 It is frequently heard; we are vaccinating so much. Is it too much? Sometimes accompanied by emotional images of a baby full of needles. What are the current facts and are we vaccinating much more? And if so, is it too much? Every country will have different vaccination schedules, so the numbers of vaccines may differ a bit from country to country and are not absolutes. (The childhood vitamine K shot is not a vaccine, the importance of providing vitamine K can be found here.) We, and of course our kids, are constantly exposed to thousands of germs every day. This happens through the food we eat, the air we breathe, and things that our kids especially put in their mouth. This non-pathogenic exposure to germs is healthy and contributes to a well-developed immune system. However, exposure to pathogens is unwanted: there is always a risk, and you really do not need to get ill to become healthier! That would be a very incorrect interpretation of the hygiene hypothesis. Why vaccination? We are born with an immune system: it is there, it develops, we do not need to interfere. That is all correct in a healthy person. Our immune systems are amazing and protect us every day from attacks. It can fight most pathogens. However, for some of the pathogens we are at elevated risk of encountering, and they are serious. These can cause actual harm, even death. The reason for this can be complex and depend on the attributes of the pathogen. For example, a pathogen can be very quick, outcompeting our slow adaptive immune system that requires 10-14 days to get up to speed. The pathogen can be evasive and trick our immune system by changing its antigens frequently. Just when your immune system is mounting a robust response, the antigens that it recognizes are no longer on the surface of the pathogen, but it has completely changed them! The malaria causing parasite, Plasmodium, is an example of a pathogen that does this. Other pathogens are not dangerous themselves but contain a highly dangerous toxin that in tiny amounts is rapidly detrimental to our health. It short, in all these cases our immune systems can benefit from help! That is the reason vaccines are strongly recommended; they prepare our immune system to be faster and better when those pathogens are encountered! Vaccines contain tiny amounts of antigens. An antigen being anything that your immune system can recognize. What do those antigens do? The antigens are presented to your child’s immune cells (B and T cells), the immune cells your child already has made and will be making throughout most part of the adult life as well. The antigens do not "do" anything, do not "make" anything. There are specialized cells, cells that are eating and digesting antigens the entire day and display these at their surface. This is part of your normal "self-checks". The most of these antigens are from you, bits, and pieces that you need to make in the cells of your body. Your immune system is trained not to recognize these. But, pathogens, and thus their bits and pieces in a vaccine, are not you! Your amazing immune system has the capacity to recognize all that is not you; Yes! Really everything, even if it comes from outer space; your immune system will have cells that recognize it. But there is the catch! Few cells. You only have a limited amount that can recognize a new antigen. The reason is that you make sufficient B and T cells to be prepared for unknown infections. To catch them all: you make B and T cells, but very few that recognize the same antigen. You will not know if you will ever need that B or T cell if you will ever encounter that antigen. We are prepared for everything, but with lesser amounts. So, the antigen in a vaccine, when presented, will select those few cells that recognize this, and only this, antigen: of course, the same antigen that is also part of the pathogen that can cause harm! The selected B and T cells will stimulate you to generate more of them and store them. That is a neat trick! Your immune system has understood that these cells recognize something you have encountered: therefore, you may encounter it again! These cells have proven to be useful for you. Therefore, you will make more, via cell division, and store sufficient in a compartment we call the memory compartment. Having more cells makes you more powerful against an invading pathogen. But that is not all. The immune cells mature; they function better and faster. T cells will develop specialized functions they did not yet have they can now help other cells much better and faster, they can kill infected cells much better and faster. B cells, which make antibodies, will have chosen a better isotype with dedicated functions (IgG, IgA, etc.), they will even have mutated the antibodies to fit the antigen even better. Upon re-encountering the antigen, they make these antibodies super-fast! This is how you strengthen the immune system, like encountering the pathogen itself, using the same bodies and cells, but without the danger of not controlling the pathogen! If we look at children under 2 and take the US CDC numbers. They have nicely compared the current vaccination schedule with that a generation ago, in the 1990s. The previous generation received fewer vaccines, protecting against 8 infectious diseases. These were more complex vaccines, containing over 3000 antigens. These vaccines were certainly good and safe, but there was still room for improvement. Scientific work over the years has made more detailed insights into our immune systems, and our technological progress has allowed new materials to be made and produced at a large scale. The under two years old of today get more advanced vaccines, protecting them from 14 infectious diseases, but they contain only about 300 antigens. So, their exposure to new antigens is much less, their immuun system concentrates more on fewer antigens. This is not necessarily good or bad, it just means a more targeted approach with fewer ingredients. The ingredients can cause confusion. Vaccines, like any medicine or food, have many ingredients. All are there for a reason! - Ingredients are added to stabilize (Stabilizers) the antigens, so the vaccine can be stored for a longer time and at higher temperatures. These are commonly found in: food products or naturally in the body and most frequently are: Sugars or gelatin. - Other ingredients protect against growth of bacteria (Preservatives), again commonly found in food products, and naturally found in fish: frequently used is Thimerosal in flu vaccines. - Exceptionally low levels of residues from vaccine production can be found in vaccines. There are maximum limits of these set by the national authorities. These include antibiotics from keeping the manufacturing process sterile (antibiotics from the penicillin family are not used due to risk of allergic reactions), cel culture materials such as egg residue (allergy danger), and reagents to kill viruses in inactivated vaccines such as formaldehyde (found naturally in your body, in fruit). Deserving special mention are adjuvants. These are compounds especially needed to activate the innate part of your immune system; to mimic there is a pathogen that is dangerous! This important and is a part that determines how well a vaccine works. They can be parts of a pathogen, such as lipids, or even RNA will be a good "danger" signal that alerts your immune system that action is required. Several are found in our surroundings such as drinking water, infant formula, others in health products such as antacids, buffered aspirin, and deodorants. A (in)famous example are aluminum salts. A list of adjuvants in different vaccines can be found here. Aluminium salts are added to specific vaccines in small quantities. This is to strengthen the robustness of the immune response due to the ability of aluminium to slowly release antigens. This results in a more prolonged antigen exposure which increases the response. Aluminium for example, a common metal found in air, water, and food, is not readily absorbed by the body, this is exactly the characteristic for which it is used. Several of the more recent vaccines do not rely on additionally added adjuvants because these are attenuated virus vaccines or vector/mRNA vaccines; these include: Chickenpox, cholera, COVID-19 (mRNA Pfizer-BioNTech, mRNA Moderna and adenoviral Johnson & Johnson/Janssen and AstraZenica), dengue, Ebola, Hib (ActHIB, HIBERIX), measles, mumps & rubella (MMR), meningococcal (Menactra, Menveo, MenQuadfi), polio (IPOL), rabies, rotavirus, seasonal influenza (except Fluad and Fluad quadrivalent), smallpox and monkeypox (ACAM2000, JYNNEOS), Typhoid, yellow fever, zoster live (Zostavax).  Is there such a thing as too many vaccines?
