| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
RESPIRATORY INFECTION |
1 Department of Microbiology and Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
2 Department of Medicine, United Christian Hospital, Hong Kong
3 Department of Medicine and Geriatrics, Caritas Medical Centre, Hong Kong
Correspondence to:
Correspondence to:
Professor K Y Yuen
Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong Special Administrative Region, China; kyyuen{at}hkucc.hku.hk
Background: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents.
Methods: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls.
Results: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 µg/ml and 50 µg/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls—both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)—but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level.
Conclusions: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.
Keywords: severe acute respiratory syndrome (SARS); coronavirus; lopinavir/ritonavir
This article has been cited by other articles:
|
|
 |
|
  S. S. Y. Wong and K.-Y. Yuen The management of coronavirus infections with particular reference to SARS J. Antimicrob. Chemother., September 1, 2008; 62(3): 437 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. G. Nichols, A. J. Peck Campbell, and M. Boeckh Respiratory Viruses Other than Influenza Virus: Impact and Therapeutic Advances Clin. Microbiol. Rev., April 1, 2008; 21(2): 274 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. C. C. Cheng, S. K. P. Lau, P. C. Y. Woo, and K. Y. Yuen Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection Clin. Microbiol. Rev., October 1, 2007; 20(4): 660 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Cowling, M. P. Muller, I. O. L. Wong, L.-M. Ho, S.-V. Lo, T. Tsang, T. H. Lam, M. Louie, and G. M. Leung Clinical prognostic rules for severe acute respiratory syndrome in low- and high-resource settings. Arch Intern Med, July 24, 2006; 166(14): 1505 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Pyrc, B. J. Bosch, B. Berkhout, M. F. Jebbink, R. Dijkman, P. Rottier, and L. van der Hoek Inhibition of Human Coronavirus NL63 Infection at Early Stages of the Replication Cycle. Antimicrob. Agents Chemother., June 1, 2006; 50(6): 2000 - 2008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Weiss and S. Navas-Martin Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus Microbiol. Mol. Biol. Rev., December 1, 2005; 69(4): 635 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-M. Chu and K.-S. Chan Ribavarin Should Be Tested in Clinical Trials in Combination With Other Antiviral Agents for Severe Acute Respiratory Syndrome Chest, December 1, 2005; 128(6): 4050 - 4050. [Full Text] [PDF]
|
|
|
|
|
|
K.-M. Yeh, T.-S. Chiueh, L. K. Siu, J.-C. Lin, P. K. S. Chan, M.-Y. Peng, H.-L. Wan, J.-H. Chen, B.-S. Hu, C.-L. Perng, et al. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital J. Antimicrob. Chemother., November 1, 2005; 56(5): 919 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M Li and P C Ng Severe acute respiratory syndrome (SARS) in neonates and children Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2005; 90(6): F461 - F465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Ghani, C. A. Donnelly, D. R. Cox, J. T. Griffin, C. Fraser, T. H. Lam, L. M. Ho, W. S. Chan, R. M. Anderson, A. J. Hedley, et al. Methods for Estimating the Case Fatality Ratio for a Novel, Emerging Infectious Disease Am. J. Epidemiol., September 1, 2005; 162(5): 479 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-E. Chiou, C.-L. Liu, M. J. Buttrey, H.-P. Kuo, H.-W. Liu, H.-T. Kuo, and Y.-T. Lu Adverse Effects of Ribavirin and Outcome in Severe Acute Respiratory Syndrome: Experience in Two Medical Centers Chest, July 1, 2005; 128(1): 263 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. F. Tang, K.-h. Chan, V. C. C. Cheng, P. C. Y. Woo, S. K. P. Lau, C. C. K. Lam, T.-l. Chan, A. K. L. Wu, I. F. N. Hung, S.-y. Leung, et al. Comparative Host Gene Transcription by Microarray Analysis Early after Infection of the Huh7 Cell Line by Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus 229E J. Virol., May 15, 2005; 79(10): 6180 - 6193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Levy, M. S. Baylor, G. R. Bernard, R. Fowler, T. J. Franks, F. G. Hayden, R. Helfand, S. E. Lapinsky, T. R. Martin, M. S. Niederman, et al. Clinical Issues and Research in Respiratory Failure from Severe Acute Respiratory Syndrome Am. J. Respir. Crit. Care Med., March 1, 2005; 171(5): 518 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Chu, W. S. Leung, V. C. C. Cheng, K. H. Chan, A. W. N. Lin, V. L. Chan, J. Y. M. Lam, K. S. Chan, and K. Y. Yuen Duration of RT-PCR positivity in severe acute respiratory syndrome Eur. Respir. J., January 1, 2005; 25(1): 12 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S.C. Hui and J. J.Y. Sung Treatment of Severe Acute Respiratory Syndrome Chest, September 1, 2004; 126(3): 670 - 674. [Full Text] [PDF]
|
|
|
|
 |
|
 W C Yu, D S C Hui, and M Chan-Yeung Antiviral agents and corticosteroids in the treatment of severe acute respiratory syndrome (SARS) Thorax, August 1, 2004; 59(8): 643 - 645. [Full Text] [PDF]
|
|
|
|
 |
|
 D S C Hui, M C H Chan, A K Wu, and P C Ng Severe acute respiratory syndrome (SARS): epidemiology and clinical features Postgrad. Med. J., July 1, 2004; 80(945): 373 - 381. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
