While there continues to be COVID news, over the last week or so, the media has been less focused on COVID and much more focused on Monkeypox. The most important thing you can do in regards to Monkeypox is to educate yourself. It is not likely to develop into the widespread, silently transmitted infection that is still with us in COVID, but it does have a reasonably high risk of significantly affecting certain high-risk communities, and any disease that has widespread effects in one risk group, can spill over into other groups, so it is better for people to be aware the factors in the paradigm and help educate everyone.
Several issues are driving the mainstream media to increase coverage of the disease. First, last week the US CDC announced that there have been two US cases of Monkeypox in children. The first was a household contact of a known monkeypox patient and the second was an international traveler transiting the US. Then, on Wednesday of this week, Dr. Tony Fauci built on the story of these children to say that this just shows that anyone is at risk for monkeypox. While this is an inherently true statement, he left out that the relative risks of various segments of the community are vastly different. Additionally, late last week, the World Health Organization put Monkeypox into the same level of international concern as COVID: A “Global Health Emergency” which requires WHO member nations to provide extensive monkeypox case data to the WHO and creates a facilitated ability for the WHO to request and use resources from member nations for characterizing and combatting the disease. While no one should dispute that resources should be applied to stop the spread of the disease, it is somewhat self-serving for WHO to make a declaration that can assist in funneling additional resources to itself. Monkeypox does need resources and the application of public health principles, but this is not even close to the severity order of magnitude of COVID19.
Monkeypox has been tracked for about the last 50 years after being identified as endemic in several African countries. Generally, there are two strains of monkeypox, the originally identified strain most commonly seen in the Congo which has less than a 1% case fatality rate, and a more recent strain identified in Nigeria that can have a case fatality rate of up to 3%. However, it is important to note that these case fatality rates in Africa are superimposed on a healthcare environment that is very different than economically developed nations as evidenced by the fact that over 19,000 cases were reported outside of the endemic countries, as of July 26th, there have only been 6 deaths. Deaths are a trailing indicator, so it is likely we will see more, but not likely to approach 1%.
The basic epidemiology of Monkeypox remains unchanged from previous discussions. It is spread by intense or prolonged contact with various body fluids, especially those in the characteristic rash, but also genital and respiratory secretions. It is not felt to be transmitted by airborne droplets, at least not easily, so it is not considered to be a respiratory spread virus-like COVID. Because the virus can be transmitted by non-sexual intimate contact, it is also not considered to technically be a sexually transmitted disease, although the prolonged intimate contact of sexual encounters does strongly facilitate transmission.
With regard to testing, it is better to think in terms of identification of disease and infectiousness: Unlike COVID which can have a prolonged asymptomatic but infectious phase, Monkeypox is generally not infectious until symptoms start, with symptoms including viral-like systemic symptoms such as fever/chills, head, and body aches, swollen tender lymph nodes, or, most importantly, a vesicular (or pustular) rash. Of note, the rash can sometimes appear without any symptoms, but almost never the reverse. This initial appearance of the rash may be reminiscent to many of chickenpox, but it occurs closer to the onset of fever, if not before, and typically begins on the face or genitalia and spreads towards the center, whereas chickenpox usually starts on the trunk and spreads outward to the extremities. Because infection generally requires these symptoms to be present, partners who know each other and are therefore more likely to know whether their partner is ill can generally avoid infection by avoiding prolonged intimate or skin-to-skin contact. Most transmission occurs in setting where people do not know each other or fail to recognize or talk with each other about flu-like symptoms or rashes. Testing does not play a major role other than for characterization of the outbreak, because the rash and symptoms are so characteristic. Again, returning to the chickenpox analogy, in the days before the widespread use of the chickenpox vaccine, when a person developed chickenpox, there was no need for testing because the diagnosis was self-evident. Still, testing is available through major labs if there is any diagnostic question or for epidemiologic purposes.
