Table 1.

Summary of findings for the included studies.

ID	First author	Countries	Year of publication	Type of study	Population (no, mean age ± SD)	Sampling location	Type of microbiota	How microbiota affect the course of the COVID‐19	How SARS‐CoV‐2 infection affect the microbiota	Summary of findings
1	40	UAE	2021	Cross‐Sectional	N = 143	Fecal	Intentinibacter Enterorhabdus Anaerostipes Prevotella Bacteroides Bifidobacterium Blautia Faecalibacterium Streptococcus Lachnospiraceae Atopobiaceae Peptostreptococcaceae	No relation between COVID‐19 viral load and bacterial microbiome Decreases severity of COVID‐19 disease	Gut microbiota diversity↑. Blautia↑ Faecalibacterium↑ Streptococcus↑ Intestinibacter↓ Enterorhabdus↓ Anaerostipes↓ Bifidobacterium↓ Bacteroides↓ Prevotella↓	Stool in COVID‐19 infected patients: richer, more variable in bacteria specie+ high lipid metabolism Gut microbiota is protective against severe COVID‐19 disease.
2	45	Saudi Arabia	2020	Experimental	‐	‐	Lactobacillus plantarum probiotics bacteria	Lactobacillus plantarum metabolites (Plantaricin BN, Plantaricin JLA‐9, Plantaricin W, Plantaricin D) can bind with RdRp, RBD, and ACE2 molecules.	‐	Plantaricin molecules can be useful against the COVID‐19 disease.
3	41	Hungary	2021	Cross‐sectional	N = 40 Age Athlete (n = 20): Age = 24.15 ± 4.7 years, Sedentary (n = 20): Age = 27.75 ± 7.5	Fecal	Actinobacteria Bacteroidetes Cyanobacteria Firmicutes Proteobacteria Tenericutes Verrucomicrobia	Decreases symptoms of Severe COVID Bacteroidetes↑	Bacteroidetes↑	Bacteroidetes in the feces have an anti‐inflammation effect and protect patients against severe COVID‐19 disease. No difference between the microbiome of athletes and sedentary patients
4	70	Iran	2021	Basic	‐	‐	Lactobacillus Plantarum Bos taurus Bacillus subtilis Morone saxatilis Crotalus durissusruruima Leuconostocgelidum Lachesanatarabaevi Limulus polyphemus	glycocin F (from Lactococcus lactis) and lactococcine G (from Lactobacillus Plantarum) have the highest affinity to some SARS‐COV‐2 virus molecules.	‐	Using dairy products containing Lactococcus lactis and Lactobacillus Plantarum with vitamin D may be helpful to combat and preventing SARS‐COV‐2 infection.
5	76	Turkey	2021	Cross‐sectional	N = 44	‐	Bifidobacterium	Single strain probiotic bifidobacterial: mortality rate↓ duration of admission ↓ (in moderate/severe COVID‐19 patients) This probiotic also helps chest CT‐Scan resolution.	‐	Bifidobacterium can be a useful treatment for moderate/severe COVID‐19 disease.
6	42	China	2021	Cross‐sectional	N = 28703 (1374 CRC patients) + 27,329 normal patients	Colon	Melissococcus, Faecalibacterium, Subdoligranulum, Bacteroides, Alistipes, Eubacterium, Parabacteroides, Ruminococcus, Blautia, Bifidobacterium.	Blautia and Ruminococcus are more prevalent in CRC (colorectal cancer) patients and are related to a more severe COVID‐19 disease in these patients.	‐	The imbalance of gut microbiota is related to COVID‐19 mortality.
7	66	China	2021	Prospective Study	N = 30 median age: 53.5	Gut		The imbalance of gut microbiota is linked to long COVID. Higher CRP levels in patients with reduced postconvalescence microbiota richness.	Gut microbiota changes in the COVID‐19 patients. microbiota richness did not normalize after a 6‐month recovery	Enhancing the microbial diversity of the gut in long COVID‐19 patients should be considered. Severe patients had lower postconvalescence microbiota richness.
