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Scientists Revive and Characterize 13 Ancient “Zombie” Viruses Isolated from Siberian Permafrost

Viruses are between 27,000 to 48,500 years old and not dangerous, but researchers say thawing permafrost may one day release pathogens capable of infecting humans

Last fall, European researchers working with virologists and genetic scientists at the Aix-Marseille University in France reported having revived and characterized 13 previously unknown “zombie” viruses isolated from Siberian permafrost samples, including one that was almost 50,000 years old. This will be of particular interest to microbiologists and clinical laboratory managers since these organisms are new to science and may be precursors to infectious agents active in the world today.

The work of the European scientists demonstrates how advancements in genome sequencing and analysis of DNA data are becoming, faster, less expensive, and more precise. That’s good because the researchers warned that, should the permafrost continue to thaw, other previously dormant viruses could be released, posing potential risks for public health.

The scientists published their findings in the open-access journal Viruses titled, “An Update on Eukaryotic Viruses Revived from Ancient Permafrost.”

The pathogens isolated by the researchers are so-called “giant viruses” that infect Acanthamoeba, a commonly found genus of amoeba, and thus are not likely to pose an immediate health threat, the researchers wrote.

However, the scientists expressed concern. “We believe our results with Acanthamoeba-infecting viruses can be extrapolated to many other DNA viruses capable of infecting humans or animals. It is thus likely that ancient permafrost … will release these unknown viruses upon thawing,” they stated in their Viruses paper.

It’s unknown how long the viruses “could be infectious once exposed to outdoor conditions (UV light, oxygen, heat), and how likely they will be to encounter and infect a suitable host in the interval,” they added. However, “the risk is bound to increase in the context of global warming, in which permafrost thawing will keep accelerating, and more people will populate the Arctic in the wake of industrial ventures.”

Paulo Verardi, PhD

“In nature we have a big natural freezer, which is the Siberian permafrost,” virologist Paulo Verardi, PhD (above), head of the Department of Pathobiology and Veterinary Science at the University of Connecticut, told The Washington Post. “And that can be a little bit concerning.” However, “if you do the risk assessment, this is very low. We have many more things to worry about right now.” Nevertheless, clinical laboratories may want to remain vigilant. (Photo copyright: University of Connecticut.)

Extremely Old, Very Large Viruses

The newly discovered viruses were found in seven different permafrost samples. Radiocarbon dating determined that they had been dormant for 27,000 to 48,500 years. But viruses contained in permafrost could be even older, the researchers wrote, as the time limit is “solely dictated by the validity range of radiocarbon dating.”

In their Viruses paper, the researchers noted that most of the 13 viruses are “at a preliminary stage of characterization,” and others have been isolated in the research laboratory “but not yet published, pending their complete genome assembly, annotation, or detailed analysis.”

“Every time we look, we will find a virus,” study co-author Jean-Michel Claverie, PhD, told The Washington Post. “It’s a done deal. We know that every time we’re going to look for viruses—infectious viruses in permafrost—we are going to find some.”

Claverie is a professor emeritus of genomics and bioinformatics in the School of Medicine at Aix-Marseille Université in Marseille, France. He leads a university laboratory known for its work in “paleovirology,” and in 2003, discovered the first known giant virus, dubbed Mimivirus. The research team included scientists from Germany and Russia.

According to CNN, unlike regular viruses that generally require an electron microscope to be viewed, giant viruses can be seen under a standard light (optical) microscope. Claverie’s laboratory previously isolated giant viruses from permafrost in 2014 and 2015.

Protecting Against Accidental Infection

To demonstrate the infectious potential of the viruses, the researchers inserted the microbes into cultured amoeba cells, which the researchers describes as “virus bait,” The Washington Post reported. One advantage of using Acanthamoeba cultures is to maintain “biological security,” the researchers wrote in their paper.

“We are using [the amoeba’s] billion years of evolutionary distance with human and other mammals as the best possible protection against an accidental infection of laboratory workers or the spread of a dreadful virus once infecting Pleistocene mammals to their contemporary relatives,” the paper noted. “The biohazard associated with reviving prehistorical amoeba-infecting viruses is thus totally negligible compared to the search for ‘paleoviruses’ directly from permafrost-preserved remains of mammoths, woolly rhinoceros, or prehistoric horses.”

