Written by JobSiteCare
June 16, 2022
Cases, on a global basis, continue to be slightly down, although we are not seeing the decided downward turn we had all hoped for with spring and summer weather. First the good news: As of right now, there are no new major variants on the horizon. The bad news, however, is that the omicron variants BA4 and BA5 are having a greater impact than we had first thought. While they do not appear to be creating a major new wave in North America, there is evidence of a small wave developing in Europe. Over the past 3 months, we saw omicron BA2 become predominant, and then it was replaced with the sub-variant BA2.12.1, which is about 25% more infectious than BA2. BA4 and BA5 came along and since they are only slightly more infectious than BA2.12.1, they do not effectively displace that variant, but they do outcompete BA2, so what is happening now is that BA2.12.1 is maintaining its market share but BA4 and BA5 are replacing BA2. Since infection with earlier variants and immunization with vaccines developed against early COVID are both progressively less protective against the newer variants, what the emergence of BA4 and BA5 has done is cause a pause in case decreases as they progress through communities. They don’t have enough virulence to cause a completely new wave in areas that did have a BA2.12.1 predominance, like North America, but areas that did not get a hard hit with BA2.12.1, such as Europe, are seeing upward pressure on cases as BA4/BA5 is more infectious than the BA2 it is replacing. We know, you really do need a picture to see how all these interplay. But the bottom line is that, in the absence of a new variant, we are beginning to see mild upward pressure on cases in Europe, while in the US, because BA12.2.1 is not significantly less infectious than the new variants, they are just replacing older variants and upward pressure towards creating a new wave has been muted.
There are some recent papers out of Europe that indicate BA4 and BA5 may tend to cause more severe lower respiratory infections, similar to Delta, but that has not been seen to any great extent in North America. Hospitalizations are up slightly, but hospitalizations and intensive care requirements are mostly in unvaccinated people, so even if BA4 and BA5 do have some Delta-like lung effects, it is fairly clear that vaccination (especially with at least one booster) is greatly protective against severe disease from any of the circulating variants.
Elsewhere in the world, Australia is seeing BA4/BA5 effects a little bit ahead of Europe with moderately increasing cases. China, which started to fully reopen just 10 days ago, is once again instituting quarantines and mass testing programs in an effort to stem outbreaks that appear to be mostly BA4/BA5 related. Other major economies in Asia, including Japan and South Korea, are through their spring waves and are now at relatively low levels. Taiwan and Singapore are well off their spring peaks, but still at moderate to high case levels.
Through all of this discussion of cases, however, with the exception of this concern about potential Delta-like illness in unvaccinated due to BA4 and BA5, the fact is that the main impact of COVID is the sheer number of cases, bringing with them disruptions in business operations due to quarantines and isolation, but not significant impacts to individuals’ health over more than a few days. With each new variant comes new concerns about a potential increased incidence of long COVID, but especially in vaccinated people, that is not as big a concern as it was early on in the pandemic.
Speaking of vaccines, there have been major developments in the past two weeks. Last week, the FDA vaccines advisory committee recommended approval of Novovax, a vaccine that is more like a traditional vaccine where an antigen that mimics the immunologic appearance of the target infectious agent is directly injected and the body then makes antibodies and cellular immunity against the injected antigen. Recall that the mRNA vaccines are completely novel in that they contain RNA code that instructs muscle cells in the body to produce the antigen.
This mRNA approach to co-opting the body into manufacturing the antigen is one of the factors that many have cited in refusing one of the mRNA vaccines. Additionally, the long approval process for Novavax may be more comfortable to more people than the somewhat politicized warp speed process used for the mRNA vaccines. Finally, prior to approval in the US, Novovax will have been very successfully used (or mass-tested as some would say) in other countries, including Canada and Australia.
The jury is still out on whether Novovax-induced immunity is as strong as the mRNA vaccines and no one has good data on whether durability may be worse or even better, than with the mRNA vaccines.
Final approval on Novovax has still not been granted by the FDA, but it is expected in the coming days. Some surveys say that between one-third and one-half of mRNA vaccine refusers will at least consider Novovax vaccination, but much of that will depend on how well the US government can market and educate people on the vaccine, and unfortunately, its track record on that has not been stellar.
With regard to the mRNA vaccines, this week marks the first major FDA meeting on them in several months. On Tuesday, the advisory committee finally granted emergency use authorization for Moderna for 6 to 17-year-olds. The actual effect of this approval will be minimal as there is no substantive difference between Pfizer and Moderna in this already very low-risk group and vaccine uptake has already plateaued in kids.
The bigger approval came on Wednesday when the same FDA external advisory committee voted to recommend emergency use authorization for both Moderna and Pfizer for younger children down to 6 months. One of the major delays in approving the vaccines in this age group has been that there are so relatively few children who develop severe-enough disease that it was difficult to find enough very ill children in either the vaccinated or unvaccinated arms of the studies to be able to detect a significant efficacy for the vaccines. Major news outlets commonly cite that there have been 45,000 children under 5 who have been hospitalized during the pandemic, with roughly 50% of those occurring during the omicron wave. However, when you go to the actual CDC data, the real peak for childhood hospitalizations, occurring during the delta wave, was an annualized rate of 5.6 per 100K. And of the children hospitalized, about 37% had underlying medical conditions that would predispose them to more severe illness. There have been 475 pediatric deaths, so that does give pause as it is comparable to just under 200 pediatric deaths in a typical flu season, and we do immunize kids for flu. There were no significant side effects noted in the study groups for either vaccine, but as has been found in some other childhood vaccines, the study sample size cannot possibly be large enough to detect uncommon complications.