8	43	Germany	2021	Cross‐Sectional	N = 322 Healthy (n = 72, Median age=36) URT (n = 112, Median age =  46) Mild COVID (n = 36, Median Age = 50) Moderate COVID(n = 37, Median Age = 57) Severe COVID (n = 65, Age = 65)	Oropharyngeal	Haemophilusin fluenzeae Parainfluenzae pittmaniae Neisseria subflava		↓nasopharyngeal microbiota diversity (in admitted COVID‐19 patients) Microbiota of moderate/severe COVID‐19 patients was more dysbiotic than in healthy patients. Haemophilus influenzeae↑ parainfluenzae↑ pittmaniae↑	Gut microbiota changes: Moderate and severe COVID‐19 patients Patients treated with antibiotics. History of mechanical ventilation during the admission. Prolonged hospitalization.
9	44	Italy	2021	Cross‐Sectional	49 Mean Age = 66.7 ± 14.4	Gut	Actinobacteria Bacteroidetes Firmicutes Proteobacteria Verrucomicrobia		Bacteroidetes was seen more in COVID + patients and decreased after recovery. Firmicutes were seen in COVID‐ patients (and after recovery of COVID+ patients). Blautia $\uparrow$ (after recovery)	Alpha diversity: similar in COVID+ and COVID− pneumonia alpha‐diversity ↑ (after the recovery)
10	20	Italy	2021	Cross‐Sectional	N = 40	Nasopharynx	Actinobacteria Bacteroidetes Firmicutes Fusobacteria Proteobacteria		Bacterial richness, diversity, and abundance were similar in both COVID+ and COVID− groups (mild disease)	Nasopharyngeal microbiota does not change in mild early COVID‐19 disease.
11	48	USA	2021	Experimental	~78 Samples	Lung and blood microbiome	(Long list)	blood microbiota COVID‐19 patients: E. coli, Bacillus sp. PL‐12 abundance, Campylobacter hominis ATCC BAA‐381 Pseudomonas sp. I‐09 Thermoanaerobacter pseudethanolicus ATCC 33223 Thermoanaerobacter iumthermosaccharolyticum DSM 571 Staphylococcus epidermis Less severe SARS‐CoV‐2 infection with Bacillus subtilis subsp. subtilis str. 168 blood	Multiple associations were seen between microbiota and COVID‐19 severity.	Interleukins modulation by the microbiota (lung and blood) results in immune system regulation.
12	46	USA	2021	Cross‐Sectional	N = 19 (9 COVID positive: Mean ± (SD) = 53.38 ± (14.93)) 10 COVID negative.	nasopharyngeal	Proteobacteria, Actinobacteria Firmicutes, Corynebacterium, Morganella Moraxella, Escherichia‐Shigella, Proteus Staphylococcus	‐	Alpha‐diversity analysis:same in COVID+ and COVID− beta‐diversity: significant variation richness ↓ in COVID+ Proteobacteria‐to Actinobacteria ratio↑in COVID+	In COVID + patients: Dysbiotic nasopharyngeal microbiota Loss of normal flora bacteria. pro‐inflammatory bacteria. ↑
13	47	USA	2021	Cohort	118 IBD patients	Gut (Endoscopy)	‐	‐	No change in the endoscopic microbiome of 12 IBD before and after SARS‐CoV‐2 infection was seen	No change in microbiota.
14	50	Italy	2021	Cross‐Sectional	N = 69 Mean Age = 73 years	Fecal	Enterococcaceae, CoriobacteriaceaeLactobacillaceae, Veillonellaceae, PorphyromonadaceaeStaphylococcaceaeBacteroidaceae, LachnospiraceaeRuminococcaceaePrevotellaceaeClostridiaceae	‐	High Dysbiosis of gut microbiota in COVID+ patients. ↓(Alpha)diversity, ↓Firmicutes, Bacteroidetes, ↑Enterococcaceae, Coriobacteriaceae,	In COVID patients: Loss of beneficial microorganisms ↑potential pathogens (ex: Enterococcus especially in ICU patients)
15	51	Chili	2020	Cross‐Sectional	>200000	Waste water	(Based on NCBI Taxonomy tree)	‐	↓Proteobacteria and ↑in other genera at the residential care home and the prison during the pandemic. COVID+ samples: ↑Prevotella, Bacteroides, ↑Simpliscira, Flavobacterium, Acinetobacter genera	The microbiota in the waste water of the COVID‐19 patients' region was different compared to the the non‐COVID individuals’ region.
