Omicron ‘Milder’ Infection View Skewed by Prior Immunity
Long COVID question closer to being answered
By Gary Evans, Medical Writer
The COVID-19 Omicron variant has been widely observed to cause “milder” disease, but this appears largely to be an illusion caused by the level of immunity via prior infection or vaccination that now exists in the human population, epidemiologists report.
A recently published commentary warns that “a portion of the observed reduction in severity stems from Omicron’s greater ability to infect people with preexisting immunity, which protects somewhat against severe disease.”1
The authors cited two modeling studies that estimate that Omicron is about 75% as likely as the Delta variant to cause hospitalization in an unvaccinated person with no history of prior SARS-CoV-2 infection.2,3
“This meaningful but fairly small difference implies that Omicron, Alpha, and wild-type SARS-CoV-2 have similar intrinsic severity,” they concluded. “Viruses don’t inevitably evolve toward being less virulent; evolution simply selects those that excel at multiplying.”
The immediate implications are that those who were not infected previously with SARS-CoV-2 and who remain unvaccinated are at greatest risk of a severe infection with Omicron.
“There must be a renewed push to vaccinate and boost those not yet protected, because Omicron is not necessarily intrinsically milder,” coauthor William Hanage, PhD, associate professor of epidemiology at Harvard T.H. Chan School of Public Health, said in a statement.
More Deaths than Delta
Daniel Griffin, MD, PhD, a clinician and research scientist at Columbia University in New York City, has been somewhat skeptical of the “less severe” narrative since the Omicron variant emerged in mid-November 2021. “Prior infections, vaccinations — these are what are really saving us from being more overwhelmed than we are,” he said in a recent clinical update via video.4
Concurring generally with the commentary authors, Griffin agreed that “the virus is under no selective pressure to become less virulent. If anything, the way we turn this into a common coronavirus is through vaccination. I still think we need to wait a bit and see the hard numbers on deaths.”
In January 2022, Omicron exceeded the daily average deaths when the Delta variant was in full surge in fall 2021. Delta has since been completely vanquished, with Omicron now causing 99% of all SARS-CoV-2 infections in the United States.
“It’s important to repeat that we are seeing more deaths per day than we ever saw with Delta,” Griffin said. “[On Jan. 29, 2022] there were 3,444 deaths from COVID. Almost all of those were among the unvaccinated. We have already reached a peak that is about 20% higher than we reached during the Delta wave.”
Mortality rates still are something of an unresolved question, but the case counts nationally were plummeting as this report was filed. As of Feb. 6, 2022, the daily average of SARS-CoV-2 cases was 295,313 nationally, a 57% decline from the prior two weeks.5 Deaths had a daily average of 2,565, an 18% increase in two weeks. Hospitalizations fell by 24% for the period, with a daily average of 119,415.
Although continued decline is expected for the near term, the Omicron variant may not go quietly in areas with large populations of unvaccinated people — making the falling wave somewhat uneven.
“Peak does not mean end, and endemic does not mean end,” says Patsy Stinchfield, RN, MS, CPNP, president-elect of the National Foundation for Infectious Diseases (NFID). “I think people are getting mixed up on this. It means that it will [join] the backdrop of our usual circulating viruses and then we’ll have to deal with [SARS-CoV-2] in a seasonal kind of way. We’re looking forward to this, but we’re not there yet.”
Meanwhile, the available data suggest those completely immune-naïve remain at greatest risk of severe outcomes. However, rather than be immunized, some will be infected based, in part, on the belief that Omicron spread is inevitable, and will function as a natural version of a live, attenuated vaccine. The authors of a recent opinion piece went so far as encouraging “speeding the spread” of Omicron by ending mask mandates and social distancing in most settings.6
Some have termed this the “inevitably camp,” a view that was given considerable momentum when two prominent public health leaders seemed to endorse it in mid-January of this year. 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, essentially said the same thing, predicting the variant’s incredible immune evasion and transmissibility “will find just about everybody.”7
Pandemic Fatigue a Century Apart
A striking similar scenario played out in the 1918 influenza pandemic that killed about 50 million people worldwide, reports John M. Barry, a professor at the Tulane University School of Public Health and Tropical Medicine, and a leading historian on the “great pandemic.” Looking at the situation today, as the COVID-19 pandemic keeps rolling through multiple waves as it enters its third calendar year, Barry warned of complacency in a recent opinion piece.8
Although it is not widely known, the 1918 flu actually had a fourth wave in 1920, a variant of the H1N1 influenza A virus that was met with the kind laissez-faire attitudes and pandemic fatigue that is being seen today, he noted.
“Yet the virus continued to kill,” Barry reported. “In some cities — among them, Detroit, Milwaukee, Minneapolis, and Kansas City, MO — deaths exceeded even those in the second wave, responsible for the vast majority of the pandemic’s deaths in the United States and elsewhere.”
There was no vaccine, but this fourth wave came at time there was widespread natural immunity from prior infection, and the mortality rate in the third wave had decreased, he noted. Warning against repeating this mistake, Barry reminded, “People were weary of influenza, and so were public officials. Newspapers were filled with frightening news about the virus, but no one cared.”
