	17	Probiotic	Dietary Supplement: Probiotics (2 strains 10 × 10∧9 UFC) or Placebo (potato starch and magnesium stearate). From Day 1 to Day 10 two capsules a day, Day 11 to Day 25 one capsule a day, maximum of 25 days, if they are admitted to the hospital treatment will stop	Duration of symptoms of the COVID-19	https://clinicaltrials.gov/ct2/show/NCT04621071
NCT04734886	Completed	Previous diagnosis of COVID-19 (by positive PCR) or previous confirmation of seropositivity to SARS-CoV-2	18−60 years	Sweden	161	Probiotic	Dietary Supplement: L. reuteri DSM 17938 + vitamin D or Placebo + vitamin D. Two capsules per day for 6 months	SARS-CoV-2 specific IgG/IgM antibodies in serum between the study arms	https://clinicaltrials.gov/ct2/show/NCT04734886
NCT04824222	Not yet recruiting	COVID-19 patients with expected survival time, not taking into account SARS-CoV-2 infection, is at least 6 months. Hospitalization due to COVID 19 disease or disease with accompanied COVID 19.	≥18 years	Not provided	366	Fecal microbiota transplantation (FMT)	FMT be administered in double cover, gastro-resistant, enteric release capsules in 60 g dose or placebo	Incidence of adverse events after administration of IMP in the phase II/III, percentage of patients requiring escalation of oxygen therapy in non-invasive and invasive methods in phase III	https://clinicaltrials.gov/ct2/show/NCT04824222
NCT04847349	Completed	SARS-CoV-2 infection > 4 months prior confirmed	18−60 years	United States	54	Probiotic	Probiotic consortium OL-1, standard dose or Probiotic consortium OL-1, high dose or Placebo (potato starch, maltodextrin). A capsule once per day with breakfast for 21 days	Change in titer of serum anti-SARS-CoV-2 immunoglobulin G (IgG)	https://clinicaltrials.gov/ct2/show/NCT04847349
NCT04854941	Completed	COVID-19 patients	18−75 years	Russian Federation	200	Probiotic	Probiotics (10∧9 CFU of each strain: Lactobacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911 and Bifidobacterium longum PDV 2301) or standard regimen for COVID-19. Three times a day during the hospital stay but for no more than 14 days, the end point was day 14 or patient’s discharge or death	The number of died patients during hospitalization	https://clinicaltrials.gov/ct2/show/NCT04854941
NCT05043376	Completed	Hospitalized confirmed (RT-PCR) COVID-19 patients not receiving mechanical ventilatory support	≥18 years	Pakistan	50	Probiotic	Dietary Supplement: BLIS K12 (Streptococcus salivarius K12). Daily 2 oral BLIS K12 tablets for up to 14 days	Recovery and live discharge, number of patients with clinical improvement	https://clinicaltrials.gov/ct2/show/NCT05043376
NCT05175833	Completed	patients hospitalized in the ICU with severe acute respiratory syndrome	≥18 years	Brazil	70	Probiotic	Oral gel containing streptococcus salivarius K12 and lactobacillus brevis CD2 or containing placebo The oral gel was applied in the mouth every 8 h for 7 days	The occurrence of symptoms and signs of secondary bacterial pneumonia	https://clinicaltrials.gov/ct2/show/NCT05175833
IRCT20080826001096N8	Recruiting	Pregnant women with mild/moderate COVID-19	≥16 years	Iran	80	Synbiotic	Lactofem capsule, contains 500 mg of 4 strains of probiotic lactobacilli including Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus gasseri and 38.5 mg of prebiotic substances including fructooligosaccharides or placebo Twice daily after meals for at least 7 days until hospitalization	Duration from the start of the study until the improvement of clinical symptoms.	https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20080826001096N8
IRCT20200117046164N2	Recruiting	Asthmatic children without positive history of COVID-19	6−18 years	Iran	90	Probiotic	Probiotic nasal spray contains Lactobacillus reuteri and Lactobacillus casei or rhinosaline nasal spray Administer twice daily, one puff in each nostril, for 1 month	Abnormality in smell, Axillary temperature above 38 Celsius degree, Development of respiratory and gasterointestinal symptoms	https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20200117046164N2
ChiCTR2000029999	Prospective registration	COVID-19 patients	≥18 years	China	60	Probiotic	Specific probiotic types not yet available	Several parameters associated to gut microbiome, fecal metabolomics, cytokines, biochemical, hematological, imageology, etc.	https://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR2000029999