16	52	China	2021	Cross‐Sectional	N = 400 Mean age: ~47 years	Oropharyngeal	Long list	‐	↓Alpha‐diversity ↑Opportunistic pathogens ↓butyrate‐producing genera In COVID+: ↑Firmicutes. ↑Bacteria_unclassified	↑The beta diversity Dysbiosis + (In COVID+) COVID‐19 patients: lipopolysaccharide‐producing bacteria ↑Leptotrichia ↑opportunistic pathogens (Granulicatella) ↓Butyrate‐producing bacterial
17	53	India	2021	Cross‐Sectional	N = 89	nasopharyngeal	OUT (Long list)		COVID+: ↓Number of Bacteria ↑Proteobacteria ↓Bacteroidetes ↑opportunistic pathogens (Haemophilus, Stenotrophomonas, Acinetobacter, Pseudomonas): ↑Chance of secondary infection. ↔Bacterial richness	In mild cases of COVID‐19 dysbiosis level returns to normal values in a short time after the recovery. In children normalization takes more time.
18	55	USA	2021	Cross‐Sectional	164 Mean age: ~63 years	Oral		Long COVID patients had inflammatory microbiota (ex. Prevotella, Veillonella which produce LPS):		Long COVID and chronic fatigue syndrome patients had similar oral microbiome. Malfunction of oral microbiota is associated with long COVID symptoms. Decreased anti‐inflammatory metabolic pathway was seen in oral microbiota of long COVID patients
19	57		2021	Cross‐Sectional	N = 7	Fecal		‐	↓Actinobacteria, ↓Firmicutes, ↓↓Bacteroidetes	↓Shannon Diversity Index (In COVID+)
20	77	Egypt	2021	Cohort	N = 200 Mean age =  37 (Mild COVID‐19), 45 (moderate COVID‐19)	‐	‐	Prebiotic‐containing foods, low sugar diet, exercise, adequate sleep, and less antibiotic use cause a milder COVID‐19 disease. Intake of probiotic yogurt :1.6 times greater risk of severe COVID‐19 disease.	‐	A healthy gut microbiome can decrease the severity of COVID‐19. But probiotic yogurt may be harmful and has an adverse effect on COVID progression.
21	31	Mexico	2021	Cross‐Sectional	N = 95 Mean age: 45 years	Upper respiratory tract	Most Common: Firmicutes, Bacteroidetes, Proteobacteria	Loss of microbial complexity structure changes prognosis of SARS‐CoV‐2 infection	↑Firmicutes, ↑Actinobacteria, ↑TM7 ↑Veillonella, ↑Staphylococcus, ↑Corynebacterium, ↑Neisseria, (Only in severe SARS‐CoV‐2 infection) ↓Bacteroidetes ↓Haemophilus ↓Alloiococcus	High dysbiosis in the respiratory microbiome of COVID‐19 patients ↓microbial diversity ↑Firmicutes/Bacteroidetes mild COVID: ↑Prevotellamelaninogenica, P. pallens, Veillonella parvula, Neisseria subflava, In Severe COVID: ↑Megasphaera, CW040. Fatal COVID: ↑ Rothiadentocariosa, Streptococcus infantis, Veillonelladispar
22	58	Bangladesh	2021	Cross‐sectional	N = 22 mean age: 41.86	Nasopharyngeal	2281 bacterial species		Opportunistic bacteria 67% of acute SARS‐CoV‐2 infection cases. (in 77% of recovered patients) In acute and recovered COVID‐19 patients 79% of healthy common bacteria were not detected in. alpha‐diversity: higher diversity in Recovered > Healthy > Acute COVID	Nasopharyngeal microbiome dysbiosis in SARS‐CoV‐2 infection decreases the diversity of the nasopharyngeal microbiome and can change the genomic of microbiomes.
