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1.
Microb Pathog ; 165: 105506, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1763898

ABSTRACT

Since its first appearance, the SARS-CoV-2 has spread rapidly in the human population, reaching the pandemic scale with >280 million confirmed infections and more than 5 million deaths to date (https://covid19.who.int/). These data justify the urgent need to enhance our understanding of SARS-CoV-2 effects in the respiratory system, including those linked to co-infections. The principal aim of our study is to investigate existing correlations in the nasopharynx between the bacterial community, potential pathogens, and SARS-CoV-2 infection. The main aim of this study was to provide evidence pointing to possible relationships between components of the bacterial community and SARS-CoV-2 in the nasopharynx. Meta-transcriptomic profiling of the nasopharyngeal microbial community was carried out in 89 SARS-Cov-2 positive subjects from the Campania Region in Italy. To this end, RNA extracted from nasopharyngeal swabs collected at different times during the initial phases of the pandemic was analyzed by Next-Generation Sequencing (NGS). Results show a consistently high presence of members of the Proteobacteria (41.85%), Firmicutes (28.54%), and Actinobacteria (16.10%) phyla, and an inverted correlation between the host microbiome, co-infectious bacteria, and super-potential pathogens such as Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Neisseria gonorrhoeae. In depth characterization of microbiota composition in the nasopharynx can provide clues to understand its potential contribution to the clinical phenotype of Covid-19, clarifying the interaction between SARS-Cov-2 and the bacterial flora of the host, and highlighting its dysbiosis and the presence of pathogens that could affect the patient's disease progression and outcome.


Subject(s)
COVID-19 , Coinfection , Microbiota , Bacteria/genetics , Coinfection/epidemiology , High-Throughput Nucleotide Sequencing , Humans , Italy/epidemiology , Microbiota/genetics , Nasopharynx/microbiology , Pandemics , SARS-CoV-2/genetics
2.
Sci Rep ; 11(1): 24042, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1574556

ABSTRACT

The microbiota of the nasopharyngeal tract (NT) play a role in host immunity against respiratory infectious diseases. However, scant information is available on interactions of SARS-CoV-2 with the nasopharyngeal microbiome. This study characterizes the effects of SARS-CoV-2 infection on human nasopharyngeal microbiomes and their relevant metabolic functions. Twenty-two (n = 22) nasopharyngeal swab samples (including COVID-19 patients = 8, recovered humans = 7, and healthy people = 7) were collected, and underwent to RNAseq-based metagenomic investigation. Our RNAseq data mapped to 2281 bacterial species (including 1477, 919 and 676 in healthy, COVID-19 and recovered metagenomes, respectively) indicating a distinct microbiome dysbiosis. The COVID-19 and recovered samples included 67% and 77% opportunistic bacterial species, respectively compared to healthy controls. Notably, 79% commensal bacterial species found in healthy controls were not detected in COVID-19 and recovered people. Similar dysbiosis was also found in viral and archaeal fraction of the nasopharyngeal microbiomes. We also detected several altered metabolic pathways and functional genes in the progression and pathophysiology of COVID-19. The nasopharyngeal microbiome dysbiosis and their genomic features determined by our RNAseq analyses shed light on early interactions of SARS-CoV-2 with the nasopharyngeal resident microbiota that might be helpful for developing microbiome-based diagnostics and therapeutics for this novel pandemic disease.


Subject(s)
Bacteria/classification , COVID-19/microbiology , Nasopharynx/microbiology , SARS-CoV-2/genetics , Sequence Analysis, RNA/methods , Adult , Aged , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/pathogenicity , Case-Control Studies , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Metagenomics , Middle Aged , Phylogeny , Symbiosis , Young Adult
3.
Exp Biol Med (Maywood) ; 247(5): 409-415, 2022 03.
Article in English | MEDLINE | ID: covidwho-1511670

ABSTRACT

The upper respiratory tract is inhabited by diverse range of commensal microbiota which plays a role in protecting the mucosal surface from pathogens. Alterations of the bacterial community from respiratory viral infections could increase the susceptibility to secondary infections and disease severities. We compared the upper respiratory bacterial profiles among Thai patients with influenza or COVID-19 by using 16S rDNA high-throughput sequencing based on MiSeq platform. The Chao1 richness was not significantly different among groups, whereas the Shannon diversity of Flu A and Flu B groups were significantly lower than Non-Flu & COVID-19 group. The beta diversity revealed that the microbial communities of influenza (Flu A and Flu B), COVID-19, and Non-Flu & COVID-19 were significantly different; however, the comparison of the community structure was similar between Flu A and Flu B groups. The bacterial classification revealed that Enterobacteriaceae was predominant in influenza patients, while Staphylococcus and Pseudomonas were significantly enriched in the COVID-19 patients. These implied that respiratory viral infections might be related to alteration of upper respiratory bacterial community and susceptibility to secondary bacterial infections. Moreover, the bacteria that observed in Non-Flu & COVID-19 patients had high abundance of Streptococcus, Prevotella, Veillonella, and Fusobacterium. This study provides the basic knowledge for further investigation of the relationship between upper respiratory microbiota and respiratory disease which might be useful for better understanding the mechanism of viral infectious diseases.


