Why Do Some People Get More Severe COVID-19 Than Others? New Research Offers Clues

Since the start of the COVID-19 pandemic, one question has continued to puzzle both scientists and the public alike: why do some people experience only mild symptoms, while others become seriously ill?

You may have heard stories of two people catching COVID-19 at the same time, yet having completely different experiences. One person might recover within a few days with little more than a sore throat and fatigue, while another may develop severe symptoms that require hospitalisation. In some cases, otherwise healthy individuals have experienced unexpectedly serious illness, while others with underlying health conditions have recovered relatively quickly.

Recent studies suggest that the way our bodies respond to COVID-19 can vary significantly from person to person. Differences in immune responses, inflammation levels, and even how the body uses energy may all play a role in determining how severely someone is affected by the virus.

We'll explore some of the key factors researchers believe may contribute to severe COVID-19 and what current research is revealing about the body's response to infection.

Why does COVID-19 affect people differently?

Part of the answer lies in the fact that every person's body is unique. Factors such as age, overall health, underlying medical conditions, and vaccination status can all influence how the body responds to infection. However, researchers are increasingly finding that these factors alone do not fully explain the differences seen between patients.

A recent study published in Genome Medicine has shown that even people with severe COVID-19 can display very different biological responses to the virus. This suggests that there is no single pathway that leads to severe illness. Instead, multiple factors appear to work together to influence how the body reacts to infection.

Scientists now believe that the severity of COVID-19 may depend not only on the virus itself, but also on how the body's immune system responds, how much inflammation develops, and how effectively the body can maintain normal functions while fighting the infection.

In other words, severe COVID-19 appears to result from a complex interaction of biological processes that researchers are still working to fully understand.

How does inflammation affect COVID-19 severity?

One of the factors researchers believe may influence the severity of COVID-19 is inflammation. While inflammation is often associated with illness, it is actually a normal and essential part of the body's immune response.

When a virus enters the body, the immune system immediately goes to work. Part of this response involves inflammation, which helps the body fight infection and begin the healing process.

In many cases, inflammation is beneficial. It helps recruit immune cells to the site of infection, supports the body's defence mechanisms, and plays an important role in recovery. Without inflammation, the body would struggle to respond effectively to harmful viruses and bacteria.

However, like many things in the body, balance is important.

Can too much of a good thing become a problem? 

Too little inflammation may make it harder to fight off an infection, while too much inflammation can place additional stress on the body's tissues and organs. Researchers of that same study believe that in some cases of severe COVID-19, the body's inflammatory response may become overly active, contributing to more serious symptoms and complications.

A useful way to think about inflammation is as a fire alarm. When a fire starts, the alarm serves an important purpose by alerting people to danger. But if the alarm continues ringing long after the emergency has passed, it can become disruptive and create additional problems. Similarly, inflammation is essential when responding to infection, but excessive or prolonged inflammation may sometimes do more harm than good.

Does your body need more than a strong immune system to fight infection?

In recent years, scientists have begun exploring how the body's metabolism may influence its ability to respond to infections such as COVID-19. Metabolism refers to the processes that allow the body to convert food into energy and provide cells with the resources they need to function properly.

This is important because fighting an infection requires a significant amount of energy. Immune cells need fuel to identify threats, communicate with one another, and help eliminate viruses from the body.

The study found that patients with severe COVID-19 often showed changes in the way their bodies processed and used important nutrients, particularly those involved in energy production and cellular function. Researchers also observed links between these metabolic changes and markers of inflammation, suggesting that the two may be closely connected.

Could these biological differences help explain long COVID?

For many people, COVID-19 symptoms resolve within a few weeks. However, some continue to experience ongoing health issues long after the initial infection has passed—a condition commonly known as long COVID.

Researchers are still working to understand why some people develop long COVID while others recover fully. One theory is that the same biological processes that influence COVID-19 severity may also play a role in longer-term recovery.

Common symptoms of long COVID can include:

• Persistent fatigue
• Brain fog and difficulty concentrating
• Shortness of breath
• Ongoing cough
• Headaches
• Sleep disturbances
• Dizziness
• Muscle and joint pain
• Changes to taste or smell
• Heart palpitations

While more research is needed, scientists continue to investigate how inflammation and changes in the body's normal biological processes may affect both short-term illness and long-term recovery following COVID-19. 

Read more about it here: Long COVID: What We Now Know & Why COVID Still Matters

COVID-19 research is evolving — and so is the way we think about treatment

Significant progress has been made in understanding COVID-19, yet the question of why the virus affects people so differently remains one of the more complex puzzles in modern medicine. Age, underlying health conditions and vaccination status all play a role — but research is now revealing that the biological factors run deeper than these alone.

What is becoming increasingly clear is that the body's response to infection may matter just as much as the virus itself. How the immune system signals a threat, how inflammation is regulated, and whether the body can sustain the metabolic demands of fighting a serious infection all appear to influence where a patient lands on the spectrum from mild to severe. Crucially, these aren't independent variables — they interact, and it's often the combination that determines the outcome.

These insights are helping researchers move away from looking for a single explanation and toward a more nuanced understanding of COVID-19 as a disease that can unfold through more than one biological pathway. That shift in thinking is what may eventually make more personalised treatment approaches possible — matching care not just to a diagnosis, but to the specific immune and metabolic profile of the person receiving it.

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