23	59	USA	2021	Prospective cohort	N = 274 Children. Median Age: Healthy: 9.2 Infected (without respiratory symptoms): 9.1 Infected + respiratory symptoms: 14.2	Nasopharyngeal	1799 ASVs 316 bacterial genera 20 phyla		(Nasopharyngeal microbiome alpha diversity: no difference. Microbiome richness ↑ in COVID+ In respiratory involved SARS‐CoV‐2 infection: ↑Corynebacterium, ↑Anaerococcus spp.	High Corynebacterium in the nasopharyngeal microbiome In SARS‐CoV‐2 infection. ↑Dolosigranulumpigrum in nasopharyngeal tissue is associated with SARS‐CoV‐2 infection (Not respiratory involvement). COVID‐19 can change the nasopharyngeal microbiome composition in children.
24	60	Italy	2021	Pilot study	N = 41 Mean Age: 47.3	Oral	Haemophilusparainfluenzae, Veillonellainfantium, Soonwooa purpurea, Prevotellasalivae, Prevotellajejuni, Capnocytophagagingivalis Neisseria perflava,		↓Richness (↓alpha diversity) Difference in beta‐diversity: ↑Prevotellasalivae ↑Veillonellainfantium Healthy: ↑Neisseria perflava ↑Rothiamucilaginosa	Different microbiota composition was seen in COVID+ patients. Seven cytokines in the oral microbiome of the COVID patients: IL‐6, IL‐5, GCSF, IL‐2, TNF‐a, GMCSF, INF‐γ
25	29	Russia	2021	RCT	N = 200, Mean age = 65 (59–71) [probiotic group] 64 (54–70) [nonprobiotic groups]		The probiotic receiving group was treated with; rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 for 14 days.	In COVID‐19 patients, the tried probiotic had no noteworthy impact on the severity of the disease or mortality.		In this study, the tried probiotic was beneficial to treat diarrhea in COVID‐19 patients.
26	30	China	2020	Observational	N = 800			Probiotics were helpful to treat COVID‐19 diarrhea.
27	61	Korea	2021	Cross‐Sectional	N = 48 Median age: 26 year	Fecal	16 S rRNA amplicon sequencing		In respiratory COVID+ Firmicutes > Proteobacteria > Actinobacteria> Bacteroidetes ↓Bacteroidetes,	The microbial diversity of COVID infected was higher than recovered cases. acute SARS‐CoV‐2 infection: ↑Firmicutes/Bacteroidetes ratio Bacteroidetes ↓ (during recovery Bacteroidetes↓)
28	62	USA	2021	Cross‐Sectional	N = 84 (48−70 years old)	Nasopharyngeal	16 S rRNA Amplicon Sequencing		↑Cyanobacterial ↑Cutibacterium ↑Lentimonas ↓Prevotellaceae ↓Luminiphilus ↓Flectobacillus ↓Comamonas ↓Jannaschia	nasopharyngeal: ↑Cyanobacterial in COVID + patients. Symptomatic COVID patients had ↑Cutibacterium ↑Lentimonas than asymptomatic patients. Dysbiosis + (May have a relation to COVID severity). Changes in microbiota may have immunogenic effects.
29	63	China	2021	Cohort	N = 66	Gut	Shotgun Metagenomic Sequencing	Associations: ALT, RBC, hemoglobin level ~Coprococcuscatus. AST~Streptococcus salivarius. RBC level~ Eubacterium hallii. Neutrophil ~Clostridium nexile,	↑Bacteroides stercoris, Bifidobacterium longum, Streptococcus thermophilus, Lachnospiraceae bacterium 5163FAA, ↓Clostridium nexile, Streptococcus salivarius, Enterobacter aerogenes, ↓Candidatussaccharibacteria	Changes in gut microbiota can change the course and severity of COVID‐19 disease ↓Microbiota variation ↑Bacteroidetes/Firmicutes ratio
30	64	China	2021	Cross‐sectional	N = 39	Sputum	Oxford Nanopore Technology sequencing platform		Severe COVID: ↓Neisseria, Rothia, Prevotella	Characteristics of sputum microbiota are variable in different COVID‐19 severity stages. After recovery, their microbiota becomes near similar to that of healthy individuals
31	33	China	2021	Interventional	N = 11 median age: 49	‐	Fecal microbiota transplantation (FMT); 10 capsules each day for 4 consecutive days.	After using FMT: microbial richness↑ alpha diversity ↔	‐	Using FMT consequences: ↓naive B cell ↑memory B cells ↑non‐switched B cells Restore the gut microbiota as: ↑Actinobacteria (15.0%) ↓Proteobacteria (2.8%) ↑Bifidobacterium ↑Faecalibacterium Palliate GI symptoms
