Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19

Ma, Shengli; Zhang, Fan; Zhou, Fengxia; Li, Hui; Ge, Wenyu; Gan, Rui; Nie, Huan; Li, Biao; Wang, Yindong; Wu, Meng; Li, Duo; Wang, Dongmei; Wang, Zheng; You, Yuhong; Huang, Zhiwei

doi:10.1038/s41392-021-00614-3

Cited by 105 publications

(151 citation statements)

References 47 publications

(52 reference statements)

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“…Specifically, the predominance of Prevotella salivae and Veillonella infantium correlated with the increase in inflammatory cytokines in oral samples in COVID-19 patients. More importantly, the oral bacterial signature and cytokine panel correlated with the serum cytokine profile in hospitalized COVID-19 patients (Iebba et al, 2020;Ma et al, 2021). Interestingly, similar specific oral bacterial preponderance that influenced pneumonia development was previously reported in influenza infections (Gu et al, 2020).…”

Section: Pathogenesis Of Taste Dysfunction In Long Covid-19supporting

confidence: 63%

Taste Dysfunction and Long COVID-19

Srinivasan

2021

Front. Cell. Infect. Microbiol.

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Chemosensory dysfunctions including anosmia, hyposmia, ageusia, and hypogeusia constitute one of the chief symptoms of SARS-CoV2 infection. Meta-analyses suggest that the prevalence of olfactory dysfunction ranged between 41.0-61.0% and that of gustatory dysfunction between 38.2-49.0% in COVID-19. Indeed, self-reported loss of smell and taste has been observed to be more prognostic than other symptoms including fatigue, fever, or cough in predicting symptomatic infection (Agyeman et al., 2020;Mastrangelo et al., 2021). Significantly, loss of taste is consistently reported as a common symptom of long COVID-19, defined as persistence of symptoms four weeks after infection (Biadsee et al., 2021). Following over four-hundred SARS-CoV-2 infected individuals for severity, improvement, and recovery of subjective chemosensory dysfunction for four months, Schwab et al. have reported that the recovery from loss of taste became stagnant after about two months with little improvement subsequently (Schwab et al., 2021). An overview of emerging research on the pathogenesis of long COVID-19 and an opinion about potential mechanisms for gustatory dysfunction is included below. GUSTATION-THE PROCESS OF TASTE PERCEPTIONGustation is an integrated event of multiple physiological processes occurring concurrently through activation of specialized taste, orosensory, and gastrointestinal fibers (Simon et al., 2006). The taste buds, that constitute the peripheral chemosensory units, are distributed in the papillae of the tongue, palate, larynx, and esophagus. Each taste bud consists of 50-100 tightly packed specialized epithelial cells called taste receptor cells that are of three types. Type-I are glial-like cells, type-II cells express

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Section: Pathogenesis Of Taste Dysfunction In Long Covid-19supporting

confidence: 63%

Taste Dysfunction and Long COVID-19

Srinivasan

2021

Front. Cell. Infect. Microbiol.

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“…However, no information on the viral loads or interferon responses of the patients were known; hence, it is not clear if the co-infection was associated with strong viral replications or with other factors. Our metagenomics analysis indicates a relationship between dysbiosis within the nasal tract microbiota and COVID-19 severity, consistent with previous studies of the gut and respiratory microbiomes 30 – 37 . However, without retrospective longitudinal data on the microbiome of our patients, it is difficult to determine whether the initial infection is more likely to occur because of a pre-existing dysbiosis.…”

