Viral Load and Sequence Analysis Reveal the Symptom Severity, Diversity, and Transmission Clusters of Rhinovirus Infections

Background Rhinovirus (RV) is one of the main viral etiologic agents of acute respiratory illnesses. Despite the heightened disease burden caused by RV, the viral factors that increase the severity of RV infection, the transmission pattern, and seasonality of RV infections remain unclear. Methods An...

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Main Authors: Ng, Kim Tien, Oong, Xiang Yong, Lim, Sin How, Chook, Jack Bee, Takebe, Yutaka, Chan, Yoke Fun, Chan, Kok Gan, Hanafi, Nik Sherina, Pang, Yong Kek, Kamarulzaman, Adeeba, Tee, Kok Keng
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Published: Oxford University Press 2018
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Online Access:http://eprints.um.edu.my/21142/
https://doi.org/10.1093/cid/ciy063
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spelling my.um.eprints.211422019-05-07T06:47:24Z http://eprints.um.edu.my/21142/ Viral Load and Sequence Analysis Reveal the Symptom Severity, Diversity, and Transmission Clusters of Rhinovirus Infections Ng, Kim Tien Oong, Xiang Yong Lim, Sin How Chook, Jack Bee Takebe, Yutaka Chan, Yoke Fun Chan, Kok Gan Hanafi, Nik Sherina Pang, Yong Kek Kamarulzaman, Adeeba Tee, Kok Keng R Medicine Background Rhinovirus (RV) is one of the main viral etiologic agents of acute respiratory illnesses. Despite the heightened disease burden caused by RV, the viral factors that increase the severity of RV infection, the transmission pattern, and seasonality of RV infections remain unclear. Methods An observational study was conducted among 3935 patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014. Results The VP4/VP2 gene was genotyped from all 976 RV-positive specimens, where the predominance of RV-A (49%) was observed, followed by RV-C (38%) and RV-B (13%). A significant regression in median nasopharyngeal viral load (VL) (P <.001) was observed, from 883 viral copies/μL at 1-2 days after symptom onset to 312 viral copies/μL at 3-4 days and 158 viral copies/μL at 5-7 days, before declining to 35 viral copies/μL at ≥8 days. In comparison with RV-A (median VL, 217 copies/μL) and RV-B (median VL, 275 copies/μL), RV-C-infected subjects produced higher VL (505 copies/μL; P <.001). Importantly, higher RV VL (median, 348 copies/μL) was associated with more severe respiratory symptoms (Total Symptom Severity Score ≥17, P =.017). A total of 83 phylogenetic-based transmission clusters were identified in the population. It was observed that the relative humidity was the strongest environmental predictor of RV seasonality in the tropical climate. Conclusions Our findings underline the role of VL in increasing disease severity attributed to RV-C infection, and unravel the factors that fuel the population transmission dynamics of RV. Oxford University Press 2018 Article PeerReviewed Ng, Kim Tien and Oong, Xiang Yong and Lim, Sin How and Chook, Jack Bee and Takebe, Yutaka and Chan, Yoke Fun and Chan, Kok Gan and Hanafi, Nik Sherina and Pang, Yong Kek and Kamarulzaman, Adeeba and Tee, Kok Keng (2018) Viral Load and Sequence Analysis Reveal the Symptom Severity, Diversity, and Transmission Clusters of Rhinovirus Infections. Clinical Infectious Diseases, 67 (2). pp. 261-268. ISSN 1058-4838 https://doi.org/10.1093/cid/ciy063 doi:10.1093/cid/ciy063
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Ng, Kim Tien
Oong, Xiang Yong
Lim, Sin How
Chook, Jack Bee
Takebe, Yutaka
Chan, Yoke Fun
Chan, Kok Gan
Hanafi, Nik Sherina
Pang, Yong Kek
Kamarulzaman, Adeeba
Tee, Kok Keng
Viral Load and Sequence Analysis Reveal the Symptom Severity, Diversity, and Transmission Clusters of Rhinovirus Infections
description Background Rhinovirus (RV) is one of the main viral etiologic agents of acute respiratory illnesses. Despite the heightened disease burden caused by RV, the viral factors that increase the severity of RV infection, the transmission pattern, and seasonality of RV infections remain unclear. Methods An observational study was conducted among 3935 patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014. Results The VP4/VP2 gene was genotyped from all 976 RV-positive specimens, where the predominance of RV-A (49%) was observed, followed by RV-C (38%) and RV-B (13%). A significant regression in median nasopharyngeal viral load (VL) (P <.001) was observed, from 883 viral copies/μL at 1-2 days after symptom onset to 312 viral copies/μL at 3-4 days and 158 viral copies/μL at 5-7 days, before declining to 35 viral copies/μL at ≥8 days. In comparison with RV-A (median VL, 217 copies/μL) and RV-B (median VL, 275 copies/μL), RV-C-infected subjects produced higher VL (505 copies/μL; P <.001). Importantly, higher RV VL (median, 348 copies/μL) was associated with more severe respiratory symptoms (Total Symptom Severity Score ≥17, P =.017). A total of 83 phylogenetic-based transmission clusters were identified in the population. It was observed that the relative humidity was the strongest environmental predictor of RV seasonality in the tropical climate. Conclusions Our findings underline the role of VL in increasing disease severity attributed to RV-C infection, and unravel the factors that fuel the population transmission dynamics of RV.
format Article
author Ng, Kim Tien
Oong, Xiang Yong
Lim, Sin How
Chook, Jack Bee
Takebe, Yutaka
Chan, Yoke Fun
Chan, Kok Gan
Hanafi, Nik Sherina
Pang, Yong Kek
Kamarulzaman, Adeeba
Tee, Kok Keng
author_facet Ng, Kim Tien
Oong, Xiang Yong
Lim, Sin How
Chook, Jack Bee
Takebe, Yutaka
Chan, Yoke Fun
Chan, Kok Gan
Hanafi, Nik Sherina
Pang, Yong Kek
Kamarulzaman, Adeeba
Tee, Kok Keng
author_sort Ng, Kim Tien
title Viral Load and Sequence Analysis Reveal the Symptom Severity, Diversity, and Transmission Clusters of Rhinovirus Infections
title_short Viral Load and Sequence Analysis Reveal the Symptom Severity, Diversity, and Transmission Clusters of Rhinovirus Infections
title_full Viral Load and Sequence Analysis Reveal the Symptom Severity, Diversity, and Transmission Clusters of Rhinovirus Infections
title_fullStr Viral Load and Sequence Analysis Reveal the Symptom Severity, Diversity, and Transmission Clusters of Rhinovirus Infections
title_full_unstemmed Viral Load and Sequence Analysis Reveal the Symptom Severity, Diversity, and Transmission Clusters of Rhinovirus Infections
title_sort viral load and sequence analysis reveal the symptom severity, diversity, and transmission clusters of rhinovirus infections
publisher Oxford University Press
publishDate 2018
url http://eprints.um.edu.my/21142/
https://doi.org/10.1093/cid/ciy063
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score 13.211869