The paper cites earlier research noting the presence of bacteria in ancient permafrost samples, “a significant proportion of which are thought to be alive.” These include relatives of contemporary pathogens such as:

How Dangerous are Ancient Viruses?

“We can reasonably hope that an epidemic caused by a revived prehistoric pathogenic bacterium could be quickly controlled by the modern antibiotics at our disposal,” the researchers wrote, but “the situation would be much more disastrous in the case of plant, animal, or human diseases caused by the revival of an ancient unknown virus.”

However, according to The Washington Post, “Virologists who were not involved in the research said the specter of future pandemics being unleashed from the Siberian steppe ranks low on the list of current public health threats. Most new—or ancient—viruses are not dangerous, and the ones that survive the deep freeze for thousands of years tend not to be in the category of coronaviruses and other highly infectious viruses that lead to pandemics.”

Cornell University virologist Colin Parrish, PhD, President of the American Society for Virology, told The Washington Post that an ancient virus “seems like a low risk compared to the large numbers of viruses that are circulating among vertebrates around the world, and that have proven to be real threats in the past, and where similar events could happen in the future, as we still lack a framework for recognizing those ahead of time.”

Anthony Fauci, MD, former Director of the National Institute of Allergy and Infectious Diseases (NIAID), responded to an earlier study from Claverie’s lab by outlining all the unlikely events that would have to transpire for one of these viruses to cause a pandemic. “The permafrost virus must be able to infect humans, it must then [cause disease], and it must be able to spread efficiently from human to human,” he told The Washington Post in 2015. “This can happen, but it is very unlikely.”

Thus, clinical laboratories probably won’t see new diagnostic testing to identify ancient viruses anytime soon. But it’s always best to remain vigilant.

Stephen Beale

Related Information:

Scientists Have Revived a ‘Zombie’ Virus That Spent 48,500 Years Frozen in Permafrost

‘Zombie’ Viruses Are Thawing in Melting Permafrost Because of Climate Change

Ancient Dormant Viruses Found in Permafrost, Once Revived, Can Infect Amoeba

Scientists Revive 48,500-Year-Old ‘Zombie Virus’ Buried in Ice

Scientists Revived Ancient ‘Zombie Viruses’ Frozen for Eons in Siberia

Scientists Warn Long-Frozen ‘Zombie Virus’ Is ‘Public Health Threat’ Amid Thaw

Scientists Did Not Release a Zombie Plague by Reviving a Dormant Virus, but Their Warning of a Potential Public Health Crisis Is Legitimate

Scientists Estimate 73% of US Population May Be Immune to SARS-CoV-2 Omicron Variant

Clinical laboratory scientists should also know experts warn that ‘herd resistance’ is more likely than ‘herd immunity’ due to low vaccination rates in many parts of the world

Scientists estimate 73% of the US population may be immune to the SARS-CoV-2 omicron variant. Whether the nation is approaching “herd immunity” against the disease, however, remains open to debate, the Associated Press (AP) reported. These estimates are relevant to medical laboratories doing serology tests for COVID-19, as different individuals will have different immune system responses to COVID-19 infections and vaccines.

More than two years into the COVID-19 pandemic in the United States, the CDC’s COVID Data Tracker shows the number of daily cases dropped to fewer than 50,000 as of March 4, 2022, after reaching a high of 928,125 on January 3, 2022.

Meanwhile, the seven-day death rate per 100,000 people stands at 2.78. That’s significantly above the seven-day death rate reached last July of .45, but well below the 7.21 mark recorded on January 13, 2021.

“We’re clearly entering a new phase of the pandemic,” William Morice, II, MD, PhD, Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minn., told KARE11, an NBC affiliate.

Is Herd Immunity Achievable?

According to the AP, an estimated 73% of the US population is likely to be immune to the Omicron variant due to vaccination or natural immunity from contracting the disease. That calculation was done for the media outlet by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle. The IHME anticipates immunity to Omicron could rise to 80% this month, as more people receive vaccination booster shots or become vaccinated.

