Coronavirus Update 54
January 31st, 2022
A graph on Dr. Peter Attia's twitter feed showing us the realities of young people's death risk based on a comparator against COVID death. This is a very poignant representation of risk and where we should be spending our monetary and energetic capital in the prevention landscape for young people. We need to have more indignation around the deaths from MVA, suicide, homicide and drug use. I would like to see a national message fighting these diseases of young adults.
We need perspective as a society. Mental health is our biggest crisis next to nutrition. Covid is not a problem in comparison. This is not to say that we should not teach people true risk from Covid and take individual mitigating measures.
It is more a reflection of where our financial and intellectual capital should be directed at this time. There are much bigger and deadlier fish to fry. Remember two things: 1) Covid is here to stay and 2) all at risk individuals can now effectively vaccinate and wear an N95 masks for their safety. (The graphic is from: https://peterattiamd.com/covid-part2/)
Omicron Overview - The world of omicron as I see it now - Skip on to the quick hits if you don't want my opinions.
Everyone knows by now that I despise emotional fear driven decision making. This entire pandemic has been a study of this process. Everyone also knows that I love and respect non emotional science based decision making. To that end, Drs. Attia, Damania, Gandhi and Makary have produced a 3 hour podcast nailing down the known science and their opinions based on same as we sit today in this endemic state of Covid. Link
Here are some of their thoughts: One study noted that with 52,000 Omicron cases - none required mechanical ventilation and 1 death. This is more like 250,000 people out their in the community as only 1/5 people are test positive and known to the healthcare system. 83% were in the hospital for less than 2 days. 98+% of current cases nationally are Omicron derived. Dr. Gandhi noted that a South African study noted that prior infection or vaccination was the bulk of the reasoning behind Omicron's death reduction. They attributed Omicron being 25% less morbid then Delta based on the genetic mutations. This remains incredibly important data for those vaccinated and/or infected prior with survival. Getting exposed to the whole virus as opposed to just the vaccine's spike protein fragment will give you a better long term immune response because the immune system will develop antibodies against all of these viral epitopes. Thus, we will see many variant antigens reacted to well. Then the subsequent antibody production is vast and varied. This is a very good reason to think about not boosting if you are healthy and with no risk factors for death which sits at 0.000033 if vaccinated.
In my opinion, our children's mental and physical health need to take primacy over pandemic fear at this time. They are in a very very very low risk scenario from COVID, however, they remain in a high risk scenario from a mental and metabolic health perspective. The scales do not favor current school based mitigation measures based on risk and health from Omicron and the downstream events relate to it.
1) If you are a young person, boosting is questionable, especially if you are a male with myocarditis risk. The WHO and European Union are not recommending it at this time. The CDC is recommending down to age 12. Let us say that you are 18 years old and male. If a young adult receives a third dose of an mRNA vaccine which provides marginal to no transmission benefit for 90 to 110 days and minimal disease severity reduction because it is already almost zero after a 2 dose series, what is the point. Are our youth supposed to protect the unvaccinated? The vaccinated and boosted with risk factors? For how long? Then what? Do it again, and again every three months as immunity wanes rapidly? Has this ever been done before or well studied? Nope. Natural infection is also providing excellent immune solvency based on recent study data. Why are the healthy youth being held to this standard because they are in school and college where the unvaccinated at risk individuals are not and cannot be forced to do the same? Why are Colleges and Universities holding these young adults hostage when they are not at risk anymore after having 2 doses? It makes no logical sense to me. The data does not support this behavior. Israel's data shows that a fourth dose is almost useless for a healthy person. Then what? 3rd dose and stop even though Omicron or the next variant doesn't stop propagating. This is just the data and my take on it. As always, each individual must weigh and measure their personal risk tolerance, life choices and guidelines as provided.
