Long COVID: Researchers Find ‘Antibody Signature’ to Identify High-Risk Patients; Two Vaccine Shots Could Stop the Syndrome
COVID-19 Science 31/01/2022 •

Researchers find two antibodies in common in people with long-COVID, the lingering post-infection condition that was recognised by the World Health Organization (WHO) last October. But scientists say symptoms and how many people develop the virus are still unclear.

Unconscious and intubated Covid-19 patients are treated in Vila Penteado Hospital’s ICU, in the Brasilandia neighbourhood of Sao Paulo.

By Maayan Hoffman

A sizable portion of the 370 million people infected with SARS-COV2 experience Post-Acute COVID Syndrome (PACS), otherwise known as “long COVID”. Doctors and scientists are starting to grapple with why people develop the syndrome and how to prevent and treat it.

Their discoveries could have important implications on future healthcare.

Researchers from the University Hospital Zurich announced last week that they had discovered an “antibody signature” that could help identify which patients are at the highest risk for developing long COVID.

Specifically, they found that low levels of IgM and IGg3 antibodies were more common in those who developed the syndrome than those who did not.

The team followed 134 individuals who tested positive for the virus for up to a year after the initial infection. They found that when combined with the patient’s age, how mild or severe a case of coronavirus the person experienced, and whether or not the individual suffered from asthma, the antibody signature was able to predict the risk of long COVID.

These antibody levels, of course, cannot be measured before a person becomes infected with the virus and therefore this method cannot be used as a pre-virus prediction of the syndrome. However, early identification of patients at elevated risk for long COVID could facilitate the study of targeted treatments, the researchers wrote in their paper, which was published in Nature Communications.

Full mRNA vaccination protects against long COVID

A separate study by researchers in Israel found that individuals who received two shots of the Pfizer coronavirus vaccine were much less likely to develop long COVID symptoms than those who were unvaccinated – suggesting that vaccination protects against long COVID.

These results were not observed in individuals who received just a single dose. Participating vaccinated and infected individuals reported no additional long COVID symptoms than individuals who were never infected with the virus.

The study was published this month on the pre-print health server MedRxiv and has not been peer-reviewed.

A child receives a vaccine through the Maccabi Health Fund in Israel in December 2021.
A child receives a vaccine through the Maccabi Health Fund in Israel in December 2021 (Credit: Maccabi)

The scientists, led by Prof Michael Edelstein of Bar-Ilan University, examined 10 commonly reported post-COVID symptoms – fatigue, shortness of breath, joint pain, chest pain, headache, palpitations, physical limitations, depression and insomnia – among 3,000 participants. They said that there was between a 50% and 80% reduction in seven of the 10 most common symptoms four to 11 months among the vaccinated participants compared to the unvaccinated.

“A double comparison of vaccinated vs. unvaccinated COVID-19 cases followed by comparing vaccinated COVID-19 cases to people reporting no infection enabled us to show not only that vaccinated people were experiencing much fewer long COVID symptoms than unvaccinated people, but that that they did not report any more symptoms than people never infected,” Edelstein said.

He noted that the results seemed “logical.”

“If we believe that these symptoms are related to the infection – caused by the virus itself – it makes sense that if you are vaccinated, even though you can still get infected, those who do get infected have less copies of the virus in the body and it hangs around in the body for less time, so it would have less opportunity to affect the body long term,” Edelstein said.

He added that the study indicates that even those who are at less risk of developing severe COVID-19 should get jabbed, since these individuals seem to be at equal risk of developing long COVID.

The study only included adults over the age of 18, but Edelstein said that the team hopes to examine the effect of the vaccine on long COVID in children, too.

Up to 57% of COVID survivors could have long COVID symptoms

He added that what is needed is a universal definition or understanding of long COVID in order to enable better studies.

The World Health Organization (WHO) rolled out a definition of PACS last October but noted that “the definition may change as new evidence emerges and our understanding of the consequences of COVID-19 continues to evolve.”

According to WHO, long COVID occurs around three months from the onset of the virus, lasts for at least two months and “cannot be explained by an alternative diagnosis.” It lists fatigue, shortness of breath and cognitive dysfunction as common symptoms, but said others could apply and that symptoms could fluctuate or relapse over time.

It is also unclear how many people actually develop long COVID. Edelstein cited Israeli studies that indicate around 30% of people infected with coronavirus will develop the syndrome, while some studies say closer to 60% of virus sufferers will have some form of PACS for up to six months.

What proportion of symptoms are attributable to the virus and whether or not these symptoms can be detected in a clinical setting could impact the future of long COVID treatment, Edelstein said.

“It is one thing reporting shortness of breath and another detecting reduced lung volume on standardized, objective testing in a clinical setting,” he said.

Over the weekend, a small study in the United Kingdom revealed that some people who reported long-lasting breathlessness after COVID infection may have hidden lung damage.

Scientists used a Hyperpolarized Xenon Magnetic Resonance  (MRI) scan to pick up on lung abnormalities not identified by routine scans. They found that for the majority of people with long COVID, the xenon gas they inhaled during the MRI moved less effectively from the lungs into the bloodstream than it did among healthy, never infected individuals.

The spectrum of medical imaging
The spectrum of medical imaging

“Hyperpolarised xenon MRI requires the patient to lie in an MRI scanner and breathe in one litre of xenon gas that has had its atomic structure altered so it can be seen using MRI,” according to the study. “Xenon is an inert gas that behaves in a very similar way to oxygen, so radiologists then can observe how the gas moves from the lungs into the bloodstream.”

The study included 11 non-hospitalized long COVID patients and 12 hospitalized patients, as well as 13 health controls. It was published by the NIHR Biomedical Research Centre, Oxford and has not yet been peer-reviewed.

Researchers said that they plan to expand the study to include at least 200 patients.

Long COVID therapeutics on the horizon?

Doctors and scientists are also focusing on developing long COVID therapeutics. An article published on Clinical Trials Arena stated that 65% of planned COVID trials for 2022 will focus on therapeutics, according to a GlobalData report, but said that the majority of the long COVID trials (76.5%) are only in Phase I or Phase II.

At least four long COVID drug trial readouts are expected in 2022, the report said, with each treatment targeting a different long COVID symptom or group of symptoms.

These include PureTech, which is working on a drug for lung tissue damage stemming from a prior COVID-19 hospitalization; Axcella Health, which is working with Oxford university on a drug to reduce inflammation and restore mitochondrial function; Massachusetts General Hospital and 9 Meters Biopharma are studying a treatment for multisystem inflammatory syndrome; and MGC Pharma is assessing the potential of its ArtemiC Support for effectiveness in treating long COVID symptoms such as dyspnea, cough, asthenia, anosmia, ageusia, headache and mental confusion.

Edelstein said that researching long COVID is urgent and essential because the syndrome “is going to be one of the major concerns going down the line.”

He explained that while the acute phase of the pandemic will eventually end, “that is not necessarily going to be the end of the impact of COVID-19, which could be felt for years due to the virus’s long-term effects.”

Long COVID could have “massive implications on the burden that will be on healthcare services in the future.”

Image Credits: Ninian Reid/Flickr, Maccabi Health Services, Martin Tornai, Wikimedia Commons .

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