"Natural Immunology" What Causes Long-COVID?

A team from UNSW's Kirby Institute and Sydney's St Vincent's Hospital has discovered a long-term immune signature of COVID that could pave the way for tailored treatments for those with persistent symptoms
.

Unvaccinated, prolonged COVID-19 patients -- even those who initially had mild or moderate infection -- had persistent inflammatory responses for at least eight months after infection, suggesting that prolonged COVID is very different from other infections
.

The new analysis from the Kirby Institute was published January 14, 2022 in the journal Nature Immunology
.
It used data from the ADAPT study at St Vincent's Hospital, which collected samples from unvaccinated people during Australia's first pandemic wave

Although several clinical studies based on patient reports (including the ADAPT study) have accumulated evidence on long-term COVID, this is the first study to describe the effects of long-term COVID on the immune system through analysis of laboratory settings
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"Our findings may confirm some of the symptoms in people who have experienced COVID for a long time," said Chansavath Phetsouphanh, a senior investigator at the Bryant Institute and co-first author of the paper
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"We found that the immune system response continued to be activated for at least eight months after the initial infection, suggesting significant ongoing inflammation

The team examined blood samples from people with and without prolonged COVID-19 infection for various "immune biomarkers.

"These biological signatures can help us define a medical condition in an accurate and reproducible way
.
We compared these people with people who didn't have COVID-19 and found persistently elevated levels of type I and type III interferons, It's a protein that cells respond to the presence of the virus

In the Kirby Institute's specialized laboratory, researchers analyzed multiple samples from 62 ADAPT patients diagnosed with COVID-19 between April and July 2020

"One of the most surprising aspects of our analysis is that people don't need to have severe COVID to experience these persistent immune changes," Dr.
Fisopan said

Dr David Darley, from St Vincent's Hospital, who is also the lead author of the paper, said there was no data to show whether different variants like Omicron would cause the same changes, or that vaccines might reduce the risk of prolonged Covid-19 infection.

"From some early international data, we are very hopeful that with a milder variant and higher vaccination rates, we may see COVID in a shorter period of time, but we need further immunization Data can be used to determine this
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"We are currently looking at some data from Delta to see if vaccination reduces the likelihood of prolonged exposure to Covid-19
.
"

Understanding the immune status of COVID-19 will aid in the development of COVID-19 treatment and management, the researchers said
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Professor Anthony Kelleher, Director of the Kirby Institute, said: "This study provides the strongest evidence yet to provide a clear biological basis for the clinically apparent prolonged COVID syndrome
.
"

"We will continue to analyze omicron waves
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At the same time, there are many unknowns with COVID and long-term COVID, and we should do everything we can to reduce transmission

like a "crime scene detective"

When researchers screen blood samples for infection or the immune response to infection, they may be looking for hundreds of different markers to help them accurately analyze the effects of disease on the body
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"As immunologists, we're almost like crime scene detectives
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We have thousands of potential biomarkers or clues to study, but only a few that reveal something useful
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We can use some of our measures of knowledge in Acute COVID and other post-viral fatigue syndromes have narrowed the investigation down a bit, but because long COVID is still a new syndrome, we have had to do extensive testing, and also enough to find evidence that looks almost everywhere," Dr Phetsouphanh said.
say
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"When conducting this study, we looked for proteins in serum
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These proteins, or biomarkers, are evidence of abnormal processes caused by disease
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We analyzed 31 different proteins that we suspect may be "triggered" by COVID-19 biomarkers and identified a small subset associated with prolonged COVID-19 syndrome
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Excitingly, by looking at subsets of cells in the immune system, we found where these biomarkers might arise, which may be critical for developing treatments
.
"

What does this mean for people with long-term COVID?

"COVID is an ongoing virus," said Ms Doris Gale, from Shellharbour, who was part of the ADAPT study
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In September 2020, she tested positive for COVID
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"My initial infection was mild, but my long-term COVID symptoms were evident
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I've lost the ability to understand pre-COVID
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I used to be a personal assistant, but I can't do that job anymore
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Hear about the study , I feel my symptoms are confirmed
.
"

About 30% of the unvaccinated people who contracted COVID and were followed in the ADAPT study experienced some prolonged COVID symptoms
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Mr Rick Walters from Roseville contracted Covid-19 in August 2020 as part of the ADAPT study
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He has experienced a prolonged period of Covid-19 symptoms, and he said the findings raised mixed emotions
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"I am very happy that this study confirms that prolonged COVID is a valid consequence of a COVID-19 infection, not something in my head
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At first, I thought I would be fine, but apparently my lung damage was Permanently, I became very anxious," he said
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"I'm having a hard time adjusting to my current state of health
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COVID-19 cannot be taken lightly
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I'm learning to accept the results
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"

Professor Gail Matthews, co-leader of ADAPT, is also Director of the Infectious Diseases Unit at St Vincent's Hospital and Head of the Vaccines and Therapeutics Research Programme at the Kirby Institute
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When someone contracts the virus, the immune system kicks in, responds to the virus and destroys it, she said
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"But what we've seen with COVID-19 for a long time is that even after the virus has completely left the body, the immune system is still kicked in
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If you measure the same thing after a standard cough or cold, we're in this study by our A control group did, and the signal wasn't there
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It's unique to patients who have been chronically infected with Covid-19
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Professor Matthews said that through research like this, we are slowly beginning to understand some of the mysteries of COVID's long-standing existence
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"In short, when we take a closer look at the immune system of COVID-19-infected patients, especially those who have been infected with COVID-19 for a prolonged period of time, it looks different from what we would expect from a healthy individual
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There may be something very unique in the pathophysiology of the disease
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The next step is to apply this new understanding to other COVID-19 variants and further study to inform the treatment and management of long-term COVID-19
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"

Reference: "Immune dysfunction persists for 8 months after initial mild to moderate SARS-CoV-2 infection" by Chansavath Phetsouphanh, David R.
Daly, Daniel B.
Wilson, Annet Howe, C.
Mayling Munier , Sheila K.
Patel, Jennifer A.
Juneau, Louise M.
Burrell, Stephen J.
Kent, Gregory J.
Dole, Anthony D.
Kelleher and Gale v.
Ma Hughes, January 13, 2022, Immunological Properties
.