Subject(s)
Bacteria/genetics , COVID-19/microbiology , Influenza, Human/microbiology , Microbiota/physiology , Nasopharynx/microbiology , Adolescent , Adult , Humans , Microbiota/genetics , Middle Aged , Retrospective Studies , Young Adult
4.
Cytokine ; 149: 155757, 2022 01.
Article in English | MEDLINE | ID: covidwho-1499766

ABSTRACT

BACKGROUND: To determine and compare nasopharyngeal microbiota (NM) composition, in vitro basal (Nil tube), provoked (Mitogen tube) production of cytokines at the early stage of COVID-19. METHODS: This cross-sectional study included 4 age and sex-matched study groups; group 1 (recovered COVID-19) (n = 26), group 2 (mild COVID-19) (n = 24), group 3 (severe COVID-19) (n = 25), and group 4 (healthy controls) (n = 25). The study parameters obtained from the COVID-19 (group 2, and 3) at the early phase of hospital admission. RESULTS: The results from the reaserch deoicted that the Mean ± SD age was 53.09 ± 14.51 years. Some of the in vitro cytokines production was significantly different between the study groups. Some of the findinggs on cytokines depicted a significant differences between study groups were interleukin (IL)-1ß Nil, IL-1ß Mitogen, and their subtraction (i.e Mitogen-Nil). Regarding IL-10, and IL-17a levels, Mitogen, and Mitogen-Nil tube production levels were significantly different between the groups. Surprisingly, most of these measures were lowest in the severe COVID-19 patients' group. Using discriminant analysis effect size (LEfSe), Taxa of NM with significant abundance was determined. About 20 taxa with an LDA score > 4 were identified as candidate biomarkers. Some of these taxa showed a significant correlation with IL-1ß and IL-10 Mitogen and Mitogen- Nil levels (R > 0.3 or < -0.3, p < 0.05). CONCLUSIONS: The findings of this perticular study regarting the early stage of COVID-19 showed that in vitro cytokines production, studies might be more useful than the ordinary cytokines' blood level measurement. Besides, the study identified some NM species that could be candidate biomarkers in managing this infection. However, further detailed studies are needed in these fields.


Subject(s)
COVID-19/metabolism , COVID-19/microbiology , Cytokines/metabolism , Microbiota/physiology , Nasopharynx/microbiology , Nasopharynx/virology , COVID-19/virology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged
5.
Microbiol Spectr ; 9(2): e0005521, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1467670

ABSTRACT

Bacterial-viral interactions in saliva have been associated with morbidity and mortality for respiratory viruses such as influenza and SARS-CoV. However, such transkingdom relationships during SARS-CoV-2 infection are currently unknown. Here, we aimed to elucidate the relationship between saliva microbiota and SARS-CoV-2 in a cohort of newly hospitalized COVID-19 patients and controls. We used 16S rRNA sequencing to compare microbiome diversity and taxonomic composition between COVID-19 patients (n = 53) and controls (n = 59) and based on saliva SARS-CoV-2 viral load as measured using reverse transcription PCR (RT-PCR). The saliva microbiome did not differ markedly between COVID-19 patients and controls. However, we identified significant differential abundance of numerous taxa based on saliva SARS-CoV-2 viral load, including multiple species within Streptococcus and Prevotella. IMPORTANCE Alterations to the saliva microbiome based on SARS-CoV-2 viral load indicate potential biologically relevant bacterial-viral relationships which may affect clinical outcomes in COVID-19 disease.


Subject(s)
Bacteria/classification , COVID-19/pathology , Microbial Interactions/physiology , SARS-CoV-2/isolation & purification , Saliva/microbiology , Bacteria/genetics , Dysbiosis/microbiology , Female , Humans , Male , Microbiota/genetics , Middle Aged , Nasopharynx/microbiology , RNA, Ribosomal, 16S/genetics , Viral Load
6.
Virol J ; 18(1): 202, 2021 10 09.
Article in English | MEDLINE | ID: covidwho-1463255