32	65	China	2021	Cohort	N = 15 27−76	Nasopharynx Urine Serum	Leptotrichiahofstadii Gemellamorbillorum Gemellahaemolysans Streptococcus sanguinis Veillonelladispar Prevotellahisticola	Increased Leptotrichiahofstadii and Gemellahaemolysans in nasopharyngeal microbiome Is linked to CME levels in serum. CME seems to be helpful to treat COVID‐19.	The nasopharyngeal microbiome of COVID‐19 patients: Leptotrichiahofstadii↓ Gemellamorbillorum↓ Gemellahaemolysans↓ Streptococcus sanguinis↑ Veillonelladispar↑ Prevotellahisticola↑	Serum of COVID‐19 patients: Chlorogenic acid methyl ester (CME) ↓ Lactic acid↓ l‐Proline↓
33	32	Belgium	2021	Cohort	N = 93 Upper respiratory = 61 (37–83) Lower Respiratory =  64 (45–85)	Respiratory tract		Some bacteria in the respiratory tract can lead to immune reactions.		Duration of hospitalization in ICU and type of oxygen therapy have higher impacts on microbiota composition than the viral load of COVID‐19.
34	49	China	2021	Cohort	N = 88 Median age: 50	Oropharynx	Rothia Pseudopropionibacterium Streptococus Veillonella Megasphaera veilonella	Changes in microbiota can be linked to immune responses and the severity of the disease. Some pathogens(Klebsiella and Serratia) were linked to more severe diseases.	Microbiota of COVID‐19 patients was changed notably. (Diversity↓ beneficial bacteria↓ Opportunistic pathogens ↑ )	In COVID‐19 patients: Rothia↓ Pseudopropionibacterium↓ Streptococcus↓ Veillonella ↑ (most specific for COVID‐19) Megasphaera↑
35	54	Pennsylvania (USA)	2021	Cross‐sectional	N = 96 Median Age (COVID‐19 group):36−91 Non‐COVID = 60 (39–94)	Nasopharynx Oropharynx Endotracheal aspirate	Staphylococcus Redondoviridae Anellovirdae	The composition of the microbiota is linked to Lymphocyte/neutrophil (ratio) and consequently, it is linked to the severity of the disease.	The microbiota of the Respiratory tract in COVID‐19 patients had notable differences in comparison with patients who had other severe diseases.	In intubated COVID‐19 patients: Staphylococcus↑ Redondoviridae↑ Anellovirdae↑
36	34	Russia	2021	Prospective Cohort	N = 100 Age:18−60		Lactobacillus plantarum Bifidobacterium bifidum	In this study administration of a probiotic formula in COVID‐19 patients improved the weakness and shortened the diarrhea duration.
37	68	China	2021	Cohort	N = 323 Median age = 70.5 (25−88)		Acinetobacter klebsiella			The study reported that changes in airway microbiota in severe COVID‐19 patients may be due to intubation.
38	69	USA	2021	Cohort	N = 112 Mean age =  56	Saliva	16 S rRNA sequencing Streptococcus, Prevotella	‐	Alpha and Beta diversity:no significant change In COVID‐19 patients: ↑Prevotellapallens ↓Rothiamucilaginosa ↓Streptococcus spp	Only a mild difference between the saliva microbiome of the COVID‐19 and healthy individuals was seen.
39	56	Portugal	2021	Cross‐sectional	N = 115, Median age: 68.0 (52.0–76.0)	Gut	Proteobacteria Roseburia Lachnospira	It seems that Gut microbiota composition can be a predictive factor for the severity of COVID‐19 disease.	Severe and moderate COVID‐19 patients had a remarkable change in Gut microbiome composition.	Gut microbiota in moderate and severe COVID‐19 patients: Roseburia (butyrate‐producing) ↓ Lachnospira (butyrate‐producing) ↓ Proteobacteria ↑
40	71	Italy	2021	Cross‐sectional	N = 38, Age (COVID‐19 group): 35−84	Nasopharynx	Fusobacterium Periodonticum		The nasopharyngeal microbiome of COVID‐19 patients was notably changed compared to Healthy persons.	The study suggests that the remarkable depletion of Fusobacterium Periodonticum may be due to its surface sialylation ability.
