Measles outbreak in Samoa: potential effects on COVID-19
By Roberta Attanasio
Measles—one of the world’s most contagious diseases—induces immune amnesia, an anomaly of the immune system that results in increased susceptibility to infections by other pathogens. Not surprisingly, there are concerns globally about populations that have recently experienced measles outbreaks. These populations could be at elevated risk of developing more severe COVID-19 illness, resulting in increased mortality.
The emergence of the current COVID-19 pandemic in the first months of 2020 occurred closely after a global resurgence of measles. According to the World Health Organization (WHO), by November 2019, measles case numbers had tripled compared with the same period in the previous year. Measles spreads easily when an infected person coughs or sneezes and, before a vaccine became widely available in the 1960s, it caused millions of deaths worldwide annually. It is estimated that between the years 2000-2018, vaccination against measles alone saved around 23 million lives. However, measles outbreaks occurred in the past few years in all regions of the world and in many countries—from the Democratic Republic of Congo (DRC), to Samoa and Ukraine. These outbreaks, along with inadequate immunization rates, threaten to derail the crucial gains obtained in the two past decades.
Last year, in Samoa—a small island country in the central South Pacific Ocean—an unprecedented measles outbreak overwhelmed the nation’s health infrastructure, with hospitals at about 300% past capacity. Before the outbreak began, vaccination rates—already lower than the approximately 95 percent required for herd immunity—had plunged to 31%.
The first case of measles was confirmed in September 2019 and, on November 15, the government declared a state of emergency. Up to 3% of the population became infected, and 87 people died, mostly very young.
The state of emergency was lifted in December 2019. However, measles may have long-term consequences. Even after recovery, immune amnesia can persist for over 2 years.
Results from a study published a few days ago indicate that, in Samoa, immune amnesia may result in more severe cases of COVID-19. To model the morbidity and mortality impact of a potential COVID-19 epidemic in the country, researchers used data from the WHO situation reports of the measles epidemic in Samoa, and assumed that immune amnesia would be present in children infected from November 2019 onward for at least 12 months and up to 36 months.
They found that immune amnesia could increase the total number of COVID-19 cases by 8% and deaths by more than 2%. The highest rate of death would be in people older than 60 years, but a smaller peak in death could occur in younger people, with more than 15% of total deaths in the age group under 20 years old. Therefore, the researchers recommended that Samoa should rapidly achieve high rates of measles vaccination and enhance surveillance for COVID-19, as the impact may be more severe due to measles-induced immune amnesia. The researchers extended the recommendation to other severely measles-affected countries in the Pacific, Europe and elsewhere.
So, what is exactly immune amnesia? The measles virus targets cells of the immune system. It starts by invading those found in the upper respiratory tract, and it rapidly replicates inside them. Then, it spreads to organs of the immune system—bone marrow, thymus, spleen, tonsils and lymph nodes. The virus gains entry into the immune system cells by attaching to a protein called CD150, which is present on their surface. Once inside the cells, it destroys them and causes immunosuppression—in other words, it suppresses the body’s innate ability to ward off infection and disease. Children who overcome the first measles infection are protected against future measles infections, but may be more vulnerable to infections caused by other pathogens.
Indeed, the virus directly infects, among other cells of the immune system, B and T memory cells, thus dismantling the immune memory earned by fighting previous infections. Memory B and T cells remember pathogens the body has already eliminated, allowing the immune system to spring into action quickly if those pathogens are encountered again. Notably, the ability to induce immune amnesia is unique to the measles virus.
Results from a recent study show that the measles virus wipes out up to three-quarters of the protective antibodies generated in response to past microbial invaders and vaccinations. For the study, researchers analyzed blood samples using a tool called VirScan, which detects the pool of antibodies produced by a person after immunization or encounters with viruses, bacteria, or other pathogens. Therefore, the tool provides a comprehensive snapshot of acquired immunity at a particular moment.
In simple terms, the study results could be explained as follows: “If a person had 100 different antibodies against chicken pox before contracting measles, they might emerge from having measles with only 50, cutting their chicken pox protection in half. That protection could dip even lower if some of the antibodies lost are potent defenses known as neutralizing antibodies.”
