Beyond Disease Severity: The Impact of Obesity on Influenza A Virus Shedding

(See the Brief Report Maier et al, on pages 1378–82.)

Between 1975 and 2016, worldwide obesity rates have nearly tripled, with >1.9 billion adults aged ≥18 years (39%) considered overweight and 650 million (13%) considered obese [1]. An increasing percentage of children are also becoming obese. While increased weight is a recognized risk factor for several diseases, including diabetes, certain cancers, and cardiovascular diseases, this is not limited to noncommunicable diseases. Epidemiologic studies during the 2009 influenza pandemic highlighted, for the first time, that obesity was a high-risk factor for developing severe complications and dying from influenza virus infection [2, 3]. Although the mechanism(s) for increased disease severity in humans is unknown, animal models suggest that the increased disease severity may be multifactorial, involving issues such as viral spread and lung repair [4, 5] neutrophil extracellular trap formation [6], and modulation of the lung metabolome [7]. However, nothing was known about the impact of obesity on viral shedding and transmission. The studies reported by Maier et al in this issue of The Journal of Infectious Diseases provide the first evidence that obesity influences may influence the transmission of the virus, in addition to disease severity [8].

Using established household transmission and cohort studies in Managua, Nicaragua, Maier et al investigated the effects of obesity on the duration of viral shedding over 3 seasons (2015–2017). They demonstrated that symptomatic obese adults shed influenza A virus 42% longer than nonobese adults, as measured by reverse transcription polymerase chain reaction analysis. Although obesity was typically associated with more symptoms and disease severity, even asymptomatic or mildly ill obese adults shed influenza virus 104% longer than asymptomatic or mildly ill nonobese adults. This increased duration of viral shedding in obese individuals was specific to influenza A viruses; no association was found between obesity and duration of influenza B virus shedding [9]. Further, obesity did not appear to influence shedding duration in children aged 5–17 years. While further studies are needed to determine whether this is correlated with increased load and shedding of infectious virus, as well as the precise shedding cessation time, a recent study that sampled exhaled breath from influenza virus–infected college students found an association between obesity and quantity of virus shed [10], suggesting that increased shedding duration may be associated with higher viral loads. Regardless, these studies imply that obesity may play an important role in influenza virus transmission.

What does this mean for public health? It could mean that, with an increasing prevalence of obesity, the number of episodes of prolonged influenza virus shedding will increase, leading to increased opportunities to infect naive and high-risk populations. It is therefore even more important to develop effective strategies to prevent and control influenza, especially in the overweight and obese population, which could be challenging because of the poor vaccine responses in this population [11–15]. With increasing focus on the development of a universal influenza vaccine [16], improved protection from influenza is on the horizon. The question remains whether these approaches will not only protect this target population, but also reduce viral shedding duration. In addition, will these findings with influenza virus extend to other respiratory pathogens? This important question remains unanswered.

Notes

Financial support. This work was supported by the National Institute for Allergy and Infectious Diseases (grants R03 AI133527 and HHSN272201400006C) and the ALSAC.

Potential conflicts of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.