Females face higher risk of developing long COVID

A new study sheds light on sex differences in long COVID

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Before we talk science, can I just say a little something about how hard summers can be for working parents? Every year I dread the last day of school, because I know my life is about to get even more hectic.

Don’t get me wrong: I love the warm weather, swimming in my pool, and tending to my vegetable patch. What I don’t love is parenting kids off school while I’m working full-time. When they were younger, I had to schedule every moment of the summer to make sure I had childcare. That was a lot of planning, wrangling kids to get ready in the morning, and drop-offs that did not always go well (like the time I showed up at a summer camp with both kids and realized I had the wrong week.)

Now I have two tween/teens, who definitely do NOT want organized activities, yet they don’t have jobs to keep them busy. If it were up to them, they would spend the summer lying around playing Roblox or watching TV shows. So, we have negotiated some teen camps/courses for a couple of weeks, but their reluctance to go and the driving involved to get them there is a lot to navigate. I’m finally at the stage in my career where I can take two weeks of vacation in the summer, but it still seems woefully inadequate to give my kids those “perfect” summers we all dream about. I’ve spent the last 15 summers swimming in guilt much more than I’ve spent them swimming in a pool.

All of these minor (and yes, privileged) inconveniences paired with the state of the world means I’m feeling a lot this week.

But enough of me complaining—let’s get to the reason why we’re here today.

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It’s been well established that sex (male or female, assigned at birth) is a factor in chronic illness, especially ones that implicate the immune system. Around 80% of people with autoimmune conditions are female, which is a staggering proportion. Scientists are just beginning to uncover the reasons why, and it’s likely something to do with our chromosomes (I might do a post on this at some point, but I’m seeking a guest writer who could adequately translate the dense science…if that’s you, please send me a message!)

Photo by engin akyurt on Unsplash

A new study out in the journal JAMA Network Open has found significant differences between females and males when it comes to long COVID. I’m sure I don’t need to give you a detailed primer on long COVID, but it’s a chronic and debilitating condition that can cause over 100 persistent symptoms, including fatigue, shortness of breath, and memory loss or brain fog. Each person will experience the condition differently, which is why it’s so hard to diagnose.

This new study used data from a large, prospective cohort study, which followed people at 83 sites in 33 states in the U.S. People were over 18 years old and had experienced a previous infection with SARS-CoV-2. The data also included sociodemographic variables, like age, sex, race and ethnicity, and other social determinants of health. This makes for an ideal cohort to study the intersection of health and social factors.

Higher risk if you’re female

The researchers found that males had more severe cases of COVID-19 and higher mortality than females, but females had a 31% higher risk of developing long COVID, which took into account demographics, social determinants of health, hospitalization during infection, and vaccination status. In a second model, the researchers only included age, race, and ethnicity, and found that female sex was associated with an even higher risk (44%) of long COVID.

Menopause and long covid

Females had the highest risk of long COVID if they were between the ages of 40 and 54, with a 42% higher risk in menopausal participants and 45% higher in non-menopausal participants. The authors speculate on a few reasons for this: 1) The menopausal transition is associated with immune activation; 2) female sex hormones decrease with age (and high estrogen/low testosterone has been associated with a higher risk for long covid among nonpregnant females); and 3) menopause and long covid share a lot of overlapping symptoms.

The authors say that a review of the literature combined with their study data suggest the higher prevalence of long covid among females younger than 55 may be partially explained by differences in hormonal levels.

Other chronic illnesses play a role

In another analysis, the researchers did not find a higher risk for females when looking at participants with comorbidities—conditions like ME/CFS (chronic fatigue) or POTS. They suggest that because females are already much more likely to have autoimmune diseases, osteoporosis, ME/CFS, and Alzheimer disease, they can then experience worsening health problems following COVID-19 infection. It’s difficult to determine if it’s the COVID or the additional health burden on top of their primary condition.

This tracks with my personal experience when I was dealing with MCAS symptoms. Following my first COVID infection, my MCAS symptoms increased by 1000% (or at least that’s what it felt like,) but now that I’m almost three years beyond my first COVID infection, I’m feeling a lot better. I’d be very interested to see data on repeated infections, and whether this could extend symptoms (it’s possible that I’ve had COVID more than once, but it’s never shown up on a test.)

What does this all mean?

Unfortunately, this is a cohort study, so you’re not going to find a lot of answers here. That said, the authors make a few interesting observations, including:

1. It will be important to target which groups would benefit from which treatments. Someone who is menopausal may need a totally different therapy from someone who is 25 and has ME/CFS, for example.

2. Steroid-based therapies may help with symptoms in females.

3. They believe that long-term illnesses will get worse due to long covid, especially for female-dominant conditions like chronic Lyme disease, ME/CFS, POTS, MCAS (and so many more!) We need more research in these populations to understand why females are at such a high risk of developing chronic conditions.

One scientist who I support in my day job is involved with a randomized controlled trial testing two different medications to treat long COVID patients, so I’m looking forward to those results.

I’ve also been intrigued by

Gill Deacon

’s story, as she used a cognitive behavioural therapy approach that teaches the brain to rewire into more adaptive patterns (i.e. neuroplasticity.) This aligns with current thinking around chronic pain, which proposes that the experience of pain can arise from expectations we have of pain based on our prior experiences.

This doesn’t mean symptoms are all in your head! They’re very real, but they’re being created by your overactive/stressed out nervous system, rather than by neural input from your sensory organs. For example, when you stub your toe, the force of the impact damages your tissue on the toe. The brain processes this sensation and creates “pain,” which can feel stabbing, sharp, or dull. You rub your toe (or ice it if it’s really bad,) and maybe you’re left with a small bruise that heals within days. In the case of chronic pain, the brain is creating the experience of pain without the event that might cause pain. Your doctors may be telling you that everything is healed, but you’re still unable to do your normal activities.

The brain basically gets into a bad habit of creating pain! Therefore (so the theory goes,) you must work on retraining the brain and nervous system. This might involve addressing things outside of your body that could be exacerbating pain, like financial stress or loneliness.

If you’ve read my book, you know how much I’m on board with this theory, because it takes into account biology, psychology and social factors of health.

Researchers are now exploring how to apply this form of treatment to other types of chronic illness like ME/CFS, which have long been thought of as incurable and even made up. Time will tell if we can get on board with this innovative approach (and more evidence always helps!)

From my heart to yours,

Misty