2) My opinion on masking. Now that Covid is endemic and there is no longer any evidence that non N95 masking helps reduce transmission of Omicron from child to teacher, masking in schools is not necessary for the average child. If a child is high risk or a teacher is unvaccinated or concerned about their risk, they should wear a well fitted N95 mask to mitigate risk. It is no longer feasible to continue masking in schools from now on based on death risk and spread risk of Omicron. This virus is here to stay and masking cannot be our children's future. Omicron is significantly less risky for children. See Quick Hit #4. I agree with everything that Dr. Gandhi states in the Peter Attia Drive podcast. Choose to mask based on your personal risk and that is wear it should end. Your risk tolerance dictates your desire and need to mask. Mandating mask use is no longer necessary nor warranted especially for the children who have suffered far too much. The cloth and surgical masks do not prevent transmission of Omicron well. These are the masks that most children are wearing in an effort to please the policy makers. This is not science driven. With previous variants these policies were somewhat defensible because transmission was less impressive and kids remained low risk spreaders anyway. Omicron has thrown this out the window. Omicron has a reproductive rate that makes anything less than a well fitted and persistently worn N95 mask useless. For me, N95 masks are better at prevention transmission, but that is for the at risk individuals only. The rest of the healthy individuals need not mask from here on out based on an endemic disease state and a vaccine availability. If you are vaccinated, your death risk is tiny. If you have higher risk, wear an N95 regardless of vaccine status, but especially if you are unvaccinated. However, vaccinate to reduce the risk if unvaccinated. Hopefully, the CDC and State School systems will begin to transition to endemic Covid strategies. I know where I stand pending better data to change my mind.
3) Hospital overwhelm is only partly related to Omicron as hospitals that are reporting whether Omicron is the reason for admission found that 50 to 70% of covid positive admissions to the hospital are incidental findings and no longer the cause of admission and or death if Omicron is the cause. The more highly vaccinated the region the higher the likelihood that the positive test result is unrelated to the admission up to 70+%. The hospitals with Delta as the main player, remain hit hard by admitted unvaccinated patients. The other issue coming to pass is that most new tested cases of Covid are greater than 98% Omicron now. This is great news for hospitals as the majority of these patients are sick for 1-2 days if they get into the hospital and no longer require ventilation and do not die like they did with Delta. As North Carolina's Data shows, the COVID ICU use has dropped from a high of 30% in October, the peak of Delta, to 16% now and dropping fast as Omicron replaces Delta. Use of ventilators reduced from a peak of 22% to 10% during the same period despite huge increases in cases for many weeks now. (NCDHHS) This is all occurring in the face of massive case volume. Thank God we are not seeing Delta's morbidity tied to Omicron's infectiousness. That would have been a train wreck like no other.
My friends in the hospital say that they are seeing lots of cases, but the severity is definitely in line with these stats.
4) Prior infection naturally and or prior vaccine has been the greatest reason for the drop in death rate in relation to ALL variants at this time. The group at greatest risk currently is unvaccinated and/or with comorbid disease/advancing age. The message will remain: IF YOU ARE UNVACCINATED AND PREVIOUSLY NEVER INFECTED, GET VACCINATED AND REDUCE YOU RISK OF DEATH. ALL CAUSE RISK IS PROBABLY 0.2%. HOWEVER, IF YOU ARE OLDER THEN 50 YEARS OF AGE AND/OR HAVE COMORBID DISEASE, YOUR RISK IS WELL NORTH OF 1% AND CLIMBS WITH AGE AND DISEASE STATE. THIS IS NOT TRIVIAL, TAKE IT SERIOUSLY.
5) We are much closer to an influenza like scenario now, minus the shift and drift mutagenesis that is unique to influenza, than a COVID pandemic scenario. We are getting massive immunity nationally as Omicron burns through the US just like the flu does annually. There are very few virus naive Americans left to infect and cause major havoc as in the early months of the pandemic. The big headache remains the elderly and the diseased citizens which is identical to influenza yearly as they remain at risk for the same.
