IntroductionWe present six adenovirus cases that emerged from a cluster of respiratory illnesses within a college population. Two patients required intensive care with complicated hospital courses and experienced residual symptoms. Four additional patients were evaluated in the emergency department (ED) with two additional diagnoses of neuroinvasive disease. These cases represent the first known occurrences of neuroinvasive adenovirus infections in healthy adults.Case SeriesAn individual presented to the ED with fever, altered mental status, and seizures after being found unresponsive in his apartment. His presentation was concerning for significant central nervous system pathology. Shortly after his arrival, a second individual presented with similar symptoms. Both required intubation and admission to a critical care setting. Over a 24-hour period, four additional individuals presented to the ED with moderate severity symptoms. All six individuals tested positive for adenovirus in their respiratory secretions. A provisional diagnosis of neuroinvasive adenovirus was made after consultation with infectious diseases.ConclusionThis cluster of cases appears to represent the first known reported diagnosis of neuroinvasive adenovirus in healthy young individuals. Our cases were also unique in demonstrating a significant spectrum of disease severity. Over 80 individuals in the broader college community ultimately tested positive for adenovirus in respiratory samples. As respiratory viruses continue to challenge our healthcare systems, new spectrums of disease are being discovered. We believe clinicians should be aware of the potential severity of neuroinvasive adenovirus disease.