Despite those optimistic totals, however, Don Milton, MD, DrPH, Professor of Environmental Health at the University of Maryland School of Public Health, suggests achieving herd immunity to COVID-19 and its variants may no longer be possible.

“Herd immunity is an elusive concept and doesn’t apply to coronavirus,” he told the Associated Press (AP).

Milton maintains populations are moving toward “herd resistance,” rather than “herd immunity.” This will transform COVID-19 into a permanent fixture with seasonal outbreaks similar to influenza.

Ali Mokdad, PhD
Epidemiologist, Ali Mokdad, PhD (above), Chief Strategy Officer for Population Health and Professor of Health Metrics Science at the University of Washington in Seattle, believes the US is now much better positioned to withstand the next wave of COVID-19 cases. “I am optimistic even if we have a surge in summer, cases will go up, but hospitalizations and deaths will not,” he told the Associated Press (AP). Mokdad worked on the IHME model that calculated the 73% Omicron-immunity figure for the AP. However, he recommends continued vigilance toward COVID-19. “We’ve reached a much better position for the coming months, but with waning immunity we shouldn’t take it for granted,” he added. And so, clinical laboratories can expect to continue to play a vital role in the fight against the spread of the SARS-CoV-2 coronavirus. (Photo copyright: University of Washington.)

Herd Immunity Varies, according to the WHO

Because antibodies that developed from vaccines—or natural immunity from a previous infection—diminish over time, waning protection means even those boosted or recently recovered from COVID-19 could be reinfected. In addition, vaccination rates vary widely around the world. Our World in Data estimates only 13.6% of people in low-income countries had received one dose of the COVID-19 vaccine as of March 7, 2022.

The World Health Organization (WHO) points out that herd immunity levels vary with different diseases. Herd immunity against measles requires about 95% of a population to be vaccinated, while the threshold for polio is about 80%.

“The proportion of the population that must be vaccinated against COVID-19 to begin inducing herd immunity is not known. This is an important area of research and will likely vary according to the community, the vaccine, the populations prioritized for vaccination, and other factors,” the WHO website states.

Living with COVID-19

Nonetheless, the US appears to be moving into a new “normal” phase of living with the disease.

In an interview with Reuters, US infectious disease expert Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases (NIAID) acknowledged a need for returning to normal living even though portions of the population—immunocompromised individuals and the unvaccinated, including children under age five who are not eligible for vaccination—remain vulnerable to more severe COVID-19.

“The fact that the world and the United States—and particularly certain parts of the United States—are just up to here with COVID, they just really need to somehow get their life back,” Fauci said. “You don’t want to be reckless and throw everything aside, but you’ve got to start inching towards that. There’s no perfect solution to this.”

Most states have lifted coronavirus-related restrictions, including masking requirements. As COVID-19 cases drop in California, Gov. Gavin Newsom put in motion a plan called SMARTER (Shots, Masks, Awareness, Readiness, Testing, Education, and Rx) that no longer responds to COVID-19 as a crisis, but instead emphasizes prevention, surveillance, and rapid response to future variant-based surges in cases.

“We have all come to understand what was not understood at the beginning of this crisis, that there’s no ending, that there’s not a moment where we declare victory,” Newsom told USA Today.

Mayo Clinic’s Morice agrees. “It can’t be out of sight, out of mind, per se, but it at least gives us hope that we can get back to some level of normalcy here over the course of the year,” he said.

Since clinical laboratories played a critical role in assay development and COVID-19 testing, medical laboratory leaders should continue monitoring COVID-19 as it moves from pandemic to endemic status due to high vaccination rates and advances in treatment options.

The COVID-19 pandemic has raised awareness among healthcare consumers as well, about the critical role laboratory medicine plays in modern medicine and healthcare. Medical laboratory leaders and pathologists would be wise to amplify this message and stress the importance of clinical laboratory testing for many diseases and healthcare conditions.

Andrea Downing Peck

Related Information:

Estimated 73% of US Now Immune to Omicron: Is That Enough?