It is clear from the table above; we do vaccinate more. Once there was only smallpox, now other dangerous infectious diseases can be prevented, notably measles, rubella, tuberculosis, hepatitis B, polio, diphtheria, tetanus, pertussis, Hemophilus influenza, Pneumococcus, rotavirus, and human papillomavirus. One is excused to think we are at danger to overload our immune system. But there is no truth in this. Once more I need to refer to how amazing the system is. It has billions of B and T cells, and they mostly each have a different antigen they can recognize. It is present from birth, it is active from birth, and it can multitask! The birth canal gives the first large encounter with bacteria, once delivered into the world, the infant will be immediately targeted by microbes. The outer surfaces such as the skin and the intestine, but also the lungs, will be colonized rapidly. And yes, the little one will manage the onslaught of all these microbes very well: it has an immune system. This highlights that a few vaccines, or 5 at the same time, not an issue is at all. One can make calculations how many antigens, and epitopes (the parts of an antigen that is actually recognised by a B or T cell) are in a vaccine, how many cells are required to be activated and produce antibodies above the threshold to neutralise a pathogen. Such an approach would indicate that our immune system can deal with 10.000 - 100.000 vaccines at a time. So, 5 or 20 vaccines is a small fraction: it is of no concern. Of course, we do not base healthcare only on calculations, the simultaneous administration of vaccines has been studied, and shown to be both efficacious and safe (1, 2, 3, 4, 5, 6, 7), and the basis why many are even provided in a single vaccine shot (e.g., DTP and MMR). So, multiple vaccines, as in use, really do not overload your immune system. Now, you could still claim that it may weaken it. But also, that would be incorrect. Large cohort studies have shown that multiple vaccines have no detrimental effect on for example the frequency or severity of illnesses from non-targeted infections (1, 2): i.e. There is no adverse association between an increasing number of vaccinations and infectious diseases. To conclude, yes, since the first vaccine against smallpox, the number of vaccines has increased. This has much reduced infectious diseases, childhood mortality, and the resulting health issues in the adult population. The increase in vaccines, which have been improved over the years, has had no negative effect, for healthy individuals, infants, or adults. There is enormous capacity of our immune system to deal with multiple stimuli simultaneously. There is no limit demonstrated for a maximum of vaccinations, with respect to their efficacy and any immune effects against non-targeted disease. It is likely that such a limit does not exist.
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After all the anti-vaccine noises in especially the last two years, are now even the vitamin K shots for newborns questioned again. The only correlation is that both are given intramuscular and via a needle.
Newborns can be very susceptible to a potential life-threatening condition called vitamin K deficiency bleeding (VKDB) or Hemorrhagic Disease of the Newborn. This can be a problem for all newborns and in the age range from birth to approximately six months of age. Without vitamin K, an essential factor in blood clotting, administered at birth the mortality rate is as high as 20%. Humans cannot produce vitamin K, it is obtained from vegetables and the activity of bacteria in your gut. Newborns cannot be given vegetables and hence, may be in short supply. Furthermore, the bacteria needed to produce vitamin K, E. coli, are not yet present in newborns, who have a quite different composition of gut bacteria due to a hugely different diet of milk. Vitamin K also does not pass into breast milk at high enough levels to treat neonatal deficiencies. In other words, the first shot of vitamin K can really be the main source of vitamin K in the first months of life. There are some known risk factors. 1) If Vitamin K is not preventatively given via an intramuscular injection at birth 2) Especially for exclusively breastfed babies. Although breastfeeding is beneficial and highly recommended, it contains less vitamin K than formula milk. 3) Babies from mothers that are on medication that reduce blood clotting or take anticonvulsants (against seizures). The supplied vitamin K is made by bacterial fermentation, the same way it is generated in our own intestine. All proteins, or enzymes, which need it, recognize the same vitamin K. Vitamin K2, the synthetic form, also occurs naturally. Unlike K1, it is fat-soluble and hence the baby's body can store it and use this deposit for the following months. In other words, there is no difference between the “natural” molecule and the so-called "synthetic" molecule. Anyone making such claims is misinformed. Such claims can be huge red flags of dishonesty. Misinterpreted warnings There are warnings on all medications. For Vitamin K, a black box warning refers to things such as the small risk associated with a large dose of it given intravenously to very rapidly reverse coagulopathy. This does not apply and is not of relevance for the much smaller dose of intramuscular vitamin K provided to newborns. The route of administration matters a lot too! The formulation of the vitamin K shot does, of course, have some other ingredients. Uptake of vitamin K and its storage need some help. Two main ingredients are Polysorbate 80 and Propylene glycol. Although Polysorbate 80 can affect the blood-brain barrier, it takes a HUGE IV dose delivered to the blood vessels in the head. There is no reported effect on the brain or neurotoxic effects https://medisca.com/NDC_SPECS/MUS/0526/MSDS/0526.pdf Propylene glycol also has no mention of neurotoxicity, and claims otherwise are again huge red flags of alternative agendas and dishonesty, http://ciscochem.com/assets/propylene-glycol,-industrial-sds.pdf For more information, I refer to these three resources: https://www.chop.edu/conditions-diseases/vitamin-k-deficiency-bleeding-hemorrhagic-disease-newborn https://publications.aap.org/pediatrics/article/149/3/e2021056036/184866/Vitamin-K-and-the-Newborn-Infant?autologincheck=redirected https://evidencebasedbirth.com/evidence-for-the-vitamin-k-shot-in-newborns/ The maintenance of cells with a proven record after an infection is one of the pillars of the adaptive immune system. It is, one could say, the most key role of the adaptive immune system. The cells of the adaptive immune system are B and T cells. Both cell types make their own receptors with which they can recognize pathogens. Importantly, these receptors are not directly found in your DNA. You do not inherit them from your parents, like you do with receptors from innate immune cells. Adoptive immune cells make their specific receptor in a complex way of cutting and pasting gene parts, adding and deleting pieces at random, to eventually end up with a receptor. Extremely important is that each cell, for understanding the basics, harbors one receptor. That is, one receptor is eventually encoded for that cell, the cell will have many of these present on its surface. Making receptors at random has huge advantages, no matter how new a pathogen is, how much it changes, you will always have some cells that will recognise that pathogen. This is extremely powerful. The billions of T and B cells can collectively really recognise everything! But, making receptors at random has pitfalls. Many are not of use at all, the worse that cannot be of use do not become part of the collective repertoire in your body. Others will recognise parts of you! That can give autoimmunity, and hence cells with such receptors will also be negatively selected to die and not be part of the circulating cells in your body. It still leaves billions of cells. Yet, the vast majority of those are also not of immediate use. The motifs (antigens) they recognise you may never encounter, and hence the turnover of T and B cells is high. Many die every day; you generate many new ones to replace these. This goes on till old age, although the rate of new cells added is slowing down with age. Helpful review here.  