The influenza pandemic did end the following year, in 1921, and there is some reasonable hope that SARS-CoV-2 could follow this path, Barry wrote, while warning against “ceding control” to what has proven to be a highly mutable coronavirus.
Add the “inevitable” sense of complacency with an active anti-vaccine movement and you can foresee the challenges to vaccine uptake in the estimated 15% of adults over 18 years old that have refused a single dose. That is roughly 39 million people.
In a U.S. Census Bureau survey of those who remain completely unvaccinated, 42% reported that they “don’t trust the COVID-19 vaccine” and 22% said they did not think the pandemic virus is “that big of a threat.”9 The survey was done in the first two weeks of December 2021, when Omicron had emerged and was beginning rapid spread that would overtake Delta later that month.
As the pandemic continues, the various groups of people against vaccines or masks have combined to become more monolithic, Stinchfield says.
“A lot of these subgroups have found each other and coalesced into larger voices, but they still are a minority — a vast minority compared to the majority of people that do get vaccinated and that vaccinate their children,” she says. “But it has definitely [undermined] COVID vaccinations, and we’re seeing that in the numbers related to all vaccines, too. So, we’ve got work to do in public health and the NFID is really committed to keeping those [vaccination] rates up.”
Long COVID Looms
Moreover, attitudes of complacency and fatalism regarding pandemic infections ignore the prospect of long COVID: a chronic set of neurological and physical maladies that have beset some people since the pandemic began in 2020.
Although there is no definitive evidence yet that Omicron will cause long COVID, the experience with prior variants suggests it could very well induce lingering symptoms.
“There’s really no reason to think that we wouldn’t see long COVID with this [variant] like we have with the others,” Stinchfield says. “I mean, it still has the kind of multiorgan system impact that Delta had and the Alpha wave had, so I would not be surprised. That’s one of the multiple reasons why we want people vaccinated against COVID.”
While protective, there have been reports of vaccinated people developing long COVID after a breakthrough infection, something Omicron is better at than any prior variant.
“We have seen many cases of patients with long COVID who had been fully vaccinated due to breakthrough infections — [these are] presumed to be the Delta variant,” says Sharagim Kemp, DO, coordinator of the Nuvance Health COVID-19 Recovery Program in New York and Connecticut. “Data [are] still emerging on whether the cases can be attributed to Omicron.”
Based on research with prior variants, some 16% (estimated range, 2% to 30%) of those infected with Omicron may develop long COVID, 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,” he says.
The data eventually will be clear and answer the question, but the more detailed causes of long COVID remain elusive.
“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 biologically,” Maley says. “So, 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, others remain chronically afflicted.
“We do see people who were in the first wave, March of 2020, they still have long COVID,” he said. “We also see people who had long COVID around that time and have recovered. Most of the people we see have made substantial steps towards recovery, but there are certainly people who still are having severe symptoms.”
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 in the body are elevated for much longer than expected after having COVID-19, compared to other viruses, Maley says.
“So, one of the theories is that persistent inflammation could be a driver of long COVID,” he 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 afterwards,” he adds.
There are some characteristics of the Omicron variant that could make long COVID more likely, said Eric Topol, MD, a professor of molecular medicine and director and founder of the Scripps Research Translational Institute in La Jolla, CA.
“There are reasons why we think it could be worse with Omicron,” he said in a recent interview at the University of California-San Francisco (UCSF).10 “First of all, we know most long COVID occurs with mild infections, some moderate. That’s where the preponderance of long COVID occurs.”
Omicron’s immune evasiveness also could be a problem in light of a recent study finding people with long COVID have persistent immune dysregulation eight months after initial infection.11
“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. And this whole idea of having millions of infections per day and ‘it’s inevitable,’ basically ignores the long COVID concern.”
REFERENCES
- Bhattacharyya RP, Hanage WP. Challenges in inferring intrinsic severity of the SARS-CoV-2 Omicron variant. N Engl J Med 2022; Feb 2. doi: 10.1056/NEJMp2119682. [Online ahead of print].
- Davies M-A, Kassanjee R, Rousseau P, et al. Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa. medRxiv 2022; Jan 12. doi: https://doi.org/10.1101/2022.01.12.22269148. [Preprint].
- Ferguson N, Ghani A, Hinsley W, Volz E. Report 50 – Hospitalisation risk for Omicron cases in England. Imperial College London. Published Dec. 22, 2021. https://www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-50-severity-omicron/
- YouTube. TWiV 862: COVID-19 clinical update #100 with Dr. Daniel Griffin. Published Feb 5, 2022. https://www.youtube.com/watch?v=j3kafmy08hA&t=356s
- The New York Times. Coronavirus in the U.S.: Latest map and case count. Published Feb. 7, 2022. https://www.nytimes.com/interactive/2021/us/covid-cases.html
The COVID-19 omicron variant has been widely observed to cause “milder” disease, but this appears largely to be an illusion caused by the level of immunity via prior infection or vaccination that now exists in the human population.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.