Human Parainfluenza 2 & 4: clinical and genetic epidemiology in the UK, 2013-2017, reveals distinct disease features and co-circulating genomic subtypes

Human Parainfluenza viruses (HPIV) are constituted by four members of the genetically distinct genera of Respirovirus (type 1 and 3) and Orthorubulavirus (type 2 and 4), causing significant upper and lower respiratory tract infections in both children and adults worldwide. However, despite frequent molecular diagnosis, they are frequently considered collectively or with HPIV4 overlooked entirely. We therefore investigated clinical and viral epidemiological distinctions of the relatively less prevalent Orthorubulaviruses HPIV2 & 4 at a regional UK hospital across four winter epidemic seasons. HPIV2 & 4 infection was observed across all age groups, but predominantly in children under 9 and adults over 40, with almost twice as many HPIV4 as HPIV2 cases. Fever, abnormal haematology, elevated C-reactive protein and hospital admission were more frequently seen in HPIV2 than HPIV4 infection. Each of the four seasonal peaks of either HPIV2, HPIV4 or both, closely matched that of RSV, occurring in November and December and preceding that of Influenza A. A subset of viruses were partially sequenced, indicating co-circulation of multiple subtypes of both HPIV2 & 4, but with little variation between each epidemic season or from limited global reference sequences.