Model Estimates 73% of Americans Immune to Omicron Variant

California is First to Unveil Plan to Live with Virus; ‘Stealth Omicron’ Could Be More Dangerous than Initial Version: COVID-19 Updates

Fauci Says Time to Start ‘Inching’ Back Toward Normality

CDC Data Tracker

Is Omicron Leading US Closer to Herd Immunity against COVID?

Scientists Identify Growing Number of COVID-19 Variants, But Not All Clinical Laboratories Have the Capability to Test for Variants

Fear that immunity-resistant mutations of SARS-CoV-2 will emerge are real and the scientific community is paying close attention

Detection of an increasing number of new variants of the SARS-CoV-2 coronavirus raises the possibility that a new strain of COVID-19 might emerge that brings new problems to the management of the pandemic. Public health officials and clinical laboratory scientists are on the alert to determine if any new COVID-19 variant is more virulent or more easily transmissible.

Pathologists, along with the rest of the scientific community worldwide, are following reports of increasing coronavirus mutations with growing concern. The Alpha variant (Lineage B.1.1.7) accounted for most of the COVID-19 cases in April of 2021 in the US, though it was first identified in the United Kingdom. That was followed by the Iota variant (Lineage B.1.526) first identified in New York City. A series of other variants were to follow. Scientists were not surprised. It is normal for viruses to mutate, so they logged and tracked the mutations.

Then, the Delta variant (Lineage B.1.617.2) emerged during a severe outbreak in India. At first, it did not seem more threatening than any other variant, but that changed very quickly. Delta was different.

“The speed with which it dominated the pandemic has left scientists nervous about what the virus will do next. The variant battles of 2021 are part of a longer war, one that is far from over,” The Washington Post reported, which added, “Today, [Delta] has nearly wiped out all of its rivals. The coronavirus pandemic in America has become a Delta pandemic. By the end of July, it accounted for 93.4% of new infections, according to the Centers for Disease Control and Prevention.”

Why is Delta the Worst COVID-19 Variant So Far?

The Delta variant has two advantages that scientists know about:

  • Stickier spike protein than the spike on the original SARS-CoV-2 coronavirus, as well as on the other, earlier variants. This means that the Delta variant stands a better chance of remaining in a person’s nose or throat long enough to reproduce.
  • Faster replication. When a virus mutation has more opportunity to reproduce, it quickly becomes the main viral strain. This is the case with the Delta variant. Experts say that the viral load in patients with Delta is around 1,000 times higher than in patients with the original virus.
Colorized scanning electron micrograph of an apoptotic cell that is infected with the SARS-COV-2 virus

The image above is a “Colorized scanning electron micrograph of an apoptotic cell (tan) heavily infected with SARS-COV-2 virus particles (orange), isolated from a patient sample,” Newsweek reported. (Photo copyright: National Institute of Allergy and Infectious Diseases/Newsweek.)

Will More Dangerous SARS-CoV-2 Variants Appear?

“The great fear is that nature could spit out some new variant that completely saps the power of vaccines and upends the progress we’ve made against the pandemic. But to virologists and immunologists, such a possibility seems very unlikely,” STAT reported.

That is because, unlike Influenza, which is also a coronavirus, SARS-CoV-2 variants are not able to share genetic materials and recombine into deadlier variants. Thus, scientists are skeptical that a variant could appear and wipe out the progress made with vaccines and treatments.

One of the reasons the Flu vaccine changes every year is Influenza’s ability to recombine into variants that can evade immunity. Therefore, scientists are beginning to suspect that SARS-CoV-2, like the Flu, will likely be around for a while.

“I don’t think eradication is on the table. But I think we could come up with something that’s better than what we have for the flu,” Sharone Green, MD, Associate Professor of Medicine, Division of Infectious Diseases and Immunology and Infection Control Officer at University of Massachusetts Medical School, told Newsweek.

Limiting Infections and Replication

Several factors combined to create the COVID-19 pandemic. But SARS-CoV-2 was a novel coronavirus, meaning it was a new pathogen of a known virus. This meant every person on the planet was a potential host.

The situation now is different. Thanks to natural immunity, vaccines, and treatments that shorten the infection, the SARS-CoV-2 coronavirus has less chance to replicate.

