Epidemiology
COVID just won’t go away. Omicron keeps churning out new variants and each is just a little bit more infectious and just a little bit further away from the original strains of COVID that immunity from vaccines and prior infections was built on. This means that even those that are vaccinated or were previously infected with COVID are once again susceptible to symptomatic infections, but, very importantly, generally not susceptible to serious infections.
The big omicron-related surge of cases in the early part of this year in most of the world was due to omicron BA1. Then BA2 emerged in the United Kingdom and then moved to both Europe and the UK. The UK emerged from the BA2 wave in early April and the European continent only experienced a small BA2 bump in March, but both have since then been on a reasonably steady downslope. Asia has generally seen a similar pattern, with the exception of Taiwan, which continues to have the most widespread outbreak in the world. The last week or so, however, has seen a reversal in the general downward trend in Japan and Singapore, but too early to call it a new upward trend. The Middle East, especially Saudi Arabia and the UAE have also seen a similar slight upward turn that bears watching.
But despite most other regions emerging from Omicron and BA2, the Americas, especially the US and the Caribbean basin, are once again seeing steady upticks in reported cases. This is primarily due to yet another new strain, BA2.12.1. As I’ve discussed in previous weeks, as you consider the data and where it is going, there are two main points to keep in mind:
- The data is no more than a sample. In the US, the CDC estimates that the real COVID level is 3 to 4 times what is reported because few people actually report their case to any authority or test through testing services or labs.
- Most, but not all, epidemiologists believe that this current slow steady wave should be running out of steam anytime now… yet it keeps increasing. A large part of that explanation is the emergence of BA2.12.1 which does not seem to be any more virulent than the other omicron variants but is infecting more people, even many who had a previous episode as recently as January in the original Omicron wave.
New Variants
Two weeks ago, we reviewed two new Omicron variants emerging in South Africa, BA4 and BA5. At the time, these variants did not seem to be making much headway out of South Africa, so there was hope that they would not present an international concern. Well, this week they were named “variants of concern” and they are beginning to be found in new areas, including India, parts of Europe, and the UK. There are very few BA4/5 cases in the US, but again, with such a low proportion of cases being tested, the epidemiologists can’t really know for sure. Of significant importance, however, there is no evidence that BA4/5 causes disease that is any more serious than BA2 and its derivatives, although it does appear that they are less susceptible to vaccine or natural immunity. I wish I could say otherwise, but these new variants do present a high risk for causing yet another wave in many parts of the world, although most likely a wave similar to what the US is seeing now, with large numbers of cases, but minimal impact on hospital capacity and few deaths. In fact, using raw weekly statistics, the case fatality rate for Omicron now appears to be nearly equivalent to the case fatality rate for flu with both right at about .1%, and both skewed heavily to elderly and compromised populations.
Speaking of populations at risk, in the last week a new lab test that effectively risk stratifies people who may be at higher risk was identified. This test measures antibodies against “Type 1 Interferons.” Interferons are messenger proteins that the body uses to trigger various types of immune responses. The hypothesis is that if someone has these antibodies, they are less likely to recruit certain components of the immune response. So far, there is no recommendation for widespread use of the test because we don’t know if this gives information that can be used to tailor prevention or treatment, but this is a first step that should allow the development of needed targeted treatments and preventive tools. Still, since these antibodies are found in increasing proportion as people age, such screening may have utility in recommending greater attention to prevention and more aggressive early treatment if infected. This is not a test that is easily available at standard labs, but this will develop into yet another tool.
Treatments
Regarding treatment, an oral antibody treatment received full approval this week. This drug, Baricitinib, which inhibits a specific protein necessary for rapid viral reproduction, has become the standard of care for more severely ill hospitalized patients over the past few months and has shown significant improvement in survival for these patients. The new approval and usage recommendations now extend to all hospitalized adults, not just those with significant oxygen requirements or worse-off.
Additionally, the experience with the antiviral, Paxlovid, has been outstanding. Paxlovid has demonstrated a 92% reduction in hospitalization risk if started within 3 days of symptom onset. Importantly, it is still only authorized in the US for patients who are considered to be at high risk for progression to severe disease, but it is now fairly widely available. Over the past few weeks, we have had no difficulties in locating paxlovid in any non-rural area. The main reported side effects are a bad taste in the mouth in about a quarter of people taking it, some GI upset, mainly diarrhea, in a much smaller subset, and reports of muscle aches. However, we have not seen that in any of our patients as that side effect is likely just attributed to the virus. It remains critical for your physician and pharmacist to review any drugs you are taking as there is potential for severe drug-drug interactions.
