Why fit, healthy women are the most at risk of long Covid

At first, it all seemed so clear-cut. 

Some – a small minority – suffered severe symptoms. Older people, those with other health problems and, intriguingly, men were more at risk.

But the overwhelming majority of those struck by Covid-19 would experience only ‘a mild illness’.

Now, almost nine months since the virus first hit Britain, a far more complex picture is beginning to emerge.

While officials say the infection lasts about two weeks for most people, thousands of corona survivors are reporting a long-lasting, debilitating illness.

Many Covid ‘long-haulers’, as they describe themselves, have faced a relentless battle – and symptoms are wide-ranging: crushing fatigue and breathing problems, palpitations, horrific headaches and brain fog, muscle pain, nausea, even hair loss, to name just a few. 

Many say they suffered only mildly to begin with at least – and they appear to be, on average, much younger than those admitted to hospital.

The latest data also tells us something far more striking: they are overwhelmingly more likely to be women.

This newspaper was among the first to report on the Long Covid phenomenon, back in May.

At the time, the lung doctor who treated Prime Minister Boris Johnson, Professor Nicholas Hart, said coronavirus could end up becoming ‘this generation’s polio’ and lead to a wave of further health problems for patients many months, or years, after their symptoms begin.

The polio epidemics of the 1950s killed thousands and left a generation with life-long mobility problems.

Also a virus, it spread via bodily fluids and infected up to 8,000 people a year in the UK between 1947 and 1956, when a vaccine was finally found.

Now Professor Tim Spector, a genetics expert at King’s College London, says information collected from 4.2 million users of his Covid Symptom Study app reveal that as many as 60,000 people in the UK are now living with effects lasting more than three months, with long-term problems ‘around twice as common in females as males’.

The revelation is backed by further research in the US and Ireland, with one study in New York suggesting that as many as 80 per cent of those with enduring symptoms are female, while support groups such as Long Covid SOS are populated mostly by women.

But the science remains unclear.

Are women the most visible face of Long Covid because they are likely to report long-term symptoms? 

Or are they, in fact, more susceptible to longer-lasting effects of the virus?

One patient who has been unable to shake off the illness is Jeannie McGinnis, 48, from Sheffield.

Originally from Texas, the voice-over artist and wellness coach was fit and healthy, and a keen kickboxer, when she first developed muscle aches, a low-grade fever and heartburn-like pains in mid-March.

But during the past six months she has endured 11 weeks of laryngitis, chest pains and a prolonged cough.

Today she is unable to exercise or perform her voiceover work, and has been taking regular naps to stave off the fatigue.

Jeannie, whose husband Daniel and children Madeline, 17, and Aiden, 14, both recovered from the virus within three weeks, said: ‘It’s been totally debilitating and it started off as a mild illness.

‘Yesterday I did some laundry and some organising at home and it left me with chest pains – I had to rest, and felt like I had jet-lag.’

Jeannie has been involved in running a global support group on Facebook for people with long-term Covid symptoms.

‘It’s clear there are a significant number of women aged from about 38 to 55,’ she says.

Also still struggling is Paula Severn Turk, 54, from Gosport, Hampshire, who spent two weeks hallucinating that her parents were still alive during the acute part of her illness in March.

Since then, the mother-of-three, a brain injury support worker, has been living in near-constant pain, with a burning sensation that she says feels like needles hammering her ‘from the inside’.

She is sensitive to light and sound and has terrible brain fog which has left her unable to read or watch television.

‘Nothing makes sense. I keep using the wrong words,’ she says.

Her previously active life, organising cabaret shows, going to the gym and to Spanish classes, has now disappeared and she rarely leaves the house.

‘I’m scared of catching something again,’ she says. ‘I’m also angry at those who think it’s a hoax, or just don’t care. I want to yell at them, ‘Don’t you realise what it can do to you?’

‘Six months of my life has just vanished. Some of it I don’t even remember. It’s very scary.’

It seems that no two people experience Long Covid in exactly the same way. Many, such as Dr Nisreen Alwan, a public health expert at the University of Southampton, have reported a ‘relapsing and remitting’ illness.

‘You feel you’ve recovered and then it hits you again,’ she says. ‘It’s a constant cycle of disappointment, not just to you but to those around you.’

Dr Rachel Pope, an archaeologist from North Wales, was left unable to walk and ‘shuffling like a zombie’ for ten weeks – despite apparently making a recovery a month after the initial symptoms of the virus began.

Her thinking abilities are largely unaffected, but she has experienced severe palpitations and symptoms similar to a heart attack. ‘There are sufferers out there who’ve been told by GPs it’s all in their head, that it’s anxiety,’ 

Dr Pope, 44, says. ‘Their families don’t understand and they’re really struggling. The disease itself is enough to be dealing with without facing a medical service that isn’t able to help. We need employers and GPs to understand how severe these symptoms are.’