41	72	Mississippi (USA)	2021	Cohort	N = 93 Mean age COVID‐19 patients:62.3 ± 13.4 Recovered patients:46.7 ± 16.1	Gut	Campylobacter Corynebacterium Klebsiella	Due to this study the composition of the gut microbiome is not related to the severity of the disease.	the gut microbial composition in COVID‐19 patients is notably changed in comparison with healthy individuals. The recovered patients’ gut microbial composition is similar to the control group.	Gut microbiome of COVID‐19 patients: campylobacter↑ corynebacterium↑
42	73	Portugal	2021	Observational					social distancing during lockdown: ↓bacterial transmission between people, leading to ↓antibiotic consumption. antibiotic resistance genes in the microbiome ↓
43	74	Germany	2021	Cohort	N = 212, Mean age in COVID‐19 group = 56 ± 19	Gut	Streptococcus Bifidobacterium Collinsella Roesburia (butyrate‐producing) Faecalibcterium (butyrate‐producing)	Reduced butyrate‐producing bacteria in the gut microbiome are linked to severe disease.	The gut microbiome of COVID‐19 patients had a much more depleted bacterial richness.	Gut microbiome of COVID‐19 patients: Streptococcus↓ Bifidobacterium↓ Collinsella↓
44	16	China	2021	Cross‐Sectional	N = 192 Age: 49−68	Oropharynx	Streptococcus Serratia Candida Enterococcus	there is a notable link between URT microbiota and inflammatory Cytokine levels and therefore disease severity/mortality.	Microbiota of the upper respiratory tract in COVID‐19 patients was different in comparison with healthy individuals.	Streptococcus was found in abundance in the URT microbiota of recovered patients. Candida and Enterococcus were detected in abundance in the URT microbiota of deceased COVID‐19 patients.
45	75	USA	2021	Cross‐ sectional	‐	‐	‐	Gut microorganisms’ impact on ACE2 and TMPRSS2 may influence the risk of SARS‐CoV‐2 infection. The gut microbiota activating MAIT cells, influence COVID‐19 severity by affecting T and B cell function. Inflammation in autoimmune disorders and COVID‐19 may be exacerbated by gut barrier impairment.	The SARS‐CoV‐2 spike protein binds directly to LPS, altering its function and aggregation state, hence increasing pro‐inflammatory activity.	The gut microbiome is vital in controlling and training the host's immune system.
46	78	Italy	2021	Cross‐sectional observational Study	39 COVID‐19 patients Mean age =  71.1 ± 18.4 years	Oral	Streptococcus, Veillonella, Prevotella, Lactobacillus, Capnocytophaga, Abiotrophia, Aggregatibacter, Atopobium,	Streptococcus↑, Veillonella, Prevotella↑, Lactobacillus↑, Capnocytophaga↑, Abiotrophia↑, Aggregatibacter↑, Atopobium↑, Haemophilus↓, Parvimonas↓,	With COVID‐19, significant drop in alpha‐diversity and bacteria species richness, with a strong link between these decreases and symptom intensity with an increase of pro‐inflammatory cytokines like IL‐6, TNFa, and IL‐1b.	The oral microbiome's fungal component showed significant variances. COVID‐19 patients had a higher oral virome than controls. TNFa and GM‐CSF concentrations were higher in COVID‐19 patients, but not statistically significant.
47	35	Russia	2021	Cross‐sectional	‐	‐	Probiotic bacteria, Lactobacillus plantarum, Bifidobacterium bifidum	Probiotic Lactobacillus strains produce organic acids, ethanol, and exopolysaccharides, all of which have antiviral effects. The Bifidobacterium genus produces organic acids, ethanol, exopolysaccharides, and cell wall‐released lipoproteins, which can block viral particle interactions with human mucous membrane receptors, halting infection progression.	‐	Bacterial probiotics prevent respiratory virus proliferation in cell culture.
