Impact of Viral Infections in Sickle Cell Disease

Patients with Sickle Cell Disease (SCD) have widespread inflammation at baseline. Alteration in inflammation due to viral infections is one of the proposed precipitating events for vaso-occlusive episodes (VOE) and acute chest syndrome (ACS). A comprehensive analysis examining clinical outcomes after viral infections in SCD has not been done. The purpose of this study is to determine if viruses identified on a multiplex, molecular assay respiratory viral panel (RVP) in the pre-COVID era contribute to worse outcomes (increased length of stay, increased rates of re-admission) in patients with SCD.

Methods: The Sickle Cell Disease Registries at two urban children's hospitals in the midwestern United States were queried to identify SCD patients who had RVPs sent between July 2015 and June 2019. We stratified patients based on the results of their RVPs then evaluated their length of stay, complications, admission rates, treatments, laboratory values, and time to next admission.

Results: In total, 129 patients with SCD were identified to have had an RVP sent during the pre-determined time frame. The most prevalent viral infections affecting our cohort were rhinovirus/enterovirus and influenza A, making up more than 50% of positive RVPs. Patients with positive RVPs had fewer transfusions than patients with negative RVPs (p<0.001). Patients with positive RVPs were less likely to be admitted to the hospital, and once admitted, had shorter length of stay (LOS) (p < 0.001). Despite shorter LOS, patients with positive RVPs returned to the hospital earlier than those with negative RVPs (p<0.05). With this in mind, we ran a multinomial logistic regression that detected a few factors that influenced earlier return to the hospital. These included history of ACS, administration of albuterol, and age as significant factors. Those with a history of ACS were 3 times more likely to be readmitted within the first 365 days after initial visit than those without a history of ACS (p <0.05). Patients with a positive RVP had a significantly lower white blood cell count (p<0.01), hemoglobin (p<0.05), and reticulocyte count (p<0.05).

Discussion: There is a paucity of data investigating the clinical sequelae of diverse respiratory viral infections in children living with SCD. Prior studies have looked at viral illnesses in patients presenting with ACS or have focused on specific viruses, such as RSV. We found that patients with positive RVPs received fewer transfusions and, if admitted, had shorter LOS. We recognize that RVPs do not detect every viral respiratory infection and do not necessarily indicate active infection, and do not exclude coinfection or superinfection. What we find most novel is that despite fewer admissions and complications, those with positive RVPs revisited the hospital sooner than patients with negative RVPs. These results may suggest that viruses change the inflammatory milieu for a longer duration than we have previously acknowledged or that symptoms in the setting of a viral illness selects for a subset of high-risk patients. Alternatively, this may reflect an aspect of our clinical practice in the setting of known viral infection that needs further elucidation. As providers were not blinded to results of the RVP and identification of viral illness may have influenced provider decision making in management. In febrile patients, for example, detection of a virus may have reassured a clinician that a bacterial infection and subsequent complications were unlikely. This may account for the reduced admission rate and shorter hospitalization in the group with positive RVPs. We hope this study paves the way for discussion on the utility of RVPs and how these tests may be utilized to influence management in this population.

No relevant conflicts of interest to declare.