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

Ward, Sarah E; Loutfy, Mona R; Blatt, Lawrence M; Siminovitch, Katharine A; Chen, Jiabing; Hinek, Anna; Wolff, Bryan; Pham, Dieu H; Deif, Hassan; LaMere, Elizabeth A; Kain, Kevin C; Farcas, Gabriella A; Ferguson, Patti; Latchford, Mary; Levy, Gary; Fung, Liasum; Dennis, James W; Lai, Enoch K Y; Fish, Eleanor N

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.