scholarly journals Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community

2017 ◽  
Author(s):  
Jing Yan ◽  
Michael Grantham ◽  
Jovan Pantelic ◽  
P. Jacob Bueno de Mesquita ◽  
Barbara Albert ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Symptom Onset ◽  
Infectious Virus ◽  
Influenza Infection ◽  
Geometric Mean ◽  
Viral Rna ◽  
Exhaled Breath ◽  
Negatively Associated ◽  
Aerosol Generation ◽  
Coarse Aerosol

AbstractLittle is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5 μm and fine <5 μm fractions) on days 1 to 3 post symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8×104/30-min fine, 1.2×104/30-min coarse aerosol sample, and 8.2×108 per NP swab. Fine and coarse aerosol viral RNA was positively associated with body mass index (fine p<0.05, coarse p<0.10) and number of coughs (fine p<0.001, coarse p<0.01) and negatively associated with increasing days since symptom onset (fine p<0.05 to p<0.01, coarse p<0.10) in adjusted models. Fine aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season (p<0.01). NP swab viral RNA was positively associated with upper respiratory symptoms (p<0.01) and negatively associated with age (p<0.01) but was not significantly associated with fine or coarse aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.SignificanceLack of human data on influenza virus aerosol shedding fuels debate over the importance of airborne transmission. We provide overwhelming evidence that humans generate infectious aerosols and quantitative data to improve mathematical models of transmission and public health interventions. We show that sneezing is rare and not important for, and that coughing is not required for influenza virus aerosolization. Our findings, that upper and lower airway infection are independent and that fine particle exhaled aerosols reflect infection in the lung, open a new pathway for understanding the human biology of influenza infection and transmission. Our observation of an association between repeated vaccination and increased viral aerosol generation demonstrated the power of our method, but needs confirmation.

scholarly journals Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community

2018 ◽  
Vol 115 (5) ◽  
pp. 1081-1086 ◽  
Author(s):  
Jing Yan ◽  
Michael Grantham ◽  
Jovan Pantelic ◽  
P. Jacob Bueno de Mesquita ◽  
Barbara Albert ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Infectious Virus ◽  
Influenza Infection ◽  
Geometric Mean ◽  
Respiratory Illness ◽  
Viral Rna ◽  
Aerosol Sample ◽  
Exhaled Breath ◽  
Negatively Associated ◽  
Coarse Aerosol

Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5-µm and fine ≤5-µm fractions) on days 1–3 after symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 × 104/30-minutes fine-, 1.2 × 104/30-minutes coarse-aerosol sample, and 8.2 × 108 per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with body mass index and number of coughs and negatively associated with increasing days since symptom onset in adjusted models. Fine-aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season. NP swab viral RNA was positively associated with upper respiratory symptoms and negatively associated with age but was not significantly associated with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.

scholarly journals SARS-CoV-2 infectious virus, viral RNA in nasopharyngeal swabs, and serostatus of symptomatic COVID-19 outpatients in the United States

2021 ◽  
Author(s):  
Katie R. Mollan ◽  
Joseph J. Eron ◽  
Taylor J. Krajewski ◽  
Wendy Painter ◽  
Elizabeth R. Duke ◽  
...  
Keyword(s):  
United States ◽  
Symptom Onset ◽  
Infectious Virus ◽  
Virus Isolation ◽  
Clinical Symptoms ◽  
Comprehensive Evaluation ◽  
Upper Airway ◽  
The United States ◽  
Viral Rna ◽  
Treatment And Prevention

Background: SARS-CoV-2 infectious virus isolation in the upper airway of COVID-19 patients is associated with higher levels of viral RNA. However, comprehensive evaluation of the relationships between host and disease factors and infectious, replication competent virus is needed. Methods: Symptomatic COVID-19 outpatients were enrolled from the United States. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. Findings: Among 204 participants within one week of reported symptom onset (median=5, IQR 4-5 days), median age was 40 (min-max: 18-82 years), median nasopharyngeal viral RNA was 6.5 (IQR 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies at baseline. Infectious virus was recovered in 7% of participants with antibodies compared to 58% of participants without antibodies (probability ratio (PR)=0.12, 95% CI: 0.04, 0.36; p=0.00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; p<0.0001) and fewer days since symptom onset (PR=0.79, 95% CI: 0.71, 0.88 per day; p<0.0001). Interpretation: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA are likely more reliable markers of infectious virus suppression than subjective measure of COVID-19 symptoms. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. Funding: Ridgeback Biotherapeutics, LP and NIH ClinicalTrials.gov Identifier: NCT04405570

scholarly journals Molecular Characterization of Influenza Virus in Intestines and its Effect on Intestinal Microbiota