Quick Hits -
1) New data shows that vaccination with two doses of mRNA vaccines followed by natural infection is equivalent to natural infection followed by vaccination in providing super immune responses. "Current COVID-19 vaccines significantly reduce overall morbidity and mortality and are vitally important to controlling the pandemic. Individuals who previously recovered from COVID-19 have enhanced immune responses after vaccination (hybrid immunity) compared to their naïve-vaccinated peers; however, the effects of post-vaccination breakthrough infections on humoral immune response remain to be determined. Here, we measure neutralizing antibody responses from 104 vaccinated individuals, including those with breakthrough infections, hybrid immunity, and no infection history. We find that human immune sera following breakthrough infection and vaccination following natural infection, broadly neutralize SARS-CoV-2 variants to a similar degree. While age negatively correlates with antibody response after vaccination alone, no correlation with age was found in breakthrough or hybrid immune groups. Together, our data suggest that the additional antigen exposure from natural infection substantially boosts the quantity, quality, and breadth of humoral immune response regardless of whether it occurs before or after vaccination." (Bates et. al. 2022)
This is a vitally important study in the march toward understanding the long view on endemic Covid. Natural infection allows the T and B cell repertoire to see all pieces of the viral structure. Therefore, we make vastly different antibody responses to all of these differing structural proteins versus just a fragment of the vaccine seeded spike protein. This provides better long term immunity. The entire purpose of vaccinating in the first place was to prevent hospitalization and death. There was a fleeting belief that we could get a herd immunity this way. That ship sailed long ago. We are in a new endemic world now. Again, we sit at a place where logic dictates that the unvaccinated get vaccinated. The vaccinated with no risk factors will get great immunity with natural Omicron infection. Those with prior natural infection, no prior vaccination and waning immunity could get one dose of an mRNA vaccine to induce excellent immunity. Very logical and real time study based options here.
2) The most common Covid 19 Omicron variant symptoms are cough, fatigue, congestion and runny nose. This is expected based on he new pathophysiology of Omicron. Other symptoms include many seen with Delta: fatigue, muscle aches, head aches, nausea/vomiting, and diarrhea. Fever is less common now owing to the reduction in systemic disease.
3) Having natural infection from Covid prior to getting infected with the Delta variant provided much better immunity than vaccination alone. This information comes to us from an analysis of New York and California data sets. They also found that people infected and vaccinated prior to seeing Delta had the best outcome. People neither infected nor vaccinated had the worst outcome. (Leon et. al. 2022)
From a Reuters article: "Health officials in California and New York gathered data from May through November, which included the period when the Delta variant was dominant. It showed that people who survived a previous infection had lower rates of COVID-19 than people who were vaccinated alone. That represented a change from the period when the Alpha variant was dominant, Silk told the briefing. "Before the Delta variant, COVID-19 vaccination resulted in better protection against a subsequent infection than surviving a previous infection," he said. In the summer and fall of 2021, however, when Delta became the predominant circulating iteration of the virus in the United States, "surviving a previous infection now provided greater protection against the subsequent infection than vaccination," he said. But acquiring immunity through natural infection carries significant risks. According to the study, by November 30, 2021, roughly 130,781 residents of California and New York had died from COVID-19. (Steenhuysen J. 2022)
This data says to me that once vaccinated, natural infection is the way to go unless you have a risk of death via a comorbidity or advanced age. I cannot find another way to spin this information. Another reason to seriously question boosting once fully vaccinated. See #4 below for more on boosting. We cannot boost our way out of this mess. Natural disease may be mother nature's way of leveling the playing field in our long term favor.
4) From a new study, we see that children under 5 years of age have significantly less risk of severe disease with the Omicron variant: "Among 7,201 infected children in the Omicron cohort (average age, 1.49 ± 1.42 years), 47.4% were female, 2.4% Asian, 26.1% Black, 13.7% Hispanic, and 44.0% White. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than those in the Delta cohort: ED visits: 18.83% vs. 26.67%; hospitalizations: 1.04% vs. 3.14%; ICU admissions: 0.14% vs. 0.43%; mechanical ventilation: 0.33% vs. 1.15%. Control studies comparing Delta-2 to Delta cohorts show no difference." (Wang et. al. 2022)
This study is very important because it gives us a measure of risk based on the new meteoric rise in cases in kids with Omicron.
