Epidemiology
Cases in Europe and the US continue a downward trajectory, with cases in the US declining by nearly 12% over the last week and in Europe by approximately 5%, led by decreases in France and Germany, but with significant increases in Romania. The UK remains at a very stubborn plateau with cases above 50 per 100,000 per day. There is no easy answer for this plateau as vaccination rates in the UK are high with about 2/3 of all residents vaccinated. The plateau did start with the reopening of most businesses and hospitality services in mid-summer, but this reopening was not substantially different than that in much of the US or Europe. Despite the stubborn case rates, deaths and hospitalizations continue a downward trend, although neither are as low as in late fall or early summer.
In India, cases have fallen to less than 1.5 per 100,000 per day, a nearly negligible level, and even lower in Bangladesh. In East Asia, Thailand and Vietnam, both of which had significantly high outbreaks with stringent control measures instituted in late summer, are returning to manageably low levels, with similar happening in Japan. Singapore is very similar to last week, with continued spikes in cases despite high vaccination rates, so another area to watch closely for clues on the future. And South Korea, after a mini spike 2 weeks ago is back to a plateau, but at a low level of just under 4 cases per 100,000 per day.
Rounding out major regions, South America continues to make good progress with overall rates lower than the US, the highest being Brazil although even there the rate is lower than the US. Africa continues relatively unscathed, with the exception of South Africa, but even there the level is below the US and just slightly above Europe.
As we see cases going down, we are also seeing other, typically minor viral respiratory illnesses increase. Unfortunately, these respiratory illnesses are often indistinguishable from early COVID or COVID in vaccinated people, so strategies for clinically balancing risks/costs/benefits of isolation and quarantine strategies will be critical. If too quick to call an infection high probability COVID, then too many people will be pulled from work or school, impacting productivity and learning, but if thresholds are too low, the chance of allowing an infected person to affect a workforce will be unacceptably high. But a consideration may be that in a fully vaccinated, low-risk workforce, a reasonable amount of infection risk is tolerable.
Testing
A major alert went out today regarding a high number of false positives from the highly touted Ellume test kits from Australia, one of the early major investments made by the current administration. The manufacturer and the FDA announced the recall of nearly a half-million kits after the company reported that nearly a quarter of the results were false positive.
This recall is going to further impact the availability of self-testing because, as many have noted, the self-test kits that were plentiful in stores and online have become extremely difficult to obtain in the US and manufacturers indicated that despite the White House support for increased availability, the manufacturing and supply chain is weeks if not months away from meeting the White House goals. Partially because of this, the White House announced yesterday a $1B initiative to increase the availability of these kits just as another new type of home antigen test received emergency use authorization. We have two concerns with the home test kits: First, at the rate we are going, this will be a classic case of the government rushing to the rescue with large supplies right after the current flare-up ends and demand has passed. Second, there is a concern that the increased use of home testing will make good statistics hard to get as people testing at home are not reporting results to health authorities. This will mean that in the near future, reporting authorities are going to have to move to a sampling and extrapolation strategy to estimate the number of new cases. Unfortunately, that will leave the data open for manipulation. PCR testing is widely available, and return times are decreasing again as the number of tests requests in the US have decreased over 30% in the last week. In addition, an increasing number of local labs have installed equipment for rapid molecular tests, making quick, but more expensive high-quality tests much more available. One last comment on testing is that even as demand may decrease as rates decrease, the need for rapid accurate tests will not be going away, so getting tests back on the shelves will be important. As new cases continue to decrease, we will get to a point where more classic public health approaches of ring management of cases will become possible. Ring management entails making it easy for people to get a diagnosis early and rapidly and then quickly performing contact tracing and case finding so contacts can be quarantined or treated to prevent infection early before they have a chance to widely spread infection. Rapid tests are key to these efforts. The volume of cases is such that this is not a viable strategy yet, but we will get there in the intermediate-term.
Treatments
The other component that will make ring management strategies viable are rapid outpatient treatments, such as the soon to get EUA oral antiviral, Molnupiravir. Already released data on early treatment of COVID is demonstrating significant decreases in bad outcomes and additional data, not yet available, is hoped to demonstrate a reduction in duration of infectivity, which could mean significant reductions in home isolation times for people with COVID. An additional study is ongoing for post-exposure prophylaxis. If this study pans out, then combining rapid testing to identify and treat cases early, with ring management strategies to identify contacts and provide post-exposure prophylaxis will all work together to break the back of the epidemic once and for all. There were some early concerns on DNA mutation possibilities with Molnupiravir, so the safety profile and ongoing animal testing will be very important to decide if this drug can be a viable part of the strategy.
One last component that is needed to finally get us through this, is vaccination of the last major group of as-yet unvaccinated people who provide a reservoir for the disease. This is, of course, younger children, below age 12. It still looks like November is on track for the grade-school-aged kids, and possibly the first of the year for the pre-school group. Once we get the grade-school age kids, highly vaccinated, then putting this together with the strategies outlined above should end this.
When is that all going to happen? Remembering that approval of a vaccine or anti-viral is just a first step and that weeks or months are required to field these new capabilities in adequate quantities, we’re probably looking at early Spring as to when we may be able to call this active phase of the epidemic over, at least in economically developed countries.
