The New Pandemic Phase

Whither the Monoclonals?

No one can mistake the near instantaneous change in the news cycle, or in people’s attitudes towards COVID. Vladimir Putin is largely responsible for reorienting the previously non-stop news coverage of COVID, but the sudden shift in personal attitudes is more complex and a huge factor is the dropping case rate. People seem to respond to the acceleration and deceleration of case numbers much more acutely than to the absolute number. After all, we are still experiencing new daily case numbers (45,000), and daily deaths (1350), well above levels that induced very conservative behavior in a large percentage of the population not very long ago. The other factor is the perception that the disease has become milder now, and that the risk of death or hospitalization is much lower for vaccinated and recovered people. There aren’t many among us who alter our behavior in any significant way, when there is a particularly bad flu season, 60,000 deaths barely make the news cycle, and besides we are all tired of COVID restrictions.

The communication that COVID was going to become endemic and not eradicated by a vaccination program was another light switch moment, although not quite as dramatic as the current great unmasking event. Quite a few people outside the infectious disease or epidemiology world didn’t have a clear picture of what endemic means to specialists in these fields. It doesn’t mean mild, it doesn’t mean uncommon or rare. It simply means that the disease occurs on a predictable, regular temporal basis within a defined frequency range of cases for a given population. Not part of the scientific definition, but quite important for understanding how people react to the disease and behave, is the realization that societies accept the occurrence of the endemic disease, even if fairly common and sometimes severe, and they do not allow it to disrupt what they consider normal life. Enter the CDC’s new advice on masking. For people at high risk of severe disease who live in areas of moderately high COVID transmission, they now recommend that you consult with your physician about whether you should wear a mask. Returning choice in the decision to individuals, and suggesting they discuss it with their own physician, seems to me a clear indication we have crossed the endemic threshold both scientifically and socially.

Now for some of that science which we have to follow. I always thought that expression was just a little off. We all have to obey science like it or not. Step off the ledge and you will hit the ground in a very predictable timeframe. Absorb too much radiation from a nuclear power plant that has been hit by one of Mr. Putin’s precision ordinance and you will die. I suppose it was destined to be formulated that way though; “follow the rules which have been decided by some government functionary’s interpretation of the scientific data they have available today”, would not have been nearly as catchy or popular.

A very good article by Amanda Morris and Sheryl Stolberg appeared Sunday in the New York Times, describing the extreme difficulties patients are encountering obtaining Evusheld, the combination of tixagevimab and cilgavimab, which is available under EUA for the prevention of COVID in people with severe and moderate immunocompromise, or who can not receive vaccination due to severe allergy. The main thrust of the article is that the confusion, which has arisen as a result of poor federal distribution planning and terrible messaging about the appropriate use guidelines, has resulted in much of the available drug sitting unused. Just to review, all the other monoclonal antibody treatments except Sotrovimab have been rendered useless by the arrival of Omicron and it’s various lineages. Evusheld is the only monoclonal approved for prevention of disease, not treatment. It was found to have reduced activity against Omicron compared to original Wuhan virus, but was still felt to be active enough. Recent data has shown that Evusheld is less active against the most common Omicron variant now in the United States, BA.1.1. Based on this, the FDA 2 weeks ago changed the recommendation for use to double the dose. Data from David Ho’s lab at Columbia suggests that the rising Omicron BA.2 is even less susceptible to Evusheld.

In my last post I demoted BA.2 from Scariant to run of the mill Omicron, but could there be a catch related to this data with the variant’s relative resistance to the monoclonals? BA.2 has continued to outstrip Omicron and it’s percentage of, admittedly falling, COVID case numbers continues to double at just over a week. So very soon it should represent the most common COVID virus in the US, as it is now in many countries. You will remember that a very popular theory among virologists as to how several of the variants have arisen is that the virus becomes chronic for a prolonged period of time in an immunocompromised person. Under the evolutionary pressure of a sub-inhibitory immune response, the virus rapidly evolves many new antibody escape mutations, until it transmits to other people, then appearing as a completely novel, highly divergent variant. Evusheld may well prevent severe illness and death in the immunocompromised population who cannot mount a response to the vaccines. It almost certainly will not prevent infection in a large number of such people. Will there be a consequence in terms of generation of highly divergent variants? My crystal ball is more of a well shaken snow globe, but I think it is something to keep an eye out for.