48	36	USA	2021	Clinical trial protocol	N = 1132 Age ≥ 1 year Children	Nasal swabs, stool samples	Lactobacillus rhamnosus GG	Taking LGG as a probiotic will protect against SARS‐CoV‐2 infection and reduce the severity of disease, and will be associated with beneficial changes in the composition of the gut microbiome.	‐	Impact of LGG on the microbiome in SARS‐CoV‐2 infection, symptomatology, and clinical complications; differences in baseline microbiome predicting COVID‐19 infection (ie, protective microbiome signature); effect of SARS‐CoV‐2 infection on changes in microbiome; the impact of LGG on the microbiome in EHC at high risk of COVID‐19 disease.
49	79	China	2021	Cross‐sectional	7 recovered COVID‐19 male patients, 3‐months after discharge.	Fecal	‐	Rothia↑ Erysipelatoclostridium↑ Streptococcus, Actinomyces, and Veillonella increases were noted but not statistically significant. anti‐inflammatory bacteria↓	‐	The gut microbiota of recovered patients varied from healthy controls in terms of Chao index, Simpson index, and b‐diversity. The unbalanced gut flora may not be totally repaired in recovered COVID‐19 patients.
50	81	Spain	2020	Retrospective cohort	N = 177 median age of 68.0 years	Nasopharyngeal	Actinobacillus spp., Citrobacter spp., Craurococcus spp., or Moheibacter spp.	‐	Reduce the risk of IMV and reduce the risk of death	The microbial αdiversity indexes were lower in patients who died, and the βdiversity analysis revealed considerable clustering. A more diverse nasopharyngeal microbiota with certain species seems to be an early biomarker of clinical improvement in hospitalized COVID‐19 patients.
51	37	China	2021	Randomized controlled trial	Patients with mild‐to‐severe COVID‐19 and suspected GMD.	Nasopharyngeal swab, feces	‐	‐	‐	The impact of WMT on organ function, homeostasis, inflammatory response, intestinal mucosal barrier function, and immunity in COVD‐19 patients suspected of having GMD. WMT is effective and safe for COVID‐19 patients.
52	15	China	2021	Cross‐Sectional	53 COVID‐19 patients	Throat swabs, fecal	‐	Blautia↓, Coprococcus↓, Collinsella↓, B. caccae↓, B. coprophilus↓C. colinum species↓; Streptococcus↑, Enterococcus↑, Lactobacillus↑, Actinomyces↑, Granulicatella ↑at the genus level, C. citroniae↑, B. longum, R. mucilaginosa↑	Neisseria↓ Corynebacterium↓, Actinobacillus↓, Moryella↓, Aggregatibacter↓, Treponema↓, and Pseudomonas↓ at the genus level, P. intermedia↓ Veillonella↑, Campylobacter↑, Kingella↑, H. parainfluenzae↑, R. mucilaginosa↑, N. subflava↑	The alpha and beta diversity indexes showed that SARS‐CoV‐2 infection altered the microbiome community in patients.
53	82	China	2021	Cross‐ sectional	11 COVID‐19	Pharyngeal swabs	‐	Streptococcus suis and S. agalactiae might induce ACE2 expression in Vero cells, promoting SARS‐CoV‐2 infection. These enhanced pathogens in pharynxes may produce secondary bacterial infections by altering the expression of the viral receptor ACE2 or modulating the host's immune system.	‐	COVID‐19 enhanced pathogens may play a role in SARS‐CoV‐2 infections. The alpha diversity of the two patient samples (COVID‐19 and non‐COVID‐19) differed significantly from the healthy individual group. Observed species and Shannon index showed no significant difference.
54	83	China	2021	Cross‐ sectional	9 COVID‐19 children, (7−139 months)	Throat swabs, nasal swabs, or feces	‐	Bacteroidetes↑, Firmicutes↑ Proteobacteria↑ in the respiratory tract Bacteroidetes↑, Firmicutes ↑ in the gut. Pseudomonas↑, in both the upper respiratory tract and the gut Comamonadaceae_U↑ in the upper respiratory tract	The microbiomes in COVID‐19 children's throat and nasal swabs were considerably less rich And the gut microbiota was found to be more even than that of healthy controls.	SARS‐CoV‐2 infection changes upper respiratory tract and gut microbiomes in nine children.
