The ongoing COVID-19 pandemic, which began in early 2020, has caused significant disruption in both our health and economic systems. The rising death toll serves as a stark reminder of our susceptibility to new infections and their severe effects.

> We have witnessed everything from bare supermarket shelves to confrontations over essential supplies like toilet paper.

While we eagerly await the development of vaccines against the SARS-CoV-2 virus, it’s important to recognize that a vaccine alone may not suffice as a universal solution.

> Not everyone who contracts SARS-CoV-2 becomes ill, and those who do can experience a wide range of symptoms.

Some individuals remain asymptomatic or only suffer mild effects, while others, especially those with compromised immune systems, face severe health challenges. A multitude of factors contributes to this variance in severity, including viral load, levels of ACE2 receptors, lifestyle habits like smoking, age, and underlying health conditions (such as heart disease, diabetes, and obesity).

The elderly and those with pre-existing health issues report the highest mortality rates due to COVID-19. Aging and many chronic conditions are often linked to persistent inflammation, which diminishes the immune system's ability to mount an effective response against invading pathogens.

This vulnerable population is at a heightened risk of infection and death. For them, the disease can escalate quickly from mild symptoms to acute respiratory distress syndrome (ARDS), which complicates breathing and can lead to organ damage. Patients suffering from ARDS often require ventilators and face a higher mortality risk.

> While vaccines bolster our adaptive immunity, not everyone responds effectively to them.

In individuals with weakened immune systems, a vaccine may not provide adequate protection. For example, influenza vaccine effectiveness varies between 40% to 60%, contributing to its significant annual death toll.

Vaccines primarily engage the adaptive immune system (B cells and T cells) to combat infections. However, in older adults and those with pre-existing conditions, vaccines may not adequately stimulate these immune components to fend off pathogens and facilitate recovery. Additionally, the rapid mutations of SARS-CoV-2 pose challenges to vaccine efficacy.

> What about innate immunity, which is typically the first line of defense against infections?

Although vaccine development targeting adaptive immunity has garnered significant attention, the role of the innate immune system in COVID-19 warrants further examination. In severe cases, harmful outcomes often arise from unchecked inflammation caused by overactive innate immune cells, leading to serious tissue damage and multi-organ failure.

The acute immune response triggered by phenomena like the “cytokine storm” and “neutrophil influx” can severely damage lung tissue and swiftly progress to ARDS, ultimately resulting in death for critically ill patients. Such detrimental immune responses stem from hyper-activated innate immune components and the immune system's failure to moderate excessive inflammation.

> To illustrate, individuals at risk are like riders on a penny farthing, characterized by a large front wheel (overactive innate immunity) and a small back wheel (underactive adaptive immunity) during their COVID-19 journey. Others with milder symptoms enjoy a more balanced ride on a conventional bicycle with equally sized wheels (well-functioning innate and adaptive immune systems).

 :width: 800 :alt: Unbalanced immunity in severe COVID-19

> Therefore, achieving immune fitness requires the proper functioning of both innate and adaptive immune responses; thus, vaccines alone cannot address COVID-19 severity.

To effectively manage COVID-19 outcomes, especially in severe cases, a well-coordinated response from both innate and adaptive immune systems is crucial. Strategies that activate adaptive immunity while controlling innate immune hyper-activation must be prioritized for COVID-19 management.

So, how can we achieve this balanced immune fitness and ensure protection against current and future biological threats?

> The answer lies within us — in our gut!

Our gut is home to approximately 70 to 80% of our immune cells, acting as a control center for immune function while also aiding digestion. This makes it a powerful organ for maintaining health and combating diseases. Almost all illnesses either originate from or impact the gut, underscoring its significance in our overall well-being.

The key to harnessing this power is through our gut microbiota — a vast community of microorganisms residing in our gastrointestinal (GI) tract. This tract hosts the largest proportion of the approximately 100 trillion microbes within the human body, often referred to as the body's microbial bank.

This microbial bank comprises various organisms, commonly known as microbiota, including bacteria, fungi, archaea, and even viruses. While bacteria have been the focus of most research, the roles of other microbes in health and disease are increasingly being studied. Maintaining diversity within the gut microbiome is essential for optimal immune fitness.

 :width: 800 :alt: Healthy versus unhealthy gut microbiota

The gut microbiota not only aids in digestion and vitamin production but also trains our immune system to identify and eliminate pathogens. Emerging studies suggest that gut microbiota significantly influences our susceptibility to various diseases, responses to treatments, and even mental health.