“The pressure is there, but the opportunity is not. The virus has to replicate in order to mutate, but each virus doesn’t get many lottery tickets in a vaccinated person who’s infected,” Jeremy Kamil, PhD, Associate Professor of Microbiology and Immunology at LSU Health in Shreveport, La., told STAT.

Tracking Variants of Interest and Variants of Concern

The World Health Organization (WHO) has been monitoring the viral evolution of SARS-CoV-2 since the beginning of the pandemic. In late 2020, the WHO created categories for tracking variants:

The WHO’s lists of VOIs and VOCs help inform the global response to the COVID-19 pandemic.

According to the CDC’s SARS-CoV-2 Variant Classifications and Definitions:

VOIs are “A variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity.”

Current VOIs include:

  • Eta (Lineage B.1.525), detected in multiple countries, designated a VOI in March 2021.
  • Iota (Lineage B.1.526), US, first detected in November 2020, designated a VOI in March 2021.
  • Kappa (lineage B.1.617.1), India, first detected in October 2020, designated a VOI in April 2021.
  • Lambda (lineage C.37), Peru, first detected in December 2020, designated a VOI in June 2021.

VOCs, on the other hand, demonstrate all the characteristics of VOIs and also demonstrate “an increase in transmissibility, more severe disease (e.g., increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.”

Current VOCs include:

  • Alpha (lineage B.1.1.7), first detected in the UK, September 2020.
  • Beta (lineage B.1.351), first detected in South Africa, May 2020.
  • Gamma (lineage P.1), first detected in Brazil, November 2020.
  • Delta (lineage B.1.617.2), first detected in India, October 2020.

Will Vaccines Stop Working?

With each new variant, there tends to be a flurry of media attention and fearmongering. That a variant could emerge which would render our current vaccines ineffective has the scientific community’s attention.

“There is intense interest in whether mutations in the spike glycoprotein mediate escape from host antibodies and could potentially compromise vaccine effectiveness, since spike is the major viral antigen in the current vaccines,” wrote Adam S. Lauring, MD, PhD, and Emma B. Hodcroft, PhD, in “Genetic Variants of SARS-CoV-2­—What Do They Mean?” published in the Journal of the American Medical Association (JAMA). 

“Because current vaccines provoke an immune response to the entire spike protein, it is hoped that effective protection may still occur despite a few changes at antigenic sites in SARS-CoV-2 variants,” they added.

Future events may justify the optimism that the ongoing effectiveness of vaccines will help with many COVID-19 variants. But pathologists and clinical laboratory leaders may want to be vigilant, because as infection rates increase, so do workloads and demands on critical resources in their medical laboratories.

Dava Stewart

Related Information

‘Goldilocks Virus’: Delta Vanquishes All Variant Rivals as Scientists Race to Understand Its Tricks

Viral Evolution 101: Why the Coronavirus Has Changed as It Has, and What It Means Going Forward

A Doomsday COVID Variant Worse than Delta and Lambda May Be Coming, Scientists Say

Tracking SARS-CoV-2 Variants

Genetic Variants of SARS-CoV-2—What Do They Mean?

Immunocompromised Patients with COVID-19 May Remain Infectious for Much Longer than Previously Thought

Clinical laboratory professionals should note that one case study describes a COVID-positive cancer patient shedding infectious particles for five months, which is much longer than expected

Just when researchers start believing they understand COVID-19 infections, something happens that reveals there is still more to learn. These additional findings are relevant for clinical laboratory managers and pathologists because the new insights often may play a role in how SARS-CoV-2 results should be interpreted for individual patients.

Researchers recently described a case where, in February, a 71-year-old woman underwent surgery related to her 10-year battle with cancer. While she was in the hospital, she was found to be positive for the SARS-CoV-2 coronavirus, though she showed no respiratory or systemic symptoms. Nevertheless, the hospital isolated her and monitored the infection.

To everyone’s surprise, the patient remained positive for five months. She underwent 15 COVID-19 tests from various diagnostics companies, as well as receiving two doses of convalescent plasma therapy, but she remained positive for the coronavirus into June.

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) wanted to know why. They conducted a study on the woman, which they later published in the journal Cell, titled, “Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer.”