According to the World Health Organization, even though a safe and cost-effective vaccine is available, there were more than 140,000 measles deaths globally in 2018, mostly among children under the age of five—the result of insufficient vaccine coverage. Previous epidemiological research into immune amnesia suggests that death rates attributed to measles could be even higher—accounting for as much as 50 percent of all childhood mortality—if researchers factored in deaths caused by infections resulting from measles’ ravaging effects on immunity.
Michael Mina, lead author of the study, said: “Imagine that your immunity against pathogens is like carrying around a book of photographs of criminals, and someone punched a bunch of holes in it. It would then be much harder to recognize that criminal if you saw them, especially if the holes are punched over important features for recognition, like the eyes or mouth.”
A previous study found that children experienced increased risk of infection and required more anti-infective prescriptions for up to 5 years following measles infection. However, “It’s important to note that, unlike measles infection, the MMR (measles, mumps, rubella) vaccine does NOT compromise previously acquired immunity.”
Therefore, widespread vaccination against measles can also potentially prevent hundreds of thousands of additional deaths caused by the lasting damage to the immune system.
11 Comments
Stephanie Michael
The article above describes immune amnesia’s effects, caused by the measles virus, on COVID-19. The mechanism in which the measles virus infects immune cells through the interaction with the CD150 protein to destroy immune cells and cause immunosuppression are discussed to explain what occurs when a person is infected. Most importantly, however, the demolishing of immune memory by infection of B and T cells highlight the measles virus’s exclusive ability to induce immune amnesia. Memory B and T cells make up the immune system’s immunological memory as they are responsible for providing a rapid response to a reoccurring pathogen. Memory B cells function to produce antibodies upon activation, while memory T cells attack infected cells and invaders. Upon infection by the measles virus, immune-mediated impairment of memory B and T cells occurs; thus, immunological memory is damaged. Therefore, the person affected develops immune amnesia, becoming more susceptible to new or old pathogens. Before the Coronavirus Pandemic of 2020, the measles virus was identified as the only virus to induce immune amnesia. However, recent research has shown the potential chance that COVID-19 could induce immune amnesia. So, the question, in this case, would be as follows: How does COVID-19 induce immune amnesia.
A study based at Harvard Medical School investigated how the SARS-CoV-2 virus affected the development of long-term immunity. Pillai et al. studied the lymph nodes and spleens of patients with acute COVIS-19. First and foremost, researchers found the severely ill patients lacked germinal centers, which are responsible for the production of memory B cells and pathogen-specific antibodies, and had a dramatic loss of B and T cells. The lack of germinal centers was associated with the reduced Bcl-6-expressing germinal center B cells and Bcl-6-expressing T follicular helper cells. Increased TH1 cells and aberrant TNF-alpha production in lymph nodes were also found in the study. COVID-19 patients were identified to have an accumulated amount of activated B cells circulating. Lastly, there were also high cytokine levels, also known as a cytokine storm, in COVID-19 patients discovered to hinder long-term immunity to the SARS-CoV-2 virus potentially. Because Bcl-6+ GC B cells and Bcl-6+ T follicular helper cells function to help T cells and B cells form germinal centers, their reduction explains the lack of germinal cells in COVID-19 patients. Consequently, memory B cells’ production is diminished as germinal centers are responsible for generating these memory cells. As a result of the lack of memory B cell production, immunological memory is impaired. Therefore, the immune system will not be able to protect the body from the SARS-CoV-2 virus. The virus will infect other immune cells, including already made memory B and T cells, leading to their destruction. Should memory B and T cells be destroyed, immune amnesia will be induced, and therefore, susceptibility to other pathogens is elevated. Subsequently, the development of robust and long-lived herd immunity following COVID-19 is vastly decreased.
