Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR

Hijano, Diego R.; Brazelton de Cardenas, Jessica; Maron, Gabriela; Garner, Cherilyn D.; Ferrolino, Jose A.; Dallas, Ronald H.; Gu, Zhengming; Hayden, Randall T.

Acute respiratory tract infections are the leading cause of morbidity and mortality in infants and children worldwide [1] . Respiratory viruses such as respiratory syncytial virus (RSV), influenza virus, parainfluenza virus, adenovirus, and picornavirus play an important role in the etiology of respiratory diseases in immunocompetent and immunocompromised patients, especially those undergoing myelosuppression and hematopoietic cell transplant [2] . PLOS Considerable advances have been made in predicting clinical outcomes for several systemic viral infections (e.g., HIV), and measuring viral load and markers of immune activation have become part of standard clinical care [3] . Unfortunately, this is not the case for influenza, RSV, and other viral respiratory infections. Despite the enormous global health impact of viral respiratory infections [4] , accurate viral and immune markers to predict clinical outcomes for patients are still lacking. Several methods have been used to precisely correlate viral copy number and disease severity [5] [6] [7] [8] [9] . Molecular quantitative assays have been suggested to detect and monitor clinical viral respiratory disease, particularly in immunosuppressed pediatric patients [10] . However, their results are conflicting and there continues to be a lack of clinical tests to accurately measure viral load [5, 6, 8, 9] . Furthermore, respiratory infections in these patients are associated with prolonged viral shedding and concerns for emergent antiviral resistance (for those in whom the viral infection is treatable). Quantitative determination of viral load may provide an important tool to directly evaluate the efficiency of antiviral therapy, to determine if changes in therapy are necessary and to assess need for further isolation to protect transmission to other highly susceptible hosts. These problems highlight the importance and potential value of developing assays for absolute, precise and reliable quantitative viral detection to improve the accuracy of clinical decision making in immunocompromised children with viral respiratory infections.