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. 2021 Jun 23;16(6):e0253293. doi: 10.1371/journal.pone.0253293

Table 1. The characteristics of all included studies.

Study Population and characteristics Control Samples or Microbiota community Timepoint at sample collection Methods of microbiome characterization Change in microbiota Treatment/Outcome Other key findings
Gu et al. (2020) 30 COVID-19 patients, China (1) 24 H1N1 flu patients Fecal samples Samples were collected at admission. V3-4 16S rRNA gene sequencing Patients with COVID-19 or influenza had reduced bacterial diversity compared with controls. Stool samples of COVID-19 patients had an abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella, and Actinomyces. In contrast, Ruminococcaceae family and several genera from the family Lachnospiraceae were reduced in COVID-19 patients. No outcome data Richness, diversity, and structure of the gut microbiota were not significantly different between general COVID-19 and severe COVID-19.
13 were women (2) 30 healthy controls (matched for age, sex, body mass index)
The median age was 55 (Range 29–70) years
10 patients had comorbidities, including hypertension (30%)
Zuo et al. (2020a) 15 COVID-19 patients, China 15 healthy controls Stool samples 2–3 times per week during hospitalization Whole-genome sequencing COVID-19 patients who were antibiotic naïve had increased opportunistic pathogens compared to controls. Among 15 COVID-19 patients, 7 were antibiotic-naive, 8 received empiric antibiotics. Clostridium ramosum and C. hathewayi were positively associated with severe COVID-19. In contrast, Alistipes onderdonkii and Faecalibacterium prausnitzii were negatively correlated with severe COVID-19.
7 were males, 6 community-acquired pneumonia
The median age was 55 (22–71) years
11 patients had moderate-severe COVID-19
Comorbidities: Hypertension (4), Hyperlipidemia (4), Diabetes (2), etc.
Zuo et al. (2020b) 30 COVID-19 patients, China 30 healthy controls Stool samples (Fungal microbiome) 2–3 times per week during hospitalization Whole-genome sequencing The mycobiome in most patients (22 of 30 COVID-19 patients) was similar to that in healthy controls. In contrast, gut microbiome in COVID-19 patients (8 of 30) had alterations, with enrichment of Candida albicans and heterogeneous composition. No treatment data COVID-19 patients had increased proportions of opportunistic pathogens (Candida albicans, C. auris, Aspergillus flavus) during hospitalization.
16 were males, 9 community-acquired pneumonia
The median age was 46 (15–71) years
11 patients had comorbidities
Zuo et al. (2020c) Same population as Zuo et al. (2020a) None Stool samples 2–3 times per week during hospitalization Whole-genome sequencing Stool with high SARS-CoV2 infectivity had a higher abundance of bacterial species, including Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, and Morganella morganii. Same treatment as Zuo et al. (2020a) Stool with low to no SARS-CoV-2 infectivity had higher abundances of Parabacteroides merdae, Bacteroides stercoris, Alistipes onderdonkii, and Lachnospiraceae bacterium.