The most important “treatment” of early infection is vaccination. As we will discuss in a moment, vaccination plays a major role in prevention, but for the first few days after a person is infected, if they recognize that they had an at-risk prolonged close intimate contact with an infectious person, they can get a post-exposure vaccination which can abort the development of an overt infection and infectiousness. This strategy of early case tracing, contact identification, and vaccination is an important public health tool in combating the disease. Should illness develop, the disease is almost always self-limited, again, similar to chickenpox, although the duration of infectiousness is typically a bit longer, typically 2 to 4 weeks, during which time isolation is recommended. Treatment, therefore, is primarily symptomatic, including Tylenol/paracetamol and/or an NSAID such as Ibuprofen for the fever, chills, and aches and pains. Regular showers are important to keep the risk of superinfection low. There is a drug that has been developed for smallpox, tecomirimat or TPOXX, which is felt to be effective against monkeypox. This drug is controlled by the US government and only available through a special CDC program to a small subset of infected patients with a higher risk of progressing to more severe disease, including people who are immunocompromised, under 8 years of age, pregnant or breastfeeding, have severe skin conditions, or those experiencing a complication of the disease.
The most important component of this 4-part paradigm is prevention. By avoiding intimate skin-to-skin contact with any higher-risk person exhibiting symptoms of a viral infection or an unexplained rash, transmission can be virtually eliminated. For this reason, probably the most important tool we have for combatting the spread of Monkeypox is education. Anyone who does have Monkeypox should try to avoid others, cover all open rashes, and regularly wash hands with an effective hand disinfectant. Anyone caring for someone with Monkeypox should use gloves and frequent hand-washing when handling soiled materials such as bedding. Again, casual contact with shared surfaces does not appear to be a common means of transmission, but this will be closely monitored. Additionally, as I noted above, there are effective vaccines against Monkeypox and these vaccines are being offered to those people in higher-risk communities. Most people over the age of 51 were vaccinated against Smallpox in a program that ended in about 1971. While immunity has likely waned somewhat in the 50 years since these vaccines were broadly administered, most authorities believe there is some residual immunity. Additionally, many people who served in the military received a booster and these people will typically have excellent immunity.
Cases and deaths remain stable, although people who are hospitalized, as opposed to new hospitalizations, has seen prolonged upward pressure. These hospitalized cases tend to be those who are unvaccinated and/or unresponsive to available treatments, so if someone does get to the point of requiring hospitalization, the disease is typically serious, requiring longer care, although ICU care requirements remain low. Importantly, over the last month, BA4 and BA5 nearly completely replaced all other variants. As this happens, the amount of upward pressure on case numbers is reduced. It does not mean that cases will immediately start to decrease, but as the steady stream of BA5 cases induce higher levels of immunity, by the end of summer, it is likely that we will start to see decreases in cases. The end of summer will also correspond with 3 months after the first cases of BA4 and BA5 were occurring, which is about the time that relatively immunity begins to wane, but that should also be about the time that a combined vaccine including BA4/BA5 should be available.
Two weeks ago, we discussed the authorization of vaccines for young children and the authorization of the Novavax vaccine. Regarding the vaccines for children under 5, the uptake of these vaccines has been lackluster. Many parents share the concern that we expressed, that risks for the average young child are pretty low, so it is important to consider the child in their environment to help make a decision: does the child have other risk factors, is the child in daycare, does the child routinely have close contact with at-risk people such as grandparents or other family members with health issues. For the average healthy young child, the numbers, don’t add up, but many will look at the other issues, as we have outlined, and decide that those risk avoidance benefits do mitigate the admittedly very low vaccine risk and will make a reasonable choice to have their children vaccinated.
Moving on to Novavax, this week, 3.2M doses of the newly approved COVID vaccine will enter US distribution channels. While there are more than enough of current mRNA vaccines to adequately immunize everyone in most developed nations who chose to get vaccinated, the availability of the Novavax vaccine is still considered an important milestone in the ongoing drive to minimize the importance of COVID as a pathogen of significant concern.
