scholarly journals Clinical practices underlie COVID-19 patient respiratory microbiome composition and its interactions with the host

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Verónica Lloréns-Rico ◽  
Ann C. Gregory ◽  
Johan Van Weyenbergh ◽  
Sander Jansen ◽  
Tina Van Buyten ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Oral Bacteria ◽  
Upper Respiratory Tract ◽  
Clinical Practices ◽  
Microbiome Composition ◽  
Research Priority ◽  
Inflammatory Phenotypes ◽  
Viral Load Determination ◽  
Respiratory Microbiome

AbstractUnderstanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the respiratory microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 respiratory microbiome studies by analyzing the upper (n = 58) and lower (n = 35) respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We find that time in the intensive care unit and type of oxygen support, as well as associated treatments such as antibiotic usage, explain the most variation within the upper respiratory tract microbiome, while SARS-CoV-2 viral load has a reduced impact. Specifically, mechanical ventilation is linked to altered community structure and significant shifts in oral taxa previously associated with COVID-19. Single-cell transcriptomics of the lower respiratory tract of COVID-19 patients identifies specific oral bacteria in physical association with proinflammatory immune cells, which show higher levels of inflammatory markers. Overall, our findings suggest confounders are driving contradictory results in current COVID-19 microbiome studies and careful attention needs to be paid to ICU stay and type of oxygen support, as bacteria favored in these conditions may contribute to the inflammatory phenotypes observed in severe COVID-19 patients.

scholarly journals Mechanical ventilation affects respiratory microbiome of COVID-19 patients and its interactions with the host

2020 ◽  
Author(s):  
Verónica Lloréns-Rico ◽  
Ann C. Gregory ◽  
Johan Van Weyenbergh ◽  
Sander Jansen ◽  
Tina Van Buyten ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Viral Load ◽  
Respiratory Tract ◽  
Oral Microbiota ◽  
Upper Respiratory Tract ◽  
Research Priority ◽  
Upper Respiratory ◽  
Inflammatory Phenotypes ◽  
Viral Load Determination ◽  
Respiratory Microbiome

AbstractUnderstanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 microbiome studies by analyzing the upper (n=58) and lower (n=35) respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We found that time in the intensive care unit and the type of oxygen support explained the most variation within the upper respiratory tract microbiome, dwarfing (non-significant) effects from viral load, disease severity, and immune status. Specifically, mechanical ventilation was linked to altered community structure, lower species- and higher strain-level diversity, and significant shifts in oral taxa previously associated with COVID-19. Single-cell transcriptomic analysis of the lower respiratory tract of ventilated COVID-19 patients identified increased oral microbiota compared to controls. These oral microbiota were found physically associated with proinflammatory immune cells, which showed higher levels of inflammatory markers. Overall, our findings suggest confounders are driving contradictory results in current COVID-19 microbiome studies and careful attention needs to be paid to ICU stay and type of oxygen support, as bacteria favored in these conditions may contribute to the inflammatory phenotypes observed in severe COVID-19 patients.

scholarly journals Factors associated with the risk of upper respiratory tract bacterial infections among HIV-positive patients

2020 ◽  
Author(s):  
Agata Skrzat-Klapaczynska ◽  
Marcin Paciorek ◽  
Ewa Firlag-Burkacka ◽  
Andrzej Horban ◽  
Justyna Dominika Kowalska
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Bacterial Infections ◽  
Cd4 Count ◽  
Hiv Positive ◽  
Upper Respiratory Tract ◽  
Detectable Viral Load ◽  
Factors Associated ◽  
Multivariate Survival ◽  
Upper Respiratory

