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Thorax. 2004 May; 59(5): 414–420.
doi: 10.1136/thx.2003.014076
PMCID: PMC1746995
PMID: 15115870

Severe acute respiratory syndrome: report of treatment and outcome after a major outbreak

J Sung, A Wu, G Joynt, K Yuen, N Lee, P Chan, C Cockram, A Ahuja, L Yu, V Wong, and D Hui
Author information Copyright and License information PMC Disclaimer

Abstract

Background: The outcome is reported of a prospective uncontrolled study based on a stepwise treatment protocol during an outbreak of severe acute respiratory syndrome (SARS) in Hong Kong.

Method: One hundred and thirty eight patients were treated with broad spectrum antibiotics, a combination of ribavirin and low dose corticosteroid, and then intravenous high dose methylprednisolone according to responses. Sustained response to treatment was defined as (1) defervescence for ⩾4 consecutive days, (2) resolution of lung consolidation by >25%, and (3) oxygen independence by the fourth day without fever. Patients with defervescence who achieved either criterion 2 or 3 were classified as partial responders. Patients who fell short of criteria 2 and 3 were non-responders.

Results: Laboratory confirmation of SARS coronavirus infection was established in 132 (95.7%). None responded to antibiotics but 25 (18.1%) responded to ribavirin + low dose corticosteroid. Methylprednisolone was used in 107 patients, of whom 95 (88.8%) responded favourably. Evidence of haemolytic anaemia was observed in 49 (36%). A high level of C-reactive protein at presentation was the only independent predictor for use of methylprednisolone (odds ratio 2.18 per 10 mg/dl increase, 95% confidence interval 1.12 to 4.25, p = 0.02). Thirty seven patients (26.8%) required admission to the intensive care unit and 21 (15.2%) required invasive mechanical ventilation. There were 15 deaths (mortality rate 10.9%), most with significant co-morbidities, whereas 122 (88.4%) had been discharged home 4 months after the outbreak onset.

Conclusion: The use of high dose pulse methylprednisolone during the clinical course of a SARS outbreak was associated with clinical improvement, but randomised controlled trials are needed to ascertain its efficacy in this condition.

