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Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection

Identifieur interne : 002660 ( Main/Exploration ); précédent : 002659; suivant : 002661

Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection

Auteurs : Kelvin K. W. To [République populaire de Chine] ; Ivan F. N. Hung [République populaire de Chine] ; Iris W. S. Li [République populaire de Chine] ; Kar-Lung Lee [République populaire de Chine] ; Chi-Kwan Koo [République populaire de Chine] ; Wing-Wa Yan [République populaire de Chine] ; Raymond Liu [République populaire de Chine] ; Ka-Ying Ho [République populaire de Chine] ; Kwok-Hong Chu [République populaire de Chine] ; Chi-Leung Watt [République populaire de Chine] ; Wei-Kwang Luk [République populaire de Chine] ; Kang-Yiu Lai [République populaire de Chine] ; Fu-Loi Chow [République populaire de Chine] ; Thomas Mok [République populaire de Chine] ; Tom Buckley [République populaire de Chine] ; Jasper F. W. Chan [République populaire de Chine] ; Samson S. Y. Wong [République populaire de Chine] ; Bojian Zheng [République populaire de Chine] ; Honglin Chen [République populaire de Chine] ; Candy C. Y. Lau [République populaire de Chine] ; Herman Tse [République populaire de Chine] ; Vincent C. C. Cheng [République populaire de Chine] ; Kwok-Hung Chan [République populaire de Chine] ; Kwok-Yung Yuen [République populaire de Chine, Hong Kong]

Source :

RBID : ISTEX:F48649F3A349C3927BF5CA4CB68181BF4473BD63

Abstract

Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.

Url:
DOI: 10.1086/650581


Affiliations:


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<name sortKey="Mok, Thomas" sort="Mok, Thomas" uniqKey="Mok T" first="Thomas" last="Mok">Thomas Mok</name>
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<name sortKey="Buckley, Tom" sort="Buckley, Tom" uniqKey="Buckley T" first="Tom" last="Buckley">Tom Buckley</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<name sortKey="Lau, Candy C Y" sort="Lau, Candy C Y" uniqKey="Lau C" first="Candy C. Y." last="Lau">Candy C. Y. Lau</name>
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<name sortKey="Tse, Herman" sort="Tse, Herman" uniqKey="Tse H" first="Herman" last="Tse">Herman Tse</name>
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<name sortKey="Cheng, Vincent C C" sort="Cheng, Vincent C C" uniqKey="Cheng V" first="Vincent C. C." last="Cheng">Vincent C. C. Cheng</name>
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<name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name>
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<wicri:noRegion>Hong Kong</wicri:noRegion>
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<div type="abstract">Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.</div>
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<name sortKey="Cheng, Vincent C C" sort="Cheng, Vincent C C" uniqKey="Cheng V" first="Vincent C. C." last="Cheng">Vincent C. C. Cheng</name>
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<name sortKey="Chu, Kwok Hong" sort="Chu, Kwok Hong" uniqKey="Chu K" first="Kwok-Hong" last="Chu">Kwok-Hong Chu</name>
<name sortKey="Ho, Ka Ying" sort="Ho, Ka Ying" uniqKey="Ho K" first="Ka-Ying" last="Ho">Ka-Ying Ho</name>
<name sortKey="Hung, Ivan F N" sort="Hung, Ivan F N" uniqKey="Hung I" first="Ivan F. N." last="Hung">Ivan F. N. Hung</name>
<name sortKey="Koo, Chi Kwan" sort="Koo, Chi Kwan" uniqKey="Koo C" first="Chi-Kwan" last="Koo">Chi-Kwan Koo</name>
<name sortKey="Lai, Kang Yiu" sort="Lai, Kang Yiu" uniqKey="Lai K" first="Kang-Yiu" last="Lai">Kang-Yiu Lai</name>
<name sortKey="Lau, Candy C Y" sort="Lau, Candy C Y" uniqKey="Lau C" first="Candy C. Y." last="Lau">Candy C. Y. Lau</name>
<name sortKey="Lee, Kar Lung" sort="Lee, Kar Lung" uniqKey="Lee K" first="Kar-Lung" last="Lee">Kar-Lung Lee</name>
<name sortKey="Li, Iris W S" sort="Li, Iris W S" uniqKey="Li I" first="Iris W. S." last="Li">Iris W. S. Li</name>
<name sortKey="Liu, Raymond" sort="Liu, Raymond" uniqKey="Liu R" first="Raymond" last="Liu">Raymond Liu</name>
<name sortKey="Luk, Wei Kwang" sort="Luk, Wei Kwang" uniqKey="Luk W" first="Wei-Kwang" last="Luk">Wei-Kwang Luk</name>
<name sortKey="Mok, Thomas" sort="Mok, Thomas" uniqKey="Mok T" first="Thomas" last="Mok">Thomas Mok</name>
<name sortKey="Tse, Herman" sort="Tse, Herman" uniqKey="Tse H" first="Herman" last="Tse">Herman Tse</name>
<name sortKey="Watt, Chi Leung" sort="Watt, Chi Leung" uniqKey="Watt C" first="Chi-Leung" last="Watt">Chi-Leung Watt</name>
<name sortKey="Wong, Samson S Y" sort="Wong, Samson S Y" uniqKey="Wong S" first="Samson S. Y." last="Wong">Samson S. Y. Wong</name>
<name sortKey="Yan, Wing Wa" sort="Yan, Wing Wa" uniqKey="Yan W" first="Wing-Wa" last="Yan">Wing-Wa Yan</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Zheng, Bojian" sort="Zheng, Bojian" uniqKey="Zheng B" first="Bojian" last="Zheng">Bojian Zheng</name>
</country>
<country name="Hong Kong">
<noRegion>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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