Zhang et al. (2020) 24 COVID-19 (nasopharyngeal swab) patients Pneumonia cases Nasopharyngeal swab, sputum samples Samples were collected during inclusion in the cohort. Whole-genome sequencing COVID-19 patients had reduced alpha diversity in the airway microbiome. Opportunistic pathogens, including Candida albicans and human alphaherpesvirus 1, were frequently detected. No treatment data None
36 non-COVID-19 (nasopharyngeal swab)
14 COVID-19 (sputum) patients, China
39 non-COVID-19 (sputum)
37% were females
The median age was 40.5 (25–82) years
De Maio et al. (2020) 18 COVID-19 patients, Italy 22 healthy controls Nasopharyngeal swab samples Samples were collected because of suspected COVID-19. Sequencing of V5-V6 hypervariable region of bacterial 16S rRNA The microbiota of the nasopharynx was not different in COVID-19 patients compared with that in controls. No treatment data None
All patients had non-critical COVID-19
Shen et al. (2020) 8 COVID-19 pneumonia patients, China 25 community-acquired pneumonia Bronchoalveolar lavage fluid samples Samples were collected at bronchoscopic examination in clinical management. Whole-genome sequencing The BALF microbiota in COVID-19 patients was similar to that in patients with community-acquired pneumonia. The microbiome had an abundance of oral and upper respiratory commensal bacteria. No treatment data None
20 healthy controls
Chen et al. (2020) 2 patients with COVID-19, China None Bronchoalveolar lavage fluid samples Samples were collected at bronchoscopic examination for a diagnostic test. Microbial next-generation sequencing analysis Authors found Capnocytophaga species and Veillonella species in BALF samples. Antiviral and anti-infectious treatment None
A 39-year-old male and a 21-year-old female
Ren et al. (2020) 5 patients with COVID-19, China None Bronchoalveolar lavage fluid samples Samples were collected at bronchoscopic examination during hospitalization. Microbial next-generation sequencing analysis Most genome reads were viral (betacoronavirus), with bacterial pathogens such as Acinetobacter, Pseudomonas, Chryseobacterium, Escherichia, Streptococcus, Enterococcus, Rothia, and Lactobacillus. 5 patients received antibiotic therapy. Outcomes are recovered (1), hospitalized (3), and died (1). None
The median age was 52 (41–65) years
2 patients were female
All had moderate to severe COVID-19
Comorbidities: hypertension, chronic liver disease
Fan et al. (2020) 20 deceased COVID-19 patients, China None Lung tissue samples Samples were collected from deceased patients. Sequencing of V3-V4 regions of bacterial 16S rRNA, ITS gene Acinetobacter was the most common bacterial genus, followed by Chryseobacterium, Burkholderia, Brevundimonas, Sphingobium, and Enterobacterales. Cryptococcus was the most prevalent fungus, along with Issatchenkia, Wallemia, Cladosporium, and Alternaria. All patients received antibacterial and antiviral therapy. None
14 were males
The median age was 66 years
Comorbidities: cardiovascular disease (10), hypertension (9), malignancy (7), diabetes (2), chronic kidney disease (2), chronic lung diseases (1)
Tao et al. (2020) 62 patients with COVID-19, China 33 seasonal influenza patients Fecal samples Samples were collected at first time of visit to the hospital. Next-generation sequencing of V4 region of the 16S rRNA COVID-19 patients had an abundance of Streptococcus, Clostridium, Lactobacillus, and Bifidobacterium in gut microbiota. In contrast, lower levels of Bacteroides, Roseburia, Faecalibacterium, Coprococcus, Parabacteroides were found. No data Alpha-diversity of gut microbiome decreased in COVID-19 compared with that in healthy control, flu patients.
40 healthy controls
Yu et al. (unpublished) 2 male patients with COVID-19, China 22 healthy cohort (Data imported from Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–80.) Anal swab samples No data No data The proportion of gut microbiota, including Corynebacterium and Ruthenibacterium, was increased. Both patients received antiviral and antibacterial agents. and both patients died. None
2 patients with COVID-19, China
65 years old male and 78 years old male
Comorbidities: prostatic hyperplasia, chronic bronchitis
Ai et al. (unpublished) 20 patients with COVID-19, China 33 pneumonia without COVID-19 Nasopharyngeal swab samples Admission day Multiplex RT-PCR assays More than half of patients had co-infection with COVID-19 and another virus, such as influenza A/B, rhino- or enteroviruses, or respiratory syncytial virus. No data None
10 were female next-generation sequencing
The median age was 37 years
Budding et al. (unpublished) 46 patients with COVID-19, Netherlands 89 SARS-CoV2 (-) patients Throat swab samples Samples were collected for routine diagnostic tests. 16S rDNA sequencing Haemophilus parainfluenzae, Neisseria cinerea, No data None
S. mitis, S. bovis, Leptotrichia buccalis, and Rothia mucilaginosa were the main composition of throat microbiome.
Xu et al. (a) (abstract only) No data, China No data Intestinal microbiome No data No data COVID-19 patients had intestinal dysbiosis with decreased Lactobacillus and Bifidobacterium. No data None
Xu et al. (b) (abstract only) No data, China No data Gut microbiome No data No data Decreased proportions of Lactobacillus and Bifidobacterium were observed in COVID-19 patients. No data None