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Selected References

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  • Lee Nelson, Hui David, Wu Alan, Chan Paul, Cameron Peter, Joynt Gavin M, Ahuja Anil, Yung Man Yee, Leung CB, To KF, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003 May 15;348(20):1986–1994. [PubMed] [Google Scholar]
  • Kuiken Thijs, Fouchier Ron A M, Schutten Martin, Rimmelzwaan Guus F, van Amerongen Geert, van Riel Debby, Laman Jon D, de Jong Ton, van Doornum Gerard, Lim Wilina, et al. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet. 2003 Jul 26;362(9380):263–270. [PMC free article] [PubMed] [Google Scholar]
  • Drosten Christian, Günther Stephan, Preiser Wolfgang, van der Werf Sylvie, Brodt Hans-Reinhard, Becker Stephan, Rabenau Holger, Panning Marcus, Kolesnikova Larissa, Fouchier Ron A M, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003 May 15;348(20):1967–1976. [PubMed] [Google Scholar]
  • Ksiazek Thomas G, Erdman Dean, Goldsmith Cynthia S, Zaki Sherif R, Peret Teresa, Emery Shannon, Tong Suxiang, Urbani Carlo, Comer James A, Lim Wilina, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003 May 15;348(20):1953–1966. [PubMed] [Google Scholar]
  • Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988 Jun;16(3):128–140. [PubMed] [Google Scholar]
  • Peiris JSM, Chu CM, Cheng VCC, Chan KS, Hung IFN, Poon LLM, Law KI, Tang BSF, Hon TYW, Chan CS, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003 May 24;361(9371):1767–1772. [PMC free article] [PubMed] [Google Scholar]
  • Hsu Li-Yang, Lee Cheng-Chuan, Green Justin A, Ang Brenda, Paton Nicholas I, Lee Lawrence, Villacian Jorge S, Lim Poh-Lian, Earnest Arul, Leo Yee-Sin. Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient and initial contacts. Emerg Infect Dis. 2003 Jun;9(6):713–717. [PMC free article] [PubMed] [Google Scholar]
  • Booth Christopher M, Matukas Larissa M, Tomlinson George A, Rachlis Anita R, Rose David B, Dwosh Hy A, Walmsley Sharon L, Mazzulli Tony, Avendano Monica, Derkach Peter, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. 2003 Jun 4;289(21):2801–2809. [PubMed] [Google Scholar]
  • Nicholls John M, Poon Leo L M, Lee Kam C, Ng Wai F, Lai Sik T, Leung Chung Y, Chu Chung M, Hui Pak K, Mak Kong L, Lim Wilina, et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet. 2003 May 24;361(9371):1773–1778. [PMC free article] [PubMed] [Google Scholar]
  • Cheung CY, Poon LLM, Lau AS, Luk W, Lau YL, Shortridge KF, Gordon S, Guan Y, Peiris JSM. Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Lancet. 2002 Dec 7;360(9348):1831–1837. [PubMed] [Google Scholar]
  • Van Reeth Kristien, Van Gucht Steven, Pensaert Maurice. In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding. Vet Immunol Immunopathol. 2002 Sep 10;87(3-4):161–168. [PMC free article] [PubMed] [Google Scholar]
  • Ning Q, Brown D, Parodo J, Cattral M, Gorczynski R, Cole E, Fung L, Ding JW, Liu MF, Rotstein O, et al. Ribavirin inhibits viral-induced macrophage production of TNF, IL-1, the procoagulant fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response. J Immunol. 1998 Apr 1;160(7):3487–3493. [PubMed] [Google Scholar]
  • Cyranoski David. Critics slam treatment for SARS as ineffective and perhaps dangerous. Nature. 2003 May 1;423(6935):4–4. [PMC free article] [PubMed] [Google Scholar]
  • Tsang Kenneth W, Ho Pak L, Ooi Gaik C, Yee Wilson K, Wang Teresa, Chan-Yeung Moira, Lam Wah K, Seto Wing H, Yam Loretta Y, Cheung Thomas M, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003 May 15;348(20):1977–1985. [PubMed] [Google Scholar]
  • So Loletta K-Y, Lau Arthur C W, Yam Loretta Y C, Cheung Thomas M T, Poon Edwin, Yung Raymond W H, Yuen KY. Development of a standard treatment protocol for severe acute respiratory syndrome. Lancet. 2003 May 10;361(9369):1615–1617. [PMC free article] [PubMed] [Google Scholar]
  • Zhong Nan Shan, Zeng Guang Qiao. Our strategies for fighting severe acute respiratory syndrome (SARS). Am J Respir Crit Care Med. 2003 Jul 1;168(1):7–9. [PubMed] [Google Scholar]
  • Wong KT, Antonio Gregory E, Hui David S C, Lee Nelson, Yuen Edmund H Y, Wu Alan, Leung CB, Rainer TH, Cameron Peter, Chung Sydney S C, et al. Thin-section CT of severe acute respiratory syndrome: evaluation of 73 patients exposed to or with the disease. Radiology. 2003 Aug;228(2):395–400. [PubMed] [Google Scholar]
  • Epler GR. Bronchiolitis obliterans organizing pneumonia. Arch Intern Med. 2001 Jan 22;161(2):158–164. [PubMed] [Google Scholar]
  • Tassios PT, Chadjichristodoulou C, Lambiri M, Kansouzidou-Kanakoudi A, Sarandopoulou Z, Kourea-Kremastinou J, Tzouvelekis LS, Legakis NJ. Molecular typing of multidrug-resistant Salmonella Blockley outbreak isolates from Greece. Emerg Infect Dis. 2000 Jan-Feb;6(1):60–64. [PMC free article] [PubMed] [Google Scholar]
  • Lai Kar Neng, Leung Joseph C K, Metz Christine N, Lai Fernand M, Bucala Richard, Lan Hui Yao. Role for macrophage migration inhibitory factor in acute respiratory distress syndrome. J Pathol. 2003 Apr;199(4):496–508. [PubMed] [Google Scholar]
  • Roberts RB, Laskin OL, Laurence J, Scavuzzo D, Murray HW, Kim YT, Connor JD. Ribavirin pharmacodynamics in high-risk patients for acquired immunodeficiency syndrome. Clin Pharmacol Ther. 1987 Oct;42(4):365–373. [PubMed] [Google Scholar]
  • Borio Luciana, Inglesby Thomas, Peters CJ, Schmaljohn Alan L, Hughes James M, Jahrling Peter B, Ksiazek Thomas, Johnson Karl M, Meyerhoff Andrea, O'Toole Tara, et al. Hemorrhagic fever viruses as biological weapons: medical and public health management. JAMA. 2002 May 8;287(18):2391–2405. [PubMed] [Google Scholar]
  • Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999 Feb 11;340(6):448–454. [PubMed] [Google Scholar]
  • Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, Malacrida R, Di Giulio P, Fumagalli R, Pelosi P, et al. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med. 2001 Aug 23;345(8):568–573. [PubMed] [Google Scholar]
  • Wang Huijun, Ding Yanqing, Li Xin, Yang Lei, Zhang Wenli, Kang Wei. Fatal aspergillosis in a patient with SARS who was treated with corticosteroids. N Engl J Med. 2003 Jul 31;349(5):507–508. [PubMed] [Google Scholar]
  • Rota Paul A, Oberste M Steven, Monroe Stephan S, Nix W Allan, Campagnoli Ray, Icenogle Joseph P, Peñaranda Silvia, Bankamp Bettina, Maher Kaija, Chen Min-Hsin, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science. 2003 May 30;300(5624):1394–1399. [PubMed] [Google Scholar]
  • Marra Marco A, Jones Steven J M, Astell Caroline R, Holt Robert A, Brooks-Wilson Angela, Butterfield Yaron S N, Khattra Jaswinder, Asano Jennifer K, Barber Sarah A, Chan Susanna Y, et al. The Genome sequence of the SARS-associated coronavirus. Science. 2003 May 30;300(5624):1399–1404. [PubMed] [Google Scholar]
  • Ruan Yi Jun, Wei Chia Lin, Ee Ai Ling, Vega Vinsensius B, Thoreau Herve, Su Se Thoe Yun, Chia Jer-Ming, Ng Patrick, Chiu Kuo Ping, Lim Landri, et al. Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection. Lancet. 2003 May 24;361(9371):1779–1785. [PMC free article] [PubMed] [Google Scholar]
  • Bakke B, Ulvestad B, Stewart P, Eduard W. Cumulative exposure to dust and gases as determinants of lung function decline in tunnel construction workers. Occup Environ Med. 2004 Mar;61(3):262–269. [PMC free article] [PubMed] [Google Scholar]
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