5) Asymptomatic cases of infected Omicron variant patients is higher than previous variants. A study analyzed the rate of positive low cycle threshold PCR tests indicating higher viral load in patients and tracked symptoms. Asymptomatic carriage is 5X higher with Omicron than with Delta. (Garrett et. al. 2021) What this study tells us is how much infectious transmission is related to the asymptomatic Omicron infected person. It appears to be significantly more than previous variants and than expected. Higher viral loads presumably indicate greater spread. Based on other previous data sets, the asymptomatic persons clear the virus rapidly leaving their spread window to be narrower. Thus, most disease is still likely occurring from the super spreaders who are symptomatic and carry comorbidities. However, all things that existed in the past may no longer be true with Omicron.
6) Fourth booster dose not adding much to the immune system's fight against Omicron. Initial reports from Israel show that the fourth booster dose with either Pfizer or Moderna vaccines show a modest increase in antibodies but clinically this added no significant benefit against Omicron. The antibody level returned the person to pre third booster dose levels. (Federman J. 2022) It remains odd that Israel is recommending a fourth dose for all over the age of 18 years. I cannot find a logical reason for doing this.
More data showing that vaccinating past the third dose for the population is of little value. In high risk groups who could die from a new variant infection, i.e. immunosuppressed persons, a fourth or even fifth dose may be necessary, but this is mere speculation. One size fits all approach is senseless.
7) Covid booster #3 added major benefits to reducing infection and the risk of hospitalization and death from Omicron in individuals over 50 years of age. 44X less hospitalization in the over 50 year age range and 49X in the over 65 year old age range. (CDC Reports) The great news is that 88% of individuals over 65 have been fully vaccinated and 63% have been boosted making this risk reduction come to life. The Over 50 group sits at 74% and 54% respectively. The take home message here remains that if you have advanced age and comorbid disease risk, boosters make a ton of logical sense if you have these risk factors.
8) New variant BA.2 appears to be very similar to omicron but possibly even more infectious. No data that it is more deadly. That is a relief.
9) "Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies." (Su et. al. 2022)
In English, this study basically says that long covid is associated with dysfunctional immune polarization due to antecedent risk factors including chronic hyperglycemia and autoimmune polarity. These issues are known to be related to intestinal dysbiosis, poor nutrition and over use of medicines including antibiotics and antacids. Dysbiosis was also noted by Dr. Fasano in children with multi inflammatory syndrome. The children with difficult delayed disease also had systemic viral proteinemia which is a hallmark of intestinal permeability. We could do a whole podcast on this topic alone. Oh, right! We are in 2 weeks with Dr. Fasano. So excited to dive deeper here.
The autoantibody theory is also well studied as we have seen over the pandemic. Individuals with autoantibodies against immune surveillance mechanisms have higher viral loads, worse disease and longer time to recovery. Men are most effected demographically.
10) States and European country data provides a unique look at death rates related to mitigation measures. Many coastal states, urban centers and countries chose to follow aggressive lockdown and fear based mitigation strategies in an effort to control a virus that could have cared less about their belief in control. Controlling nature has never been a human strong suit. We more often make things worse in an effort to control. We see data that New York and New Jersey had over 3000 deaths per hundred thousand just like Florida and other southern states that took an entirely different approach. Sweden once called negative things by the New York Times and many other media outlets far outperformed the United States, Germany, France, The United Kingdom and others despite much more liberal non restrictive policies that kept their population mentally untaxed and economically solvent, as much as possible in a global pandemic.
Repeated for their importance in case you missed them last Covid Update:
1) According to a study from Kaiser Permanente, the risk of death from Omicron is 91% less than Delta. The authors state: Our analyses included 52,297 cases with SGTF (Omicron) and 16,982 cases with non-SGTF (Delta [B.1.617.2]) infections, respectively. Hospital admissions occurred among 235 (0.5%) and 222 (1.3%) of cases with Omicron and Delta variant infections, respectively. Among cases first tested in outpatient settings, the adjusted hazard ratios for any subsequent hospital admission and symptomatic hospital admission associated with Omicron variant infection were 0.48 (0.36-0.64) and 0.47 (0.35-0.62), respectively. Rates of ICU admission and mortality after an outpatient positive test were 0.26 (0.10-0.73) and 0.09 (0.01-0.75) fold as high among cases with Omicron variant infection as compared to cases with Delta variant infection. Zero cases with Omicron variant infection received mechanical ventilation, as compared to 11 cases with Delta variant infections throughout the period of follow-up. Median duration of hospital stay was 3.4 (2.8-4.1) days shorter for hospitalized cases with Omicron variant infections as compared to hospitalized patients with Delta variant infections, reflecting a 69.6% (64.0-74.5%) reduction in hospital length of stay. (Lewnard et. al. 2022)
The study also noted 74% less ICU care needed and 54% less hospitalization. The reason behind these changes seems to be related to the mutations that made the Omicron variant more likely to infect the upper lung tissue and the nasopharynx leading to less tissue damage in the terminal lung tissue where oxygen and blood are exchanged. This appears to lead to less inflammation and downstream damage systemically. This is all good news overall.
