Viral Loads and Duration of Viral Shedding in Adult Patients Hospitalized with Influenza

Lee, Nelson; Chan, Paul K.S.; Hui, David S.; Rainer, Timothy Hudson; Wong, Eric; Choi, Kin Wing; Lui, Grace; Wong, Billy; Wong, Rlc; Lam, Wai Yip; Chu, Ida Miu-Ting; Lai, Robin Kit-Ho; Cockram, Clive S.; Sung, Joseph J.Y.

doi:10.1086/600383

Cited by 481 publications

(567 citation statements)

References 45 publications

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“…In addition, our test subjects were college‐aged ambulatory outpatients with no other reported respiratory illnesses or significant health conditions. Patients who are more severely ill would generally be expected to have higher viral loads and may be more likely to produce cough and exhalation aerosols containing infectious influenza virus, especially in the early stages of illness 40, 42. Patients who are younger or older, immunocompromised, or have underlying pulmonary illness such as asthma or chronic obstructive pulmonary disease also may have very different infectious aerosol generation patterns.…”

Section: Discussionmentioning

confidence: 99%

Viable influenza A virus in airborne particles expelled during coughs versus exhalations

Lindsley

Blachère

Beezhold

et al. 2016

Influenza Resp Viruses

144

117

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BackgroundTo prepare for a possible influenza pandemic, a better understanding of the potential for the airborne transmission of influenza from person to person is needed.ObjectivesThe objective of this study was to directly compare the generation of aerosol particles containing viable influenza virus during coughs and exhalations.MethodsSixty‐one adult volunteer outpatients with influenza‐like symptoms were asked to cough and exhale three times into a spirometer. Aerosol particles produced during coughing and exhalation were collected into liquid media using aerosol samplers. The samples were tested for the presence of viable influenza virus using a viral replication assay (VRA).ResultsFifty‐three test subjects tested positive for influenza A virus. Of these, 28 (53%) produced aerosol particles containing viable influenza A virus during coughing, and 22 (42%) produced aerosols with viable virus during exhalation. Thirteen subjects had both cough aerosol and exhalation aerosol samples that contained viable virus, 15 had positive cough aerosol samples but negative exhalation samples, and 9 had positive exhalation samples but negative cough samples.ConclusionsViable influenza A virus was detected more often in cough aerosol particles than in exhalation aerosol particles, but the difference was not large. Because individuals breathe much more often than they cough, these results suggest that breathing may generate more airborne infectious material than coughing over time. However, both respiratory activities could be important in airborne influenza transmission. Our results are also consistent with the theory that much of the aerosol containing viable influenza originates deep in the lungs.

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Section: Discussionmentioning

confidence: 99%

Viable influenza A virus in airborne particles expelled during coughs versus exhalations

Lindsley

Blachère

Beezhold

et al. 2016

Influenza Resp Viruses

144

117

View full text Add to dashboard Cite

show abstract

“…Multivariate analyses confirmed their independent associations, accounted for disease severity, time interval from onset, virus strain, age, and comorbidity. Reduced viral load was associated with milder illness 5, 21. These observations were unlikely the sole result of adaptive immunity, as patients were studied within 48 hours of their illnesses 3, 5, 20.…”

Section: Discussionmentioning

confidence: 99%

“…In brief, patients presenting with acute febrile respiratory illnesses would be considered for hospitalization if they had developed potentially serious medical conditions/complications, exacerbation of underlying illnesses, or severe constitutional and respiratory symptoms unmanageable at home. Nasopharyngeal samples were collected to test for influenza viruses, regardless of perceived etiology and disease severity 21. Patients with Influenza were identified and enrolled by the research team on a daily basis;20, 22 after obtaining informed written consent, peripheral venous blood samples were taken immediately for TLR assays, prior to antiviral treatment.…”

Section: Methodsmentioning

confidence: 99%

“…All nasopharyngeal aspirates (or flocked swabs in some cases) collected at presentation were subjected to influenza and other respiratory virus detection using immunofluorescence or PCR assays as described; virus isolation was performed in parallel 19, 21. Subsequent virus subtyping (A/H3N2, A/H1N1pdm09) was performed by the National Influenza Centre, Centre for Health Protection, Hong Kong 18, 19, 21.…”

Section: Methodsmentioning

confidence: 99%

“…The relationships between TLR expression levels and nasopharyngeal viral loads were analyzed using Spearman's rank correlation coefficient rho ( r ) 20, 22. Independent factors affecting viral load were examined using multivariate linear regression (backward) model analysis 21. Relationships between TLRs, signaling molecules, and plasma cytokine levels were analyzed using Spearman's correlation.…”

Section: Methodsmentioning

confidence: 99%

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Role of human Toll‐like receptors in naturally occurring influenza A infections

Lee

Wong

Hui

et al. 2013

Influenza Resp Viruses

Self Cite

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BackgroundWe investigated the roles of Toll‐like receptors (TLRs) in naturally occurring influenza.MethodsA prospective, case – control study was conducted. Adults hospitalized with virologically confirmed influenza A infections (onset <48 hours, before treatment) were compared with age‐/gender‐matched controls. TLRs (2, 3, 4, 7, 8, 9) expression in monocytes and dendritic cells (DCs – total, myeloid, plasmacytoid) was quantitated using flow cytometry. Gene expression of RLRs (RIG‐1, MDA‐5) was evaluated using real‐time PCR. Concomitant signaling molecules expression, plasma cytokine/chemokine concentrations, and respiratory tract viral loads were measured. PBMCs were cultured and stimulated ex vivo with TLR‐specific ligands for cytokine responses.ResultsForty two patients with influenza (24 A/H3N2, 18 A/H1N1pdm09) and 20 controls were studied. Patients' mean age was 68 ± 16 years; 81% had respiratory/cardiovascular complications. There were increased cellular expressions of TLR9, TLR8, TLR3, and TLR7 during influenza; TLR2 and TLR4 were suppressed. Results were similar for both virus strains. Higher TLR expression levels at presentation significantly correlated with lower viral loads (Spearman's rho: −0·46 to −0·69 for TLR9, TLR8, and TLR3; P‐values <0·05). Multivariate regression models (adjusted for age, comorbidity, disease severity, time from onset) confirmed their independent associations. Increased signaling molecules (phospho‐MAPKs, IκB) and inflammatory cytokines (IL‐6, sTNFR‐1, CCL2/MCP‐1; CXCL10/IP‐10, IFN‐γ) correlated with increased TLR expression. RLRs were upregulated simultaneously. PBMCs of patients with influenza showed significant, dynamic changes in their cytokine responses upon TLR stimulation, compared with controls.ConclusionsOur results suggest that TLRs play an important role in early, innate viral inhibition in naturally occurring influenza. Inflammatory cytokine responses are concomitantly induced. These findings support investigation of TLR targeting as a novel intervention approach for prophylaxis against influenza.

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Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada

Kumar

Zarychanski

Pinto³

et al. 2009

JAMA

1,244

122

1,124

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Viral Loads and Duration of Viral Shedding in Adult Patients Hospitalized with Influenza

Abstract: Patients hospitalized with severe influenza have more active and prolonged viral replication. Weakened host defenses slow viral clearance, whereas antivirals started within the first 4 days of illness enhance viral clearance.

Cited by 481 publications

References 45 publications

Viable influenza A virus in airborne particles expelled during coughs versus exhalations

Viable influenza A virus in airborne particles expelled during coughs versus exhalations

Role of human Toll‐like receptors in naturally occurring influenza A infections

Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada

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