As the world grapples with the rapid spread of Omicron, and daily recorded COVID-19 cases reach frightening heights, a handful of new studies are delivering potent reminders that even a mild SARS-CoV-2 infection can lead to the chronic illness that has been dubbed long COVID. Cedars-Sinai researchers are reporting even mild COVID-19 cases show lingering signs of an overactive immune system months after the acute disease and experts are concerned the massive volumes of Omicron infections right now could lead to huge rates of long COVID over the coming months and years.
Most people understand the role antibodies play in an effective immune response. These are the frontline immune cells that patrol the body, constantly on the lookout for specific pathogens.
When our immune system is working as it should, these antibodies can easily identify and ignore healthy cells, but sometimes these antibodies glitch out and learn to target non-threatening molecules (such as certain foods) or normal tissue. These rogue, self-attacking proteins are known as autoantibodies.
Autoantibodies play a role in many autoimmune diseases, from rheumatoid arthritis to lupus. These rogue immune cells have also been implicated in severe COVID-19, with a key study from Yale University recently affirming correlations between disease severity and autoantibody levels.
A new study from researchers at Cedars-Sinai has for the first time investigated levels of autoantibodies in recovered COVID-19 patients up to six months past their acute infection. The researchers found signs of elevated autoantibodies in all recovered COVID-19 patients, even those who initially experienced mild or asymptomatic infection.
"We found signals of autoantibody activity that are usually linked to chronic inflammation and injury involving specific organ systems and tissues such as the joints, skin and nervous system," says co-senior author Susan Cheng.
Persistent autoantibody activity following an acute viral infection has previously been hypothesized to play a role in chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME). Some researchers have also suggested lingering autoantibody activity may explain the symptoms behind long COVID.
"These findings help to explain what makes COVID-19 an especially unique disease," explains co-senior author on the Cedars-Sinai research, Justyna Fert-Bober. "These patterns of immune dysregulation could be underlying the different types of persistent symptoms we see in people who go on to develop the condition now referred to as long COVID-19."
The new findings affirm chronic autoantibody activity can be generated by mild or even asymptomatic SARS-CoV-2 infections. A recent interview with Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, offered a pertinent reminder that even mild cases of COVID-19 can lead to long COVID.
“We should always be aware that when people get symptomatic infection … anywhere from 10 to up to 30-plus percent of people will go on to have persistence of symptoms,” Fauci said in an interview with Spectrum News.
Fauci also said it is too early to tell whether the extraordinary transmissible Omicron variant is less likely to cause long COVID than previous variants. He stressed prior evidence indicates long COVID can occur regardless of the specific variant one is initially infected with.
“Long COVID can happen no matter what virus variant occurs,” said Fauci. “There's no evidence that there's any difference between Delta or Beta or now Omicron.”
A striking metastudy published in late December 2021 looked at data from 81 research articles tracking fatigue and cognitive impairment in people at least 12 weeks after COVID-19. The findings revealed lingering fatigue in 32 percent of all COVID-19 patients at least three months after the acute disease, and signs of cognitive impairment in 22 percent of all patients.
Even more significantly, the research found no difference in the rate of fatigue and cognitive impairment between hospitalized and non-hospitalized populations. While other symptoms of long COVID did seem to correlate with initial disease severity, these two specific factors seemed to be persistent regardless of how mild the original case was.
The biggest uncertainty right now is just what Omicron means for future rates of long COVID. A new survey from the Office of National Statistics estimates around 1.3 million people in the United Kingdom currently suffer from long COVID. That is about two percent of the total population. And, it was calculated before the Omicron wave hit.
South African researcher Salim Abdool Karim recently co-authored a commentary in The Lancet trying to understand what Omicron means for the future of the pandemic. His concern is that even if Omicron leads to lower hospitalizations and milder acute disease, the stunning transmissibility of this variant is a serious problem.
“I have no idea what’s in store for us as far as long COVID is concerned,” Karim recently said. “It’s a really important question, and it’s particularly so because Omicron is spreading so fast and so widely so quickly – the number of people getting infected is so big that … if it’s a common consequence of even mild infection, you can imagine, even if in 10 percent of people, there’s going to be a lot of people with long COVID. It’s certainly something we want to keep a beady eye out on.”
Another issue researchers are closely tracking is the effect of reinfection on long COVID. With some studies finding Omicron 10 times more likely to reinfect those who have previously experienced a SARS-CoV-2 long COVID, experts are worried a second infection may make the chronic condition worse in those already suffering lingering symptoms.
"We have seen people in our clinic who have been reinfected with COVID with the other variants," explained John Barrata, co-founder of University of North Carolina at Chapel Hill’s long COVID clinic . "They have new or worsened long COVID symptoms after their reinfection."
The new Cedars-Sinai research was published in The Journal of Translational Medicine.
Source: Cedars-Sinai Medical Center
