Among US Military Health System (MHS) beneficiaries diagnosed as having COVID-19, obesity was independently and strongly associated with hospitalization, need for oxygen therapy, higher viral load, and an altered immune response, according to a prospective study late last week in the Journal of Infectious Diseases.
A team led by researchers from the Uniformed Services University of the Health Sciences in Bethesda, Maryland, used logistic regression models to compare the viral loads and immune responses in obese and non-obese patients at seven military treatment sites, stratified by hospitalization. Patients were included if they had confirmed or suspected COVID-19 or had a recent high-risk exposure to the virus.
Underweight or normal body mass index (BMI) was considered less than 24.8 kg/m2, overweight was 25 to 29.9 kg/m2, obese was 30 to 34.9 kg/m2, and severely obese was 35 kg/m2 and higher.
Of 511 COVID-19 patients, 24% were obese, and 14% were severely obese. Obesity was tied to hospitalization (adjusted odds ratio [aOR], 1.91) and need for supplemental oxygen (aOR, 3.39). Over three-quarters of COVID-19 cases occurred in overweight participants. Among outpatients, those who were severely obese had higher viral loads and greater peak anti–SARS-CoV-2 spike protein immunoglobulin G (IgG) concentrations.
The researchers noted that the increased viral loads in obese outpatients were not observed in inpatients. "It is unknown whether this reflects antiviral drug use in inpatients or sampling of inpatient illness relatively later in their course of illness when viral loads may be expected to fall more precipitously," they wrote.
The study sample was 64.2% male, 62% were 18 to 44 years old, 51.5% were active-duty military, and 48.6% were dependents or retired military. Of all participants, 25% were hospitalized, ranging from 14% in normal or underweight patients to 52% in those with severe obesity.
Mechanisms likely multifactorial
Average BMI was higher in inpatients than in outpatients and in those who required oxygen therapy than in those who didn't. Thirty-five percent of enrollees had one or more underlying illnesses, ranging from 25% in underweight or normal participants to 68% in those with severe obesity. The most common underlying diseases were high blood pressure (20.1%) and diabetes (12%), and both were increasingly common with higher obesity categories.
"In a population of Military Health System beneficiaries, obesity was strongly correlated with COVID-19 severity, viral load, and antibody response, suggesting the relationship between obesity and COVID-19 severity may be mediated by increased viral load in those with a higher body mass index," the authors concluded.
The researchers said the mechanisms behind the strong link between obesity and severe COVID-19 are probably multifactorial and may include impaired cardiovascular, respiratory, metabolic, and thrombotic function, amplified or dysregulated immune responses that lead to more viral replication and a greater inflammatory immune response, and higher levels of angiotensin-converting enzyme 2 receptors, which allow SARS-CoV-2 to enter cells.
Future COVID-19 studies should examine the role of inflammatory biomarkers and innate immunity (eg, natural killer cells, memory T cells) in obese patients, obesity-related insulin resistance, microbiome derangement, and mechanisms such as excess soft tissue in the upper respiratory tract that obstructs the airway, the authors concluded.
More antibodies not necessarily better
In an editorial in the same journal, authors from the Washington University School of Medicine in St. Louis said the study results raise questions that merit further study.
Such questions include whether differences in viral load and antibody production can be demonstrated in other populations, whether the more robust IgG response in obesity is related to greater viral exposure, and what the elevated viral load in obese outpatients means in terms of viral transmissibility. "If the viral load differences found in this study are also seen for emerging variants with higher transmission rates, such as the Delta variant, the effect could be multiplicative," they wrote.
Another important question is whether higher anti-spike protein antibody levels in obese patients translate to better or more enduring immunity. "There is an open question about whether the antibodies produced by obese patients are as efficient at neutralizing SARS-CoV-2 compared to antibodies produced by non-obese patients," Lewis and colleagues said. "More does not necessarily mean better antibodies."
Overall, they wrote, the study's suggestion that obese patients have altered host-pathogen interactions is an important one. "Increasing our understanding of how obesity leads to more severe COVID-19 disease may shed some new light on mechanisms of anti-viral immunity, how metabolic diseases such as obesity influence immune system function, and potentially reveal approaches to identify patients most at risk of requiring hospitalization or more advanced care," they wrote.
