Influenza and dengue virus co‐infection impairs monocyte recruitment to the lung, increases dengue virus titers, and exacerbates pneumonia

Abstract

Co-infections of influenza virus and bacteria are known to cause severe disease, but little information exists on co-infections with other acute viruses. Seasonal influenza and dengue viruses (DENV) regularly co-circulate in tropical regions. The pandemic spread of influenza virus H1N1 (hereafter H1N1) in 2009 led to additional severe disease cases that were co-infected with DENV. Here, we investigated the impact of co-infection on immune responses and pathogenesis in a new mouse model. Co-infection of otherwise sublethal doses of a Nicaraguan clinical H1N1 isolate and two days later with a virulent DENV2 strain increased systemic DENV titers and caused 90% lethality. Lungs of co-infected mice carried both viruses, developed severe pneumonia, and expressed a unique pattern of host mRNAs, resembling only partial responses against infection with either virus alone. A large number of monocytes were recruited to DENV-infected but not to co-infected lungs, and depletion and adoptive transfer experiments revealed a beneficial role of monocytes. Our study shows that co-infection with influenza and DENV impairs host responses, which fail to control DENV titers and instead, induce severe lung damage. Further, our findings identify key inflammatory pathways and monocyte function as targets for future therapies that may limit immunopathology in co-infected patients.

Invisible Facial Flushing in Two Cases of Dengue Infection and Influenza Detected by PC Program and Smartphone App: Decorrelation Stretching and K-Means Clustering

“…Both dengue and influenza are potentially fatal diseases, and a high index of suspicion is necessary among the treating physicians for early diagnosis and best outcomes. Influenza and dengue virus coinfection impairs monocyte recruitment to the lung, increases dengue virus titers, and exacerbates pneumonia [25]. e possible clues for suspicious diagnosis include (a) acute febrile illness, (b) copresentation between respiratory and bleeding symptoms, (c) CBC show lymphocytosis with atypical lymphocytosis and decreased platelet, (d) abnormality of chest X-ray, and (e) history of living in or visiting to a dengue endemic area [26].…”

The value of lung involvement in recognizing severe dengue-A retrospective study

“…Micro abscesses existed in heart, brain, lung and kidney of the reported dengue cases with MODS after autopsy [5]. Secondly, other complicated infections such as staphylococcus aureus, fungi or in uenza A virus could aggravate the lung damage or even induce pulmonary cavity, acute respiratory distress syndrome (ARDS) and MODS [22][23][24][25]. Therefore, patients with lung involvement need more surveillance on their risk of more advanced disease.…”

Impact of recent influenza A virus infection on clinical characteristics and outcomes in severe coronavirus disease 2019 adult inpatients

“…Although there was no nucleic acid result to con rm in uenza A infection, some of the patients with in uenza A IgM positive in this study may have co-infection with two viruses (in uenza A virus and SARS-CoV-2). Viral co-infection can affect the course of infectious diseases [30][31][32]. Angiotensin Converting Enzyme 2 (ACE2) was proven to be one of the major receptors that mediate the entry of SARS-CoV-2 into human cells [33,34].…”