55	84	China	2021	Cohort	N = 100, 36.4 ± 18.7	Gut	Eubacterium rectale Bifidobacteria Faecalibacterium prausnitzii Bacteroides dorei	The composition of gut microbiota in COVID‐19 patients is notably linked to the level of inflammatory cytokines and severity of the disease. Lasting gut microbiota changes in COVID‐19 patients after recovery leads to persistent symptoms.	Gut microbiota is meaningfully changed in COVID‐19 patients.	Gut microbiota in COVID‐19 patients: Eubacterium rectale↓ Bifidobacteria↓ Faecalibacterium prausnitzii↓ Bacteroides dorei↑
56	85	China	2021	Cross‐sectional	N = 66, Mean = 42.6 ± 19	Gut	Bifidobacterium adolescentis F prausnitzii Ruminococcus bromii Bacteroides dorei Bacteroides ovatus Bacteroides thetaiotaomicron	The microbiota changes in COVID‐19 patients lead to increased symptoms and more severe disease.	The gut microbiota of COVID‐19 patients, (especially in severe disease) changed meaningfully compared to healthy individuals. Bifidobacterium↓ F prausinitzii↓	The changes in the microbiota in COVID‐19 patients lead to Lower levels of l‐Isoleucine and SCFA (Short‐Chain Fatty Acid) and l‐Isoleucine even one month after recovery and this causes more severe disease.
57	38	China	2021	Cohort	N = 375 Median age = 50 (Nonprobiotic) 48 (Probiotic)	Gut	Lactobacillus, Bifidobacterium Enterococcus	Probiotics reduced the length of COVID‐19 illness and hospitalization.		Administration of probiotics enhanced the condition of COVID‐19 patients.
58	39	China	2022	Clinical Trial	N = 55	Gut	Bifidobacteria	Administration of SIM01 (a microbiome compound) in COVID‐19 patients led to increased antibodies and lower levels of inflammatory markers.
59	86	China	2021	Cross‐sectional	N = 187 Mean age: 39 (32–57)	Gut	Saccharomyces cerevisiae Enterococcus faecalis Bacteroides fragilis	The gut microbiota in COVID‐19 patients with fever was different from those without fever. it seems that the gut microbiota changes can play a part in causing fever through inflammatory reactions.		In COVID‐19 patients with fever: Saccharomyces cerevisiae↑ Enterococcus faecalis↑ COVID‐19 patients without fever: Bacteroides fragilis↑
60	87	China	2021	Cohort	N = 29 Age: 28−41 Median: 29	Gut	F prausnitzii Escherichia unclassifies	The lasting gut microbiota dysbiosis of healthcare workers 3 months after recovery leads to persistent symptoms.	The Gut microbiota of Healthcare workers with previous SARS‐CoV‐2 infection was different in comparison to non‐COVID group even 3 months after recovery. (beneficial bacteria↓ Opportunistic pathogens ↑)
61	67	China	2021	Pilot observational study	N = 15, Mean= 53.8	Gut	Morganellamorgani Collinsella aerofaciens Streptococcus infantis		In COVID‐19 patients, the gut microbiota was changed and opportunistic pathogens were increased.	Gut microbiota in COVID‐19 patients: Morganellamorgani↑ Collinsella aerofaciens↑ Streptococcus infantis↑
62	88	China	2020	Cross‐scectional	N = 69, Median Age: 46 (COVID‐19) 63 (Pneumonia) 34 (Healthy)	Gut	Aspergillus flavus Candida albicans Candida auris		In COVID‐19 patients, the gut microbiome was different in comparison with the non‐COVID group. Candida species↑	In COVID‐19 patients Aspergillus flavus, Candida albicans, and candida Auris were increased in the gut microbiome and they were not found in healthy individuals
63	80	China	2020	Cross‐sectional	N = 36, Median Age: 55 (COVID +) 50 (Pneumonia +) 48 (Healthy)	Gut	Coprobacilum Clostridium ramosum Clostridium hathewayi F prausnitzii	The changes in the gut microbiome of COVID‐19 patients can cause more severe disease.	The gut microbiome was different in COVID‐19 patients compared to non‐COVID group. (beneficial bacteria↓ Opportunistic pathogens↑)	Coprobacilum, ramosum Clostridium, ramosum and Clostridium hathewayi were linked to more severe disease, while F prausnitzii has a negative correlation to the severity of the disease.