Yet despite the growing clamour of voices – many of them belonging to doctors or scientists recounting their own experiences of Long Covid – solid evidence is scant.

In July, the Government ploughed £8.4 million into a study on the long-term effects of Covid-19 on 10,000 patients. But it will focus its work on those who were admitted to hospital, not those who were ill ‘in the community’.

Many ‘long-haulers’ – such as Jeannie, Paula, Nisreen and Rachel – were not deemed sick enough to go to hospital.

And because many fell ill at the beginning of the pandemic, when only those admitted to hospital were being tested, it is hard to determine with certainty whether they were infected, making them a difficult group to study.

Frustratingly, antibody tests, which can reveal a historic infection, often come back negative because too much time has passed.

It means that many Long Covid sufferers are not even counted in infection numbers, and have struggled to get doctors to take their continuing illness seriously in the absence of a confirmed diagnosis.

Dr David Putrino, director of rehabilitation innovation at New York’s Mount Sinai hospital, has been tracking a group of patients referred to hospital during the crisis but who weren’t ill enough to be admitted. ‘Our data suggests it’s primarily women [who have long-term symptoms] – about 80 per cent,’ he says.

They’re also relatively young, fit and healthy, he adds, with an average age of 43. About a third were athletes or had run marathons.

It’s a conundrum – why were these women struggling to fight off the virus?

Dr Putrino is in early discussions with Dr Akiko Iwasaki, an immunologist at Yale University, whose research has pointed to the immune system as a possible culprit.

Dr Iwasaki has found that women whose immune systems react strongly to the virus were more likely to have longer-term difficulties. Why that is remains unclear.

What is already known is that female immune systems are more robust than men’s.

Inside the nucleus of every cell, DNA is packaged into thread-like structures called chromosomes. These contain sequences of ‘code’ called genes, which determine how cells function and, as a result, everything from hair and eye colour to blood type.

The usual number of chromosomes in every cell in the body is 46 – or 23 pairs. We inherit half from our mother and half from our father. One pair of these is sex chromosomes – they determine whether a person is born male or female.

Sex chromosomes in men and women differ in structure: women have two that are, when looked at under an extremely powerful microscope, shaped like an X. Men have one shaped like an X and one like a Y.

A number of key immune genes are located on the X chromosome – hence women are often better equipped to fight off infection.

It’s also believed that the female sex hormones oestrogen and progesterone help to boost the immune response and reduce inflammation. 

Studies show that women consistently produce twice as many antibodies to flu vaccines, for example. But this is a double-edged sword, according to Professor Philip Goulder, an immunologist at the University of Oxford.

A robust immune system can cause collateral damage, he says, as well as leaving women overwhelmingly more susceptible to autoimmune conditions – diseases such as multiple sclerosis, lupus and rheumatoid arthritis – in which the immune system mistakenly turns on and attacks the body’s own healthy tissues.

This might partly explain what is going on in Long Covid, say experts.

Another piece of the jigsaw comes, perhaps, from the link between Long Covid and chronic fatigue. Prof Spector’s data shows that 98 per cent of those with extended symptoms suffer from fatigue.

Parallels can be drawn between conditions such as chronic fatigue syndrome (CFS) and ME, which both cause extreme tiredness, and Long Covid.

Many cases of CFS and ME emerge following viral infection. And they share similarities with autoimmune conditions in that they are most common in women and involve inflammation in the body. 

Research will now investigate the links between Long Covid and CFS, and whether there are genetic similarities in those who develop either.

The study is being led by Dr David Strain, senior clinical lecturer at the University of Exeter and co-chairman of the British Medical Association’s medical academic committee, who runs a CFS clinic.

‘Looking at our referral patterns, more women are attending with symptoms of CFS they’re attributing to having had Covid,’ he says. ‘But we don’t know if they’re just more likely to come forward than men, which is true of many other chronic health problems.’

Dr Strain suggests that coronavirus might affect the mitochondria – the powerhouse of cells that supplies them with energy. 

And, crucially, this is more likely to impact women than men, since women have fewer mitochondria in their cells, and therefore have less in reserve when they are attacked.

In the meantime, Prof Spector’s data suggests that a specific cluster of symptoms in the first week of infection could indicate an increased risk.

He said: ‘If you’ve got a persistent cough, hoarse voice, headache, diarrhoea, you skip meals and get shortness of breath in the first week, you are two to three times more likely to get longer-term symptoms.’

Interestingly, this list does not include a fever or loss of taste and smell, both considered key indicators of a Covid-19 infection. It isn’t clear why, but is likely to be linked to the body’s immune response.

What those still suffering want now is two-fold.

Firstly, to be counted as victims of the crisis. And secondly, to warn the young and healthy that a mild illness could still result in longer-term ill health.

Dr Alwan says: ‘Death and ICU admission are not the only bad outcomes.

‘So-called mild Covid results in thousands of previously healthy folk not being able to do daily activities or work for months. It’s an issue that can no longer be ignored.’