2020 ◽  
Author(s):  
Heba Al Khatib ◽  
Muna Al Maslamani ◽  
Peter Coyle ◽  
Sameer Pathan ◽  
Asmaa Al Thani ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Molecular Characterization ◽  
Intestinal Microbiota ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
Viral Rna ◽  
Intestinal Infection ◽  
Virus Growth ◽  
Fecal Samples

Background: Influenza predominantly causes respiratory diseases; however, gastrointestinal symptoms are not uncommonly reported, particularly among high-risk groups. Influenza virus RNA has been also detected in stools of patients infected with pandemic and seasonal influenza, however, the role and the clinical significance of intestinal infection has not been clearly demonstrated. Methods: Here, we used NGS technology to investigate molecular characterization of viral RNA shedding in feces of adults with active influenza infection. Paired nasal and fecal samples were collected from 295 patients showing to emergency department at Hamad Medical Corporation with flu-like symptoms during January 2018 and April 2019. Results: Among these, 90 nasal samples were positive for influenza, of which, 26 fecal samples were positive for influenza in real-time PCR and only five showed virus growth in both monolayer and 3D cell culture. Full genome sequencing of isolated viruses revealed some unique mutations that we are currently in the process of studying their effect on virus kinetics. Then, we investigated the potential impact of respiratory influenza infection on intestinal microbiota diversity and composition. Microbiome analysis results suggest that changes in gut microbiota composition in influenza-infected patients are significantly associated with (1) influenza virus type, and (2) the presence of viral RNA in intestines of infected patients. We also identified bacterial taxa for which relative abundance was significantly higher in the patients with severe respiratory symptoms. Conclusion: Altogether, our findings suggest that influenza viruses can affect intestinal environment either by direct intestinal infection or indirectly by modulating intestinal microbiota.

scholarly journals Daily Viral Kinetics and Innate and Adaptive Immune Response Assessment in COVID-19: a Case Series

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Pauline Vetter ◽  
Christiane S. Eberhardt ◽  
Benjamin Meyer ◽  
Paola Andrea Martinez Murillo ◽  
Giulia Torriani ◽  
...  
Keyword(s):  
Immune Response ◽  
Symptom Onset ◽  
Infectious Virus ◽  
Case Series ◽  
Viral Rna ◽  
Adaptive Responses ◽  
Innate Response ◽  
Viral Control ◽  
Virus Shedding ◽  
Viral Loads

ABSTRACT Viral shedding patterns and their correlations with immune responses are still poorly characterized in mild coronavirus (CoV) disease 2019 (COVID-19). We monitored shedding of viral RNA and infectious virus and characterized the immune response kinetics of the first five patients quarantined in Geneva, Switzerland. High viral loads and infectious virus shedding were observed from the respiratory tract despite mild symptoms, with isolation of infectious virus and prolonged positivity by reverse transcriptase PCR (RT-PCR) until days 7 and 19 after symptom onset, respectively. Robust innate responses characterized by increases in activated CD14+ CD16+ monocytes and cytokine responses were observed as early as 2 days after symptom onset. Cellular and humoral severe acute respiratory syndrome (SARS)-CoV-2-specific adaptive responses were detectable in all patients. Infectious virus shedding was limited to the first week after symptom onset. A strong innate response, characterized by mobilization of activated monocytes during the first days of infection and SARS-CoV-2-specific antibodies, was detectable even in patients with mild disease. IMPORTANCE This work is particularly important because it simultaneously assessed the virology, immunology, and clinical presentation of the same subjects, whereas other studies assess these separately. We describe the detailed viral and immune profiles of the first five patients infected by SARS-CoV-2 and quarantined in Geneva, Switzerland. Viral loads peaked at the very beginning of the disease, and infectious virus was shed only during the early acute phase of disease. No infectious virus could be isolated by culture 7 days after onset of symptoms, while viral RNA was still detectable for a prolonged period. Importantly, we saw that all patients, even those with mild symptoms, mount an innate response sufficient for viral control (characterized by early activated cytokines and monocyte responses) and develop specific immunity as well as cellular and humoral SARS-CoV-2-specific adaptive responses, which already begin to decline a few months after the resolution of symptoms.

scholarly journals Influenza infection in immunosuppressed patients: clinical characteristics, risk factors and effect of antiviral therapy