While the article above higlhights the significance of increased vaccination against measles, it fails to push for vaccination against all diseases and illnesses. With the recent FDA approval of Pfizer-BioNTech COVID-19 Vaccine, vaccination for prevention of COVIA-19 is possible. However, given the climate we currently live in, many people worldwide have expressed fear in obtaining the COVID-19 vaccine or vaccinations in general. Therefore, while I agree that it’s essential to get vaccinated for measles, we must promote vaccinations in general. Otherwise, long-lived herd immunity for COVID-19 will be impossible, and we will face a similar pandemic to the 2020 Pandemic in the future.
Stephanie Michael
Articles used for the comment above:
https://www.cell.com/action/showPdf?pii=S0092-8674%2820%2931067-9
https://mgriblog.org/2020/09/16/covid-19-could-be-causing-immune-system-amnesia/
Fortino Pineda Veloz
Immune amnesia causes immune suppression by decreasing the level of memory B and T cells. The recent measles outbreak has debilitated the population of Samoa as many now may experience immune amnesia. Besides the general effects of immune suppression, there is a high likelihood of specific suppression by loss of adaptive immunity to common coronaviruses. Immunological memory of common coronaviruses (OC43, HKU1, 229E, and NL63) which usually only cause mild symptoms have been shown to decrease the probability of severe reaction to SARS-CoV-2 as seen in the study conducted by Dijkstra and Hashimoto. There are over 200 epitopes shared between strains which would improve the adaptive immunity response to SARS-CoV-2 and dampen the number of severe cases. The loss of memory B cells to aid in this attack due to measles-induced immune amnesia does not bode well. Therefore, it is necessary for the people of Samoa to attribute recent measles inflection as a preexisting condition and remain wary. The severity of one’s infection may be orders of magnitude worse for said reason.
The author did note that a general vaccination of common coronaviruses would not be the greatest route for production as the epitopes are matches at smaller amino acid lengths. Furthermore, the piece of SARS-CoV-2 that is most likely to induce antibody production and immunity is not conserved across the common strains. Yet, it is hypothesized that due to the prevalence of common coronaviruses, much of the world population has some form of immunological resistance to COVID-19. However, Samoa must improve surveillance to monitor the path at which SARS-CoV-2 spreads in the nation.
I do wonder what is the prevalence of adults who had contracted measles as much of Samoa’s population is not vaccinated. Since older humans mount a weaker adaptive immunity response. The loss of memory B cells, particularly those of common coronavirus strains, in adults is much more detrimental than that of younger Samoans.
Dijkstra, J. M., & Hashimoto, K. (2020). Expected immune recognition of COVID-19 virus by memory from earlier infections with common coronaviruses in a large part of the world population. F1000Research, 9, 285. https://doi.org/10.12688/f1000research.23458.2
https://pubmed.ncbi.nlm.nih.gov/32595955/
Fortino Pineda Veloz
Immune amnesia is a topic that I had not seen before, nor was I aware of its presence following measles infection. The debilitating effects it has on memory B and T cells dampens future immune response to previously encountered pathogens as mentioned in the article. In addition, it is a real threat due to its prolonged term lasting one to three years. I wonder why immune amnesia has not been broadcast to increase vaccination rates for MMR? To the many who choose to avoid vaccination, I believe this is a great discussion point.
As we enter the winter of the SARS-CoV-2 pandemic and flu season, people are on their toes to protect themselves on two fronts. The latter is nothing new. Flu shots have been marketed for years and there is public trust. The former does not have that precedent. However, those with preexisting conditions do not feel the same and are awaiting the COVID-19 vaccine. Singh, Gupta, and Misra have found associations with hypertension, diabetes, and cardiovascular disease that increase the case fatality rate of COVID-19 patients by 6.5%, 7.3%, and 10.5%, respectively. With 38% of the population in Samoa classified as hypertensive, cases may be more severe and overwhelm their health system just as measles did and may continue to due with immune amnesia.
Samoa is well below the vaccination rate necessary for herd immunity for measles with over two-thirds of the population unprotected from measles and its prolonged effects on the immune system. I believe that increasing knowledge of immune amnesia would drive this number up to mitigate future health system overloads; just as preexisting conditions have raised awareness and adherence to public health policies in the COVID-19 pandemic.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144598/
https://www.samoaobserver.ws/category/article/57857#:~:text=Among%20the%20key%20findings%2C%20the,38.1%20per%20cent%20in%202018.