Background The risk and characteristics of upper respiratory tract (URT) bacterial infections (URT-BI) among HIV (+) patients is understudied. We analyzed factors associated with its occurrence and the spectrum of pathogens among patients routinely followed at the HIV Out-Patient Clinic in Warsaw. Methods All symptomatic HIV (+) patients with available URT swab culture were included into analyses. Patients were followed from the day of registration in the clinic until first positive URT swab culture or last clinical visit. Cox proportional hazard models were used to identify factors associated with positive URT swabs culture (those with p<0.1 in univariate included into multivariable). Results In total 474 patients were included into the analyses, 166 with positive URT swab. In general 416 (87.8%) patients were male, 342 (72.1%) were infected through MSM contact, 253 (53.4%) were on antiretroviral therapy. Median follow-up time was 3.4 (1.3-5.7) years, age 35.2 (30.6-42.6) years and CD4+ count 528 (400-685) cells/μl. The most common pathogens were S. aureus (40.4%) and S. pyogenes (13.9%) (Table 1). Patients with URT-BI were more likely to be MSM (68.5% vs 78.9%; p<0.016), have detectable viral load (20.9% vs 12.0%; p<0.0001) and CD4+ cell count <500 cells/μl (55.2% vs 39.0%; p=0.003) (Table 2). In multivariate survival analyses detectable viral load (HR3.13; 95%Cl: 2.34-4.19) and MSM (1.63;1.09-2.42) were increasing, but older age (0.63;0.58-0.69, per 5 years older) and higher CD4+ count (0.90;0.85-0.95, per 100 cells/μl) decreasing the risk of URT-BI (Table 2). Conclusions URT BI are common among HIV (+) positive patients with high CD4+ count. Similarly to general population most common patogens are S. aureus and S. pyogenes. Risk factors identified in multivariate survival analysis indicate that younger MSM patients with detectable HIV viral load are at highest risk. In clinical practice this group of patients requires special attention.

scholarly journals Effect of prophylactic use of intra-nasal oil formulations in the hamster model of Covid-19

2021 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Manas Ranjan Tripathy ◽  
Nishant Sharma ◽  
Sandeep Goswami ◽  
N Srikanth ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Viral Entry ◽  
Body Weight Loss ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Hamster Model ◽  
Reduced Body ◽  
Upper Respiratory ◽  
Prophylactic Use

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in upper respiratory tract leading to coronavirus disease 2019 (Covid-19). Severe Covid-19 is characterized by pulmonary pathologies associated with respiratory failure. Thus, therapeutics aimed at inhibiting entry of the virus or its internalization in the upper respiratory tract, are of interest. Herein, we report the prophylactic application of two intra-nasal formulations provided by the National Medicinal Plant Board (NMPB), Anu oil and Til tailya in SARS-CoV2 infection hamster model. Prophylactic nasal instillation of these oil formulations exhibited reduced viral load in lungs, and resulted in reduced body weight loss and pneumonitis. In line with reduced viral load, histopathlogical analysis revealed a reduction in lung pathology in Anu oil group as compared to the control infected group. However, Til tailya group did not show a significant reduction in lung pathology. Furthermore, molecular analysis using mRNA expression profiling indicated reduced expression of pro-inflammatory cytokines genes, including Th1 and Th17 cytokines for both the intra-nasal formulations as a result of decreased viral load. Together, the prophylactic intra-nasal application of Annu oil seems to be useful in limiting both the viral load and disease severity disease in SARS-CoV2 infection in hamster model.

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric C. Rouchka ◽  
Julia H. Chariker ◽  
Brian Alejandro ◽  
Robert S. Adcock ◽  
Richa Singhal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
Respiratory Tract ◽  
Disease Severity ◽  
Critical Factor ◽  
Interferon Response ◽  
Upper Respiratory Tract ◽  
Viral Loads ◽  
Antiviral Responses ◽  
Upper Respiratory

AbstractKey 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.

scholarly journals Diversity and genomic determinants of the microbiomes associated with COVID-19 and non-COVID respiratory diseases

2020 ◽  
Author(s):  
M. Nazmul Hoque ◽  
M. Shaminur Rahman ◽  
Rasel Ahmed ◽  
Md. Sabbir Hossain ◽  
Md. Shahidul Islam ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Diseases ◽  
Sequence Data ◽  
Chronic Obstructive ◽  
Upper Respiratory Tract ◽  
Cadmium Resistance ◽  
Human Respiratory Tract ◽  
Obstructive Pulmonary Disease ◽  
Genomic Features ◽  
Microbiome Composition

