Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions

Background. Investigations concerning the severity of respiratory syncytial virus (RSV) disease as related to (1) RSV type and genotype determined respectively by PCR and restriction enzyme analysis and (2) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) values in samples of nasopharyngeal secretion (NPS) have not been previously reported. Methods. We prospectively studied 105 RSV infections in the lower respiratory tract of infants and young children admitted to a pediatric department in Copenhagen during three winter seasons, 1993, 1994 and 1995. RSV strains were typed and genotyped, respectively, by PCR and nucleic acid restriction analysis and correlated to the severity of the disease. The ratio IL-6:TNF-alpha, determined from IL-6- and TNF-alpha values in samples of NPS, was related to the severity of the disease. Concentrations of IL-6 and of TNF-alpha were determined in serum samples taken during 5 weeks after the onset of illness. Results. Type B infections produced more severe disease than did type A infections, as assessed on the length of the hospital stay, use of respiratory support and the presence of an infiltrate on a chest radiograph. This difference was age-related. It was observed in infants 0 to 5 months old, but not in older age groups. Type B genotype B1122 produced more severe disease than type A genotype A2311 in infants 0 to 11 months old. Increased serum concentrations of IL-6 and TNF-alpha were detected in samples taken 1 to 2 days after the onset of illness. Whereas TNF-alpha serum concentrations remained high, IL-6 serum concentrations decreased during the following 3 to 4 weeks. The IL-6:TNF-alpha ratio in samples of NPS was related to the severity of the disease. A high ratio was related to a low severity. Conclusions. The severity of disease in patients admitted with acute RSV infections can be correlated to the RSV type as determined by PCR, to the RSV genotype as determined by nucleic acid restriction analysis and to the ratio IL-6:TNF-alpha in NPS.