Fikir Wordofa
This article was a fascinating read. This is the first time that I’ve come across the concept of immune amnesia which as the article outlined, is a disadvantageous mechanism of the measles virus to essentially wipe out protective memory cells of the immune system. The wiping out of such memory B and T immune cells greatly diminishes the protective ability of the immune system and predisposes individuals to reinfection by pathogens that they had built an immunity to pre-measles infection.
The study linked in this article shows that immune amnesia secondary to measles exposure was linked to higher susceptibility and morbidity/mortality to covid-19. This exemplifies an emerging issue embedded in the growing distrust of science and vaccines and the “anti-vax” movement.
Since 2016, according to data from the CDC, the number of measles cases are on the rise; while there were only 86 cases in 2016, in 2019 that number had grown to 1282 – a growth rate of almost 350%!
As global urbanization continues, the risk of epidemics and pandemics will continue to grow. As important as finding new therapeutic interventions will be, equally important will be in ensuring funding for education and vaccination programs to build public trust. This period of time during and post-Covid may be an opportune time to meet vaccination and education goals.
Immune amnesia that affects both the innate and adaptive immune system can usually be reversed through re-exposure to pathogens and the building up of the immune system (as stated in the article cited below). However, the danger lies in the time between when the immune system is weak and opportunistic pathogens can prevail. Therefore, the article below poses an interesting recommendation for physicians to do a round of vaccinations, especially for lethal diseases such as hepatitis or polio (region-specific) to give the immune system a boost of antibodies for its protection.
Publication referenced:
Wesemann DR. Game of clones: How measles remodels the B cell landscape. Sci Immunol. 2019 Nov 1;4(41):eaaz4195. doi: 10.1126/sciimmunol.aaz4195. PMID: 31672863.
https://pubmed.ncbi.nlm.nih.gov/31672863/
Laniece Dennis
This article does a great job of explaining how the measles disease could suppress the immune system. The resurgence of measles globally and decreased immunization rates are threatening to derail the immense progress made in fighting this contagious disease in recent years. Vaccination against this virus is estimated to have saved almost 24 million people between 2000 and 2018. With the reemergence of measles, we expect to see an increase in immune amnesia, a common side effect of the virus that weakens the immune system. A suppressed immune system makes the body susceptible to infections by other pathogens. An example of such a pathogen is the opportunistic streptococcus pneumonia, the most common cause of pneumonia.
According to Kim, Seon, and Rhee, a recent report by the World Health Organization (WHO) shows that respiratory diseases are among the top 10 causes of death worldwide, with pneumonia being the leading cause. Although most people recover from pneumonia or stop displaying any symptoms, the infection can be fatal for individuals with weakened immune systems, including infants, young children, the elderly, and persons suffering from chronic underlying conditions.
Immune amnesia infects immune B and T memory cells responsible for remembering and fighting previous pathogens that the body has successfully eliminated. This memory allows the body to produce specific antibodies that respond rapidly in subsequent infections. Unfortunately, the measles virus wipes out a large percentage of the different antibodies that protect against pathogens a person was previously immune to. Thus, when a person develops pneumonia while experiencing immune amnesia, any memory of prior pneumonia infection would have been lost with the destruction of the B and T cells and antibodies produced. Since immune amnesia could last longer than two years, according to MacIntyre, Costantino, and Heslop, people who survive the measles virus will gradually regain any previous immunity to other viruses and bacteria as they get re-exposed to them. However, the re-exposure process may take months to years, and during that time, individuals will remain vulnerable to complications that might accompany those infections. Hence, someone who develops pneumonia has an increased risk of complications that may lead to death. If they survive the disease, they will emerge with a strong measles virus specific immunity.
