Why women are more likely to suffer from long Covid

When Covid-19 burst into our world, the initial focus was on how to prevent death. Older men were more likely to die from the virus than young people or women, and it became clear that not all humans suffered or died at an equal rate. Covid-19 infection was fatal in some and asymptomatic in others.

Throughout human evolution, this has been the situation. A new infectious threat arises, and humans with an immune system best suited to resisting the infection survive.

With time, we’ve seen the emergence of Post-Covid Syndrome, colloquially known as long Covid. The initial infection resolves, yet symptoms persist, or new symptoms develop, resulting in prolonged suffering even where the original infection was mild. The story of Covid-19, of who dies and who suffers, is a story about how our individual immune systems react to viruses we come in contact with.

The world has seen coronavirus epidemics before, so we have past experience to look back on. The Sars (Severe Acute Respiratory Syndrome) epidemic of 2002, and the Mers (Middle Eastern Respiratory Syndrome) epidemic of 2015 were both caused by coronaviruses.

In both cases, men were more likely to die of their infection than women, healthcare workers were at high risk of infection from their patients, and a proportion of survivors suffered ongoing symptoms. Post-Covid, Post-Sars and Post-Mers syndromes all include persistent fatigue and pain, and show strong similarities to Chronic Fatigue Syndrome, a condition more common in women than men.

Related: Women are more susceptible to long Covid, but will we listen to them?

Importantly, these conditions are all associated with excessive activation of immune cells in the blood (eg macrophages), and immune-competent cells in the brain (glia). The initial immune response occurs, at least in part, via special receptors on the surface of innate immune cells called Toll-Like Receptors. When TLRs recognise Covid-19 within the body, their cell releases molecular signals called cytokines that make us feel unwell. Cytokine storm, the extreme form of cytokine release, is a feature of the most severe aspects of Covid-19 infection. Repeated TLR stimulation provides a stimulus to chronic medical conditions, including chronic pain and the severity of symptoms is associated with the severity of glial activation within the brain.

There are many ways in which Covid-19’s effect on women may differ from its effect on men. Overall, women resist viral and bacterial infections more effectively than men. They die less during a pandemic. They live longer than men. But a stronger immune system comes at a price. Women have a higher lifetime risk of inflammatory immune conditions such as chronic pain, chronic fatigue and autoimmune disease. If you look in the waiting room of a health practitioner who cares for people with long-term pain conditions, most of their patients will be female.

Conditions including severe period pain, endometriosis and chronic pelvic pain are already associated with an increase in TLR activity, and the presence of Chronic Fatigue Syndrome is highly associated with pre-existing gynaecological pain conditions. Repeated stimulation of the immune system predisposes to chronic pain conditions, and infection with Covid-19 presents a major immune stimulus.

Whether Covid-19 infection will worsen pre-existing immune-based symptoms in women, even if their Covid-19 infection was mild, is yet to be determined.

The majority of studies so far have understandably been in people who were sick enough to be in hospital. Over time, the effect on those with milder infections will become apparent. A clinic in Paris followed more than 50,000 patients with Covid-19 infection who were monitored at home because their infection was not severe. In the months following infection those patients with prolonged fatigue, muscle pains and anxiety symptoms were predominantly female (four females for every male), and relatively young (average age 40 years).

We no longer live in a world where avoiding Covid-19 infection over the long term appears possible. For humans with access to a vaccine, they will choose between being vaccinated, or taking a chance on Covid-19 infection. Although neither option is risk free – the vaccine is relatively new and it’s true we don’t know everything about it yet – infection with Covid-19, even where mild, is a certain immune stimulus. In addition, the life-threatening risk of thromboembolic disease present during a Covid-19 infection complicates the use of common hormonal medications used by women, such as the oral contraceptive pill.

Women make up 67% of the frontline, global healthcare workforce in their roles as doctors, nurses, teachers, childcare workers, aged-care workers and cleaners, and our community relies on their wellbeing. As such, they are at a higher risk of exposure to the virus than women in the general community, and may present a large group of humans with specific and important Covid-19 needs.

Sufferers of chronic pain have long been told it’s all in their head. We now know that’s not true. The pain that can’t be seen looks at why doctors are playing catch-up on chronic pain conditions like endometriosis, migraine and more – and what they have to do with long Covid.

• Susan Evans is a gynaecologist and chair of the Pelvic Pain Foundation of Australia. Mark Hutchinson is a professor within the Adelaide Medical School who specialises in pain research