Table 2.

Candidate probiotics in various clinical COVID-19 evaluations

Title	Country	Description	References
Study to Evaluate the Effect of a Probiotic in COVID-19 (NCT04390477)	Spain	In this recent perspective case-control pilot investigation, the potential influence of a probiotic mix on symptoms, duration of hospitalization and the rate of patients with negative PCR after infection with SARS-CoV-2 was evaluated. In this study, the investigators demonstrated a positive effect of probiotics on the gut microbiome and less severe clinical symptoms of the disease. The daily oral capsule containing probiotic strains with maltodextrin as an excipient that was administered for 30 days.	[30]
Evaluation of the Probiotic Lactobacillus coryniformis K8 on COVID-19 Prevention in Healthcare Workers (NCT04366180)	Spain	This study aims to assess the effects of Lactobacillus coryniformis K8 on the frequency and severity of COVID-19 in health workers exposed to the virus. This is a preventive study. The probiotic group will receive one capsule with Lactobacillus K8 per day (3 × 109 cfu/day) for two months.	[27]
Evaluation of the effect of taking Newgen beta-gluten probiotic composite powder to nutrition intervention of patients with novel coronavirus pneumonia (COVID-19) (ChiCTR2000030897)	China	This study intends to use beta-gluten probiotic composite powder as nutrition interference in subjects with COVID-19 to investigate the practical clinical pathway, which is of great importance for the prevention and therapy of SARS-CoV-2. This study plans to collect 20 random subjects. The study cases will randomly be allocated to the nutrition interference group and the control group.	[78]
A clinical study for probiotics in the regulation of intestinal function and microflora structure of novel coronavirus pneumonia (COVID-19) (ChiCTR2000029999)	China	Aims of this study included: (1) investigating intestinal impairment in the course of new coronavirus pneumonia, and blood or imaging indicators of clinical intestinal impairment; (2) using metagenomics and macro virus genomics to investigate the dynamic variations of intestinal flora abundance and structure and metabolomics before and after intervention with microecological agents as well as their impact on the clinical outcome. (3) The use of specific strains and metabolites to promote probiotics and nutritional products for novel influenza.	[167]
A prospective, multicenter, open-label, randomized, parallel-controlled trial for probiotics to evaluate efficacy and safety in patients infected with 2019 novel coronavirus pneumonia (COVID-19) (CHICTR2000029974)	China	Inclusion criteria included: 1. The patient or his/her legal guardian consented to participate in the investigation and signed the informed consent. 2. Those diagnosed with mild or moderate novel coronavirus pneumonia (NCP) or those with severe NCP could take medicines orally or via a stomach tube. NCP cases were identified based on the following pathogenic evidence: 2-1) The presence of novel coronavirus in respiratory samples or blood specimens was confirmed by real-time RT-PCR. 2-2) The genetic sequence of the virus discovered in respiratory or blood specimens was highly similar to that of the known coronavirus. 3. Patients were adults aged ≥ 18 years. 4. The subjects could interact well with researchers and complete the study according to the protocol. Exclusion criteria: 1. The inability to consume medications or take medicine via a stomach tube; critical severe NCP 2. Severe hypo-immunity due to, but not restricted to, one of the following: 2-1) HIV/AIDS, the status was still variable in the manner of mediation, and the last measured level of CD4+ T lymphocytes was less than 200. 2-2) Organ transplantation and systematic immune therapy. 2-3) Long-term systematic management with corticosteroids described as a daily intake of over 40 mg of prednisone or equivalent in the 14 days before the first medication. 3. Allergy to test medicines. 4. Poor conversation skills, comprehension, ability to follow the protocol to finish the study. 5. Severe illnesses such as malignancy or mental illness, or inability to participate in the study according to investigators’ judgment.	[148]
Washed Microbiota Transplantation for Patients With 2019-nCoV Infection (NCT04251767)	China	Gut dysbiosis co-exists in cases with SARS-CoV-2 pneumonia. Some of these patients would improve secondary bacterial infections and antibiotic-associated diarrhea (AAD). The current study on employing washed microbiota transplantation (WMT) as saving therapy in critically ill patients with AAD demonstrated the critical clinical advantages and safety of WMT. This clinical trial aims to evaluate the outcome of WMT coupled with standard treatment for patients with SARS-CoV-2 pneumonia, particularly for those with dysbiosis-related conditions.	[25]
Efficacy of L. plantarum and P. acidilactici in Adults With SARS-CoV-2 and COVID19 (NCT04517422)	Spain	Clinical research focuses on evaluating the influence of a combination of L. plantarum and P. acidilactici as a coadjuvant in adults positive for SARS-CoV-2 with mild clinical COVID-19 symptoms. The primary purpose is to evaluate how this combination of probiotics decreases the risk of development of moderate or severe COVID and risk of death. Additionally, this RCT is beginning to examine the benefits of the combination of these strains to modulate fecal microbiome and investigate how this correlates with clinical improvement.	[26]
Symbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection (SynCov) (NCT04420676)	Austria	Researchers hypothesize that the consumption of Omni-Biotic® 10 AAD can diminish the duration of diarrhea in COVID-19 patients. Researchers further hypothesize that Omni-Biotic® 10 AAD can decrease stool frequency, improve stool consistency, improve other gastrointestinal symptoms of COVID-19, lessen disease duration and severity, reduce intestinal inflammation and improve dysbiosis. The investigators aim to perform a randomized, double-blind, placebo-controlled study using telemedicine in patients with COVID-19.	[28]
Oxygen-Ozone as Adjuvant Treatment in Early Control of COVID-19 Progression and Modulation of the Gut Microbial Flora (PROBIOZOVID) (NCT04366089)	Italy	Italy was the first European country influenced by a severe outbreak of the SARS-CoV-2 epidemic, with high morbidity and mortality correlated with the disease. In light of its pandemic spread and the minimal therapeutic options, COVID-19 is deemed an unusual global health challenge. Hence, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a preference in clinical investigations. This is an interventional, non-pharmacological, open, randomized, prospective, non-profit study on the adjuvant use of oxygen-ozone therapy plus probiotic supplementation in the early control of disease progression in patients with COVID-19. Contextually, all cases are treated with the current standard of care based on the interim guidelines of the Italian Society of Infectious and Tropical Diseases. The main purpose of the study is to evaluate the effectiveness of an ozone therapy-based intervention (accompanied by supplementation with probiotics) in containing the progression of COVID-19 and in preventing the need for hospitalization in intensive care units.	[30]
Efficacy of Intranasal Probiotic Treatment to Reduce Severity of Symptoms in COVID19 Infection (NCT04458519)	Canada	The current study is a randomized, single-blinded trial. In this study, patients with a diagnosis of COVID-19 infection within the past 96 hours and not needing hospitalization will be recruited into a trial of BID nasal irrigation for 14 days, followed by a 14 day observation period. Spraying will be performed with either Probiorinse probiotic nasal irrigation solution or NeilMed Sinus rinse. In this study, patients will be able to recognize their treatments, but study staff will be blinded.	[29]