In their published study, they wrote, “Although it is difficult to extrapolate from a single individual, our data suggest that long-term shedding of infectious virus may be a concern in certain immunocompromised people. Given that immunocompromised individuals could have prolonged shedding and may not have typical symptoms of COVID-19, symptom-based strategies for testing and discontinuing transmission-based precautions, as recommended by the Centers for Disease Control and Prevention (CDC), may fail to detect whether certain individuals are shedding infectious virus.”

Clinical laboratory professionals and pathologists will find it significant that patients with major health conditions may be shedding viral material for weeks longer than originally thought. This is relevant because it may be prudent to COVID test patients who present with compromised immune systems, and who are asymptomatic, and then repeat that testing at appropriate intervals.

The graphic above taken from the NIAID study
The graphic above taken from the NIAID study shows how long it took for the SARS-CoV-2 coronavirus to clear the 71-year-old immunocompromised cancer patient’s system, and at which points the convalescent plasma doses were administered. (Graphic copyright: National Institute of Allergy and Infectious Diseases.)  

Immunocompromised Patients May Handle COVID-19 Differently

The NIAID researchers believe the reason the patient continued to shed infectious virus for so long was because she was immunocompromised. They wrote, “Many current infection control guidelines assume that persistently PCR-positive individuals are shedding residual RNA and not infectious virus, with immunocompromised people thought to remain infectious for no longer than 20 days after symptom onset. Here we show that certain individuals may shed infectious, replication-competent virus for much longer than previously recognized. Although infectious virus could be detected up to day 70, sgRNA, a molecular marker for active SARS-CoV-2 replication, could be detected up until day 105.”

In the United States, some three million people have compromised or weakened immune systems. This is a significant population, Science Alert reported.

“As the virus continues to spread, more people with a range of immunosuppressing disorders will become infected, and it’s more important to understand how SARS-CoV-2 behaves in those populations,” Vincent Munster, PhD, Chief, Virus Ecology Unit at the National Institute of Allergy and Infectious Diseases and co-author of the NIAID study, told Science Alert.

The NIAID study findings match knowledge about other coronaviruses. For example, Science Alert reported that immunocompromised people with Middle East Respiratory Syndrome (MERS) have been shown to shed common seasonal coronaviruses for up to a month following infection.

Asymptomatic Patients Are a Mystery

There is still much that is unclear about asymptomatic patients. A paper published in JAMA, titled, “Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients with SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea,” questioned the viral load differences in patients who tested positive but had no symptoms compared to those who were symptomatic.

That study included 303 patients, of which 193 were symptomatic. During the course of the study, 21 of the asymptomatic patients developed symptoms, however, the viral load was similar in all of the patients, regardless of symptoms.

“Isolation of asymptomatic patients may be necessary to control the spread of SARS-CoV-2,” concluded the JAMA researchers. But how long should asymptomatic patients remain isolated?

Official Guidance Is Based on Symptoms

The CDC updated its guidelines for who should isolate and for how long in October. The guidelines cover:

  • People who have or had COVID-19 and had symptoms;
  • People who tested positive for COVID-19 but did not have symptoms;
  • People who either had severe symptoms of COVID-19 or who have a compromised immune system;
  • People who were exposed to COVID-19, and
  • People who have been reinfected.

Regarding those who are immunocompromised and had COVID-19, the CDC says they “may require testing to determine when they can be around others.”

In addition to noting that people who are immunocompromised may require additional testing, the CDC is also continuously updating its published list of people who are at risk for complications and severe illness if they contract COVID-19. However, as the NIAID study showed, even those with underlying medical conditions can be asymptomatic.

And as the NIAID researchers note, there is more to learn. “Understanding the mechanism of virus persistence and eventual clearance will be essential for providing appropriate treatment and preventing transmission of SARS-CoV-2 because persistent infection and prolonged shedding of infectious SARS-CoV-2 might occur more frequently. Because immunocompromised individuals are often cohorted in hospital settings, a more nuanced approach to testing these individuals is warranted, and the presence of persistently positive people by performing SARS-CoV-2 gRNA and sgRNA analyses on clinical samples should be investigated.”