So the question is whether or not to immunize children when these vaccinations become available, most likely next week. To be honest, it’s a close call. With the numbers we outlined above, many people are going to say, “I vaccinate my kids against a bunch of diseases, including flu, that have less impact than COVID, so why wouldn’t I vaccinate them?” while others will recognize that for an annualized rate of 5.6 hospitalizations per 100k kids when you consider that many of those hospitalized are young babies, who are not eligible for vaccines anyway, and many are kids with underlying problems, and many of those ‘hospitalizations’ include ER observation stays, the real number of typical kids beyond infancy who are truly hospitalized is more likely 1-2 per 100K per year, and that was when a more severe strain of COVID was at its peak. Parents who look at it that way will likely wait to see how the first couple of million childhood vaccinations goes. To be sure, just based on statistics, there will likely be a small number of pediatric deaths in kids who could have been immunized, but there is still the unknown of vaccination effects when applied against a large population. To us, it’s a close call. When we have an omicron-specific vaccine, our thoughts may change. There is one important caveat though, most kids have already had COVID, so they already have some baseline immunity that will protect them against future severe disease. For that vanishingly small number of children who have dodged COVID up to now, we would maybe think differently, but our sense is that the initial pediatric COVID vaccine uptake is going to be fairly low.
Speaking of immunity due to getting COVID: Another study came out this week supporting the CDC’s position that immunity from illness is not as effective in producing immunity as COVID vaccines. This is different than what we see with most other viral illnesses, but COVID is not acting like other illnesses in many ways. I will reiterate that all the data I have seen supports that the risk:benefit calculus clearly supports vaccination and at least one booster. For other than at-risk individuals, the evidence is NOT as strong for a second booster, but that will likely change when we have omicron-specific booster formulations. The FDA has confirmed that they will be addressing the omicron-specific formulation for the mRNA vaccines over the next few weeks, so we fully expect that we will have this upgraded booster this fall.
Closing things out for COVID, we do need to address what everyone is seeing: lots of people around you have cold and flu symptoms. Many test positive for COVID, but many do not, and many who don’t test positive have significant-close exposures to documented COVID cases! What’s going on? There are a few things happening at once: First, we are, in fact, seeing many of the typical fall/winter cold/flu viruses circulating at much greater levels than typical for this time of year. The reason is two-fold. First, in the fall and winter, we are constantly exposed to these viruses, some of which our immune system fights off, while getting recharged against that virus in the process, and sometimes they do in fact cause typical seasonal colds causing us to develop at least short term immunity against these viruses. Over the last couple of seasons, however, as we have all been masking, washing our hands, and social distancing, these viruses have not circulated as much and we have all had less opportunity to develop immunity against them. Now that most people are back out and about and unmasked, even though it’s spring, these viruses are hitting a population with much lower immunity and we are experiencing more seasonal colds.
But the other factor is that COVID is circulating at fairly high levels and it appears that some people who have fair immunity develop mild symptoms, here’s the important part, their immunity is enough to prevent the viral load in their nose and throat from reaching a high enough level to turn the test positive. The good news is that if that’s the case, they’re probably not very infectious, if at all. So the bottom line is that if you have cold or flu symptoms and test positive, you most certainly have COVID. If you test negative, who knows, maybe, maybe not. But it would still be best that if you have cold or flu symptoms you should isolate yourself, at least until your symptoms clear. And if you do test positive, isolate until you have completed 5 days of isolation AND have a negative antigen test. If you reach 10 days and the antigen test is still positive and your symptoms, especially fever, have pretty much cleared, you can still break out of isolation.
One last COVID news item: The CDC this week has dropped any testing requirements for people flying into the United States. This decision will be reviewed in 90 days, but for now, travel is back to standard procedures. We do still advocate at least considering a mask in crowded areas of the airport and when on the plane and the engines are not running, but otherwise, back to the way things were before 2020.
Finally, this week, a monkeypox update. The CDC is beating a drum that this is not a disease limited only to those participating in high-risk sexual behavior and everyone is potentially at risk. And from a technical, theoretical standpoint that is true and you should be careful about contact with people with strange blistering diseases. But as the CDC says at the top of their monkeypox information page, “The threat of monkeypox to the general U.S. population remains LOW.” As of Wednesday evening, there have been a grand total of under 100 cases identified in the US and many of those are documented to have been contracted during travel outside the US. The numbers in some countries outside the US may be slightly higher on a relative basis, but nowhere does this represent a significant threat to the general population. As we have learned with COVID, viruses can mutate and anytime there is an outbreak of any viral disease, it certainly bears monitoring, but unless you or people you have very close contact with are engaging in higher-risk behaviors, your risk is very low. And even if you were to get it, unless you have a compromised immune system, the resulting disease is generally a mild viral illness. So, the key point here is not to let the media hype about this rare disease worry you. If you are in an at-risk population, be careful and be very aware of who you do have contact with.