Viral co-infections are associated with increased rates of hospitalization in those with influenza.

BACKGROUND: Influenza causes significant morbidity and mortality in the United States. Among patients infected with influenza, the presence of bacterial co-infection is associated with worse clinical outcomes; less is known regarding the clinical importance of viral co-infections. The objective of this study was to determine rates of viral co-infections in emergency department (ED) patients with confirmed influenza and association of co-infection with disease severity. METHODS: Secondary analysis of a biorepository and clinical database from a parent study where rapid influenza testing was implemented in four U.S. academic EDs, during the 2014-2015 influenza season. Patients were systematically tested for influenza virus using a validated clinical decision guideline. Demographic and clinical data were extracted from medical records; nasopharyngeal specimens from influenza-positive patients were tested for viral co-infections (ePlex, Genmark Diagnostics). Patterns of viral co-infections were evaluated using chi-square analysis. The association of viral co-infection with hospital admission was assessed using univariate and multivariate regression. RESULTS: The overall influenza A/B positivity rate was 18.1% (1071/5919). Of the 999 samples with ePlex results, the prevalence of viral co-infections was 7.9% (79/999). The most common viral co-infection was rhinovirus/enterovirus (RhV/EV), at 3.9% (39/999). The odds of hospital admission (OR 2.33, 95% CI: 1.01-5.34) increased significantly for those with viral co-infections (other than RhV/EV) versus those with influenza A infection only. CONCLUSION: Presence of viral co-infection (other than RhV/EV) in ED influenza A/B positive patients was independently associated with increased risk of hospital admission. Further research is needed to determine clinical utility of ED multiplex testing.

Impact of coinfection status and comorbidity on disease severity in adult emergency department patients with influenza B.

BACKGROUND: Influenza B accounts for approximately one fourth of the seasonal influenza burden. However, research on the importance of influenza B has received less attention compared to influenza A. We sought to describe the association of both coinfections and comorbidities with disease severity among adults presenting to emergency departments (ED) with influenza B. METHODS: Nasopharyngeal samples from patients found to be influenza B positive in four US and three Taiwanese ED over four consecutive influenza seasons (2014-2018) were tested for coinfections with the ePlex RP RUO panel. Multivariable logistic regressions were fitted to model adjusted odds ratios (aOR) for two severity outcomes separately: hospitalization and pneumonia diagnosis. Adjusting for demographic factors, underlying health conditions, and the National Early Warning Score (NEWS), we estimated the association of upper respiratory coinfections and comorbidity with disease severity (including hospitalization or pneumonia). RESULTS: Amongst all influenza B positive individuals (n = 446), presence of another upper respiratory pathogen was associated with an increased likelihood of hospitalization (aOR = 2.99 [95% confidence interval (95% CI): 1.14-7.85, p = 0.026]) and pneumonia (aOR = 2.27 [95% CI: 1.25-4.09, p = 0.007]). Chronic lung diseases (CLD) were the strongest predictor for hospitalization (aOR = 3.43 [95% CI: 2.98-3.95, p < 0.001]), but not for pneumonia (aOR = 1.73 [95% CI: 0.80-3.78, p = 0.166]). CONCLUSION: Amongst ED patients infected with influenza B, the presence of other upper respiratory pathogens was independently associated with both hospitalization and pneumonia; presence of CLD was also associated with hospitalization. These findings may be informative for ED clinician's in managing patients infected with influenza B.

Identification of pathogens from the upper respiratory tract of adult emergency department patients at high risk for influenza complications in a pre-Sars-CoV-2 environment.

The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic highlights the morbidity and potential disease severity caused by respiratory viruses. To elucidate pathogen prevalence, etiology of coinfections and URIs from symptomatic adult Emergency department patients in a pre-SARS-CoV-2 environment, we evaluated specimens from four geographically diverse Emergency departments in the United States from 2013-2014 utilizing ePlex RP RUO cartridges (Genmark Diagnostics). The overall positivity was 30.1% (241/799), with 6.6% (16/241) coinfections. Noninfluenza pathogens from most to least common were rhinovirus/enterovirus, coronavirus, human metapneumovirus and RSV, respectively. Broad differences in disease prevalence and pathogen distributions were observed across geographic regions; the site with the highest detection rate (for both mono and coinfections) demonstrated the greatest pathogen diversity. A variety of respiratory pathogens and geographic variations in disease prevalence and copathogen type were observed. Further research is required to evaluate the clinical relevance of these findings, especially considering the SARS-CoV-2 pandemic and related questions regarding SARS-CoV-2 disease severity and the presence of co-infections.

Intravenous peramivir vs oral oseltamivir in high-risk emergency department patients with influenza: Results from a pilot randomized controlled study.

BACKGROUND: Peramivir offers a single-dose intravenous (IV) treatment option for influenza (vs 5-day oral dosing for oseltamivir). We sought to compare outcomes of emergency department (ED) patients at high risk for influenza complications treated with IV peramivir vs oral oseltamivir. METHODS: During the 2015-16 and 2016-17 influenza seasons, adult patients in two US EDs were randomized to either oral oseltamivir or IV peramivir treatment group. Eligibility included positive molecular influenza test; met CDC criteria for antiviral treatment; able to provide informed consent and agree to follow-up assessment. Outcomes were measured by clinical end-point indicators, including FLU-PRO Score, Ordinal Scale, Patient Global Impression on Severity Score, and Karnofsky Performance Scale for 14 days. Non-inferior t test was performed to assess comparative outcomes between the two groups. RESULTS: Five hundred and seventy-five (68%) of 847 influenza-positive patients were approached. Two hundred and eighty-four met enrollment criteria and 179 were enrolled; of these 95 (53%) were randomized to peramivir, and 84 to oseltamivir. Average FLU-PRO score at baseline was similar (peramivir: 2.67 vs oseltamivir: 2.52); the score decreased over time for both groups (day 5: peramivir: 1.71 vs oseltamivir: 1.62; day 10: peramivir: 1.48 vs oseltamivir: 1.37; day 14: peramivir: 1.40 vs oseltamivir: 1.33; all P < .05 for significantly non-inferior). Influenza-related complications were similar between two groups (All: peramivir: 31% vs oseltamivir: 21%, P > .05; pneumonia: peramivir: 11% vs oseltamivir: 14%, P > .05). CONCLUSIONS: Clinical outcomes of influenza-infected patients treated with single-dose IV peramivir were comparable to those treated with oral oseltamivir, suggesting potential utility of peramivir for influenza-infected patients in the ED.