SARS-CoV-2 Science Is Young

An additional takeaway for pathology lab professionals is the reminder that the scientific research surrounding the novel coronavirus that causes COVID-19 is very young. New insights and understanding will continue to emerge, probably for many years.

One reason why the development of vaccines for COVID-19 has been so quick is that it built on scientific knowledge of the first SARS outbreak and MERS. It’s interesting to note that both SARS and MERS are relatively new as well: SARS emerged in 2002 and MERS in 2012. Compared to a disease like HIV, which was first identified in 1959, scientists have only been working on these particular coronaviruses for a short period of time.

The NIAID study is yet another example of new knowledge and insights emerging about how SARS-CoV-2 infects individuals. Collectively, these findings make it challenging for medical laboratory professionals to stay current with everything relevant and associated with the proper interpretation of COVID-19 test results.

—Dava Stewart

Related Information:

Prolonged Infectious SARS-SoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer

Startling Case Study Finds Asymptomatic COVVID-19 Carrier Who Shed Virus for 70 Days

Shedding of Infectious Virus in Hospitalized Patients with Coronavirus Disease-2019 (COVID-19): Duration and Key Determinants

SARS-CoV-2: The Viral Shedding vs Infectivity Dilemma

Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients with SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea

When You Can Be Around Others

People with Certain Medical Conditions

NAIAD: Coronaviruses

COVID Research Updates: Immune Responses to Coronavirus Persist Beyond Six Months

Where Did all the Antibodies Go? Emory University’s Vaccine Center Studies Bone Marrow to Find Out Why Influenza Vaccines are Short-Lived

Pathologists and clinical laboratory scientists know that influenza vaccines typically produce short-lived protection and researchers have new clues as to why this is true

With so much interest in development of a COVID-19 vaccine, findings by researchers at Atlanta’s Emory Vaccine Center into why the vaccine for influenza (Flu) is so short-lived offer a new window on how the body’s immune system responds to invading viruses and what happens to the immunity over time.

Because the autumn influenza season is just weeks away, these insights into the body’s immune response to influenza will be of interest to clinical laboratories that provide testing for influenza, as well as SARS-CoV-2, the coronavirus that causes COVID-19.

Clinical laboratory managers recognize that an influenza vaccine is an annual imperative for people—especially the elderly and those with existing comorbidities—and medical laboratory tests are typically used to diagnose the illness and identify which strains of viruses are present. The flu vaccine is even more important amid the COVID-19 pandemic, infectious disease authorities say.

The scientists at the Emory Vaccine Center published their findings in the journal Science.  

How Does Influenza Differ from Other Viruses?

Vaccines for some viruses, such as Hepatitis A, Hepatitis B, and the human papillomavirus, may be taken only one time, but the immunity can last a lifetime.  

Not so with influenza vaccines. The immunity they impart generally only lasts for a single flu season and are “lost within one year,” the Emory study notes.

As Genetic Engineering and Biotechnology News (GEN) explains, the influenza genome has eight RNA segments which can change as the virus enters a cell. This antigenic shift creates new influenza strains that require updated vaccines, GEN noted.

However, the Emory researchers stated that “The fact that a small number did persist over one year raises prospects that the longevity of flu vaccines can be improved and provides key information for the development of universal vaccines against influenza.”

Bone Marrow Has Major Role in Producing New Flu Antibodies

The Emory study focused on the influenza vaccine’s role in how it affects the immune system and what needs to change to create a longer-lasting influenza vaccine. “Our results suggest that most bone marrow plasma cells (BMPC) generated by influenza vaccination in adults are short-lived. Designing strategies to enhance their persistence will be key,” the Emory researchers wrote in Science.

The scientists analyzed bone marrow from 53 healthy volunteers (age 20 to 45). An Emory news release states that bone marrow is the “home base for immune cells producing antibodies.”

Besides the bone marrow, the researchers also examined blood samples from the volunteers, all of which was collected between 2009 and 2018:

  • before influenza vaccination,
  • one month after influenza vaccination, and
  • one year post vaccination.

Through DNA sequencing the samples, the Emory researchers found the number of flu-specific cells increased from 0.8% to 1.9% after one month. They concluded that an annual vaccine does increase antibody-producing cells for influenza in bone marrow.

