It is vital to understand the role of the microbiome in immunity and vaccine response, and how the microbiome may impact the effectiveness of COVID-19 vaccine programs in the real world.
The world is depending on the success of vaccine programs to end the ongoing COVID-19 pandemic. To curb the spread of the virus, it is essential for a population to reach herd immunity, where a significant proportion has developed immunity to infection. There are currently 11 vaccines authorized/approved for use in multiple countries worldwide. According to clinical trial data, these vaccines have demonstrated relatively high efficacy in preventing COVID-19 infection. However, this does not mean that the vaccines will be as effective in the real world. Vaccine response can vary at an individual level and can be influenced by a multitude of biological factors, including the function of the microbiome.
The microbiome plays a significant role in immunity, and may be an underlying factor explaining why elderly people and those with certain comorbidities are at higher risk of infection. The underlying impact of microbiome dysbiosis on immunity may not only increase instances of severe disease in high-risk groups but may also affect their response to the COVID-19 vaccines. Therefore, it is vital to understand the role of the microbiome in immunity and vaccine response, and how it may impact the effectiveness of vaccine programs in the real world.
The Role Of The Microbiome In COVID-19 Immunity
The microbiome is a complex system of symbiotic microbes (including bacteria, fungi, viruses, and other microbial species), which reside throughout the body, predominantly in the gut, and play a significant role in human physiology. In recent years, in-depth research of the microbiome and its function has demonstrated its role in maintaining health and causing disease. A functioning and health-inducing microbiome is very much dependent on a fine balance of specific microbiota populations. The microbiome may become imbalanced when there are too many ‘bad’ microbiota compared to ‘good,’ which results in dysbiosis. Dysbiosis is associated with a range of health conditions, including multiple autoimmune and inflammatory diseases, due to the microbiome’s role in immunity and inflammatory responses. When functioning well, the microbiome effectively plays a role in immune system development and gauges appropriate innate and adaptive immune responses in response to infection.
While COVID-19 is considered a respiratory disease, evidence suggests that often many patients also experience gastrointestinal (GI) symptoms when infected. Moreover, although the lungs and gut are not linked anatomically, they are physiologically linked and interact with the immune system through the microbiome’s gut-lung axis. Evidence suggests that gut microbiota play a role in the immune response against acute respiratory infections such as influenza. Also, viral GI symptoms cause inflammation and damage to the gut, which in turn affects the function of the microbiome, and therefore the effectiveness of the immune system. So, gut dysbiosis may affect COVID-19 outcomes and recovery. Indeed, a recent cohort study conducted across two hospitals demonstrated that gut microbiome composition was significantly altered in COVID-19 patients compared to uninfected individuals. Moreover, the study showed that severity of disease was proportionate to levels of immunomodulatory gut microbiota (including Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacterial), and patients with lower levels had more severe disease.
While SARS-CoV-2 has the ability to infect anyone, the WHO recommends prioritizing those most at risk of severe disease for vaccination, including those aged 65+ years or with various comorbidities (including diabetes, chronic respiratory disease, cardiovascular disease and obesity). Age is a major risk factor for severe disease and death in COVID. In the US, 80% of all recorded deaths from COVID-19 have been in adults aged over 65 years. The microbiome may be an important factor explaining why elderly people are so vulnerable to severe illness.
Aging is associated with significant changes in microbiome composition, and elderly people have a higher level of pro-inflammatory ‘bad’ microbiota than ‘good’ immunomodulatory microbiota. Dysbiosis is also evident in many people with various comorbidities, including those which increase risk for severe effects of COVID-19. Obesity is a particularly prevalent comorbidity for COVID-19 across the globe. According to an analysis of global pooled data on obese patients with COVID-19, risk of hospitalization and death is ~50% higher in infected obese patients compared to non-obese patients, and this is partially driven by reduced immune response to infections as a result of obesity. Microbiome dysbiosis is a feature of obesity as it influences dysregulation of nutrient metabolism and energy expenditure. The underlying impact dysbiosis has on immunity may explain why obese individuals are at a higher risk of COVID-19. Considering that dysbiosis is associated with many of the risk factors for severe COVID-19, when prioritizing people for vaccination, the health of the microbiome may be an important underlying mechanism to consider when assessing risk and potential efficacy of vaccination.