ABSTRACT

BACKGROUND: The effect of SARS-CoV-2 on existing respiratory pathogens in circulation remains uncertain. This study aimed to assess the impact of SARS-CoV-2 on the prevalence of respiratory pathogens among hospitalized children. METHODS: This study enrolled hospitalized children with acute respiratory infections in Shenzhen Children's Hospital from September to December 2019 (before the COVID-19 epidemic) and those from September to December 2020 (during the COVID-19 epidemic). Nasopharyngeal swabs were collected, and respiratory pathogens were detected using multiplex PCR. The absolute case number and detection rates of 11 pathogens were collected and analyzed. RESULTS: A total of 5696 children with respiratory tract infection received multiplex PCR examination for respiratory pathogens: 2298 from September to December 2019 and 3398 from September to December 2020. At least one pathogen was detected in 1850 (80.5%) patients in 2019, and in 2380 (70.0%) patients in 2020; the detection rate in 2020 was significantly lower than that in 2019.The Influenza A (InfA) detection rate was 5.6% in 2019, but 0% in 2020. The detection rates of Mycoplasma pneumoniae, Human adenovirus, and Human rhinovirus also decreased from 20% (460), 8.9% (206), and 41.8% (961) in 2019 to 1.0% (37), 2.1% (77), and 25.6% (873) in 2020, respectively. In contrast, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased from 6.6% (153), 9.9% (229), and 0.5% (12) in 2019 to 25.6% (873), 15.5% (530), and 7.2% (247) in 2020, respectively (p < 0.0001). CONCLUSIONS: Successful containment of seasonal influenza as a result of COVID-19 control measures will ensure we are better equipped to deal with future outbreaks of both influenza and COVID-19.Caused by virus competition, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased in Shenzhen,that reminds us we need to take further monitoring and preventive measures in the next epidemic season.


Subject(s)
Antibiosis , COVID-19/epidemiology , Respiratory Tract Diseases/epidemiology , SARS-CoV-2/isolation & purification , Adenoviruses, Human/genetics , Adenoviruses, Human/isolation & purification , Adolescent , COVID-19/virology , Child , Child, Hospitalized , Child, Preschool , China , Enterovirus/genetics , Enterovirus/isolation & purification , Female , Humans , Infant , Influenza A virus/genetics , Influenza A virus/isolation & purification , Male , Metapneumovirus/genetics , Metapneumovirus/isolation & purification , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/isolation & purification , Nasopharynx/microbiology , Nasopharynx/virology , Prevalence , Respiratory Syncytial Viruses/genetics , Respiratory Syncytial Viruses/isolation & purification , Respiratory Tract Diseases/microbiology , Respiratory Tract Diseases/virology , Respirovirus/genetics , Respirovirus/isolation & purification , SARS-CoV-2/genetics
7.
Nat Immunol ; 22(11): 1428-1439, 2021 11.
Article in English | MEDLINE | ID: covidwho-1392873

ABSTRACT

Coordinated local mucosal and systemic immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either protect against coronavirus disease 2019 (COVID-19) pathologies or fail, leading to severe clinical outcomes. To understand this process, we performed an integrated analysis of SARS-CoV-2 spike-specific antibodies, cytokines, viral load and bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct patients with COVID-19 during acute infection. Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and also with spike-specific neutralizing antibodies. By contrast, nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities. Potential pathogenic microorganisms, often implicated in secondary respiratory infections, were associated with mucosal inflammation and elevated in severe COVID-19. Our results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes.


Subject(s)
COVID-19/immunology , Microbiota/immunology , Nasopharynx/immunology , SARS-CoV-2/physiology , Acute Disease , Adolescent , Adult , Aged , Antibodies, Viral/blood , Cohort Studies , Female , Humans , Immunity, Humoral , Immunity, Mucosal , Interferons/blood , Male , Middle Aged , Nasopharynx/microbiology , Spike Glycoprotein, Coronavirus/immunology , Viral Load , Young Adult
9.
Microbiol Spectr ; 9(2): e0019721, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1381169

ABSTRACT

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic variants that may alter viral fitness highlights the urgency of widespread next-generation sequencing (NGS) surveillance. To profile genetic variants of the entire SARS-CoV-2 genome, we developed and clinically validated a hybridization capture SARS-CoV-2 NGS assay, integrating novel methods for panel design using double-stranded DNA (dsDNA) biotin-labeled probes, and built accompanying software. This test is the first hybrid capture-based NGS assay given Food and Drug Administration (FDA) emergency use authorization for detection of the SARS-CoV-2 virus. The positive and negative percent agreement (PPA and NPA, respectively) were defined in comparison to the results for an orthogonal real-time reverse transcription polymerase chain reaction (RT-PCR) assay (PPA and NPA, 96.7 and 100%, respectively). The limit of detection was established to be 800 copies/ml with an average fold enrichment of 46,791. Furthermore, utilizing the research-use-only analysis to profile the variants, we identified 55 novel mutations, including 11 in the functionally important spike protein. Finally, we profiled the full nasopharyngeal microbiome using metagenomics and found overrepresentation of 7 taxa and evidence of macrolide resistance in SARS-CoV-2-positive patients. This hybrid capture NGS assay, coupled with optimized software, is a powerful approach to detect and comprehensively map SARS-CoV-2 genetic variants for tracking viral evolution and guiding vaccine updates. IMPORTANCE This is the first FDA emergency-use-authorized hybridization capture-based next-generation sequencing (NGS) assay to detect the SARS-CoV-2 genome. Viral metagenomics and the novel hybrid capture NGS-based assay, along with its research-use-only analysis, can provide important genetic insights into SARS-CoV-2 and other emerging pathogens and improve surveillance and early detection, potentially preventing or mitigating new outbreaks. Better understanding of the continuously evolving SARS-CoV-2 viral genome and the impact of genetic variants may provide individual risk stratification, precision therapeutic options, improved molecular diagnostics, and population-based therapeutic solutions.