There is another problem; you have billions of cells, but few that recognise a given pathogen. This is the reason that adaptive immunity is slow, 10-14 days until it is a bit up and running, with maturation of it that can take many months. Maturation is in large part the refinement of the response, making increasingly better antibodies by, at random, mutating the B cell receptor genes. The B cell receptors, when secreted, are called antibodies. By mutating the antibodies, and a complex system of different B cells competing for the same antigen, there is a process of mini evolution going on in your lymph nodes. The result is antibodies with an incredibly high affinity and specificity. Those T and B cells that do recognize a part of a pathogen, and help you clear it are unbelievably valuable. These have proven that they recognize a pathogen you have encountered and can get infected with again in the future. Hence, you really want to keep those! These cells will become part of your memory compartment. This compartment is independently regulated from all those cells that have never encountered the antigen they have a receptor for (the naïve cell compartment). The size of the memory compartment is also not infinite, regulated by physical space and survival cytokines such as interleukin-15. This does mean that there will be some loss over time. Unfortunately, this loss is the highest in old age. This, combined with a reduced naïve compartment, makes the elderly more susceptible to infections. Any infection. The fact that memory cells can recognize a pathogen that you may encounter again is useful. But that is only part of the story. Remember the billions of naïve cells, most with a unique receptor. You have very few that recognize the same antigen. In the memory compartment you save many with the same specificity. So, you start the next infection with many more cells to rely on. This will give you much advantage to contain and clear the pathogen. In addition, memory T cells adhere to different rules. They can be activated much quicker. They migrate to the site of infection fast, within a day often. Many are already there and patrol the regions where you first encountered the infection! Their functional capacities do not need to mature, the transcriptional program is already determined and active: the result is an extremely fast response, a day or 1-4, well worth keeping! How do we know about memory cells? Many experiments and studies have been performed over many decades to gain many insights about memory cells. A lot, on the molecular and cellular level, has been done in laboratory animals, especially mice, but also rats and non-human primates. In humans, many of these obtained insights have been reproduced and observed to hold very well. I will give a brief overview. Some good examples here show the existence of a memory compartment in humans, with effector functions, as initially obtained from mouse studies. These cells have many of the same molecules on their surface (markers) by which immunologists can recognize and classify the memory cells and study their functionality. Here you see what happens if you activate naïve T cells (a) and see how much of the important cytokine IFNg they make, compared with memory T cells (b) at the same time.  A particularly helpful review of the state of the field in 2004, can be found here.
In human we can find memory cells against many of the pathogens that regularly infect us, such as Candida albicans and Mycobacterium tuberculosis, Hepatitis C virus, HIV and CMV, and of course many others such as those vaccinated against. Influenza is a prime example where elderly respond weaker, due to a complex array of issues that hamper immune responses. Therefore, is a vaccine so important, to prepare much better for any potential infection. However, not everyone will respond robustly enough. Also, antibodies can easily be detected in blood. Although their levels drop and active production may come to a near halt, a boost will very rapidly increase these to extremely elevated levels: it is the memory B cells that are responsible for this. This can be done for all vaccines for example. With some especially relying on this response to provide disease protection even after contact with a pathogen (e.g., Tetanus). COVID-19 There are stories circulating on social media to cause confusion about our protection against SARS-CoV-2. Some people, even several that should know better, make claims of uncertainty about the memory we build up against SARS-CoV-2 and how long it will last. Claims are accompanied by false statements about not knowing how memory T cells are maintained and the absence of data on memory cells from other infections. This is shameful; there is no reason to assume SARS-CoV-2 is dramatically different from all those pathogens, it has not behaved particularly different to most other pathogens. https://www.thematic-ai.eu/prof-marc-veldhoen/sars-cov-2-new-and-familiar Furthermore, we know that memory cells last an exceptionally long time. First, the vaccine and the virus will generate an immune response. An immune response severe enough to recruit B and T cells, to activate them, and hence, to generate a memory response. We know all of that, it was tested in mice and non-human primates. Of course, it was confirmed in humans. In September 2020, very good T and B cell response. Subsequently a flurry of papers showing good B and T cell responses and memory responses. https://www.nature.com/articles/s41586-021-03791-x https://www.nature.com/articles/s41564-022-01106-y https://www.science.org/doi/10.1126/scitranslmed.abi9915 https://www.science.org/doi/10.1126/sciimmunol.abm8389 https://www.science.org/doi/10.1126/science.abm0829 https://www.science.org/doi/10.1126/sciimmunol.abl5344 https://www.sciencedirect.com/science/article/pii/S0092867422000769 Memory cells have been studied over time in humans too. The most famous is the response after the Spanish flu in 1918, with memory B cells still capable of producing neutralizing antibodies detected in 2008, 90 years later! And of course, SARS is the most recent example of a similar virus, present at least 17 years later. And we know, these cells respond quickly. B cells make antibodies very rapidly, memory T are recruited to the site of infection and do make all the difference to contain and clear the virus. In other words, SARS-CoV-2 has provided us with immunology in real time. It has once more confirmed all those principles and aspects of our immune system we have been studying for decades. It is a textbook virus with a textbook response. This also counts for the memory response we generate, maintain, and will rely upon successfully to fight SARS-CoV-2 infection. SARS-CoV-2, the coronavirus that is the cause of COVID-19, is new but also familiar. What we have seen in the past 3 years is virology and immunology in real time unfolding. SARS-CoV-2 has behaved much as we expected it to behave. The route of infection, the cells its infects, its transmission, replication, in large part its evolutionary path, its selection criteria, the epidemiology, the way the immune system detects it and responds, the antibodies that bind it and wane, the T cell response that stays, the reinfections, how to detect it, and how to target it with a vaccine, did not hold much mystery. We knew much, expected most, but certainly not everything was and is understood! Let´s start with some statements to avoid confusion:
We know a lot about viruses and immunity. What we have seen happening in the past three years is infection and immunity in real time. Not only that, but we have also seen much of what was predicted from decades of study of viruses and the immune system. SARS-CoV-2 has confirmed a lot of the things we know. That does not mean there were totally no surprises, it does not mean we should not have studied it and it certainly does not mean we know all there is to know. There are major gaps in some things. But overall, SARS-CoV-2 and the immune response were textbook. This will need explanation and quantification. Let´s start with the virus. Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the cause of coronavirus disease 2019 (COVID-19) is a strain of coronavirus. Coronaviruses are not new; they are enveloped positive-sense single-stranded RNA viruses with a large genome. Many strains are found in many hosts. Hosts include bats, farm animals, pets and yes, humans. The name, corona, comes from the Latin for crown, thanks to their distinctive crown-like look.   The original observation, the discovery of human coronaviruses, happened in 1960 by June Almeida and David Tyrrell, after developing novel culture methods enabling the propagation of this respiratory virus. That is over 60 years ago, and much has been discovered since. But the earliest descriptions of coronavirus disease are over 100 years ago, in the 1920s, of respiratory disease in chickens, infectious bronchitis virus (IBV). The first corona cold virus was named 229E, OC43 followed with NL63 and HKU1 later discoveries, and together making up the 4 human coronaviruses that give common colds. However, as stated above, do not think too lightly of these viruses. You are exposed in early life to these, when your immune system makes a strong innate response (interferons, IFNs) protecting most of us against these viruses. This will enable the generation of memory B and T cells over time, providing life-long immune protection. Yet, as so often, in old age many systems start to fail. Our immune system is no exception and the risk these viruses cause can be life threatening. These coronaviruses are seasonal and have characteristic annual waves. Although common, its contribution to mortality in children and the elderly is much less known. Much of their molecular workings, the proteins they use, are known. That includes Spike proteins, critical for all these viruses to gain cell entry. The Spike of NL63 has the specificity for our host receptor ACE2. Their detection and identification, yes, using PCR. Coronavirus infection results in hijacking the host cell protein and metabolic machinery, eventually causing cell stress and cell death. Hence, HCoV-229E, -OC43, -NL63, and -HKU1 are considered pathogens, causing upper, and lower, respiratory tract disease and responsible for up to 15%–30% of common colds in adults. In addition, enteric coronaviruses also exist and can cause gastroenteritis and intestinal infections. Of course, most well-known are the SARS and MERS coronavirus outbreaks in 2002 and 2013. These provided a renewed impulse to more detailed investigations into coronaviruses, their pathophysiology, and the design of the first vaccines. In other words, a lot of knowledge about how these viruses operate. Do we know everything? No, of course not. Is every coronavirus the same? Also not, each has their own characteristics. But, in broad terms, the scientific community, especially virologists, know a lot about viruses and coronaviruses. SARS-CoV-2 is hence not an unknown entity. i.e. it is a coronavirus. We know a lot about coronaviruses. This general knowledge has been held up very well. The virus mutates, some recombination is possible, it has abilities to reduce immune detection (reduced expression of HLA-1, reduction of detection by innate receptors and IFN production), but it does not escape detection. It does not go latent (long-term infections in immunocompromised does happen), it does not integrate in our genome, it does not attack or kill B or T cells, etc. Yet, that does not mean it was not dangerous, or that we knew everything. It was new on another level. So, SARS-CoV-2 is not an exception compared with other coronaviruses. Its infection in children is often, but certainly not always, mild. IFN responses are strong and the adaptive response is not relied upon as much, but certainly starts to participate and will provide, over several exposures, good immunity. Infection of vulnerable people, those with reduced immune responses, can have severe consequences. These include the elderly. But with an immunologically new virus, we are all vulnerable. SARS-CoV-2 caused many victims, not only via mortality but also long-term damage (LongCOVID) to our tissues and systems. Some explanation required again. People are diverse, a complex interplay between the host, its health status, much is genetic, and the pathogen can give wide-ranging outcomes. These include long-term problems, associated with many infections, referred to as "idiopathic" or in plain English; "we are clueless what causes it". They are the consequence of the host - pathogen interaction and a variable that is not understood. This is a knowledge gap, but not SARS-CoV-2 specific. However, we are now very much confronted with a new wave of long-term consequences, due to the COVID-19 pandemic, and it would be great if progress can be made to understand this much better, identify the risk factors and, in the best case, find treatments if not cures. But be aware. This is a complex issue, which takes time and resources. Also be aware this is not SARS-CoV-2-specific. SARS-CoV-2 has no magical properties, does not do something particularly scary that other pathogens, especially coronaviruses do not do. Sure, we only recently could establish, it was suspected for a long time, that EBV infection can indeed cause multiple sclerosis; that measles can wipe out some of your B cell memory cells. i.e. we discover new aspects; we are better and better at doing this with recent technologies. There are things about SARS-CoV-2 we do not know much about. But, for most things it is a textbook virus. Hence, it is better not to get infected, but, after obtaining immunity and not having underlying conditions that make you particularly vulnerable, infection will be overcome, mostly without additional consequences. Again, like most infections. Every autumn and winter, you will be infected with many pathogenic viruses. SARS-CoV-2 will highly likely become one of them. It is also true that from all the other viruses and infections of causes we do not know everything there either. Yet, all those victims and the substantial amounts of long-term consequences, SARS-CoV-2 is a new virus, a new virus to our immune systems. Although I have argued that we know a lot about SARS-CoV-2, that knowledge is in books, papers, the internet and in the collective brains of scientists. Our immune system does not have that knowledge. Yet, it is not clueless either. This needs again more explanation. Our innate system has many receptors that are inherited from generation to generation and can detect and recognize conserved elements of pathogens. This, conserved elements, means structures our own cells do not make. Some sugar or fat groups, the way DNA is packaged or the presence of RNA where it should not be. Our innate system, although never, ever having seen SARS-CoV-2 before, will detect it and, importantly, will identify it as an RNA virus we need to deal with as quickly as possible. Depending on the dose you received, your age, your genes, you may even deal with the SARS-CoV-2 infection and be asymptomatic. For the vast majority, it will require more reaction. This is normal for these types of viruses. They are extremely fast and can overwhelm our innate immune system. Also, with the 4 common cold HCoVs, you experience symptoms, and you need more than your innate system. Here is where you need the adaptive part of your immune system. Textbooks will have a strict divide of innate and adaptive immunity. That is for educational purposes, the