2020 ◽  
Author(s):  
YaFen Liu ◽  
Yue Wang ◽  
YuanYuan Chen ◽  
BaiYi Liu ◽  
YiSi Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Influenza Virus ◽  
Influenza Vaccination ◽  
Symptom Onset ◽  
Clinical Characteristics ◽  
Influenza Infection ◽  
Antiviral Treatment ◽  
Double Dose ◽  
Neuraminidase Inhibitors ◽  
Immunosuppressed Patients

Abstract Background: Influenza infection was a vital threat to immunosuppressed patients with longer viral shedding; however, data on these populations in China are still lacking. We analyzed clinical characteristics, risk factors for admission to intensive care unit (ICU) and death, and effect of antiviral therapy in these populations.Methods: We analyzed 73 immunosuppressed inpatients tested positive for influenza virus using reverse-transcription polymerase chain reaction during the 2018-2019 influenza season. Medical data were analyzed using descriptive statistics. Univariate analysis and multivariate logistics analysis were used to identify risk factors. Results: The most common immunosuppression type was malignancies with chemotherapy 73.9% (54/73), then hematopoietic stem cell transplantation 19.2% (14/73). The most common presenting symptom was fever in 91.8% (67/73) patients, then cough 59.6% (34/57) and muscular soreness 35.1% (20/57). Complications and co-infections were found in 38.4% (28/73) and 17.8% (13/73) patients respectively, which significantly prolonged the hospital stay. Antiviral treatment after 48 hours was significantly associated with admission to ICU, mechanical ventilation and death. Combination and double dose of neuraminidase inhibitors did not significantly reduce the admission to ICU and death. 15.1% (11/73) patients were admitted to ICU and 8.2% (6/73) patients died. Risk factors for admission to ICU were long symptom onset (OR 5.60, P=0.018) and co-infection with other infections (OR 68.66, P=0.019), and presence of dyspnea was independently associated with death (OR 48.00, P=0.003) through multivariate logistics analysis. Seasonal influenza vaccination in preceding 12 months only took up 2.7% (2/73).Conclusion: Fever and other classical symptoms may be absent in immunosuppressed recipients, and conducting influenza virus detection at the first time is a good choice for early diagnosis. Antiviral treatment within 48 hours is of significance; however, patients may not benefit from combination and double dose of neuraminidase inhibitors. Immunosuppressed patients with dyspnea, long symptom onset and co-infection with other infections are of note needed, because these people have high-risk to severe cases. Inactivated influenza vaccination should be taken into account in immunosuppressed patients.

scholarly journals Performance of case definitions and clinical predictors for influenza surveillance among patients followed in a rural cohort in Senegal

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mamadou Aliou Barry ◽  
Florent Arinal ◽  
Cheikh Talla ◽  
Boris Gildas Hedible ◽  
Fatoumata Diene Sarr ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Sore Throat ◽  
Predictive Value ◽  
Influenza Infection ◽  
Clinical Signs ◽  
Influenza Virus Infection ◽  
Nasal Discharge ◽  
Age Group ◽  
Case Definitions

Abstract Background Influenza is a major cause of morbidity and mortality in Africa. However, a lack of epidemiological data remains for this pathology, and the performances of the influenza-like illness (ILI) case definitions used for sentinel surveillance have never been evaluated in Senegal. This study aimed to i) assess the performance of three different ILI case definitions, adopted by the WHO, USA-CDC (CDC) and European-CDC (ECDC) and ii) identify clinical factors associated with a positive diagnosis for Influenza in order to develop an algorithm fitted for the Senegalese context. Methods All 657 patients with a febrile pathological episode (FPE) between January 2013 and December 2016 were followed in a cohort study in two rural villages in Senegal, accounting for 1653 FPE observations with nasopharyngeal sampling and influenza virus screening by rRT-PCR. For each FPE, general characteristics and clinical signs presented by patients were collected. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for the three ILI case definitions were assessed using PCR result as the reference test. Associations between clinical signs and influenza infection were analyzed using logistic regression with generalized estimating equations. Sore throat, arthralgia or myalgia were missing for children under 5 years. Results WHO, CDC and ECDC case definitions had similar sensitivity (81.0%; 95%CI: 77.0–85.0) and NPV (91.0%; 95%CI: 89.0–93.1) while the WHO and CDC ILI case definitions had the highest specificity (52.0%; 95%CI: 49.1–54.5) and PPV (32.0%; 95%CI: 30.0–35.0). These performances varied by age groups. In children < 5 years, the significant predictors of influenza virus infection were cough and nasal discharge. In patients from 5 years, cough, nasal discharge, sore throat and asthenia grade 3 best predicted influenza infection. The addition of “nasal discharge” as a symptom to the WHO case definition decreased sensitivity but increased specificity, particularly in the pediatric population. Conclusion In summary, all three definitions studies (WHO, ECDC & CDC) have similar performance, even by age group. The revised WHO ILI definition could be chosen for surveillance purposes for its simplicity. Symptomatic predictors of influenza virus infection vary according the age group.

