Dynamic changes in clinical features and cytokine/chemokine responses in SARS patients treated with interferon alfacon-1 plus corticosteroids.

Severe acute respiratory syndrome (SARS), caused by a novel coronavirus, emerged in early 2003 as a major international health crisis. We report on serum cytokine levels, viral load and clinical parameters over the course of the disease in a cohort of nine adult SARS patients treated with steroids and interferon alfacon-1 at North York General Hospital in Toronto, Ontario. Considerable variation among SARS patients with respect to circulating viral load and patterns of SARS-CoV-evoked cytokine responses was recorded. No single cytokine profile was observed in all patients, yet serum concentrations of interferon (IFN)-gamma, interleukin (IL)-10, CXCL10, CCL5 and CXCL8 were found to be elevated above normal levels during the course of the disease in all patients. Expression levels for IL-10, IFN-gamma and CXCL10 consistently peaked within 4 days of peak viral load. IL-12p70, IL-4 and tumour necrosis factor-alpha concentrations were consistently highest within 5 days of peak viral load. These results suggest that elevated levels of inflammatory cytokines are sensitive correlates of disease severity, including lung abnormalities and viral load in serum, and may provide a tool for monitoring disease progression in affected individuals.

Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study.

CONTEXT: Severe acute respiratory syndrome (SARS) is a new clinical entity for which no effective therapeutic strategy has been developed. OBJECTIVE: To provide preliminary results on the potential therapeutic benefit and tolerability of interferon alfacon-1 plus corticosteroids for SARS. DESIGN, SETTING, AND PATIENTS: Open-label study of 22 patients diagnosed as having probable SARS at North York General Hospital, Toronto, Ontario, between April 11 and May 30, 2003. INTERVENTIONS: Thirteen patients were treated with corticosteroids alone and 9 patients were treated with corticosteroids plus subcutaneous interferon alfacon-1. MAIN OUTCOME MEASURES: Clinical parameters, including oxygen saturation and requirement, laboratory measures, and serial chest radiography results. RESULTS: Resolution of fever and lymphopenia were similar between the 2 treatment groups. Of the 13 patients treated with corticosteroids alone, 5 (38.5%) were transferred to the intensive care unit, 3 (23.1%) required intubation and mechanical ventilation, and 1 (7.7%) died. Of the 9 patients in the interferon alfacon-1 treatment group, 3 (33.3%) were transferred to the intensive care unit, 1 (11.1%) required intubation and mechanical ventilation, and none died. The interferon alfacon-1 treatment group had a shorter time to 50% resolution of lung radiographic abnormalities (median time, 4 days vs 9 days; P =.001), had better oxygen saturation (P =.02), resolved their need for supplemental oxygen more rapidly (median, 10 days vs 16 days; P =.02), had less of an increase in creatine kinase levels (P =.03), and showed a trend toward more rapid resolution of lactate dehydrogenase levels compared with the group receiving corticosteroids alone. CONCLUSIONS: In this preliminary, uncontrolled study of patients with SARS, use of interferon alfacon-1 plus corticosteroids was associated with reduced disease-associated impaired oxygen saturation, more rapid resolution of radiographic lung abnormalities, and lower levels of creatine kinase. These findings suggest that further investigation may be warranted to determine the role of interferon alfacon-1 as a therapeutic agent for the treatment of SARS.

Severe acute respiratory syndrome: quantitative assessment from chest radiographs with clinical and prognostic correlation.

OBJECTIVE: This study examined findings of severe acute respiratory syndrome (SARS) on chest radiographs and presented a classification scheme using quantitative radiographic data supported by clinical parameters. MATERIALS AND METHODS: Three radiologists who were blinded to the identity, diagnosis, treatment protocol, and outcome of each patient independently evaluated serial chest radiographs from 67 patients with confirmed SARS. In addition to the chest radiographic abnormalities and percentage of involvement, several quantitative improvement parameters, including the peak to 50% improvement time (PIT(50)), were collected. Correlation between PIT(50) and clinical parameters (duration of fever, cough, dyspnea, oxygen supplementation, intubation, and death) were evaluated using Wilcoxon's rank sum testing and Spearman's correlation. RESULTS: The most common initial findings were unifocal air-space disease in the periphery of the lower lungs occurring a mean of 3.6 +/-2.4 (SD) days from symptoms onset. Peak abnormalities were seen at 10.4 +/- 2.9 days. PIT(50) was dependent on disease severity, showing a strong linear correlation with the clinical parameter duration of oxygen supplementation (r = 0.44, p = 0.0015). Three patterns of disease were recognized: pattern A (severe, 29.9%) with PIT(50) of more than 10 days, pattern B (typical, 44.8%) with PIT(50) of 10 or fewer days, and pattern C (mild, 25.4%) with minimal findings throughout the course of the disease. This classification was supported by collaborative clinical parameters. CONCLUSION: The quantitative radiographic parameter PIT(50) has strong clinical correlation and can be used to differentiate severity of disease into severe, typical, and mild types.