two arms are very intertwined. Of course, B cells (that make antibodies) and T cells play their specific role in fighting infection. But they also support and strengthen the cells of the innate system. e.g., antibodies bind to the virus, making it easier to detect and for cells to "eat" it. Both B and T cells do not make use of inherited receptors but uniquely make new ones. Each T or B cell has generated a unique receptor, collectively the billions of cells will really be able to recognize anything, no matter how new or strange. T cells will boost those eating cells (macrophages) so they work harder en better. Of course, B cells also make neutralizing antibodies, these can even prevent infection. Other antibodies target infected cells for cell death (ADCC, NK cells). The generation of antibodies is a complex process we know a great deal about, and ideally also requires the help of T cells. T cells in their turn can kill infected cells, thereby limiting the spread of the virus. All this is indeed textbook. It is also textbook that we can prime the adaptive response using vaccines. That Spike protein is important, it is the only protein against which neutralization of infection is possible. This is the reason that vaccination was considered so important. To allow a much improved innate and adaptive response against infection with SARS-CoV-2. Without this, some people would be asymptomatic, several would get severely ill, and some would die. With vaccine-induced immunity, the same B and T cells acquired after infection, this disease spectrum shifts towards much less severe disease and mortality. The data shows, textbook, that it worked. No, this does not mean that nobody gets severely ill, remember that there are always some people susceptible: due to disease, medicine, old age, or genetics, and we have been at the beginning of this immunity build up. It just happens very much less and will end up being in line with other infections. It is just that SARS-CoV-2 is studied in such detail that we may not realize there are many other infections doing something remarkably similar but are not assessed at the same level of detail and many therefore appear less frequently. No, it also does not mean you will not get infected. This is something that is difficult for many people to understand. You will be regularly infected. That is again, textbook. SARS-CoV-2 behaves just like other coronaviruses, very much like other respiratory viruses: it must be quick and adapt to our immune responses. Every virus will have to infect to replicate and remain in the population. SARS-CoV-2 is not different. It has the main selection criteria to do so: speed, location, and mutations. Speed is important: it will infect and start replicating very vastly, with, like other respiratory viruses, symptoms of inflammation within days. This contrasts with measle virus, which has an incubation time of a good week (8-10 days to complete its life cycle of replication deep inside our bodies). Once immunity has been gained, it will respond very swiftly, well within a week, so you may not notice that you have been infected, and viral load has remained low, without giving any symptoms. For respiratory viruses, your response may be very quick, quick enough to avoid viral dissemination from the upper airways to the lungs or other organs (chance of severe disease), but the infection will have taken hold, just on the surfaces of your upper respiratory tract and you can transmit viable new virus particles. Secondly, it is an RNA virus. Mutational space is not as broad as influenza, which relies on two proteins, NA, and HA, but much more than measles virus. Initially, the virus adapted to us humans, beter binding to ACE2, infection, speed, and some interference with innate responses (all predicted). But there will be an optimum reached. The gear change in infection and speed of the Delta variant was an unexpected one; requiring a third vaccine dose to ensure more optimal immune responses. Secondly is the mutation selection to reduce neutralizing antibodies, a difference with measles that has much less space to do so. This will give the virus more potential hosts and time to infect. This cannot be stopped, although the mutational space here will subdue a bit as well. There are areas within Spike that are not easy to alter due to functional and structural needs. It also cannot be stopped due to the nature of our own response: antibodies wane. They always do, no matter the vaccine or infection. On the short-term vaccines can prevent infection, reduce the chance over the mid-term, but they cannot stop it. You need constant vast amounts of antibodies to prevent respiratory virus infection and transmission. But you can prevent severe disease. Because SARS-CoV-2 was new to our bodies: the immune response can be severe, such as cytokine storms. The response compares here well with a new strain of influenza. The acute response can be damaging to self in severe cases. Similarly, a temporal sensitivity to co-infections, bacteria, or fungi, can be seen. This is again to be expected to the naive immune status of adults, never having seen SARS-CoV-2 before. There is yet another layer of complexity, mucosal immunity. Although B cells cannot continue to pump out substantial amounts of antibodies systemically, if all B cells would do that your blood with be a thick syrup, at the body´s surfaces, they can do this for much longer. But the cells that do this, plasma cells, will also die. There are specialized T cells, which can integrate at the site of infection, called tissue resident memory T (Trm) cells that can give immediate protection against infection. Without memory T and B cells, without immunity, the virus can be too quick to control and reach all organs in the body, with severe damage and pathology, therefore. This means that hybrid immunity, vaccination, and infection, offers the best protection against infection, around 8 months. The 8 months infection protection is not dissimilar to our protection against other respiratory HCoVs, and, once immunity is synchronized, dictates a more seasonal pattern of SARS-CoV-2 infection. Again, that is textbook, but does not mean it cannot change from year to year, e.g., the RSV wave was in the summer of 2022, not that it cannot transmit out of season! We monitor SARS-CoV-2 a lot, e.g., via wastewater, which we do not do for other infections, which are around throughout the year, just at low transmission levels. There was no seasonal pattern for SARS-CoV-2; it was new for our immune systems. It could infect so many people with so much ease, it did not need more optimal conditions for infection. Yet, there was a gap between the March/April outbreak, and the subsequent autumn outbreak, the second peak caused by Alpha variant, causing many victims prior to vaccine roll out. There was a summer peak caused by Delta, with relative limited impact in counties' already with a high vaccination grade, but severe in others (e.g., India). Subsequently, there was the Omicron outbreak at the end of 2022, followed by rapid selection of subvariants later in 2022, such as BA.5. It has remained quiet since, in part due to less testing. Although wastewater analysis shows more distinct peaks, hospital records show the huge clinical impact of immunity.  In summary, SARS-CoV-2 is not an unfamiliar virus as far as our knowledge is concerned. It was a new virus for our immune system, but also that phase has passed. SARS-CoV-2 is adopting to a seasonal pattern, from the start in 2020, but due to its immune-novelty, and measures taken, that pattern is a bit more distorted yet. SARS-CoV-2 has gone endemic, we will be regularly infected. As we had written in 2020. It is important to note that "endemic" or "seasonal" does not imply dangerous or mild. It is and remains a pathogen that can cause damage and death. Seasonal also does not imply it cannot transmit out of season, the same as RSV, Influenza, etc.