Subject(s)
Genetic Variation/genetics , Genome, Viral/genetics , Microbiota/genetics , Nasopharynx/microbiology , SARS-CoV-2/genetics , Anti-Bacterial Agents/pharmacology , COVID-19/pathology , Drug Resistance, Bacterial/genetics , High-Throughput Nucleotide Sequencing , Humans , Limit of Detection , Macrolides/pharmacology , Metagenomics/methods , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/isolation & purification
10.
J Breath Res ; 15(4)2021 09 13.
Article in English | MEDLINE | ID: covidwho-1379422

ABSTRACT

The evidence that severe coronavirus disease 2019 (COVID-19) is a risk factor for development of mycotic respiratory infection with an increased mortality is rising. Immunosuppressed are among the most susceptible patients andAspergillusspecies is the most feared superinfection. In this study we evaluated mycotic isolation prevalence on bronchoalveolar lavage (BAL) of patients who underwent bronchoscopy in search of severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA. Moreover, we described the clinical characteristics and main outcomes of these patients. We included 118 patients, 35.9% of them were immunosuppressed for different reasons: in 23.7% we isolated SARS-CoV-2 RNA, in 33.1% we identified at least one mycotic agent and both in 15.4%. On BAL we observed in three casesAspergillusspp, in six casesPneumocystisand in 32Candidaspp. The prevalence of significant mold infection was 29.3% and 70.7% of cases were false positive or clinically irrelevant infections. In-hospital mortality of patients with fungal infection was 15.3%. The most frequent computed tomography (CT) pattern, evaluated with the Radiological Society of North America consensus statement, among patients with a mycotic pulmonary infection was the atypical one (p< 0.0001). Mycotic isolation on BAL may be interpreted as an innocent bystander, but its identification could influence the prognosis of patients, especially in those who need invasive investigations during the COVID-19 pandemic; BAL plays a fundamental role in resolving clinical complex cases, especially in immunosuppressed patients independently from radiological features, without limiting its role in ruling out SARS-CoV-2 infection.


Subject(s)
Bronchoalveolar Lavage , COVID-19/diagnosis , COVID-19/epidemiology , Mycoses/diagnosis , Mycoses/epidemiology , Nasopharynx/microbiology , SARS-CoV-2 , Aged , Aged, 80 and over , COVID-19/virology , Female , Humans , Immunocompromised Host , Male , Middle Aged , Mycoses/microbiology , Nasopharynx/virology , Pandemics , Prevalence , Prognosis , RNA, Viral/analysis , RNA, Viral/genetics , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
11.
mBio ; 12(4): e0177721, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1360545

ABSTRACT

Viral infection of the respiratory tract can be associated with propagating effects on the airway microbiome, and microbiome dysbiosis may influence viral disease. Here, we investigated the respiratory tract microbiome in coronavirus disease 2019 (COVID-19) and its relationship to disease severity, systemic immunologic features, and outcomes. We examined 507 oropharyngeal, nasopharyngeal, and endotracheal samples from 83 hospitalized COVID-19 patients as well as non-COVID patients and healthy controls. Bacterial communities were interrogated using 16S rRNA gene sequencing, and the commensal DNA viruses Anelloviridae and Redondoviridae were quantified by qPCR. We found that COVID-19 patients had upper respiratory microbiome dysbiosis and greater change over time than critically ill patients without COVID-19. Oropharyngeal microbiome diversity at the first time point correlated inversely with disease severity during hospitalization. Microbiome composition was also associated with systemic immune parameters in blood, as measured by lymphocyte/neutrophil ratios and immune profiling of peripheral blood mononuclear cells. Intubated patients showed patient-specific lung microbiome communities that were frequently highly dynamic, with prominence of Staphylococcus. Anelloviridae and Redondoviridae showed more frequent colonization and higher titers in severe disease. Machine learning analysis demonstrated that integrated features of the microbiome at early sampling points had high power to discriminate ultimate level of COVID-19 severity. Thus, the respiratory tract microbiome and commensal viruses are disturbed in COVID-19 and correlate with systemic immune parameters, and early microbiome features discriminate disease severity. Future studies should address clinical consequences of airway dysbiosis in COVID-19, its possible use as biomarkers, and the role of bacterial and viral taxa identified here in COVID-19 pathogenesis. IMPORTANCE COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the respiratory tract, results in highly variable outcomes ranging from minimal illness to death, but the reasons for this are not well understood. We investigated the respiratory tract bacterial microbiome and small commensal DNA viruses in hospitalized COVID-19 patients and found that each was markedly abnormal compared to that in healthy people and differed from that in critically ill patients without COVID-19. Early airway samples tracked with the level of COVID-19 illness reached during hospitalization, and the airway microbiome also correlated with immune parameters in blood. These findings raise questions about the mechanisms linking SARS-CoV-2 infection and other microbial inhabitants of the airway, including whether the microbiome might regulate severity of COVID-19 disease and/or whether early microbiome features might serve as biomarkers to discriminate disease severity.


