Adenovirus diseases: a systematic review and meta-analysis of 228 case reports.

Objective: The clinical characteristics of various adenovirus (ADV) infection are underexplored up till now. To investigate the risk factors, manifestation, current status of ADV species, treatment and prognosis of this disease.

Methods: We performed a Pubmed and Embase systematic review for case report reporting the ADV infection to analyze the clinical characteristics of disease.

Results: Initial database searched identified articles of which 168 (228 cases) were included in the final analysis. Previous solid organ transplantation [odds ratio (OR) = 3.45, 95% CI 1.31-9.08, P = 0.01], hematopoietic stem cell transplant (OR = 4.24, 95% CI 1.33-13.51, P = 0.01) and hematological malignancy (OR = 4.78, 95% CI 1.70-13.46, P = 0.01) were associated with increased risk of disseminated ADV infection. Use of corticosteroids (OR = 3.86, 95% CI 1.21-12.24, P = 0.02) was a significant risk factor for acquiring urinary tract infections. A total of six species (21 types) of ADV infection have been identified in 100/228 (43.9%) cases. ADV B was the most common species. ADV B species (26/60, 52.0% or 5/41, 12.2% P = 0.001) were more isolated in patients with ADV pneumonia. ADV C (13/15, 86.7% versus 35/86, 40.7% P = 0.001) species were more identified in patients with disseminated disease. The species associated with keratoconjunctivitis is only ADV D in our analysis. Urinary tract ADV infections were observed in ADV A/B/D species. Cidofovir (CDV) (82/228, 36.0%) remained the most commonly antiviral therapy in our cases, followed by ribavirin (15/228, 6.6%), ganciclovir (18/228, 7.9%), and brincidofovir (12/228, 5.3%). Brincidofovir was administered as salvage therapy in 10 cases. Death was reported in 81/228 (35.5%) patients. Mortality rate was higher among patients with gastrointestinal (GI) ADV infection (5/10, 50.0%), ADV pneumonia (20/45, 44.4%) and disseminated ADV infection (53/122, 43.4%).

Conclusion: Previous solid organ transplantation, hematopoietic stem cell transplant and hematological malignancy were risk factors for disseminated ADV infection. Use of corticosteroids was significant for urinary tract ADV infection. Different species correlated with different clinical manifestations of infection. Mortality rate was higher among patients with GI disease, pneumonia and disseminated disease. Our review clarified the current treatment of ADV infections, and more treatment required further investigation.