In many aspects the virus and its response to it have been textbook. This also concerns its detection (PCR, antigen tests), its countermeasures (distancing, masks, testing, quarantine). For any following pandemic, all will be part of the playbook. Infections will remain; the virus will mutate, and our antibodies will wane. Every infection will boost immunity, new epitopes will become part of our immune memory: we will immunologically mature. Infection is unlikely every year, but every 3-4 years is quite possible, with asymptomatic or mild disease the most likely outcomes. We have gained long-term, immunological memory to the virus, the same as we do against other pathogens. This was achieved with vaccination and infection. Continued infection may still strengthen this further. For other respiratory infections, we would have been infected several times before we reach adulthood. Adults now exposed to SARS-CoV-2 have not had the opportunity to build up immunity from an early age, so damage from a new pathogen was expected and vaccination has been an incredible help to avoid more. With vaccination we are like adolescents, with additional infections we will be immunologically speaking, adults again. This takes some time, nothing much more can be done about it. There is a gap in our knowledge, for other pathogens as well, how SARS-CoV-2 can cause debilitating damage in some people with long-term consequences. We know too little about how this works, how to prevent, how to treat and heal. A new frontier of research that hopefully will bring understanding and solutions. In line with this, the WHO SAGE advice is that adults without underlying conditions should have three vaccine dosages. The elderly and vulnerable may need an annual booster to reduce infection chance and increase the memory pool. The role of children is a little more contentious: It is likely that they develop particularly good immunity and undergo SARS-CoV-2 infections well: just like all the other infections, thereby building up immunity. This is less clear in older children (>5 years), that should have two dosages of the vaccine to catch up on memory cell development. The next generation will be fine getting infected and building up immunity without the need of vaccination. But like for influenza and soon RSV, it would be right to offer the vaccine to those who want it and those vulnerable groups that need it. Er wordt bewust, ten onrechte, een conclusie gesuggereerd dat als de vaccins de menstruatiecyclus veranderen, ze schadelijk moeten zijn voor de vrouwelijke vruchtbaarheid. “Menstruele veranderingen, zelfs met één dag in de cyclus, beïnvloeden de ovulatie, bevruchting, implantatie en baarmoederafscheiding. Dus elke verstoring zal vrijwel zeker leiden tot afname van de vruchtbaarheid." COVID-19 vaccinaties, vruchtbaarheid en menstruatieKort nadat de Covid-19-vaccins waren uitgerold kwamen er verhalen over de gevaren van die vaccins. Dit was geen verrassing, antivaxxers zijn een bekend fenomeen. Het is een lang bestaande beweging, doordrenkt in een bepaalde manier van denken. Je zou het een traditie kunnen noemen, een traditie die terug te leiden is naar het allereerste vaccin tegen pokken. Eén van de meest ernstige bangmakerijen richt zich op vrouwen. Bangmakerij m.b.t. hun vruchtbaarheid en ongeboren baby's. Een zwangerschap of zwangerschapswens is een emotionele tijd, waar natuurlijk de gezondheid van moeder en baby vanuit alle hoeken wordt bekeken. Spookverhalen hierover, met vaccins in de hoofdrol, zijn al terug te leiden tot de allereerste vaccins. Kort na het begin van vaccineren tegen Covid-19- werden precies dezelfde spookverhalen gerecycled. Het vaccin zou de vruchtbaarheid negatief beïnvloeden en schadelijk zijn voor moeder en (ongeboren) baby. Er werd met cijfers gegoocheld die zouden moeten aantonen dat gedurende de 3 klinische trials van het Pfizer/BioNTech vaccin er veel miskramen zouden zijn. Gelukkig is hier geheel niets van waar. Leugens dus, maar de spookverhalen blijven rondzingen. ‘De antivaxxer’ bestaat niet. Er zijn vele vormen van weerstand variërend van enigszins sceptisch tot aan volledig ondergedompeld in complottheorieën Er is ook nog een geniepiger vorm. Dat is de groep die naar eigen zeggen niet tegen vaccinatie is, maar wel luid twijfel verkondigd over nut en noodzaak van Covid-19 vaccinaties. Het komt voor onder alle lagen van de bevolking, ook bij wetenschappers en artsen, die eigenlijk beter zouden moeten weten. Echter, welke vorm dan ook, de argumenten die worden gebruikt zijn niet nieuw. Ze zijn gelijk aan de spookverhalen die al rondgaan sinds de introductie van de eerste vaccins. Die werden toen al afgekeurd als een aanval op de “vrijheid” van het individu en de “lichamelijke soevereiniteit” (van kinderen). De moderner klinkende uitdrukking "burgerlijke vrijheden" werd vaak ter sprake gebracht in de antivax discussies van 1860, en de woorden "despotisme" en "tirannie" waren toen al gebruikelijk. Er werden dramatische, bloemrijke voorbeelden van vaccinatieschade door het pokkenvaccin aangehaald en er waren beweringen dat de vaccinatie de patiënt de ziekte, waartegen gevaccineerd werd, of andere vreselijke ziekten bezorgde. Antivaxxers voerden destijds ook aan dat de ontwikkeling van vaccins overhaast was. Een