Subject(s)
Bacteria/classification , Dysbiosis/microbiology , Lung/microbiology , Nasopharynx/microbiology , Oropharynx/microbiology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Anelloviridae/classification , Anelloviridae/genetics , Anelloviridae/isolation & purification , Bacteria/genetics , Bacteria/isolation & purification , COVID-19/pathology , Female , Humans , Lymphocyte Count , Male , Microbiota , Middle Aged , RNA, Ribosomal, 16S/genetics , Severity of Illness Index
12.
J Infect Dev Ctries ; 15(6): 761-765, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1304764

ABSTRACT

INTRODUCTION: The aim of this study is to determine the coinfections with other respiratory pathogens in SARS-CoV-2 infected children patients in a pediatric unit in Istanbul. METHODOLOGY: This retrospective descriptive study was conducted in a 1000-bedded tertiary education and research hospital in Istanbul. All children hospitalized with the diagnosis of SARS-CoV-2 infection had been investigated for respiratory agents in nasopharyngeal secretions. Laboratory confirmation of SARS-CoV-2 and the other respiratory pathogens were performed using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: A total of 209 hospitalized children with suspected SARS-CoV-2 infection between March 2020-May 2020 were enrolled in this study. Among 209 children, 93 (44.5%) were RT-PCR positive for SARS-CoV-2 infection, and 116 (55.5%) were RT-PCR negative. The most common clinical symptoms in all children with SARS-CoV-2 infection were fever (68.8%) and cough (57.0%). The other clinical symptoms in decreasing rates were headache (10.8%), myalgia (5.4%), sore throat (3.2%), shortness of breath (3.2%), diarrhea (2.2%) and abdominal pain in one child. In 7 (7.5%) patients with SARS-CoV-2 infection, coinfection was detected. Two were with rhinovirus/enterovirus, two were with Coronavirus NL63, one was with adenovirus, and one was with Mycoplasma pneumoniae. In one patient, two additional respiratory agents (rhinovirus/enterovirus and adenovirus) were detected. There was a significantly longer hospital stay in patients with coinfection (p = 0.028). CONCLUSIONS: Although the coinfection rate was low in SARS-CoV-2 infected patients in our study, we found coinfection as a risk factor for length of hospital stay in the coinfected patient group.


Subject(s)
COVID-19/microbiology , COVID-19/virology , Coinfection/microbiology , Coinfection/virology , Viruses/genetics , Adenoviridae/genetics , Adolescent , COVID-19/diagnosis , Child , Child, Preschool , Coinfection/diagnosis , Coinfection/epidemiology , Hospitalization/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/isolation & purification , Nasopharynx/microbiology , Nasopharynx/virology , Qualitative Research , Respiratory System/microbiology , Respiratory System/virology , Retrospective Studies , SARS-CoV-2/genetics , Tertiary Care Centers/statistics & numerical data , Turkey/epidemiology , Viruses/classification , Viruses/isolation & purification
13.
PLoS One ; 16(6): e0253293, 2021.
Article in English | MEDLINE | ID: covidwho-1280625

ABSTRACT

BACKGROUND: Human microbiotas are communities of microorganisms living in symbiosis with humans. They play an important role in the host immune response to respiratory viral infection. However, evidence on the human microbiome and coronavirus disease (COVID-19) relationship is insufficient. The aim of this systematic literature review was to evaluate existing evidence on the association between the microbiome and COVID-19 in humans and summarize these data in the pandemic era. METHODS: We conducted a systematic literature review on the association between the microbiome and COVID-19 in humans by searching PubMed, Embase, and the Cochrane Library, CINAHL, and Web of Science databases for articles in English published up to October 31, 2020. The results were analyzed qualitatively. This study is registered with PROSPERO (CRD42020195982). RESULTS: Of the 543 articles identified by searching databases, 16 in line with the research objectives were eligible for qualitative review: eight sampled the microbiome using stool, four using nasopharyngeal or throat swab, three using bronchoalveolar lavage fluid, and one using lung tissue. Fecal microbiome dysbiosis and increased opportunistic pathogens were reported in COVID-19 patients. Several studies suggested the dysbiosis in the lung microbiome of COVID-19 patients with an abundance of opportunistic pathogens using lower respiratory tract samples. The association between COVID-19 severity and the human microbiome remains uncertain. CONCLUSION: The human fecal and respiratory tract microbiome changed in COVID-19 patients with opportunistic pathogen abundance. Further research to elucidate the effect of alternation of the human microbiome in disease pathogenesis is warranted.


