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

Abstract

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.

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

“…Moreover, the strong atrophic process of the thymus observed during HPAIV infection is a common feature of severe diseases like AIDS, rabies, and Chagas disease (19). Our results give rise to the assumption that this mechanism of increased pathogenesis is not only due to influenza viruses with pandemic potential, but also to infections with other new or re-emerging pathogens like foot-and-mouth disease virus, Chikungunya, severe acute respiratory syndrome, and West Nile Virus (20)(21)(22)(23)(24).…”

Clinical features of three avian influenza H7N9 virus‐infected patients in Shanghai

“…The development of secondary infection, especially Gram‐negative rod infection, can be explained by several factors, such as exposure to high‐risk procedures, use of glucocorticoids, severity of underlying diseases and frequent use of medical instruments, all of which may facilitate development of nosocomial bacteremia , so appropriate empirical antibiotic treatment may be indicated for initial management of severe A H7N9 virus pneumonia. Glucocorticoids are used in all of our cases while they are still controversial in the routine treatment of influenza . Because of the limited number of patients, our experiences are not conclusive; whether the continuous activity of virus replication is associated with glucocorticoid is unknown.…”

Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients

“…Lymphopenia have been found in a large portion of SARS and COVID-19 patients, although the underlying mechanism remains unclear [4,6,[44][45][46][47]. Viral infection of lymphocytes was barely detected in SARS patients [48].…”

“…Due to its anti-inflammatory effect, glucocorticoids have been widely used to stop the progression of the acute lung injury and acute respiratory distress syndrome in SARS and COVID-19 patients by suppressing lung inflammation [4,49]. However, glucocorticoids treatment has been criticized for its significant side effects including immunosuppression, impaired antibody responses, delayed viral clearance and more severely, avascular necrosis and osteoporosis [44,[49][50][51]. Collectively, lymphopenia in SARS and COVID-19 patients was more likely caused by endogenous or exogenous glucocorticoids which ultimately led to apoptosis of lymphocytes, rather than direct viral infection of these cells [44,50].…”