Section: Discussionsupporting

confidence: 91%

Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients

Rouchka

Chariker

Alejandro

et al. 2021

Sci Rep

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Key elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined cohort. To address this important question, we sought to understand how these four key components interplay in a cohort of COVID-19 patients. We determined the viral loads and gene expression using high throughput sequencing and various virological methods. We found that viral loads in the upper respiratory tract in COVID-19 patients at an early phase of infection vary widely. While the majority of nasopharyngeal (NP) samples have a viral load lower than the limit of detection of infectious viruses, there are samples with an extraordinary amount of SARS-CoV-2 RNA and a high viral titer. No specific viral factors were identified that are associated with high viral loads. Host gene expression analysis showed that viral loads were strongly correlated with cellular antiviral responses. Interestingly, however, COVID-19 patients who experience mild symptoms have a higher viral load than those with severe complications, indicating that naso-pharyngeal viral load may not be a key factor of the clinical outcomes of COVID-19. The metagenomics analysis revealed that the microflora in the upper respiratory tract of COVID-19 patients with high viral loads were dominated by SARS-CoV-2, with a high degree of dysbiosis. Finally, we found a strong inverse correlation between upregulation of interferon responses and disease severity. Overall our study suggests that a high viral load in the upper respiratory tract may not be a critical factor for severe symptoms; rather, dampened antiviral responses may be a critical factor for a severe outcome from the infection.

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“…Regarding microbiota and COVID-19 severity, Ma et al [19] explored the oropharyngeal microbiome in COVID-19 patients (n=31) with various severities (mild, moderate, severe, or critical) compared with flu patients (n=29) and healthy controls (n= 28) using highthroughput metagenomics. They showed that critical COVID-19 patients presented with a significant diminution in α diversity (Shannon index), while noncritical patients exhibited no significant change from the normal group.…”

Section: Discussionmentioning

confidence: 99%

“…The available evidence suggests a potential role of microbiota in susceptibility to SARS-CoV-2 infection and COVID-19 severity, but longitudinal studies evaluating the microbiota as a prognostic factor for severity of disease progression are lacking. The data regarding the association between nasopharyngeal microbiota features and disease severity are scarce, and limited in terms of showing a decrease in α diversity or identifying specific genera with relevance to critical illness [19,20]. Since the sampling of this location is very accessible, with the nasopharyngeal aspirate swab diagnostic confirmation procedure able to obtain this information, it should be a priority to address the relationship between nasopharyngeal microbiota and COVID-19 outcomes.…”

Section: Introductionmentioning

confidence: 99%

Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients: a retrospective cohort study in a Mediterranean area

Ventero

Moreno-Pérez

Molina-Pardines

et al. 2021

Preprint

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Background: There is mounting evidence suggesting that the microbiome composition could be different in COVID-19 patients. However, the relationship between microbiota and COVID-19 severity progression is still being assessed. This study aimed to analyse the diversity and taxonomic composition of the nasopharyngeal microbiota, to determine its association with COVID-19 clinical outcome. Methods and Findings: Samples came from a retrospective cohort of adult patients with COVID-19, hospitalised in a tertiary centre. To study the nasopharyngeal microbiota, we utilized 16S rRNA sequencing. Raw sequences were processed by QIIME2. The associations between the microbiota, invasive mechanical ventilation (IMV), and all-cause mortality were analysed by multiple logistic regression (OR; 95%CI), adjusted for age, gender, and comorbidity. 177 patients were included: median age 68.0 years, 57.6% males, 59.3% had a Charlson comorbidity index ≥3, and 89.2% with pneumonia. The microbiota α diversity indexes were lower in patients with a fatal outcome, and this association persisted after adjustment for the main confounders; whereas the β diversity analysis showed a significant clustering, grouping the patients with a fatal outcome. After multivariate adjustment, the presence of Selenomonas spp., Filifactor spp., Actinobacillus spp., or Chroococcidiopsis spp., was associated with a reduced risk of IMV (adjusted OR 0.06[95%CI 0.01–0.047], p = 0.007). Conclusions: The microbiota diversity and taxonomic composition are related to COVID-19 severity. Higher diversity and the presence of certain genera in the nasopharyngeal microbiota seem to be early biomarkers of a favourable clinical evolution in hospitalised patients with moderate to severe SARS-CoV-2 infections.

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Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19

Cited by 105 publications

References 47 publications

Taste Dysfunction and Long COVID-19

Taste Dysfunction and Long COVID-19

Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients

Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients: a retrospective cohort study in a Mediterranean area

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