- Researchers looked at more than 300 cases of COVID-19 and found four potential risk factors for long COVID.
- These factors include high viral load early in the disease, reactivation of Epstein-Barr virus, type 2 diabetes, and autoantibodies.
- More research is needed to understand what causes long-term COVID and how to prevent it.
So far, the mechanisms behind prolonged COVID have not been understood. Now, a new study is helping us understand who may be at risk for these long-term symptoms.
recently published in cellResearchers conducted a longitudinal survey of more than 300 COVID-19 patients to investigate biomarkers that may indicate an increased risk of developing long COVID later in life.
They found four factors that may be associated with higher lingering symptoms, including:
- High viral load early in infection
- Reactivation of the Epstein-Barr virus
- have type 2 diabetes
- Presence of specific autoantibodies
The study was largely exploratory, and more research is needed to verify the association of these factors with long-term COVID. However, they are biologically plausible, and the findings could help us get closer to some of the answers.
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high viral load
According to the researchers, one of the potential risk factors for long-term COVID is the level of coronavirus RNA in the blood early in the disease, which indicates viral load.
“The amount of viremia reflects the extent of uncontrolled viral infection,” Martin J. Blaser, MD, chair of the Human Microbiome and director of the Rutgers Center for Advanced Biotechnology and Medicine, told VigorTip. “The higher the level, the more out of control the host’s immune mechanisms are. Even after things subsided, there was a big perturbation.”
Currently, we have antiviral pills that inhibit viral replication, such as monupavir and Paxlovid, thereby reducing the viral load in the body.
“We know that higher viral loads are associated with more severe COVID-19 and a higher risk of death,” Beth Oller, MD, a family physician at Solomon Valley Family Medicine, told VigorTip. “It makes sense that a higher viral load can equal more symptoms. If the infection is more severe, it takes longer for the body to clear the virus, which is why a higher viral load is associated with a higher long-term COVID risk one of the reasons.”
If a high viral load does increase the risk of long-term COVID, it means we can prevent it by reducing the viral load early in the disease, as with antiviral drugs, Oller said.
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type 2 diabetes
The study suggests that type 2 diabetes may predict long-term COVID at initial diagnosis. About 1 in 10 Americans have diabetes, and about 90-95% have type 2 diabetes.
“Patients with type 2 diabetes are more likely to experience fatigue, cough and other respiratory symptoms of prolonged COVID,” Oller said. “We already know that people with type 2 diabetes are more likely to develop serious complications or die from COVID-19, so it’s no surprise that long-term COVID is also more likely.”
COVID-19 may make blood sugar control more difficult for people with diabetes. The two were also found to influence each other. Severe COVID-19 can worsen hyperglycemia, which can lead to worse COVID-19 outcomes.
“High blood sugar, or poorly controlled diabetes, weakens the immune system, making it less able to fight infection, so well-controlled diabetes can reduce risk,” Olle said. “It is speculated that the pre-existing low-grade inflammatory state seen in type 2 diabetes may worsen and remain elevated after COVID, which may lead to increased symptoms.”
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Reactivate Epstein-Barr virus
According to the study, reactivation of Epstein-Barr virus (EBV), a member of the herpesvirus family, may be associated with long-term COVID. Most people are infected with EBV in childhood, and the virus can stay dormant in the body as the disease progresses.
“back [the] Dr. Bryan Lau, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health and co-leader of the Johns Hopkins Long-Term Study of COVID, told Good. “EBV reactivation is stress-related, so previous studies have suggested that COVID-19 may cause EBV reactivation.”
A small 2021 study found that 55.2% of hospitalized patients with confirmed COVID-19 cases were infected with EBV. Another study reported that among COVID-19 patients, patients with EBV reactivation had higher mortality rates and required more immunosupportive therapy than those without EBV reactivation.
Although research suggests that prolonged COVID symptoms may be caused by EBV reactivation caused by the inflammation of COVID-19, We still need more research to be sure.
“It’s worth noting that EBV itself has been associated with some symptoms reported in long-term COVID patients,” Liu said. “Past studies have linked EBV reactivation to cardiomyopathy and myocarditis, as well as tinnitus and hearing loss, each of which has been reported in long-term COVID patients. Therefore, some long-term COVID may be due to EBV reactivation, But we really don’t know right now.”
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the presence of certain autoantibodies
According to the researchers’ analysis, the most influential indicator was the presence of certain autoantibodies, which were observed in two-thirds of patients.
The immune system produces autoantibodies, which react with the body’s naturally produced proteins rather than foreign elements such as viruses or bacteria. In simple terms, the body mounts an immune response that mistakenly attacks its own tissues. Some examples of autoimmune diseases include lupus, multiple sclerosis, and rheumatoid arthritis.
The body’s immune response is like a sharp knife — it cuts in both directions, Blaser said. It defends against invaders such as pathogens and viruses, but it can overrun and attack the body’s own tissues, triggered by an immune response to pathogens.
“Depending on the specific target, they can cause specific damage,” he added. “Some autoantibodies affect the immune cells themselves and may prolong the fight against the virus.”
A study published in Journal of Translational Medicine It was found that, regardless of disease severity, COVID-19 can trigger multiple autoantibodies for up to six months after the initial course of the disease. Another study found that a subset of hospitalized COVID-19 patients developed autoantibodies over the course of their illness.
“The idea that long-term COVID may be the result of autoimmunity has been a prominent hypothesis,” Liu said. The question is whether COVID-19 increases the risk of developing persistent antibodies that do not diminish over time and could lead to the development of autoimmune disease. However, he added, we need more research to determine this.
“It is unclear whether the six autoantibodies tested in this study are the cause of long-term COVID symptoms, directly damage cells, or if they are simply markers of disease,” Oller said. “Patients with autoantibodies also have small amounts of protective antibodies that neutralize the virus, which may predispose patients to lingering symptoms.”
what does this mean to you
The study found four possible factors that could predict long-term COVID, but are currently uncertain. The best way to prevent long-term COVID is to avoid contracting COVID-19 in the first place by wearing a mask, getting vaccinated and boosted, and staying away from poorly ventilated indoor spaces.
more research needed
Experts say little is still known about long-term COVID, and studies like this are important to determine if there are ways to predict risk to prevent its development and symptoms. This condition may be caused by a combination of factors, but there is no clear answer yet.
“The wide range of symptoms people report in prolonged COVID suggests that different phenotypes may have different underlying biological mechanisms, including interactions between different factors,” Lau said.
It’s important to continue studying the mechanisms behind long-term COVID to find out what’s at work, understand how to prevent them from happening, and better learn how to treat them.
“The human immune system’s response to infection is an extremely complex interaction between host and pathogen,” Lau said. “By studying immune mechanisms, we can better understand what’s going on and what may go wrong in the immune system’s response to SARS-CoV-2. Understanding these mechanisms helps us identify possible ways to prevent or mitigate long-term COVID-19 potential intervention targets for development.”
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