Despite the development of effective treatments, the importance of vaccination should not be minimized. We are once again hearing a vocal minority saying that there is no point in getting a vaccination because even vaccinated people are getting COVID at a high rate. That misses the point. Vaccinations are not about preventing mild illness, but mostly about preventing hospitalizations and deaths, and the data is excellent that they do that. The side benefits include decreasing the likelihood of passing on an infection and a moderate decrease in the risk of mild symptomatic disease.
Boosters
In previous weeks, we have not pushed hard on second boosters for most people. The main reason why is that the second booster is showing little increase in protection against severe disease because the protection is already good with just one booster, and we only see a very moderate protection against lower levels of infection with the newer variants. For people who are at high risk of severe disease, especially those over 70 or with immune compromise, or their caregivers, we do think that even a moderate decrease in risk from a second booster is worth it. If the rates of infection continue to increase, especially if associated with higher hospitalization rates in your area, then we would consider a second booster more broadly. In the US, a good gauge is the CDC county-level community risk maps which assign each county a green, yellow, or red. It’s the red areas or yellow areas that are trending towards red, in which we recommend considering a second booster for those who are eligible, which includes people over 50 and anyone over 12 who has an immunocompromising condition. CDC is considering modifying its recommendations to allow boosters for all adults in higher risk areas and we should have more on that over the next few days.
Vaccines
Most of the upcoming vaccines will be spread throughout the month of June, but the FDA did approve Pfizer booster shots for older children (ages 5-11) earlier this week. The CDC Advisory Committee on Immunization Practices will meet tomorrow to make a recommendation on use. Giving a booster to this age group is not a slam-dunk because there is still a question of whether the booster really decreases already low risk enough to overcome potential risks. We are not going to take a position on this until we see the results of the Advisory Committee’s deliberations as they typically put out a well-supported document explaining the reasoning behind their decision.
Practical Thoughts
To wrap up this update, we will conclude with some practical thoughts for both individuals and organizations. On the individual level, most of the questions we are receiving are along the lines of someone trying to think through their risks of travel or attending an event this summer. You have to think of risks at two levels:
- If I get COVID, do I have a high risk of significant disease? Most people do not. Their risk is comparable to their risk of a bad outcome with flu. That being said, no one likes getting the flu and in a bad flu season, everyone should consider things they can do to decrease their risk, but without changing the basic way we go about our lives.
- Is my risk of getting COVID high? The fact is that, without regard to what the statistics are currently saying about the incidence of COVID, the risk is high. You’ve probably seen it yourself with many friends and family members getting COVID in the last month or so. The White House just predicted 100M cases of COVID this year, a scary number (as they intended so they could press their case for another tranche of billions of “COVID relief” funding). But to put this in perspective: there are about a billion viral colds every cold season. 40% of those are coronaviruses, and there are 4 primary coronaviruses in circulation. That means that each of those coronaviruses causes about 100M colds each year, along with some severe cases. So now we’ve just added another coronavirus to the mix. As we as a people develop immunity, we are still going to have a higher proportion of COVID cases with bad outcomes than with the other coronavirus, at least for the near future. But, with the available therapeutics, we know how to manage those cases.
So, should you just throw up your hands and assume you’re going to get it at some point? Our view is that COVID today is not something to fear as original COVID was, but you still would prefer NOT to get it, so yes, you should apply layered defenses to decrease your risk, but don’t be surprised or scared if you get it anyway. Most people who are on the younger side (less than 50 to 60) have very few worries, even without treatment, and those who have minimal to moderate risk factors, including just age, now have access to good and effective treatments and should make use of these treatments.
For companies, I recommend keeping 4 COVID management goals in mind:
- Comply with any COVID regulations or laws
- Maximize your workforce’s productivity which means balancing efforts to exclude COVID from the workplace with tolerating a small amount of risk to allow people to maintain productivity.
- Demonstrate to your workforce that you care about their health and wellbeing
- Be good corporate citizens in caring about the community.
The key tools are the layers of protection we’ve talked about extensively in previous updates including:
- maximizing vaccinations in the workforce
- controlling density in the workplace
- maximizing ventilation in work areas
- reducing contacts through the use of virtual meetings where possible
- case tracing at various levels of detail corresponding to operational and community risk; and
- considering testing programs in certain situations.
These tools can be dialed up or down and different tools employed or removed as covid impacts go up and down. There is no one “right” formula but considering the impacts of each tool on each aspect of the COVID management goals is an effective way to come up with what will work in your organization or situation.
