What caused lymphopenia in SARS and how reliable is the lymphokine status in glucocorticoid-treated patients?

Severe Acute Respiratory Syndrome (SARS) outbreak in 2002–03 caused morbidity in over 8000 individuals and mortality in 744 in 29 countries. Lymphopenia along with neutrophilia was a feature of SARS, as it is in respiratory syncytial virus (RSV) and Ebola infections, to name a few. Direct infestation of lymphocytes, neutrophils and macrophages by SARS coronavirus (CoV) has been debated as a cause of lymphopenia, but there is no convincing data. Lymphopenia can be caused by glucocorticoids, and thus any debilitating condition has the potential to induce lymphopenia via stress mechanism involving the hypothalamic–pituitary–adrenal axis. Cortisol levels are elevated in patients with RSV and Ebola, and cortisol was higher in SARS patients with lymphopenia before any steroid therapy. Glucocorticoids also down-regulate the production of proinflammatory lymphokines. Because of the insidious presentation, SARS was treated with antibacterial, antiviral and supra-physiological doses of glucocorticoids. Treatment with glucocorticoids complicated the issue regarding lymphopenia, and certainly calls into question the status of lymphokines and their prognostic implications in SARS.