Abstract
Influenza virus (IV) coinfection, i.e., simultaneous infection with IV and other viruses, is a common occurrence in humans. However, little is known about the incidence and clinical impact of coinfection with two different IV subtypes or lineages (“dual infections”). We report the incidence, standardized disease severity, and follow-up of IV dual infections from a hospital-based digital surveillance cohort, comprising 6073 pediatric patients fulfilling pre-defined criteria of influenza-like illness in Berlin, Germany. All patients were tested for IV A/B by PCR, including subtypes/lineages. We assessed all patients at the bedside using the mobile ViVI ScoreApp, providing a validated disease severity score in real-time. IV-positive patients underwent follow-up assessments until resolution of symptoms. Overall, IV dual infections were rare (4/6073 cases; 0.07%, incidence 12/100,000 per year) but showed unusual and/or prolonged clinical presentations with slightly above-average disease severity. We observed viral rebound, serial infection, and B/Yamagata-B/Victoria dual infection. Digital tools, used for instant clinical assessments at the bedside, combined with baseline/follow-up virologic investigation, help identify coinfections in cases of prolonged and/or complicated course of illness. Infection with one IV does not necessarily prevent consecutive or simultaneous (co-/dual) infection, highlighting the importance of multivalent influenza vaccination and enhanced digital clinical and virological surveillance.
Highlights
Influenza virus (IV) infection poses a serious health threat, especially to particular risk groups, including immunocompromised, elderly, and young individuals [1–3].According to the latest International Committee on Taxonomy of Viruses’ (ICTV) Virus Taxonomy Release ratified in March 2021, the Orthomyxoviridae family comprises seven genera and nine species, including Influenza A virus (IAV), Influenza B virus (IBV), Influenza C virus (ICV), and Influenza D virus (IDV) [4]
Disease severity, and clinical follow-up of IV dual infections in a well-defined cohort of 6073 influenza-like illness (ILI) patients of all cases presenting to one of Europe’s largest pediatric academic medical centers
Our understanding of IV dual infections mainly relied on singular case reports or small retrospective case series without denominator data as would be required for the determination of incidence and risk [15,16,18,20,21,33,34]
Summary
Influenza virus (IV) infection poses a serious health threat, especially to particular risk groups, including immunocompromised, elderly, and young individuals [1–3]. According to the latest International Committee on Taxonomy of Viruses’ (ICTV) Virus Taxonomy Release ratified in March 2021, the Orthomyxoviridae family comprises seven genera and nine species, including Influenza A virus (IAV), Influenza B virus (IBV), Influenza C virus (ICV), and Influenza D virus (IDV) [4]. IDV and ICV may be associated with mild or asymptomatic infection in humans [5–7] whereas IAV and IBV infection can cause severe and fatal diseases [2,8]. IAVs are further divided into subtypes based on their surface proteins hemagglutinin (H) and neuraminidase (N), of which A(H1N1)pdm and A(H3N2) are currently circulating amongst humans. IBVs are further classified into two distinct lineages, B/Victoria and B/Yamagata [8]. IAV subtypes and IBV lineages are antigenically different
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