An Epidemic of Long COVID May Be the Legacy of Omicron
The loosening of COVID-19 policies and shortening duration of precautions signal the emergence of what some call the “inevitability camp”: those who believe everyone will contract the rapidly spreading omicron variant, thereby generating herd immunity.
There is one major problem with this view. It is becoming increasingly apparent that 14% (estimated range 2%-30%) of those infected with omicron will develop long COVID, a prolonged set of neurological and physical maladies that have haunted some people since the pandemic began in 2020, says Jason Maley, MD, director of the COVID-19 Survivorship Program at Beth Israel Deaconess Medical Center and an instructor at Harvard Medical School.
“They’re still in the earlier phase, but we are seeing patients who have post-acute sequalae, lasting long COVID symptoms, that we suspect are most likely from omicron, based on the timing,” Maley tells Hospital Employee Health.
While much remains unknown, if even some small percentage of omicron infections lead to long COVID, the numbers of cases and demand for treatment will be unprecedented.
“Given how many people it’s affected, it’s certainly concerning that in the coming months, we could see an increase in the number of people with these symptoms coming to seek care in our clinics,” Maley says. “It’s going to be hard, just from the perspective of treating long COVID, to keep up with the number of people needing help. It’s already so common and there’s not enough care out there for them. Every clinic I know of is very backed up, trying to get patients in, because of just the number of people experiencing this.”
Long COVID and Breakthrough Infections
Prior long COVID cases with other variants largely occurred in the unvaccinated. However, the enhanced ability of omicron to cause breakthrough infections has raised concerns that a greater level of long COVID could manifest in the fully immunized. This would be most cases that hit healthcare workers, given the U.S. Supreme Court’s recent approval of vaccine mandates for personnel in hospitals, long-term care, and other settings. (See story on the Supreme Court decision in this issue.)
Healthcare workers are experiencing long COVID. Researchers in the United Kingdom found healthcare workers were one of the most likely groups to self-report, although it did not break down how many are experiencing the condition. “An estimated 1.3 million people living in private households in the U.K. (2% of the population) were experiencing self-reported long COVID symptoms persisting for more than four weeks … as of Dec. 6, 2021,” the researchers noted.1
In Israel, a study of 39 breakthrough infections (involving the alpha variant) in vaccinated workers included nine with symptoms serious enough to take a leave of absence.
“On follow-up questioning, 31% of all infected workers reported having residual symptoms 14 days after their diagnosis,” the researchers reported. “At six weeks after their diagnosis, 19% reported having ‘long COVID-19’ symptoms, which included a prolonged loss of smell, persistent cough, fatigue, weakness, dyspnea, or myalgia. Nine workers took a leave of absence from work beyond the 10 days of required quarantine; of these workers, four returned to work within two weeks. One worker had not yet returned after six weeks.”2
“There are recent data suggesting that vaccination may reduce the risk of having long COVID if you have a breakthrough infection, [compared to the] unvaccinated,” Maley says.
Of course, vaccination protects people from initial infection, thereby immediately preventing the later emergence of long COVID. But the emerging studies are somewhat mixed and not greatly reassuring, giving even those who are fully vaccinated reason to avoid COVID-19 exposures.
The results of a study conducted before omicron appeared revealed that following SARS-CoV-2 infection, those who received two vaccine doses were 49% less likely to experience symptoms beyond four weeks than those who are unvaccinated.3 Another study in preprint showed little evidence of vaccine prevention of long COVID after a breakthrough infection, concluding “how COVID-19 vaccination affects the broad spectrum of sequelae of SARS-CoV-2 infection remains elusive.”4
Maley reports mixed results in people who take the vaccine after developing long COVID.
“There are people who feel much better after having a vaccine, and there are others who feel like there’s a flare in their symptoms and worsening,” he says. “It’s certainly not consistent. It’s not clear why that might be the case, but there may be some relationship between that individual person’s immune system and how they respond to the vaccine.”
The Indecipherable Threat
Indeed, if much about COVID-19 remains unknown, long COVID recalls Churchill’s description of Russia as a “a riddle, wrapped in a mystery, inside an enigma.”5
“There’s no clear treatment for the underlying cause of long COVID, which is in part because we don’t understand what the true driver of these symptoms is within the body,” Maley says. “Treatments are largely focused on either treating symptoms or rehabilitating from the injury that seems to have occurred to people’s cognition. For people who have shortness of breath and breathing issues, [treatment includes] pulmonary-focused rehabilitation and using medications that will treat the different symptoms.”
Some recover, while others remain chronically afflicted.
“We do see people who were in the first wave — March of 2020 — still have long COVID,” Maley says. “We also see people who had long COVID around that time and have recovered. Most of the people we see have made substantial steps toward recovery, but there are certainly people who still are having severe symptoms now, over a year and a half out.”
Those include fatigue, shortness of breath, clouded thinking or “brain fog” as well as a diverse panoply of other symptoms and conditions, including swollen “COVID toes.”
In general, inflammatory markers or molecules in the body are elevated for much longer than expected after having COVID-19, compared to other viruses.
“One of the theories is that persistent inflammation could be a driver of long COVID,” Maley says. “There are other theories suggesting autoimmunity — developing inflammation that’s directed against your own body. [In other autoimmune diseases] it seemed likely it wasn’t a persistence of the infection itself, but they were probably people who were genetically prone to having this type of reaction and prolonged inflammation. That could explain why some people develop this while others make a full, quick recovery from the same virus and have a very different course of recovery afterward.”
