Dynamics and predisposition of respiratory viral co-infections in children and adults.

Mandelia, Yamini; Procop, Gary W; Richter, Sandra S; Worley, Sarah; Liu, Wei; Esper, Frank

OBJECTIVES The epidemiology of respiratory co-infection pairings is poorly understood. Here we assess the dynamics of respiratory viral co-infections in children and adults and determine predisposition for or against specific viral pairings. METHODS Over 5 respiratory seasons from November 30, 2013 through June 6, 2018, mono- and co-infection prevalence of 13 viral pathogens were tabulated at The Cleveland Clinic. Employing a model to proportionally distribute viral pairs utilizing individual virus' co-infection rate with prevalence patterns of concurrent co-circulating viruses, we compared predicted-to-observed occurrences of 132 viral pairing permutations using binomial analysis. RESULTS Of 30,535 respiratory samples, 9,843 (32.2%) were positive for ≥1 virus of which 1,018 (10.8%) were co-infected. Co-infected samples predominantly originated from children. Co-infection rate in pediatric population was 35.0% (2068/5906), compared to only 5.8% (270/4591) in adults. Adenovirus C (ADVC) had the highest co-infection rate (426/623, 68.3%) while influenza B had the lowest (55/546, 10.0%). ADVC-rhinovirus (HRV), RSVA-HRV, and RSVB-HRV pairings occurred at significantly higher frequencies than predicted by the proportional distribution model (p<0.05). Additionally, several viral pairings had fewer co-infections than predicted by our model: notably metapneumovirus (hMPV)-PIV3, hMPV-RSVA, and RSVA-RSVB. CONCLUSIONS This is one of the largest studies on respiratory viral co-infections in children and adults. Co-infections are substantially more common in children, especially under 5 years of age and the most frequent pairings occurred at a higher frequency than would be expected by random. Specific pairings occur at altered rates than those predicted by proportional distribution suggesting either direct or indirect interactions result between specific viral pathogens.