scholarly journals Influenza vaccine failure in the tropics: a retrospective cohort study of waning effectiveness

2020 ◽  
Vol 148 ◽  
Author(s):  
B. E. Young ◽  
T. M. Mak ◽  
L. W. Ang ◽  
S. Sadarangani ◽  
H. J. Ho ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Cohort Study ◽  
Influenza Vaccine ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Influenza Infection ◽  
Winter Season ◽  
Temperate Climate ◽  
Vaccine Failure ◽  
Virus Activity

Abstract Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2–49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2–9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42–49 (95% confidence interval (CI) 52–92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06–1.50, P = 0.010).

scholarly journals Differential Roles of Viral RNA and cRNA in Functional Modulation of the Influenza Virus RNA Polymerase

2001 ◽  
Vol 276 (33) ◽  
pp. 31179-31185 ◽  
Author(s):  
Ayae Honda ◽  
Atsushi Endo ◽  
Kiyohisa Mizumoto ◽  
Akira Ishihama
Keyword(s):  
Influenza Virus ◽  
Rna Polymerase ◽  
Viral Rna ◽  
Virus Rna ◽  
Functional Modulation

scholarly journals Quantitative measurement of infectious virus in SARS-CoV-2 Alpha, Delta and Epsilon variants reveals higher infectivity (viral titer:RNA ratio) in clinical samples containing the Delta and Epsilon variants.

2021 ◽  
Author(s):  
Hannah W Despres ◽  
Margaret G Mills ◽  
David J Shirley ◽  
Madaline M Schmidt ◽  
Meei-Li Huang ◽  
...  
Keyword(s):  
Quantitative Measurement ◽  
Infectious Virus ◽  
Viral Rna ◽  
Clinical Samples ◽  
Rt Pcr ◽  
Genome Copy ◽  
Live Virus ◽  
High Degree ◽  
The Relationship ◽  
Rna Levels

ABSTRACT Background Novel SARS-CoV-2 Variants of Concern (VoC) pose a challenge to controlling the COVID-19 pandemic. Previous studies indicate that clinical samples collected from individuals infected with the Delta variant may contain higher levels of RNA than previous variants, but the relationship between viral RNA and infectious virus for individual variants is unknown. Methods We measured infectious viral titer (using a micro-focus forming assay) as well as total and subgenomic viral RNA levels (using RT-PCR) in a set of 165 clinical samples containing SARS-CoV-2 Alpha, Delta and Epsilon variants that were processed within two days of collection from the patient. Results We observed a high degree of variation in the relationship between viral titers and RNA levels. Despite the variability we observed for individual samples the overall infectivity differed among the three variants. Both Delta and Epsilon had significantly higher infectivity than Alpha, as measured by the number of infectious units per quantity of viral E gene RNA (6 and 4 times as much, p=0.0002 and 0.009 respectively) or subgenomic E RNA (11 and 7 times as much, p<0.0001 and 0.006 respectively). Conclusion In addition to higher viral RNA levels reported for the Delta variant, the infectivity (amount of replication competent virus per viral genome copy) may also be increased compared to Alpha. Measuring the relationship between live virus and viral RNA is an important step in assessing the infectivity of novel SARS-CoV-2 variants. An increase in the infectivity of the Delta variant may further explain increased spread and suggests a need for increased measures to prevent viral transmission.

scholarly journals Routine blood parameters are helpful for early identification of influenza infection in children

2020 ◽  
Author(s):  
Ronghe Zhu ◽  
Cuie Chen ◽  
Qiu Wang ◽  
Xixi Zhang ◽  
Chaosheng Lu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Early Identification ◽  
Influenza A ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Cutoff Value ◽  
Routine Blood ◽  
Influenza A Virus Infection

Abstract Purpose Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), LYM*PLT and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children.Methods We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 hours of the onset of fever for influenza virus infection.Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the >6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the >6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924.Conclusions Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly influenza A virus infection.

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