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

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.

[1]  P. Stewart,et al.  Cumulative exposure to dust and gases as determinants of lung function decline in tunnel construction workers , 2004, Occupational and Environmental Medicine.

[2]  M. Chan-yeung,et al.  High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome. , 2003, American journal of respiratory and critical care medicine.

[3]  J. Sung,et al.  Thin-section CT of severe acute respiratory syndrome: evaluation of 73 patients exposed to or with the disease. , 2003, Radiology.

[4]  Xin Li,et al.  Fatal aspergillosis in a patient with SARS who was treated with corticosteroids. , 2003, The New England journal of medicine.

[5]  J. Peiris,et al.  Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome , 2003, The Lancet.

[6]  G. Zeng,et al.  Our strategies for fighting severe acute respiratory syndrome (SARS). , 2003, American journal of respiratory and critical care medicine.

[7]  Elizabeth Rea,et al.  Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. , 2003, JAMA.

[8]  Y. Leo,et al.  Severe Acute Respiratory Syndrome (SARS) in Singapore: Clinical Features of Index Patient and Initial Contacts , 2003, Emerging infectious diseases.

[9]  Obi L. Griffith,et al.  The Genome Sequence of the SARS-Associated Coronavirus , 2003, Science.

[10]  Christian Drosten,et al.  Characterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome , 2003, Science.

[11]  Yi Guan,et al.  Lung pathology of fatal severe acute respiratory syndrome , 2003, The Lancet.

[12]  Philip M. Long,et al.  Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection , 2003, The Lancet.

[13]  L. Poon,et al.  Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia : a prospective study , 2003 .

[14]  Peter Cameron,et al.  A major outbreak of severe acute respiratory syndrome in Hong Kong. , 2003, The New England journal of medicine.

[15]  Christian Drosten,et al.  Identification of a novel coronavirus in patients with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[16]  M. Chan-yeung,et al.  A cluster of cases of severe acute respiratory syndrome in Hong Kong. , 2003, The New England journal of medicine.

[17]  J. A. Comer,et al.  A novel coronavirus associated with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[18]  K. Yuen,et al.  Development of a standard treatment protocol for severe acute respiratory syndrome , 2003, The Lancet.

[19]  D. Cyranoski.  Critics slam treatment for SARS as ineffective and perhaps dangerous , 2003, Nature.

[20]  R. Bucala,et al.  Role for macrophage migration inhibitory factor in acute respiratory distress syndrome , 2003, The Journal of pathology.

[21]  J. Gerberding,et al.  Update: Outbreak of severe acute respiratory syndrome--worldwide, 2003. , 2003, MMWR. Morbidity and mortality weekly report.

[22]  Y. Guan,et al.  Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? , 2002, The Lancet.

[23]  Philip K. Russell,et al.  Hemorrhagic fever viruses as biological weapons: medical and public health management. , 2002, JAMA.

[24]  M. Pensaert,et al.  In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding , 2002, Veterinary Immunology and Immunopathology.

[25]  M. Fine,et al.  Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. , 2001, American journal of respiratory and critical care medicine.

[26]  ntonio,et al.  EFFECT OF PRONE POSITIONING ON THE SURVIVAL OF PATIENTS WITH ACUTE RESPIRATORY FAILURE , 2001 .

[27]  D. Fisman.  Hemophagocytic syndromes and infection. , 2000, Emerging infectious diseases.

[28]  D. Schoenfeld,et al.  Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. , 2000, The New England journal of medicine.

[29]  I. Kushner,et al.  Acute-phase proteins and other systemic responses to inflammation. , 1999, The New England journal of medicine.

[30]  Ming Liu,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. , 1998, Journal of immunology.

[31]  L. Hansson,et al.  C‐reactive protein: its role in the diagnosis and follow‐up of infectious diseases , 1997 .

[32]  L. Mandell,et al.  Hospital-acquired pneumonia in adults: Diagnosis, assessment of severity, initial antimicrobial therapy, and preventative strategies: A consensus statement , 1996 .

[33]  F. Barbé,et al.  [Bronchiolitis obliterans with organizing pneumonia]. , 1993, Anales de medicina interna.

[34]  B. Yangco,et al.  CDC definitions for nosocomial infections. , 1989, American journal of infection control.

[35]  J M Hughes,et al.  CDC definitions for nosocomial infections, 1988. , 1988, American journal of infection control.

[36]  H. Murray,et al.  Ribavirin pharmacodynamics in high‐risk patients for acquired immunodeficiency syndrome , 1987, Clinical pharmacology and therapeutics.

[37]  J. Longstreth,et al.  Ribavirin disposition in high‐risk patients for acquired immunodeficiency syndrome , 1987, Clinical pharmacology and therapeutics.