When properly cared for, these tiny organisms can keep us healthy and ward off illness. Conversely, neglecting gut health can lead to sickness and reduced vaccine efficacy.

> Surprisingly, these microorganisms play a crucial role in determining our health outcomes, influencing whether we face a challenging illness or a more manageable one. Thus, they act as gatekeepers of our health.

The gut microbiota is a complex ecosystem, balancing beneficial bacteria and opportunistic pathogens. Beneficial bacteria compete with pathogens for resources, maintaining a healthy balance.

These beneficial microbes also ferment prebiotic dietary fibers (indigestible components of plant foods) to produce vital compounds that offer significant health benefits.

Among these compounds, short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate, generated through bacterial fermentation, nourish the intestinal lining and promote immune fitness.

> SCFAs are potent bacterial by-products that can activate both innate and adaptive immune responses, ensuring the immune system is equipped to combat infections.

The immune functions mediated by SCFAs extend beyond the gut, affecting distant sites like the brain (via the gut-brain axis) and lungs (via the gut-lung axis). Additionally, SCFAs and antimicrobial substances create an environment unfavorable to pathogens, reducing their chances of proliferation.

Problems arise when the balance between beneficial and harmful microbes is disrupted, a condition known as dysbiosis.

 :width: 800 :alt: Production of beneficial metabolites versus toxic metabolites in healthy and dysbiotic gut

Several factors can disturb the gut's microbial community, leading to immune dysfunction. These include antibiotic exposure, stress, and unhealthy dietary habits characterized by low fruit and vegetable intake.

Dysbiosis and diminished immune responses are especially common among the elderly, increasing their susceptibility to severe infections. Chronic inflammatory conditions like gastrointestinal disorders, obesity, diabetes, cardiovascular diseases, cancer, and even mental health issues often coincide with gut microbiota disturbances.

In these inflammatory states, the immune system struggles to deploy the appropriate defenses against pathogens, hampering recovery. Consequently, elderly individuals and those with chronic conditions face elevated risks of infection and severity, as highlighted by COVID-19.

Emerging research indicates that alterations in the gut microbiota of COVID-19 patients correlate with disease severity. Maintaining a diverse microbiota and addressing disruptions in gut health can significantly mitigate COVID-19 severity. The good news is that fostering microbial balance and rectifying dysbiosis are achievable goals.

Consuming a balanced diet is essential for promoting gut microbiota diversity and ensuring robust immunity. Adequate nutrients from a well-rounded diet are crucial for supporting immune health, while excessive intake of refined carbohydrates, sugars, processed fats, and salt is linked to inflammation and microbial imbalance.

> The most effective investment in your gut health, which bolsters your microbiota's inner economy, is a diet rich in prebiotic fibers and probiotic bacteria.

Providing your gut microbiota with various plant-based fibers (from fruits, vegetables, and whole grains) promotes microbial diversity and the production of beneficial SCFAs. Other natural food sources rich in healthy fats, proteins, vitamins, and minerals, such as fish, nuts, and meat, also support immune function.

Certain gut bacteria convert prebiotic fibers into SCFAs, while others produce intermediate by-products that nourish other beneficial gut bacteria. A diverse array of whole-plant fibers ensures that all beneficial bacteria receive adequate sustenance.

Moreover, fermented foods containing probiotic bacteria (such as yogurt, kefir, kombucha, sauerkraut, and kimchi) enhance gut microbiota diversity and strengthen immune defenses against infections. The combination of prebiotic fibers and probiotic bacteria, known as synbiotics, offers a particularly effective strategy for enhancing gut health and immune fitness against viral infections.

Synbiotics represent a dual approach: the probiotics replenish beneficial gut bacteria, while the prebiotics nourish both the newly introduced probiotics and existing microbiota. This results in SCFA production and improved immunity, benefiting everyone involved!

Vaccines remain an invaluable public health measure and should continue to be promoted for disease prevention at both community and global levels. A thriving inner economy of diverse gut microbiota provides additional support for the immune system, enhancing its ability to clear viruses, respond effectively to vaccines, and recover health with minimal organ damage.

So, nurture your gut with the right nutrients and reap the immune fitness benefits during the COVID-19 pandemic and beyond.

Take care of your gut, and good health will follow!