2) From MMWR: Among 1,228,664 persons who completed primary vaccination during December 2020–October 2021, severe COVID-19–associated outcomes (0.015%) or death (0.0033%) were rare. Risk factors for severe outcomes included age ≥65 years, immunosuppressed, and six other underlying conditions. All persons with severe outcomes had at least one risk factor; 78% of persons who died had at least four.
If you had a primary 2 dose vaccine series against SARS2, you have a 0.0033% chance of dying or 0.000033 which is 33 in 100,000 cases. If you add in the age and underlying comorbid disease risk, most of us have zero risk of dying. This data set is earily similar to initial data at the beginning of the pandemic. Age and comorbid disease is the route to a bad outcome in almost all cases. This data was all Delta variant related which means that the numbers are orders of magnitude smaller for Omicron. Keep it all in perspective.
Thus, again we sit here with data points for booster decisions. To vaccinate with boosters that are minimally effective against Omicron is a personal choice that is highly recommended by the medical community to protect the unvaccinated, the immune suppressed and the genetically at risk.
3) If you received a covid vaccine, the longer the time interval between the vaccine and a breakthrough infection was associated with better long term immunity. It appears that the later breakthrough infection occurs when the antibodies circulating against covid have waned significantly leading to the response to come from the memory long lived plasma cells. This also allows for a robust retraining through the lymph nodes germinal centers where antibody variations can occur to mimic the viral mutations.
From the article:"“It’s an interesting study,” says immunologist Jenna Guthmiller at the University of Chicago in Illinois. She cautions that the results are solely correlative, but adds that they are in line with immunologists’ general understanding of how antibody responses mature over time. Guthmiller explains that vaccination leads to an emergency blast of antibody production, as a natural infection would. If a person gets infected soon after vaccination, these antibodies are probably still circulating in the blood, where they’ll bind to the virus and quickly eliminate it. But when a person becomes infected months after vaccination, the antibodies that respond come from a new and improved batch made by long-lived cells that carry a memory of the pathogen. When the body encounters the pathogen again, these memory cells are called back to duty and have a chance to refine the antibodies, providing better protection against subsequent infections."(Sidik S. 2022)
This may be the exact mechanism behind the data showing that spacing out the vaccine interval was associated with better immune responses over time. Thus, if you had a Covid infection or vaccine recently, your immune response will be correspondingly less robust to generate new protective variant antibodies to the new variant exposure. I.e. if you recently had a vaccine and get Omicron within weeks, you will not get significant symptoms, but you will also not have a great long term immune response. My take on this data is hypothetical in that if you have a booster recently and then see Omicron, you will have minimal to no symptoms but will also have a weaker long term benefit. Therefore, will you need frequent boosters in the absence of natural infection? I think so. If the vaccine wanes in 3 to 4 months normally, then you will be set up for recurrent need. If you have a 0.0033% chance of dying once vaccinated, maybe it makes more sense to obtain natural disease if you are young and or older with no risk factors. Thinking out loud.
Here is more of what I believe: ( This is all opinion based on the science and new social consequence data ) Skip this section if you don't want my opinions as some of them are aggressive judgements.