First, a little background: we are going to focus on the US because there is better access to this data. Currently, about 2/3rd of eligible Americans are vaccinated. With still 1/3rd of Americans unvaccinated, that makes it fairly easy to compare the impact of vaccination on cases and severity. While many jurisdictions do not break down case, hospitalization, or death reporting by vaccination status, many do, and from that data, it is evident that vaccines have a major impact on infection, disease, and deaths. For example, CDC reports that unvaccinated people have 3 times the risk of testing positive for COVID 19 and over 6 times the risk of dying versus people who had their primary series. The death risk for unvaccinated versus vaccinated with 2 booster doses (for those over 50) is 29 times as great. At the same time, the risk associated with the mRNA vaccines has been minimal, with the risk of serious allergic reaction at about 5 per million doses (lower than most other vaccines), platelet-related bleeding disorders at 4 per million, and in adolescents, especially males, a rate of generally self-limited heart inflammation at 50-106 cases per million depending on age.
Still, many people are resistant to vaccination, with over 100M Americans unvaccinated, despite the risk:benefit information. Many hope that Novavax will overcome some of the key reasons that people cite in refusing vaccination. The following addresses the most commonly cited reasons for refusing vaccination and provides information on how Novavax helps to overcome these issues. There are still issues with a general distrust of vaccines in a non-insignificant proportion of the community, and nothing about Novavax can address that.
Resistance To Vaccination
- mRNA technology injects the mRNA “code” for instructing muscle cells in the body to make a protein that looks to the immune system to be the COVID virus. This is a completely novel approach to vaccination and has never been used before in large vaccination programs. Many people are concerned about injecting active genetic material because they fear that it may disrupt other critical genetic pathways.
- Novavax, on the other hand, is a protein-based vaccine. This is similar technology to just about every other vaccine people have had over their lifetime. Proteins that look to the body to be the “business end” of COVID virus particles are injected and the body develops antibodies and cellular immunity against these proteins. The proteins are otherwise inactive in and of themselves and are cleared out of the body by the usual housekeeping mechanisms.
- Over 70% of survey respondents say that they are more comfortable with this approach to developing immunity than with co-opting one’s cells to be mini-vaccine factories as is the case with mRNA vaccines.
- Some vaccine refusers feel that the mRNA vaccines were rushed. There is no doubt that the process from the development of the mRNA vaccines to fielding was the fastest in human history. Many are concerned that uncommon, but potentially impactful, issues would not have been uncovered in the few months allocated for testing.
- Novavax has been under development and testing, including extended tracking of early phase test vaccinees for over 2 years, and while not as long as the typical test cycle for routine vaccines, this is well more than the six months which is generally recognized as the appropriate monitoring window for identification of uncommon side effects.
- The mRNA vaccines were linked through research and cell lines used in manufacturing cells from aborted fetuses. Despite review from the US Conference of Catholic Bishops and other religious and ethics organizations that agreed the relationship was so remote as to not have significant religious or ethical concerns, some people take a more absolutist view
- Novavax has no direct link to fetal cell lines. Some still argue that any vaccine research and development is built on studies that did utilize fetal cell lines, and because of that, essentially all vaccine development is tainted, while others look at whether the actual direct R&D specifically related to the technologies or manufacturing of the vaccines utilized these cell lines. Novavax did not use fetal cell lines in the direct chain of development or manufacture of the vaccine.
Given this information, CDC’s initial polling showed that 1/3rd to 1/2 of current vaccine refusers would consider vaccination, but now that the vaccine is here, the newer polling is not so optimistic with the assessment being that many feel they have made their decision and are simply sticking to it. We hope that people can help with educating their friends and relatives and encourage them to take a fresh look at their decision. Many will choose to stick to their guns and that’s their prerogative, but given the overwhelming data on risk reduction from vaccines, infection and complication rates in unvaccinated, and the new fact pattern of Novavax, we hope people will reconsider.
With the relatively flat case, hospitalization, and death data, we do not see a strong argument for putting people back in masks mandatorily, but we still support people choosing to wear or not wear masks in crowded public places based on their individual assessment of risk and still advocate strongly for the application of the layered approach to risk mitigation for organizations.