andere parallel met de moderne antivaxbeweging was het pleiten voor ‘veilige’ pseudowetenschappelijke remedies in plaats van de ‘schadelijke’ vaccins. Één van de meest verwarrende berichten betreft effecten op de menstruatiecyclus. Sommige vrouwen melden korte veranderingen in hun menstruatiecyclus na een Covid-19-vaccin. Omdat er vaak veel variabiliteit is in periodecycli, was het niet duidelijk of de vaccins noodzakelijkerwijs de veranderingen veroorzaakten. Dit werd snel opgepikt door influencers en “freelancejournalisten” die hier een kans zagen om verwarring en twijfel te zwaaien bij bepaalde groepen, om zo draagvlak te creëren voor hun antivax agenda. Dit gebeurde vaak geniepig met zinnen als “ik ben niet tegen vaccineren, maar...”, “Ik stel alleen maar vragen”, “Maar wat als...”, “Stel je voor…”, “Op de lange termijn kunnen we niet zeker zijn...”. Als het gaat om de gezondheid, dan werkt het beïnvloeden van vrouwen, aanstaande moeders en kinderen in het algemeen zeer goed, Zij zijn vaak toch de primaire verzorgers en hebben een grote inspraak op beslissingen over het gezin en de familie. Behalve de vermelding dat er door vaccinatie geen bewezen negatieve verandering is m.b.t. vruchtbaarheid, het aanstaande moederschap en baby’s zal ik in dit blog niet verder op dit onderwerp ingaan. Veel data over de veiligheid en effectiviteit van vaccins in dit opzicht, is verzameld en overzichtelijk beschreven door Dr Vikki Male en kan hier gevonden worden: Explainer on COVID19 vaccine and fertility.docx - Google Drive Ondanks robuust bewijs m.b.t. de veiligheid van Covid-19 vaccins, blijven sommige mensen wijzen op eventuele veranderingen in de menstruatiecyclus, om ongegrond te suggereren dat de Covid-19-vaccins onveilig zijn. Die suggesties worden onderbouwd met verkeerde cijfers uit de “Pfizer documenten” of via bekende antivax organisaties met (undercover) video’s van misleidende conversaties.’. Het is belangrijk om deze, expres emotionele berichten, te zien voor wat ze zijn; een tactiek om opinies te beïnvloeden. Ze zijn geen afspiegeling van de werkelijkheid. De menstruatiecyclus is altijd onderhevig aan veranderingen. Het staat onder de controle van hormonen. Het niveau hiervan kan beïnvloed worden door externe factoren zoals: voeding, lichaamsbeweging, stress, medicijngebruik, maar ook ziekte en ontsteking. Het veroorzaken van een korte ontsteking is precies wat een vaccin doet. Die korte ontsteking veroorzaakt door het vaccin, wekt een immuunreactie op die je beschermt tegen een eventueel latere veel heftigere ontsteking, door het pathogeen waartegen gevaccineerd wordt. Een goed voorbeeld is rodehond. Dit virus is erg gevaarlijk voor een ongeboren baby. Daarom wordt het aan ongevaccineerde vrouwen met een kinderwens sterk aangeraden dit vaccin alsnog te nemen. Ook dit vaccin, dat een levend RNA-virus bevat, veroorzaakt een kleine en korte ontstekingsreactie, en een kleine schommeling in de cyclus kan hierdoor soms plaatsvinden. De zeer waarschijnlijke verklaring hiervoor ligt in de hoeveelheden hormonen en de functie van sommige immuun cellen. Ons immuunsysteem kan directe invloed hebben op onze hormoonspiegel via cytokines. Cytokines zijn stofjes die onze cellen uitscheiden en door je lichaam getransporteerd worden. Het zijn regelaars. Zo kunnen ze je een gevoel van honger of misselijkheid geven, maar ook je temperatuur aanpassen (koorts). Vele van deze cytokines hebben een directe invloed op immuun cellen die de afbraak van het baarmoederslijmvlies regelen. Het is dus niet zo dat het vaccin in de baarmoeder of eierstokken terecht komt, zoals soms ook beweerd wordt. Het eerste gedetailleerde wetenschappelijke onderzoek met betrekking tot de vaccins en menstruatie, suggereerde dat Covid-19-vaccinatie veranderingen in iemands cyclus kan veroorzaken. Meerdere vervolgonderzoeken hebben nu aangetoond dat een Covid-19-vaccindosis gepaard kan gaan met een korte vertraging tot de volgende menstruatie. Dit is gemiddeld minder dan één extra dag. Deze vertragingen zijn binnen de volgende cyclus of twee verdwenen. Belangrijk om te onthouden is dat deze schommelingen geheel natuurlijk zijn en ook van korte duur. Daarnaast hebben diverse studies aangetoond dat er geen effect is op de vruchtbaarheid. De deskundigen die de onderzoeken hebben uitgevoerd, wetenschappers en artsen, hebben dan ook benadrukt dat de veranderingen niet zorgwekkend zijn De menstruatiecyclus is van nature verschillend. Verschillend tussen vrouwen, maar ook verschillend van maand tot maand. Het is daarom moeilijk om vrouwen één-op-één te vergelijken. Veel onderzoeken kijken daarom voornamelijk naar veranderingen voor en na de vaccinatie bij dezelfde vrouw. Een aantal van de onderzoeken: Een van de eerste onderzoeken volgde bijna 4.000 deelnemers in de VS die een normale menstruatie hadden en geen hormonale anticonceptie gebruikten. De vrijwilligers namen deel aan het onderzoek voorafgaand aan enige Covid-19-vaccinatie en ongeveer 60% van deze mensen werd gevaccineerd. Een vervolgstudie was een onderzoek bij bijna 20.000 mensen, deze vond een toename in cycluslengte van minder dan één dag die binnen één cyclus weer normaal werd. Een ander onderzoek, keek naar menstruatiegegevens die waren ingevoerd door bijna 10.000 iPhone-gebruikers en identificeerde