AbstractThe novel coronavirus disease 2019 (COVID-19) is a rapidly emerging and highly transmissible disease caused by the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). Understanding the microbiomes associated with the upper respiratory tract infection (URTI), chronic obstructive pulmonary disease (COPD) and COVID-19 diseases has clinical interest. We hypothesized that the diversity of microbiome compositions and their genomic features are associated with different pathological conditions of these human respiratory tract diseases (COVID-19 and non-COVID; URTI and COPD). To test this hypothesis, we analyzed 21 whole metagenome sequences (WMS) including eleven COVID-19 (BD = 6 and China = 5), six COPD (UK = 6) and four URTI (USA = 4) samples to unravel the diversity of microbiomes, their genomic features and relevant metabolic functions. The WMS data mapped to 534 bacterial, 60 archaeal and 61 viral genomes with distinct variation in the microbiome composition across the samples (COVID-19>COPD>URTI). Notably, 94.57%, 80.0% and 24.59% bacterial, archaeal and viral genera shared between the COVID-19 and non-COVID samples, respectively, however, the COVID-19 related samples had sole association with 16 viral genera other than SARS-CoV-2. Strain-level virome profiling revealed 660 and 729 strains in COVID-19 and non-COVID sequence data, respectively and of them 34.50% strains shared between the conditions. Functional annotation of metagenomics sequences of thevCOVID-19 and non-COVID groups identified the association of several biochemical pathways related to basic metabolism (amino acid and energy), ABC transporters, membrane transport, replication and repair, clustering-based subsystems, virulence, disease and defense, adhesion, regulation of virulence, programmed cell death, and primary immunodeficiency. We also detected 30 functional gene groups/classes associated with resistance to antibiotics and toxic compounds (RATC) in both COVID-19 and non-COVID microbiomes. Furthermore, a predominant higher abundance of cobalt-zinc-cadmium resistance (CZCR) and multidrug resistance to efflux pumps (MREP) genes were detected in COVID-19 metagenome. The profiles of microbiome diversity and associated microbial genomic features found in both COVID-19 and non-COVID (COPD and URTI) samples might be helpful for developing the microbiome-based diagnostics and therapeutics for COVID-19 and non-COVID respiratory diseases. However, future studies might be carried out to explore the microbiome dynamics and the cross-talk between host and microbiomes employing larger volume of samples from different ethnic groups and geoclimatic conditions.

scholarly journals Spatial and temporal dynamics of SARS-CoV-2 in COVID-19 patients: A systematic review

2020 ◽  
Author(s):  
Anne Weiss ◽  
Mads Jellingsoe ◽  
Morten Otto Alexander Sommer
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Symptom Onset ◽  
Temporal Dynamics ◽  
Adult Patients ◽  
Clinical Severity ◽  
Upper Respiratory Tract ◽  
Viral Detection ◽  
Spatial And Temporal Dynamics ◽  
Over Time