Subject(s)
COVID-19/microbiology , Dysbiosis/microbiology , Microbiota , Nasopharynx/microbiology , Bronchoalveolar Lavage Fluid , Dysbiosis/virology , Feces/microbiology , Gastrointestinal Microbiome , Humans
14.
Virol J ; 18(1): 127, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1269882

ABSTRACT

BACKGROUND: In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes. METHODS: Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. RESULTS: We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38-8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08-2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2). CONCLUSIONS: Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality.


Subject(s)
COVID-19/mortality , Coinfection/mortality , Influenza, Human/mortality , Adult , Aged , Bacterial Infections/epidemiology , Bacterial Infections/mortality , Bacterial Infections/pathology , COVID-19/epidemiology , COVID-19/pathology , Coinfection/epidemiology , Coinfection/pathology , Female , Hospitalization , Humans , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/epidemiology , Influenza, Human/pathology , Intensive Care Units , Male , Middle Aged , Nasopharynx/microbiology , Nasopharynx/virology , Prevalence , SARS-CoV-2/isolation & purification , Saudi Arabia/epidemiology
15.
Sci Rep ; 11(1): 8922, 2021 04 26.
Article in English | MEDLINE | ID: covidwho-1203450

ABSTRACT

The coronavirus disease 2019 (COVID-19) has rapidly spread around the world, impacting the lives of many individuals. Growing evidence suggests that the nasopharyngeal and respiratory tract microbiome are influenced by various health and disease conditions, including the presence and the severity of different viral disease. To evaluate the potential interactions between Severe Acute Respiratory Syndrome Corona 2 (SARS-CoV-2) and the nasopharyngeal microbiome. Microbial composition of nasopharyngeal swab samples submitted to the clinical microbiology lab for suspected SARS-CoV-2 infections was assessed using 16S amplicon sequencing. The study included a total of 55 nasopharyngeal samples from 33 subjects, with longitudinal sampling available for 12 out of the 33 subjects. 21 of the 33 subjects had at least one positive COVID-19 PCR results as determined by the clinical microbiology lab. Inter-personal variation was the strongest factor explaining > 75% of the microbial variation, irrespective of the SARS-CoV-2 status. No significant effect of SARS-CoV-2 on the nasopharyngeal microbial community was observed using multiple analysis methods. These results indicate that unlike some other viruses, for which an effect on the microbial composition was noted, SARS-CoV-2 does not have a strong effect on the nasopharynx microbial habitants.


Subject(s)
COVID-19/microbiology , Microbiota , Nasopharynx/microbiology , SARS-CoV-2/physiology , Adult , Aged , COVID-19/virology , Female , Humans , Male , Microbiota/genetics , Middle Aged , RNA, Ribosomal, 16S/genetics
16.
PLoS One ; 16(3): e0248750, 2021.
Article in English | MEDLINE | ID: covidwho-1144198

ABSTRACT

BACKGROUND: Severe acute respiratory infection (SARI) results in a tremendous disease burden worldwide. Available research on active surveillance among hospitalized adult patients suffering from SARI in China is limited. This pilot study aimed to identify associated etiologies and describe the demographic, epidemiological and clinical profiles of hospitalized SARI patients aged over 16 years in Jinshan, Shanghai. METHODS: Active surveillance was conducted at 1 sentinel hospital in Jinshan district, Shanghai, from April 2017 to March 2018. Hospitalized SARI patients aged over 16 years old were enrolled, and nasopharyngeal swabs were collected within 24 hours of admission and tested for multiple respiratory viruses (including 18 common viruses) and Mycoplasma pneumoniae with real-time polymerase chain reaction. Demographic, epidemiological and clinical information was obtained from case report forms. RESULTS: In total, 397 SARI patients were enrolled; the median age was 68 years, and 194 (48.9%) patients were male. A total of 278 (70.0%) patients had at least one underlying chronic medical condition. The most frequent symptoms were cough (99.2%) and sputum production (88.4%). The median duration of hospitalization was 10 days. A total of 250 infection patients (63.0%) were positive for at least one pathogen, of whom 198 (49.9%) were positive for a single pathogen and 52 (13.1%) were positive for multiple pathogens. The pathogens identified most frequently were M. pneumoniae (23.9%, 95/397), followed by adenovirus (AdV) (11.6%, 46/397), influenza virus A/H3N2 (Flu A/H3N2) (11.1%, 44/397), human rhinovirus (HRhV) (8.1%, 32/397), influenza virus B/Yamagata (Flu B/Yamagata) (6.3%, 25/397), pandemic influenza virus A/H1N1 (Flu A/pH1N1) (4.0%, 16/397), parainfluenza virus (PIV) type 1 (2.0%, 8/397), human coronavirus (HCoV) type NL63 (2.0%, 8/397), HCoV 229E (1.5%, 6/397), HCoV HKU1 (1.5%, 6/397), PIV 3 (1.5%, 6/397), human metapneumovirus (HMPV) (1.5%, 6/397), PIV 4 (1.3%, 5/397), HCoV OC43 (1.0%, 4/397), influenza virus B/Victoria (Flu B/Victoria) (0.5%, 2/397), respiratory syncytial virus (RSV) type B (0.5%, 2/397), and human bocavirus (HBoV) (0.3%, 1/397). The seasonality of pathogen-confirmed SARI patients had a bimodal distribution, with the first peak in the summer and the second peak in the winter. Statistically significant differences were observed with respect to the rates of dyspnea, radiographically diagnosed pneumonia and the presence of at least one comorbidity in patients who were infected with only M. pneumoniae, AdV, HRhV, Flu A/H3N2, Flu A /pH1N1 or Flu B/Yamagata. The differences in the positivity rates of the above 6 pathogens among the different age groups were nonsignificant. CONCLUSIONS: M. pneumoniae, AdV and Flu A/H3N2 were the main pathogens detected in hospitalized SARI patients aged over 16 years old in Jinshan district, Shanghai. Our findings highlight the importance of sustained multipathogen surveillance among SARI patients in sentinel hospitals, which can provide useful information on SARI etiologies, epidemiology, and clinical characteristics.