een toename van de menstruatiecyclus van een halve dag of minder na een Covid-19-vaccin. Ook deze toename verdween binnen de cyclus na vaccinatie. Een klein onderzoek met 79 mensen in het VK, vond ook dat vaccinatie gepaard ging met een kleine vertraging in de volgende menstruatie, die snel weer normaal werd, zonder veranderingen in de cycluslengte bij gevaccineerde mensen die hormonale anticonceptie gebruikten. Een studie onder bijna 4.000 verpleegsters in de VS, volgde mensen voor zes maanden en vond een 48% risico om een korte of langere menstruatiecyclus te hebben na vaccinatie, die bij het invullen van de volgende vragenlijst was genormaliseerd. Deze onderzoeken laten zien dat er geen verschillen zijn in bloedingstijd, maar, zoals geschreven, kan vaccinatie bij sommige vrouwen tot een verlengde cyclusduur (minder dan een dag) leiden. Binnen een groep vrouwen zijn er dus verschillen, met velen die geheel geen verschil wat betreft hun cyclus merkten en een klein aantal die één of twee dagen verlenging ervaarden. Dat laatste werd vooral opgemerkt als twee vaccinaties gegeven werden binnen één menstruatiecyclus. Al deze veranderingen verdwenen de volgende maand of maand daarna. Dit patroon wordt gezien door vele onafhankelijke onderzoeken in verschillende landen. Natuurlijk is het goed dat vrouwen zich bewust zijn van de mogelijkheid, dat vaccinatie een milde invloed kan hebben op hun menstruatie. Daarom is het ook mogelijk om dit te melden als bijwerking en staat dit sinds enige tijd ook vermeld als mogelijke bijwerking van het vaccin. Dat wil niet zeggen dat deze of andere bijwerkingen ook optreden, of serieus van aard zijn. Toch suggereren mensen op sociale media dat de cyclusveranderingen een bewijs zijn van vaccinatieschade.
Dit wordt steeds herhaald, door grote internationaal opererende organisaties en politici en snel verspreidt door de hierboven genoemde influencers en “freelancejournalisten”. Vooral als deze schrijven voor- en invloed kunnen uit oefenen op vrouwen en (aanstaande) moeders, door het plaatsen van suggestieve opmerkingen over correlaties zonder causaal verband. Zoals: “Veel vrouwen hebben problemen met hun menstruatiecyclus gemeld na het nemen van de vaccins.” Of: “vrouwen hebben miskramen gemeld na vaccinatie. We hebben antwoorden nodig. Is het vaccin wel veilig?” De suggestie wordt gewekt dat de genoemde miskramen door vaccinaties komen. Het is helaas een feit dat 10-20% van alle zwangerschappen in een miskraam resulteert. Maar dat wordt bewust niet benoemd. Daarnaast is er zeer veel wetenschappelijk bewijs dat miskramen niet vaker voorkomen na COVID-19 vaccinatie. De vaccins zijn veilig voor en tijdens de zwangerschap, en beschermen moeder en baby zeer goed. Er wordt bewust, ten onrechte, een conclusie gesuggereerd dat als de vaccins de menstruatiecyclus veranderen, ze schadelijk moeten zijn voor de vrouwelijke vruchtbaarheid. “Menstruele veranderingen, zelfs met één dag in de cyclus, beïnvloeden de ovulatie, bevruchting, implantatie en baarmoederafscheiding. Dus elke verstoring zal vrijwel zeker leiden tot afname van de vruchtbaarheid." Dit is geheel ongegrond. Talrijke studies hebben geen enkel effect van vaccinatie op de vrouwelijke vruchtbaarheid gevonden. Studies vinden zelfs geen significante invloed op de menstruatiecyclus waarin iemand wordt gevaccineerd. De mogelijke verstoring is gemiddeld minder dan een dag. Dit betekent niet dat een verstoring helemaal niet kan voorkomen, en het betekent ook niet dat als het voorkomt het daadwerkelijk door de vaccinatie komt. Met zo´n groot aantal mensen gevaccineerd op dezelfde tijd, tijdens een pandemie die levens veranderde, zijn er veel dingen mogelijk, ook veel die gewoon toeval blijken. Belangrijkste vraag is, hoe gaan we deze desinformatie tegen? Hier is een belangrijke rol weggelegd voor de media, die deze boodschappen een platform geeft. Daarnaast moeten sociale media platformen hand in eigen boezem steken. Zij hebben het bereik van de antivax beweging de afgelopen jaren aanzienlijk vergroot. Het internet heeft ook een reeks alternatieve gezondheidsbeïnvloeders, van wie velen antivaccinatie-inhoud op sociale media posten, een groter en internationaler bereik gegeven. De belangrijkste rol is weggelegd voor artsen en wetenschappers. Zij kunnen uitleg geven over hoe de vork werkelijk in de steel zit, het liefst met hulp van diezelfde (sociale) media. Maar ook daar zitten notoire desinformatieverspreiders tussen. In Nederland hebben we bijvoorbeeld Het Artsen Collectief, wiens foutieve boodschappen veel meer tegengas zouden moeten krijgen door betere en duidelijkere uitleg. Hier is ook een belangrijke rol voor beroepsorganisaties weggelegd, om beschikbare informatie uit onderzoek duidelijk uit te leggen in vakbladen naar collega’s en ook in huis-aan-huis bladen en de media. Arts en Auto, Medisch Contact, en multimedia platformen die alle artsen en ook studenten geneeskunde bereiken zouden hier een speerpunt van moeten maken. Context: any virus tries to reduce immune detection and response. |
Professor Marc Veldhoen is an immunology expert and leads the MVeldhoen lab at the Instituto de Medicina Molecular (iMM) in Lisbon, Portugal.
Twitter: @marc_veld Google Scholar profile
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