However, in follow-up visits one year after vaccination, they found that the number of cells present in the volunteers had fallen back to the starting point.

“Specific cells produced by the vaccine … produced unique antibodies that can be identified using sequencing techniques,” Carl Davis, PhD, postdoctoral fellow in the Rafi Ahmed Laboratory at Emory and first author of the paper, said in the news release, adding, “We could see that these new antibodies expanded in the bone marrow one month after vaccination and then contracted after one year.”

He continued, “On the other hand, antibodies against influenza that were in the bone marrow before the vaccine was given stayed at a constant level over one year.”

Vaccine Adjuvants Help Boost Immunity

A vaccine additive called an adjuvant could be the answer to extending the power of  influenza vaccines, the Emory scientists noted.

“Just getting to the bone marrow is not enough. A plasma cell has to find a niche within the bone marrow and establish itself there and undergo gene expression and metabolism changes that promote longevity,” Rafi Ahmed, PhD, Director of the Emory Vaccine Center, said in the news release.

Adjuvants could boost BMPC, because they act as “irritants” to beef up immune response, an article in Science titled, “Why Flu Vaccines Don’t Protect People for Long,” explained.

“It’s totally crazy (that the most commonly used influenza vaccines don’t include an adjuvant), Ahmed told Science. “I’m hoping that things will change in the influenza vaccine world, and 10 years from now, you will not be getting any nonadjuvanted vaccines.” 

Adjuvants used in vaccine studies for the SARS-CoV-1 coronavirus could be useful in developing vaccines for the SARS-CoV-2
Taken from the published study, “Potential Adjuvants for the Development of a SARS-CoV-2 Vaccine Based on Experimental Results from Similar Coronaviruses,” the graphic above shows adjuvants used in vaccine studies for the SARS-CoV-1 coronavirus could be useful in developing vaccines for the SARS-CoV-2 coronavirus as well. (Graphic copyright: Immunopharmacology/Elsevier.)

Are Adjuvants the Answer for COVID-19 Vaccines?

According to USA Today, about 20-million “essential” workers will likely be the first to receive the new COVID-19 vaccine and participate in check-in text messages with the Centers for Disease Control and Prevention (CDC) by the end of 2020.

In its COVID-19 vaccine testing, Novavax, a late-state biotechnology company, suggests that “an adjuvant is critical to its vaccine working well,” National Public Radio (NPR) reported in “The Special Sauce That Makes Some Vaccines Work.” However, vaccine developers may be reluctant to share their adjuvant research.

“Adjuvants end up being very proprietary. It’s kind of the secret sauce on how to make your protein vaccine work,” Barney Graham, MD, PhD, Deputy Director, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, told NPR.

Still, a study published in Immunopharmacology revealed potential adjuvants for the COVID-19 vaccine based on vaccine studies of other coronaviruses. While there are many adjuvants available, not all have safety track records that can be leveraged to gain clearance from regulatory bodies, the researchers pointed out. But some do.

CpG 1018, MF59, and AS03 are already approved for human vaccine and their inclusion may expedite the vaccine development process. Further, Protollin has shown promising results in pre-clinical studies,” the authors wrote.

Clinical laboratories that provide influenza testing will want to follow these types of research studies. Findings on immunity will affect development of vaccines that medical labs provide—including for COVID-19.

—Donna Marie Pocius

Related Information:

Why Flu Vaccine Immunity is Short-Lived

Influenza Vaccine-induced Human Bone Marrow Plasma Cells Decline Within a Year After Vaccination

Seasonal Flu Vaccinations Don’t “Stick” Long-Term in Bone Marrow

Why Flu Vaccines Don’t Protect People for Long

First COVID-19 Vaccine Recipients Get Daily CDC Check Texts

Administration Announces $200 Million From CDC to Jurisdictions for COVID-19 Vaccine Preparedness

All You Wanted to Know About the Coronavirus Vaccine Science but Were Afraid to Ask

Potential Adjuvants for the Development of a SARS-CoV-2 Vaccine Based on Experimental Results from Similar Coronaviruses