Omicron
The news this last week has been dominated by the omicron variant and what we know and don’t know about it. We did a fairly extensive introduction to omicron a couple of days ago in a special update. In this update, we will review what we have learned over the beginning of this week.
The short answer is that we have not definitively learned much about omicron itself, but we have learned more about what the issues are and a rough timeline for when we can expect to know more. First, as we noted in the special update, there are three major characteristics of any new variant that need to be assessed: Its infectivity, the severity of disease it causes, and how well our countermeasures (vaccines, medications) work to reduce its impact. We are now about a week into the omicron phase of this epidemic here’s what is developing in each of those areas:
Infectivity
We have some reason to believe it is more infectious, but that still must be confirmed. In fact, the data on this is conflicting. On one hand, what caught people’s attention last week was that the number of cases in South Africa took a notable turn upwards beginning about two weeks ago and initial reports were that a substantial proportion of these new cases were due to a new variant, which we now know to be omicron. But then epidemiologists in South Africa and Israel took a closer look at the data and have estimated a reproductive rate of only 2, meaning that in the absence of vaccines or other controls, each infected person will likely spread the infection to 2 others. 2 still means that this could double cases roughly every week but compare this against delta which has a reproductive rate somewhere above 5. There is no way that omicron should out-compete delta if this is true. So, the bottom line is that there is much more that we need to learn about infectivity. If it is high, we will have the opportunity to learn rapidly as the omicron variant has been detected, albeit in very low numbers, in most developed countries, and as of Wednesday afternoon, including the United States. If it is more infectious than delta, then it will likely spread through the US over a period of 4 to 6 weeks, but we simply don’t know now.
Severity
Concerns about severity are based on the nature of the mutations seen. There is still no clinical evidence of increased severity and multiple authorities in South Africa continue to note that they are seeing less severity. Hospitalizations in South Africa are on the increase, but not out of proportion to the increase in cases, although there are timing issues as hospitalizations trail diagnoses by 5 to 7 days, so we have not had enough time to make a judgment on severity. Until we have more data, do not get swept up in the media message that features of the virus raise the chance that it is more severe. That could be true, but it could also be true that these mutations have made it less severe as the South African doctors are noting. We just don’t know yet.
Mitigation
Again, the media is focused on the number of mutations seen at the spike protein and expresses concern that this will change the geometry enough that current vaccines, and possibly, natural immunity, will be rendered ineffective. Is this possible? Yes, but this is really the biggest unknown. What we do know with reasonable certainty, however, is that the virology community will need about 2 weeks to grow the virus and then directly measure how much it is controlled by antibodies in blood from people who at various ages, number of vaccinations, time out from vaccinations, and, importantly, current formulations of monoclonal antibodies. Many authorities say that by the week of December 13, we’ll start to have good data on antibody immunity. Note that it will take longer to develop data on cellular immunity. At the same time, however, epidemiologists will be gathering data on real-life experience with the virus in the wild and will develop practical data that can be compared with the lab-based predictions on the effectiveness of mitigations. With regard to the monoclonal antibodies, if there is a drop-off in their effectiveness, then even more rapidly than new vaccines can be developed, new versions of monoclonal antibodies can be developed and manufactured in large quantities, so we would not in any way be sitting ducks until new vaccines are available.
Vaccines
Addressing how fast vaccines could be developed, both the Moderna and Pfizer CEO addressed that in press conferences this week. Both indicate that the development and large-scale production of vaccines tailored for a new variant would take about 3 months. Preliminary work on this has already started and the FDA long ago said that if a retooled vaccine is ever required, they will not require a full 3 phase trial program in order to grant authorization. Instead, they would likely require a relatively short safety study only. Putting that all together means that if a retooled vaccine is required, it could be ready in early Spring. But remember, in any event, it is exceedingly unlikely that the current vaccines could be ineffective, just that it is possible that a new variant could make them less than optimally effective and retooling could bring them back up to full effect.
One other point on vaccines. With the current vaccine, the World Health Organization has been very loudly complaining that developed nations are hoarding vaccines and not allowing developing economies enough access. Data over the last couple of weeks is showing that availability in developing economies is not being limited by supplies as much as by a combination of low demand and problems with distribution. Distribution is primarily in the realm controlled by the World Health Organization, so as they are running into shortcomings on their end, watch for them to ramp up complaints about supply to cover up distribution issues. In any event, it does not appear that people in developed countries need to feel guilty that they are primarily responsible for depriving others of vaccines, supplies are good and increasing and as soon as Novovax goes into large-scale distribution, many of the logistic issues related to cold-chains will go away.
Epidemiology
Moving away from omicron, looking at the epidemiology this week, we are reminded of the old truism that association does not prove causality, but the link between the number of months past full vaccination for large portions of populations and increased case rates in those same populations are pretty strong. Additionally, we are seeing in multiple populations that when booster rates increase, case rates decrease. In fact, in every state where the booster rate exceeds 27%, cases are dropping by double-digit percentages week over week.
In other parts of the world, cases remain low in most regions, with Europe and the US remaining as areas with the highest overall case rates. It’s hard to interpret trends in the US due to the effects of last week’s Thanksgiving holiday, both because there were two days of little tracking due to office closures as well as uncertainty over the transmission effect of the single biggest travel weekend since Thanksgiving 2019. In Europe, some countries are up, and some are down, so it’s hard to pull out any clear trends. Case trends in the UK, however, appear to have started back down, just as predicted two weeks ago by the National Health Service modelers.
Therapeutics
Merck’s antiviral drug, Molnupiravir, was given a green light by the FDA’s external vaccine advisory group, but only by a vote of 16 to 10… not exactly a rousing endorsement. In the final data, the Merck drug only decreased hospitalizations and ICU admissions by about 30%. Generally, antivirals are considered successful if they can have a 50% decrease in these rates. The Pfizer antiviral, Paxlovid, however, is reported to have an efficacy of nearly 90%. The FDA has not yet completed its review of Pfizer’s data and has not scheduled a committee review although this will likely happen before the Christmas holiday. Importantly, neither Merck nor Pfizer expects omicron to alter their efficacies by any significant amount as neither pill targets proteins affected by the mutations on the spike protein seen in omicron.
Common Questions
The most common question we have received this week is, “Right now, do I need to do anything differently because of omicron.” Our answer, for right now, and probably for at least the next two weeks, is, “generally, no.” Unless you are thinking about international travel, we do not see any need to change behaviors in response to this. While information is developing, we would be careful about planning international travel in the near future. We are seeing countries that are suddenly closing borders to international air travel. Most only for travel from Southern Africa, but others have shut down all non-citizen entry into their country. If omicron has been quietly spreading undetected in other countries as many suspect, then you won’t know if where you are visiting may suddenly find itself on the travel ban list, making a return home much more difficult. Even though for all the reasons we went through at the outset of this, we don’t how bad this variant is or isn’t, the nature of governments around the world is that they are extremely risk-averse as it is more politically safe for them to overreact than under-react.