The Inevitability Camp
There certainly are other risks, but the threat of an exponential increase in long COVID probably is the best argument against viewing rampant omicron spread as a fait accompli.
However, this view has gained traction, with even experienced public health leaders adding to the sense of inevitability in recent news reports. Janet Woodcock, MD, acting commissioner of the Food and Drug Administration, told Congress, “Most people are going to get COVID.” Anthony Fauci, MD, the top pandemic advisor to the government, said essentially the same thing, predicting the variant’s incredible immune evasion and transmissibility “will find just about everybody.”6
Some are disturbed at these signs of capitulation to a virus that still poses great risk. Perhaps foremost among them is Eric Topol, MD, a professor of molecular medicine and director and founder of the Scripps Research Translational Institute in La Jolla, CA.
One issue in the inevitability camp that should be immediately debunked is the view that being infected with omicron is like getting a live, attenuated virus vaccine, Topol said.
“That couldn’t be further from the truth,” he said in an interview on a UCSF Grand Rounds program at the University of California, San Francisco.7
“I think it was unfortunate when both Janet Woodcock and Tony [Fauci] made comments about most people are going to get it, because that kind of really fosters the sense of inevitability,” Topol said. “Let’s get through these next few weeks where there’s such high circulating virus, then regroup. But let’s not invite an unpredictable virus that can cause long COVID — there’s some rationale why that would be a concern — and can cause secondary attacks to people who are immunocompromised.”
This sense that omicron infection is inevitable prompts highly questionable ideas, like ending control measures and facilitating spread of the variant.
“Policies designed to slow the spread of omicron may end up creating a supervariant that is more infectious, more virulent, and more resistant to vaccines. That would be a man-made disaster,” the authors of an opinion piece opined.8 “To minimize that risk, policymakers must tolerate the rapid spread of milder variants. This will require difficult trade-offs, but it will save lives in the long run. We should end mask mandates and social distancing in most settings not because they don’t slow the spread — the usual argument against such measures — but because they probably do.”
Topol, who has more than 600,000 followers of his medical commentary on Twitter, said he was stunned and “almost tweetless” after reading the editorial.
“Here, basically, was the exact opposite of everything,” he said. “It’s like turning the world upside down about the pandemic and saying that, essentially, we should have chickenpox parties and speed the spread. Can you imagine?”
Topol then added, with arch sarcasm, “They acknowledged that there may be a little risk involved.”
One such risk would be long COVID, which Topol has seen in other healthcare workers. “I have colleagues with long COVID — young, healthy people who still have really serious problems in functionality. This is a real deal.”
As Maley makes clear, there are few data on long COVID and omicron, given the first suspect cases are just beginning to appear.
“But there’s a reason why we think it could be worse with omicron,” Topol said. “First of all, we know most long COVID occurs with mild infections, some moderate. That’s where the preponderance of long COVID occurs. Secondly, omicron’s immune evasiveness. There’s an important study in Nature Immunology, which shows how there’s persistent immune dysregulation eight months after mild COVID infections in people with long COVID.”
The authors of the study reported “an abnormal immune profile in patients with COVID-19 at extended time points after infection and provides clear support for the existence of a syndrome of long COVID.”9
Omicron is the Houdini of immune escape, suggesting it could resist and evade the immune system indefinitely in someone with long COVID.
“This is the most immune escape we’ve seen by far of any version of this virus,” Topol said. “It could make it more difficult for people to get over it. This whole idea of having millions of infections per day and it’s inevitable, basically ignores the long COVID concern.”
Interviewer Robert Wachter, MD, interjected an editorial comment at this point, saying “What I find interesting is you hear all the time, ‘I’m really worried about the long-term side effects of the vaccine.’ I say, ‘I’m about a thousand times more worried about the long-term side effects of COVID.”
- Office for Government Statistics. Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK: 6 January 2022.
- Bergwerk M, Gonen T, Lustig Y, et al. COVID-19 breakthrough infections in vaccinated health care workers. N Engl J Med 2021;385:1474-1484.
- Antonelli M, Penfold RS, Merino J, et al. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: A prospective, community-based, nested, case-control study. Lancet Infect Dis 2022;22:43-55.
- Taquet M, Dercon Q, Harrison, PJ. Six-month sequelae of post-vaccination SARS-CoV-2 infection: A retrospective cohort study of 10,024 breakthrough infections. medRxiv 2021;10.26.21265508. https://doi.org/10.1101/2021.10.26.21265508. [Preprint].
- Cowell A. Churchill’s definition of Russia still rings true. The New York Times. Aug. 1, 2008.
- KHN Morning Briefing. A dire forecast from health officials: Most of us will get Covid. Kaiser Health News. Jan. 12, 2022.
- UCSF Medicine. The omicron whirlwind: A conversation with Eric Topol — the current and future state of the pandemic. Jan. 13, 2022.
- Ramaswamy V, Ramaswamy A. Slow the spread? Speeding it may be safer. The Wall Street Journal. Jan. 10, 2022.
- Phetsouphanh C, Darley DR, Wilson DB, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol 2022;Jan 13. doi: 10.1038/s41590-021-01113-x. [Online ahead of print].
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