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Can muscle inflammation explain some of the symptoms of long COVID?

Some people with post-acute complications of COVID-19 (called long COVID) can experience intense fatigue and muscle weakness. Scientists are exploring possible reasons for these issues. Studies in Germany and the U.S. suggest that people who died from COVID-19-related complications had muscle inflammation. Emerging research suggests that the muscle inflammation is likely caused by intense immunological reactions. Such reactions occur during acute COVID-19 in some people. 

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It is at least plausible that some people with long COVID also have muscle inflammation, but research needs to be done to confirm this and to find possible causes of such inflammation.

Study 1 – Berlin

Scientists at Charité Hospital (a leading biomedical research centre) in Berlin have reported findings from a study that compared muscle tissue taken at autopsy from two groups of people:

  • 43 people who died from COVID-19-related complications
  • 11 people who died from complications unrelated to SARS-CoV-2 infection

The vast majority of these people had been admitted to an intensive care unit (ICU) in the hospital prior to their death. People who died from COVID-19-related complications did so between March 2020 and February 2021.

Key findings

  • Muscle biopsies from people who had recently died from COVID-19 showed signs of inflammation and injury.
  • Generally, these muscle samples had higher-than-normal levels of CD8+ T-cells and natural killer cells inside of them.
  • Use or non-use of corticosteroids before death did not seem to affect inflammation of muscles.

The finding about the infiltration of cells of the immune system into muscle tissue suggests that the immune system played a role in their inflammation and possibly tissue injury. The researchers could not find SARS-CoV-2 in the muscle tissue samples they analyzed. Some muscles (such as those of the heart) have a protein on their surface called ACE2. This protein is used by SARS-CoV-2 to infect cells, and other studies have found SARS-CoV-2 in muscle cells in the heart. Other muscles, such as those that are connected to the skeleton (skeletal muscles), do not appear to have ACE2, and this may account for the difficulty the scientists had in finding any virus in the biopsies of muscle tissue. The scientists did not find a similar degree of muscle inflammation in people who were not infected with SARS-CoV-2 and who died. Also, most people who died from COVID-19 did not have antibodies that attacked their muscles. Therefore, the scientists suspect that the muscle injury that arises in COVID-19 may be due to the intense inflammation that is a key part of severe COVID-19.  

Study 2 – Harvard University hospital system

Another team of scientists at Boston hospitals affiliated with Harvard University has analyzed muscle and associated nerves biopsied from 35 people who died from COVID-related complications and 10 other people who died but who did not have SARS-CoV-2 infection. Participants died between April and mid-June 2020.

Key findings

  • 25 of the 35 people in the Boston study had biopsies that found inflammation in muscles and nerves.
  • SARS-CoV-2 could not be found in these biopsies.
  • The researchers think that the muscle and nerve inflammation found in their study was due to the immune system. Specifically, such injury was a consequence of an intense inflammatory reaction as the body attempted to defend itself from SARS-CoV-2 infection.

Bear in mind

Both teams of scientists in Germany and the U.S. have found that people who died from COVID-19 had muscles that were inflamed. In addition to muscle inflammation, the U.S. team also found nerve injury arising from inflammation in their autopsies.

The scientists from both countries suspect that some people who develop SARS-CoV-2 undergo intense inflammatory reactions as the body attempts to defend itself from this virus. The intense inflammatory reactions may help reduce virus levels in muscles and nearby nerves, but, as a side effect, they cause tissue injury—in this case, injury to skeletal muscles and associated nerves. The Harvard University scientists stated that “viral RNA may be cleared from muscle and nerve tissue due to efficient type I interferon response or other mechanisms, but may not be cleared from higher burdened organs like the lungs”

This potential explanation for the findings of muscle and nerve injury seems incomplete. There are many chemical messengers (cytokines) associated with inflammation that have been found in other studies of people with COVID-19, including the following:

  • IL-1 (interleukin-1)
  • IL-6 (interleukin-6)
  • TNF (tumour necrosis factor)
  • GM-CSF (granulocyte-macrophage colony-stimulating factor)

Unfortunately, neither the German nor the U.S. scientists were able to access blood samples to analyze levels of cytokines in the people they studied.

The research from Germany and the U.S. is a good first step in identifying a problem that occurs in some people with COVID-19—inflammation-related injury of muscles and nerves. The inflammation appears to be indirectly caused by the immune system.

Additional research is needed to explore the issue of muscle and tissue injury in people who are living with long COVID. In these people, analysis of biopsies may be useful in providing insight into the health of their muscles and peripheral nerves.

—Sean R. Hosein

REFERENCES:

  1. Aschman T, Schneider J, Greuel S, et al. Association between SARS-CoV-2 infection and immune-mediated myopathy in patients who have died. JAMA Neurology. 2021; in press.
  2. Suh J, Mukerji SS, Collens SI, et al. Skeletal muscle and peripheral nerve histopathology in COVID-19. Neurology. 2021; in press.