Background The spatial and temporal dynamics of SARS-CoV-2 have been mainly described in form of case series or retrospective studies. In this study, we aimed to provide a coherent overview from published studies of the duration of viral detection and viral load in COVID-19 patients, stratified by specimen type, clinical severity and age. Method We systematically searched PubMed/MEDLINE and Cochrane review database for studies published between 1. November 2019 and 23rd of April 2020. We included studies that reported individual viral data over time measuring negative conversion by two consecutive negative tests, individual clinical severity and age. We excluded studies that reported viral data as patient fraction, reported only baseline data, included solely asymptomatic patients or were interventional studies. Extracted data included author, title, design, sample size, thresholds and genes of RT-PCR, patient age, COVID-19 severity, clinical characteristics, treatment, location of viral sampling, duration of viral detection, and viral load. We pooled the data of selected studies to determine effect estimates of duration of viral detection. Combined viral load was visualized over time. Findings Out of 7226 titles screened, 37 studies met the inclusion criteria and were included in the qualitative analysis and 22 studies in the quantitative analysis comprising 650 COVID-19 patients. The pooled estimate of the duration of positive detection of the virus was in mild adult patients 12.1 days (CI: 10.12, 14.05) after symptom onset in the upper respiratory tract (URT), 24.1 days (CI: 10.02, 38.19) in lower respiratory tract (LRT), and 15.5 days (CI: 8.04, 22.88) in faeces. Further, in mild adult patients, the maximum viral load was ~ 6.61 x 108 viral copies/mL in the URT and ~ 2.69 x 108 viral copies/mL in the LRT, within the first week of symptom onset. The maximum viral load in faeces was reported as ~ 3.55 x 107 copies/mL on Day 9. In moderate-severe adult patients, the pooled estimate of mean duration of positive viral detection in the URT was 15.8 days (CI: 11.12, 20.56) after symptom onset, 23.2 days (CI: 21.49, 24.97) in the LRT, 20.8 days (CI: 16.40, 25.17) in faeces. The maximum viral load was 4.60 x 109 copies/mL on Day 8 in the URT, 3.45 x 108 copies/mL on Day 11 in the LRT, 2.76 x 106 copies/mL on Day 18 in faeces and 1 x 104 copies/mL on Day 3 in blood. In children with mild symptoms, the pooled estimate of the mean duration of positive SARS-CoV-2 viral detection was 11.1 days (CI: 7.14, 15.11) in the URT and 16.0 days (CI: 11.49, 20,47) in the faeces, without reporting quantitative viral data. Viral positivity was detected in the urine and eye in one patient. Interpretation Our analysis showed consistent viral detection from specimen from the URT, the LRT and faeces, irrespective of the clinical severity of COVID-19. Our analysis suggests that SARS-CoV-2 persists for a longer duration in the LRT compared to the URT, whereas the differences in the duration of viral detection between mild and moderate-severe patients is limited in the LRT, but an indication of longer duration of viral detection in feces and the URT for moderate-severe patients was shown. Further, viral load was demonstrated to peak in the URT within first weak of infection, whereas maximum viral load has been observed to occur later and within the second week of infection in the LRT. Funding This study was funded by Innovation Fund Denmark.

scholarly journals Paired nasopharyngeal and deep lung testing for SARS-CoV2 reveals a viral gradient in critically ill patients: a multi-centre study

2020 ◽  
Author(s):  
Islam Hamed ◽  
Nesreen Shaban ◽  
Marwan Nassar ◽  
Sam Love ◽  
Martin D Curran ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Lower Respiratory Tract ◽  
Limit Of Detection ◽  
Upper Respiratory Tract ◽  
Rt Pcr ◽  
Multi Centre Study ◽  
Upper Respiratory

Introduction Samples for diagnostic tests for SARS-CoV-2 can be obtained from the upper (nasopharyngeal/oropharyngeal swabs) or lower respiratory tract (sputum or tracheal aspirate or broncho-alveolar lavage - BAL). Data from different testing sites indicates different rates of positivity. Reverse-transcriptase polymerase chain reaction (RT-PCR) allows for semi-quantitative estimates of viral load as time to crossing threshold (Ct) is inversely related to viral load. Objectives The objective of our study was to evaluate SARS-CoV2 RNA loads between paired nasopharyngeal (NP) and deep lung (endotracheal aspirate or BAL) samples from critically ill patients. Methods SARS-CoV-2 RT-PCR results were retrospectively reviewed for 51 critically ill patients from 5 intensive care units in 3 hospitals ; Addenbrookes Hospital Cambridge (3 units), Royal Papworth Cambridge (1 unit), and Royal Sunderland Hospital (1 unit). At the times when paired NP and deep lung samples were obtained, one patient had been on oxygen only, 6 patients on non-invasive ventilation, 18 patients on ECMO, and 26 patients mechanically ventilated. Results Results collected showed significant gradient between NP and deep lung viral loads. Median Ct value was 29 for NP samples and 24 for deep lung samples. Of 51 paired samples, 16 were negative (below limit of detection) on NP swabs but positive (above limit of detection) on deep lung sample, whilst 2 were negative on deep sample but positive on NP (both patients were on ECMO). Conclusions It has been suggested that whilst SARS-CoV1 tends to replicate in the lower respiratory tract, SARS-CoV2 replicates more vigorously in the upper respiratory tract. These data challenge that assumption. These data suggest that viral migration to, and proliferation in, the lower respiratory tract may be a key factor in the progression to critical illness and the development of severe acute respiratory syndrome (SARS). Factors which promote this migration should be examined for association with severe COVID-19. From a practical point of view, patients with suspected severe COVID-19 should have virological samples obtained from the lower respiratory tract where-ever possible, as upper respiratory samples have a significant negative rate.

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