Case Presentation: A 39-year-old man with history of treatment-resistant tumefactive multiple sclerosis (MS) on plasmapheresis presented with a sore throat and persistent fevers for 2 days. His wife recently also had a mild cough and viral conjunctivitis. He was noted to have a temperature of 103.2 F, heart rate of 135, and oxygen saturation of 92% requiring 4 liters of nasal cannula. On physical exam he appeared to be in mild distress with bilateral bibasilar inspiratory crackles. Labs were notable for a WBC 18.3 and lactate 2.7. Chest x-ray demonstrated a right upper lobe consolidation concerning for pneumonia. Respiratory viral panel was obtained and pending. He was initially started on antibiotics for presumed community-acquired pneumonia, but he remained persistently febrile up to 104.7 F with increasing oxygen. His respiratory viral panel returned positive for adenovirus. Despite this finding on the respiratory viral panel, it was unclear if there was another concomitant pulmonary infection, such as bacterial or fungal. The patient ultimately required intubation and went into multi-organ failure requiring continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO). Extensive infectious workup included a bronchoscopy with bronchoalveolar lavage (BAL), which only showed thick white secretions. Blood and respiratory cultures and serologies were negative for any organisms, including fungal infections and tuberculosis. Serum adenovirus PCR revealed a viral load > 10,000,000 copy/mL. This high-viral load was likely the result of an adenovirus pneumonia with significant viremia. He was started on brincidofovir, an investigational anti-viral agent. Over the course of the next few weeks, the patient was able to come off ECMO and had renal recovery. His adenovirus viral load was followed serially and was undetectable prior to discharge.
Discussion: Adenovirus infections are typically mild and self-limiting in the immunocompetent individual, but in the immunocompromised patient, adenovirus infections can cause a wider spectrum of clinical disease, with more end-organ involvement, disseminated disease, and higher morbidity and mortality. The highest risk for disease and mortality is in hematopoietic stem cell transplant (HSCT) recipients, where progression to disseminated disease occurs in approximately 10%–20% of patients. Treatment for disseminated disease includes cidofovir, a cytosine analogue that inhibits DNA polymerase. Its use can incur significant nephrotoxicity. In this case, the patient had developed significant renal injury, and was placed on an investigational drug, brincidofovir, that is being studied for the treatment of adenovirus infections. This class of agent exhibits enhanced in vitro activity against adenoviruses and has lower potential for nephrotoxicity than cidofovir. In our case, the patient had a successful response and rapid decline of the adenovirus viral load after being started on brincidofovir.
Conclusions: This case demonstrates the clinical impact of adenovirus in the relatively immunocompromised patient. For the hospitalist, early recognition of significant adenovirus infections in this population should prompt to explore the options of anti-viral agents, such as cidofovir or brincidofovir.