1) We have let our children down. I will go to my grave knowing this fact and we did nothing to stop it do to fear. I am beyond frustrated and have lost so much faith in our systems of government and organization especially teacher's unions that prioritized teacher's health over a child's health despite very very clear data that children were never the issue in the pandemic and adults were not being affected by the children. We have left them masked, afraid, uneducated, over tested, over involved and mentally stressed. Worse yet, the inner city/rural poverty based communities that forced their children to zoom for a year left them stuck in toxic homes without respite and struggling to learn a thing. We will rue the day that we ushered in an era of panic leading to policies that stressed our children. They are our future, yet we cared more about those who have already lived much. Backwards actions for a society.
2) The CDC and Government have caused an unbelievable volume of mistrust by not understanding the value and truth of natural immunity for survivors of the first and second wave of the pandemic as well as the value of targeting vaccination to high risk groups as the data poured out as opposed to draconian policies of fear. This led many to not trust the government and therefore shun vaccines altogether. Having natural infection from Covid prior to getting infected with the Delta variant provided much better immunity than vaccination alone. This information comes to us from an analysis of New York and California data sets. They also found that people infected and vaccinated prior to seeing Delta had the best outcome. People neither infected nor vaccinated had the worst outcome. (Leon et. al. 2022) We have long known that natural immunity is very useful in the fight against disease. Somehow we forgot this reality in this pandemic and shamed anyone who spoke up against this point.
Vaccines are so vitally important in the fight against infectious disease, but the messaging was so bad that we left a large swath of America not trusting and therefore not partaking leading to lots of death. It was very clear that if you had Covid and survived, then your immunity would be excellent as your immune system had seen the entire virus and your subsequent risk of death would be zero or very close to zero. These people did not need a 2 dose ( 3week spaced ) series to be immune solvent. In fact, studies showed that the second dose made people feel worse and added no benefit immunologically if you had been previously naturally infected. Again, no nuance to policy. Broken trust. The immediate answer should have been: if you have had Covid naturally, a booster dose of a vaccine will give you super immunity. Stop there. No vaccine cards mandating 2 doses.
Then Delta shows up and we see weakened vaccine effectiveness for transmission, but excellent coverage against death and hospitalization. The answer was not boosters for all, but boosters for the known high risk groups and then natural infection for all else if one so chooses. Hospitalization and death is always the metric to fight. We knew the groups at risk. Which is now even further relevant to the vaccine escaping Omicron variant. To boost now means that you are essentially declaring that you will boost every 3-5 months in perpetuity. We have zero evidence that repeated boosters are safe and have good evidence now that natural infection is very useful if previously infected or vaccinated. And, oh by the way, Omicron is 91% less deadly than Delta and studies show that the hospitalized are not suffering from the lung disease as before as this version is no longer systemic and associated with terminal lung hyaluronic acid flooding and damaging. Again, the science has always been here. However, the scientists are not leading the policy decisions. The policy makers are suppressing good science to push a policy that most of us realize is dysfunctional.
It was also very clear early on which individuals were dying from Covid and why they were dying as shown in the Covid pathophysiology paper in section III below. From early 2020, we should have messaged risk where it lay: age, obesity, hypertension, cardiovascular disease, diabetes. Essentially, mostly diseases related to lifestyle choices that are immune damaging. We fear discussing these lifestyle decisions more than shaming people into mask wearing and carrying vaccination cards (just went to Boston and had to present a vaccine card to eat at a restaurant where the same inane masking policies are in play where 90% of patrons are maskless unless they are walking to the bathroom or leaving). What about a natural infection card? Why is that less realistic as protection? No idea. It was also very clear early on that a longer range between doses 1 and 2 of the vaccine provided much better immunity, yet the CDC prevaricated. No nuanced approach yet again.
A person who receives an mRNA vaccine develops immunity to the spike protein only and as shown to date needs repeated boosters to maintain some form of transmission prevention and does not develop variable antibodies against mutant proteins as happens with natural immunity. This again states the obvious: if you are high risk, the vaccine and boosting repeatedly is a risk worth taking. For the rest of us, I am not sure this makes any sense. If my risk of death is 0.000033 once vaccinated with a two dose series or survived natural infection coupled to the fact that the vaccines no longer effectively prevent against transmission, what are we talking about then???