Within the past few years, many of us have had the unfortunate experience of staring down the end of a rapid test, only to see a damning pair of pink lines staring back: COVID positive. For the majority, a few days of quarantine and bed rest are all that is needed to recover fully from the virus. However, one in eight people experience a chronic condition after the initial infection called long COVID, marked by debilitating symptoms like extreme fatigue and cognitive impairment. To date, scientists have been unable to determine who will experience long COVID and who will recover fully. Very recently, however, a group of researchers discovered that low levels of cortisol may predict which COVID patients later develop this condition.

To investigate the origins of long COVID, the researchers compared the immune systems of people who experienced long COVID and those who did not. They discovered that many people with long COVID still had pieces of the virus lingering in their bodies, constantly activating their immune systems and causing chronic inflammation and immune cell exhaustion. With the help of machine learning, the researchers also identified that cortisol, a hormone critical for regulating inflammation, is present in significantly lower quantities in people with long COVID. Their findings suggest that long COVID could be caused by constant immune system activation and exhaustion and that patients with low cortisol levels may be at high risk of developing long COVID. 

With this knowledge, doctors may be able to preemptively identify long COVID patients by testing their cortisol levels, allowing them to begin treatment even before symptoms develop. This breakthrough in our understanding of long COVID gives hope that the condition may soon cease to be as debilitating as it is today.

Edited 3/25/24: Other researchers have raised concerns regarding the methodology and interpretation of the cortisol measurements in this study. For more information, check out this commentary in The American Journal of Medicine .

This study was led by researchers at the Yale School of Medicine and the Icahn School of Medicine at Mount Sinai. The lead authors are Jon Klein, Jamie Wood, Jillian Jaycox, Rahul M. Dhodapkar, Peiwen Lu, Jeff R. Gehlhausen, and Alexandra Tabachnikova. The corresponding authors are David van Dijk, Aaron M. Ring, David Putrino, and Aikko Iwasaki.

Managing Correspondent: Jenny Kim

Press Article: Immune and hormonal features of Long COVID (NIH)

Original Journal Article: Distinguishing features of Long COVID identified through immune profiling (Nature)

Image Credit: Pexels/Anna Shvets

5 thoughts on “Low cortisol? You may be at risk of developing long COVID

  1. Hi
    I am experiencing 🙁 long covid for 3 years now.
    All the different problems are not easy to deal with, mostly because you do not look ill…
    Too intensive activities are almost always resulting in multiples complaints. Ssri anti-anxiety medicin is helping to cope on the mental side, but has no impact on the physical side. One of the most difficult things for many people is the unpredictability, you feel good in the morning, you are bad a few hours later.
    Hope the studies will continue and will result at least in some really usefull findings.

    Peter

  2. I have reservations about the article’s findings. While the link between low cortisol levels and long COVID is intriguing, we should exercise caution. The study doesn’t establish causation, and more research is needed. Additionally, the size and diversity of the study sample aren’t mentioned, making it hard to assess the findings’ generalizability. We should await further studies for a clearer picture.

    1. I’m 16 months post covid and are still unwell
      My cortisol levels are high ( blood and 24 hr urine tests )
      I assumed most other long haulers would have higher than normal cortisol levels

      1. Hi Nicola,
        I just had Covid for the first time, 8 weeks ago this week. Something changed after that in the realm of anxiety. At first I thought it might be “reactive hypoglycemia “, but in checking my blood sugar during stress episodes, it was normal; so, I now suspect adrenal fatigue and high cortisone levels… also insulin resistance because my stress seems to happen after eating around dinner time. It’s a miserable feeling and I hope it goes away on its own because I didn’t have this frequent occurrence before Covid.

        Fran

      2. I had to look twice to see if this was my post that I had forgotten about. I have the exact same issues, high cortisol in 24hr urine. I am now about 4 years with this condition. Did you find any solution?

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