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Thursday 24 September 2020

long covid

Anatomy of a storm

There are only theories about the causes of Long Covid, but one of the most compelling is a rampaging overreaction of the immune system

By Xavier Greenwood

So many things still puzzle us about Covid-19. Why are young people less affected by the disease? How do people deteriorate so rapidly from mild symptoms to critical illness? What explains the tens of thousands of people in the UK (and even more worldwide) who are still reporting symptoms of the virus many months after their diagnosis, and long after they have tested negative?

One possible answer for all these question starts in human bodies which don’t just attack the virus, but attack themselves.

It starts in the eye of a cytokine storm.


“An infection triggers an inflammatory response. Your body is wanting to produce a response that says I need to fight this disease…”

Dr Monica Verduzco-Gutierrez, chair of the Department of Rehabilitative Medicine at UT Health San Antonio


When the body encounters a virus, cells in the immune system set off a chain of events which triggers an immune response.

Cytokines are small pro-inflammatory proteins, which regulate the function of other cells. They are chemical messengers.

They recruit T cells, which rush to the site of the infection.

In a healthy response, the team of immune cells (T cells and others) deals with the virus by causing local inflammation in the infection site. When the body has successfully fought off the virus, the immune system switches itself off.

But in the case of Covid-19, the response triggered by the immune system can become far more serious.


“… sometimes it just ends up being a storm.”

Dr Monica Verduzco-Gutierrez


Covid-19 has the ability to take over the body for days, taking over host cells and reproducing while evading the immune system response. When it is finally detected, the immune system can panic, releasing excessive cytokines…

… which in turn activate excessive numbers of T cells, which then stimulate more cytokines, creating a cascading effect.

An immune response of this amplitude can attack healthy tissues and cause hyper-inflammation. In the case of Covid-19, this hyper-inflammation can weaken the alveoli, the tiny air sacs responsible for the uptake of oxygen, and make them leaky, allowing fluid to fill the lung cavities.

The hyper-inflammation can become systemic, affecting the entire organ. As blood oxygen levels plummet, breathing becomes difficult or impossible.

Respiratory distress syndrome follows and other organs begin to fail.


This cytokine storm can end in death, and is thought by many scientists to be what kills a great deal of Covid-19 patients. Dr Arne Akbar, an immunology professor at University College, London, has written in the journal Science about the higher levels of baseline inflammation in older, frailer people (Covid-19 sufferers aged 80 or older are hundreds of times more likely to die than those aged under 40).

An immune imbalance in those with pre-existing conditions that often provoke chronic, low-grade inflammation, such as obesity, which is associated with significantly higher Covid-19 mortality rates, might also compound the immune system’s response to the virus.

Most intriguingly, the cytokine storm might also explain why many of those infected by the virus, even mildly, survive but continue to suffer; why there are long-haulers who experience an unpredictable and recurring set of symptoms throughout the body months after they first contracted the coronavirus.

An initial response develops into post-viral autoimmunity, a low-intensity variant of the cytokine storm, which triggers cycles of inflammation long after the person has tested negative for the virus.


“My hypothesis is that in some patients Covid triggers an inflammatory cascade that changes the milieu of your hormonal responses in your body and affects the autonomic nervous system, your physical system. And then it takes time to get back into the state you were in before.”

Dr Monica Verduzco-Gutierrez


Those patients might not even have felt very ill in the first place.


“For some it is critical, they’re in ICU and they need intubation… And for other people, maybe their breathing is not that bad, they’re at home. But they’re more fatigued, they can’t do the exercise they did before. They are having painful, more long-haul symptoms.”

Dr Monica Verduzco-Gutierrez


The cytokine storm is one, compelling, theory for what is going on in severely ill or long-suffering Covid-19 patients.

But just a couple of weeks ago, scientists at Radboud University Medical Center in the Netherlands found that the seriously ill Covid-19 patients they studied had significantly less elevated levels of cytokines than in patients with septic shock and acute respiratory distress syndrome, disputing months of research which suggests quite the opposite.

We still know very little. With this disease we dive into the eye of one storm, only to find that perhaps we ought to have been looking in another.

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