Subject(s)
DNA Viruses/isolation & purification , Mycoplasma pneumoniae/isolation & purification , RNA Viruses/isolation & purification , Respiratory Tract Infections/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , China , Cough/etiology , Female , Glucocorticoids/therapeutic use , Hospitals , Humans , Male , Middle Aged , Nasopharynx/microbiology , Nasopharynx/virology , Pilot Projects , Prognosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Young Adult
17.
Front Cell Infect Microbiol ; 11: 625581, 2021.
Article in English | MEDLINE | ID: covidwho-1116652

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the pandemic Coronavirus Disease 2019 (COVID-19). This virus is highly transmissible among individuals through both droplets and aerosol leading to determine severe pneumonia. Among the various factors that can influence both the onset of disease and the severity of its complications, the microbiome composition has also been investigated. Recent evidence showed the possible relationship between gut, lung, nasopharyngeal, or oral microbiome and COVID-19, but very little is known about it. Therefore, we aimed to verify the relationships between nasopharyngeal microbiome and the development of either COVID-19 or the severity of symptoms. To this purpose, we analyzed, by next generation sequencing, the hypervariable V1-V2-V3 regions of the bacterial 16S rRNA in nasopharyngeal swabs from SARS-CoV-2 infected patients (n=18) and control (CO) individuals (n=12) using Microbiota solution A (Arrow Diagnostics). We found a significant lower abundance of Proteobacteria and Fusobacteria in COVID-19 patients in respect to CO (p=0.003 and p<0.0001, respectively) from the phylum up to the genus (p<0.001). The Fusobacterium periodonticum (FP) resulted as the most significantly reduced species in COVID-19 patients respect to CO. FP is reported as being able to perform the surface sialylation. Noteworthy, some sialic acids residues on the cell surface could work as additional S protein of SARS-CoV-2 receptors. Consequently, SARS-CoV-2 could use sialic acids as receptors to bind to the epithelium of the respiratory tract, promoting its clustering and the disease development. We can therefore speculate that the significant reduction of FP in COVID-19 patients could be directly or indirectly linked to the modulation of sialic acid metabolism. Finally, viral or environmental factors capable of interfering with sialic metabolism could determine a fall in the individual protection from SARS-CoV-2. Further studies are necessary to clarify the precise role of FP in COVID-19.


Subject(s)
COVID-19/epidemiology , Fusobacterium Infections/microbiology , Fusobacterium/growth & development , Microbiota , N-Acetylneuraminic Acid/metabolism , Pandemics , SARS-CoV-2/isolation & purification , Adult , Aged , Aged, 80 and over , COVID-19/virology , Female , Fusobacterium/genetics , Humans , Male , Middle Aged , Mouth/microbiology , Nasopharynx/microbiology
18.
J Clin Virol ; 135: 104737, 2021 02.
Article in English | MEDLINE | ID: covidwho-1033542

ABSTRACT

The GenMark Dx ePlex Respiratory Pathogen Panel (RP) is a multiplexed nucleic acid test for the qualitative detection of common viral and a few bacterial causes of respiratory tract infections. The ePlex RP has received FDA clearance for nasopharyngeal swab (NPS) specimens collected in viral transport media. In this study, we evaluated the performance of the ePlex RP panel in comparison to the NxTAG Respiratory Pathogen Panel (NxTAG-RPP) from Luminex in use in our laboratory, not only for NPS but also for bronchoalveolar lavage specimens (BAL). We also evaluated the impact of implementing the ePlex RP on the test turn-around time (TAT). The newest panel from GenMark Dx, the ePlex Respiratory Pathogen Panel 2 (RP2), which added the SARS-CoV-2 target to the RP was also evaluated for NPS. Verification of the performance of the ePlex RP for both NPS and BAL showed 93.3 % and 84.9 % total agreement with the NxTAG-RPP respectively. An overall comparison of the TAT after implementing the ePlex RP as compared to the NxTAG-RPP assay showed an average decrease of almost seven-fold.


