TABLE 1.

Clinical trials of probiotics in the treatment of COVID‐19.

Study/country	Participants (control/intervention)	Intervention	Follow‐up time	Side effect	Outcome	Conclusion
Vaezi et al. (2023)/Iran 138	Adult COVID‐19 patients (38/38)	Multistrain probiotics (e.g., Lactobacillus, Bifidobacterium, Streptococcus), 1018 CFU per day, twice daily for 2 weeks	14 days	None	COVID‐19 clinical features, levels of proinflammatory IL‐6, CRP, ESR, and so on	Synbiotic adjuvant therapy can be effective to modulate inflammatory responses against COVID‐19.
Sandra et al. (2023)/Spain 139	COVID‐19 subjects who required more than 48 h of hospital admission (99/101)	Multistrain probiotic (e.g., Lacticaseibacillus, Bifdobacterium), 109 CFU, three times a day for no more than 14 days	During the hospital stay	NA	Mortality, digestive symptoms, hospital stays	It was effective in treating diarrhea associated with COVID‐19.
Richard et al. (2023)/Sweden and UK 140	Healthy adults (78/81)	Probiotic product containing a minimum of 1 × 108 CFU of Limosilactobacillus reuteri DSM 17938 + 10 µg vitamin D3, twice daily for 6 months	6 months	Gastrointestinal complaints	Serum‐specific antibody titers, symptom duration and severity after infection and so on.	Supplementation with specific probiotics might improve the long‐term efficacy of mRNA‐based COVID‐19 vaccines via enhanced IgA response.
Pedro et al. (2022)/Mexico 141	Adult symptomatic COVID‐19 outpatients (150/150)	Lactiplantibacillus plantarum, plus strain Pediococcus acidilactici, totaling 2 × 109 CFU, for 30 days	30 days	None	Nasopharyngeal viral load, duration of both digestive and nondigestive symptoms, fecal microbiota	Probiotic supplementation significantly increased specific IgM and IgG. It is thus hypothesized this probiotic primarily acts by interacting with the host's immune system rather than changing colonic microbiota composition.
Saviano et al. (2022)/Italy 142	Patients with COVID‐19 interstitial pneumonia (40/40)	Bifidobacterium lactis LA 304, Lactobacillus salivarius LA 302, and Lactobacillus acidophilus LA 201, probiotic mix twice a day for 10 days in addition to the standard COVID‐19 therapy	10 days	None	FECAL inflammatory markers (fecal calprotectin and CRP), any reduction in the need for nasal cannula or Ventimask oxygen support, the length of hospital stay	Supplementation with a mix of probiotics for 10 days in patients with COVID‐19 interstitial pneumonia significantly reduces inflammatory markers.
De boeck et al. (2022)/Belgium 143	Unvaccinated COVID‐19 outpatients exhibiting mild‐to‐moderate symptoms (37/41)	Multispecies probiotic throat spray with Lacticaseibacillus casei AMBR2, Lacticaseibacillus rhamnosus GG, and Lactiplantibacillus plantarum WCFS1, for 14 days by spraying two puffs containing approximately 9.5 × 108 CFU of lactobacilli multiple times a day	1 week	NA	Symptom severity, time to improvement, viral loads, antibodies, and the respiratory microbiome	It may reduce nasopharyngeal viral loads and acute symptoms.
Francesco et al. (2022)/Italy and UK 144	COVID‐19 hospitalized patients (non‐ICU and not already receiving mechanical ventilatory support) (25/25)	Oral probiotic S. salivarius K12 plus standard of care, up to 14 days	14 days	NA	Biochemical parameters, fever, oxygen saturation level, need and length of oxygen therapy, the rate of progression to ICU and death	The adjuvant use of S. salivarius K12, an oral probiotic endowed with a well‐known capability to colonize the oral environment, improved the blood parameters and reduced the death rate.

COVID‐19, coronavirus disease 2019; CFU, colony forming units; IL‐6, interleukin‐6; CRP, C‐reactive protein; ESR, erythrocyte sedimentation rate; ICU, intensive care unit.