With that said, MacIntyre, Costantino, and Heslop’s article make it very clear why researchers are concerned that immune amnesia as a result of measles infection could increase the total number of COVID-19 cases in Samoa. The emergence of the COVID-19 pandemic closely after measles resurgence put many immunosuppressed people at risk of mortality, with the highest rate of deaths in elderly individuals over 60 years and a lower rate in younger people under 20 years.
https://pubmed.ncbi.nlm.nih.gov/28735461/
https://pubmed.ncbi.nlm.nih.gov/33028283/
Stephanie Michael
Laniece,
Great job providing streptococcus pneumonia as an example to explain how measles-induced immune amnesia leads to increased susceptibility to infections. By doing so, you effectively highlighted how disruptions in immunological memory provide a mechanism where easily contractible pathogens, like the SARS-CoV-2 virus responsible for COVID-19, can lead to severe infections. A study completed in Jiangsu Province supported this by showing co-infections to be a dominant attribute to patients with COVID-19. The study highlighted streptococcus pneumonia, Klebsiella pneumonia, and Haemophilus influenza as the most prevalent bacterial co-infections in COVID-19 patients. With the onset of 1 – 4 days, results indicated an increased co-infection rate amongst patients between the ages of 15 – 44 and a decreased co-infection rate for patients younger than 15 years old. The study tested patients for viral, bacterial, and fungal co-infections; however, 91.8% of patients indicated a bacterial co-infection.
The COVID-19-bacterial co-infection is made possible through a mutualistic relationship. In specific to bacteria respiratory co-infection, the SARS-CoV-2 virus invades the lungs and initiates an immune response. The virulence factors invade innate immune cells causing comprised innate immunity. For example, invasion of SARS-CoV-2 leads to increased susceptibility to bacterial infections through the decline levels of type I IFNs. If the patient has been exposed to bacteria, such as streptococcus pneumonia, the compromised innate immunity allows for the increased attachment, growth, and dissemination of the bacterial. Thus, bacterial infection becomes prominent and enables the flourishing of the SARS-CoV-2 virus. Bacterial colonization compromises the innate immune host defenses, such as inflammation, granulocytes, co-stimulatory and co-inhibitory molecules, and dendritic cells, by decreased host defense signaling activation. For instance, Klebsiella pneumonia infection decreases activation of NF-K8-governed responses while other bacterias induce type I and III IFNs. Research indicates that the IFN gene stimulates the ACE2 receptor on the SARS-CoV-2. As a result, SARS-CoV-2 infection thrives from the bacterial infection’s influence on the virus’s survival, replication, and pathogen. The overall consequences of the co-infection include tissue damage resulting from elevated inflammatory responses.
Therefore, I support your claim on why researchers are concerned about the measles outbreak in Samoa and other parts of the world. From the article above, measles was identified to induce immune amnesia, which leads to an increased risk of severe COVID-19 illnesses. 21% of patients infected with the SARS-CoV-2 were found to be co-infected with respiratory pathogens. Co-infections have been confirmed to increase illness severity and mortality. If a previously or currently infected measles patient has immune amnesia, the opens up the window elevated risk of developing co-infections. As a result, there is a possible chance that disease severity and mortality rates could increase. Also, there is an increased risk of spreading infections other than COVID-19. This proves to be problematic for countries dealing with measles and COVID-19 outbreaks as now researchers will have another mission on their hands.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213959/pdf/main.pdf
https://www.embopress.org/doi/pdf/10.15252/emmm.202012560
https://jamanetwork.com/journals/jama/fullarticle/2764787
Ray Kinney
Some of recent research into Covid 19 treatment using ivermectin might help clarify some protective mechanisms of action for immune memory? Likely, the huge public health push toward advancing Covid 19 protection via prophylactic boosts to immune system abilities may soon include clarification of efficacy of inexpensive generic drugs suitable for public health gain in all countries.IMHO
Ali Nayebi
This article describes how the measles virus can contribute to the phenomena known as immune amnesia. The virus that causes measles functions by targeting cells of the immune system and is most prevalent in an individual’s upper respiratory tract. This virus can also quickly duplicate and travel to other organs in the immune system through the CD150 protein. What would happen if an individual is born with asthma, and they come into contact with this virus? How would their overall immune function and breathing capability be affected while being infected with this virus? My best assumption is that the child, or anyone with respiratory illnesses or conditions, is most vulnerable to further infections. Since the breathing capacity and function is hindered due to asthma, the individual could become more susceptible to other pathogens entering their respiratory system and further damaging their immune system. That being said, I am not sure as to the extent to which age demographic is the most vulnerable. I am not aware of the age breakdown by population in Samoa, but those with a weakened or not fully developed immune system will likely be at the most risk if encountered by the measles virus. This brings it all back to Memory B cells and T cells. These cells of the immune system help by remembering pathogens that have been previously destroyed by the body and are not foreign to the immune system. Memory B cells can survive for an extended period of time and function by developing an antibody-mediated immune response in the situation where re-infection may occur. That being said, the measles virus has a unique ability to cause immune amnesia in an individual, causing their respiratory system to be in danger. We can only hope that future research can be conducted into how the immune system can recover if it undergoes amnesia. Maybe a study can be done to compare those who have been vaccinated with the measles vaccine and compare their immune system to those who have not been vaccinated.