Subject(s)
Diagnostic Tests, Routine/methods , Molecular Diagnostic Techniques/methods , Multiplex Polymerase Chain Reaction/methods , Respiratory Tract Infections/diagnosis , Bronchoalveolar Lavage/methods , COVID-19/diagnosis , Humans , Nasopharynx/microbiology , Nasopharynx/virology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , SARS-CoV-2/genetics
19.
Hum Vaccin Immunother ; 17(6): 1628-1634, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-1031000

ABSTRACT

Background: SARS-CoV-2 is the new virus, and Streptococcus pneumoniae is one of the most important pathogens affecting humans. However, we do not yet know whether these microorganisms interact. Thus, we aimed to evaluate the relationship between Streptococcus pneumoniae and SARS-CoV-2 in pediatric patients.Methods: This study was conducted retrospectively by means of medical records of pediatric patients who were tested for SARS-CoV-2 between March 11 and June 04, 2020, in the University of Health Sciences, Ankara Educating and Training Hospital and Hacettepe University Faculty of Medicine.Results: We evaluated 829 pediatric patients for S. pneumoniae and SARS-CoV-2 from their nasopharyngeal specimen. Of 115 children positive for SARS-CoV-2, 32.2% had a positive S. pneumoniae test, whereas of 714 children negative for SARS-CoV-2, 14.1% had a positive S. pneumoniae test (p < .01). We compared patients with positive vs. negative SARS-CoV-2 tests according to S. pneumoniae positivity There were no statistically significant differences in terms of gender, underlying disease, fever, cough, leukocytosis, lymphopenia, increased CRP, increased procalcitonin, findings of chest x-ray, severity of disease, and treatment.Conclusion: The nasopharyngeal S. pneumoniae carriage rate in patients with COVID-19 was higher than in non-infected children, while S. pneumoniae carriage did not affect the course of COVID-19 disease. Pneumococcal vaccination is significant, such that we do not know the outcomes of increased pneumococcal carriage for the upcoming months of pandemic.


Subject(s)
COVID-19 , Carrier State , Pneumococcal Infections , COVID-19/complications , COVID-19/microbiology , Carrier State/epidemiology , Carrier State/microbiology , Child , Humans , Nasopharynx/microbiology , Pandemics , Pneumococcal Infections/epidemiology , Retrospective Studies , Streptococcus pneumoniae , Turkey
20.
Laryngoscope ; 131(6): E2074-E2079, 2021 06.
Article in English | MEDLINE | ID: covidwho-908740

ABSTRACT

OBJECTIVES/HYPOTHESIS: To determine whether the presence of detectable upper respiratory infections (URIs) at the time of adenoidectomy/adenotonsillectomy is associated with increased morbidity, complications, and unexpected admissions. STUDY DESIGN: Prospective double-blinded cohort. METHODS: In this prospective cohort study, nasopharyngeal swabs were obtained intraoperatively from 164 pediatric patients undergoing outpatient adenoidectomy/tonsillectomy with or without pressure equalization tubes (PETs) and were analyzed with PCR for the presence of 22 known URIs, including SARS-CoV-2. Surgeons and families were blinded to the results. At the conclusion of the study, rates of detectable infection were determined and intraoperative and postoperative events (unexpected admissions, length of PACU stay, rates of laryngospasm/bronchospasm, oxygen desaturation, bradycardia, and postoperative presentation to an emergency department) were compared between infected and uninfected patients. RESULTS: Of the 164 patients (50% male, 50% female, ages 8 mo-18 y), 136 patients (82.9%) tested positive for one or more URI at the time of surgery. Forty one patients (25.0%) tested positive for three or more URIs concurrently, and 11 (6.7%) tested positive for five or more URIs concurrently. There were no significant differences in admission rates, length of PACU stay, rates of laryngospasm/bronchospasm, oxygen desaturation, bradycardia, or postoperative presentation to an emergency department between positive and negative patients. No patients tested positive for SARS-CoV-2. CONCLUSIONS: A recent positive URI test does not confer any additional intraoperative or postoperative risk in the setting of outpatient adenoidectomy/tonsillectomy in healthy patients. There is no utility in preoperative URI testing, and delaying surgery due to a recent positive URI test is not warranted in this population. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2074-E2079, 2021.


Subject(s)
Adenoidectomy , Air Microbiology , Ambulatory Surgical Procedures , Respiratory Tract Infections/microbiology , Surgical Wound Infection/microbiology , Tonsillectomy , Adolescent , Child , Child, Preschool , Cohort Studies , Double-Blind Method , Female , Humans , Infant , Male , Nasopharynx/microbiology , Prospective Studies , Risk , Risk Factors
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