For example, a study conducted in the Netherlands showed how a measles outbreak occurred in an orthodox protestant community that did not vaccinate themselves on the basis of their religion, which led to over 2,500 cases. The researchers in this experiment wanted to understand the pathogenesis of the immune suppression function of measles in those children who were not vaccinated in this community. In 2018, Brigitta M. Laksono and Rory D. de Vries described how the mononuclear cells of the measles patient had CD4 and CD8 memory cells that were infected and infected memory B and T cells. In the samples that they collected, de Vries and Laksono described how they noticed a decrease in the frequency of memory B cells circulating in the blood and an increase of regulatory T cells in the blood in patients after they contracted measles. Through here, it is determined that the measles virus is mediated by memory T cells that are infected and that those patients who become infected with the virus undergo a change in the number of lymphocytes in their body. To conclude this, we can see the effect that immune amnesia plays in the body and how it can severely hinder and sometimes inhibit the function of valuable immune cells that perform a daily function. Immune Amnesia can affect any individual, regardless of their age. Still, it would be very harmful if they contact the measles virus and are not vaccinated to protect themselves from it.
https://pubmed.ncbi.nlm.nih.gov/30470742/
Laniece Dennis
Ali,
You did a great job of describing how immune amnesia puts the respiratory system in danger. As it relates to future research into how the immune system may recover from immune amnesia, the article by MacIntyre, Costantino, and Heslop explains that the immune system could be compromised by immune amnesia for over two years. During this time, a person regains immunity to various infections as they become infected with said infections. However, the process of reacquiring new immunity and recovering those destroyed antibodies may take months to years. I would assume it may take years for most people because they might be scared of the risks involved in getting a disease or infection when their body is unable to fight it at full strength. Of course, the greatest risks of these diseases and reinfections are complications that might lead to death. I think a safe way to help rescue a person’s immune system from immune amnesia would be to get revaccinated for the diseases as a child would during his/ her lifetime. I think this would give the immune system a boost and decrease death chances during reinfection by some of the milder pathogens.
Another option that came to mind for the treatment of immune amnesia, at least until the immune system is fully recovered, is immunoglobulin (IG) therapy. In their review article, Johnson and Hollingsworth detail that IG therapy contains antibodies IgG, with small amounts of IgA and IgM, which can be used to treat patients with primary and secondary immune deficiency diseases, autoimmune and inflammatory conditions. Na, Buckland, and Agnostini explain that secondary immunodeficiency (SID) is caused mainly due to other diseases or side effects of medical treatments. Since immune amnesia occurs due to measles infection, it would be considered a secondary immune deficiency. Immunoglobulins or antibodies aid our immune system in destroying pathogens. Thus, in a person who is not producing sufficient immunoglobulins to protect them against infections, like those inflicted with immune amnesia, consistent IG therapy should provide a safeguard until their immune system is strong enough to provide that protection.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297324/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539273/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849602/