As you know, every now and then I like to try to evaluate where we are in regard to the epidemic and the responses to it. That includes understanding the nature of the virus, the nature of the illness it can cause in some people, the nature of our immune response to the virus and the appropriateness of governmental responses to the epidemic.
Some things are pretty clear. This is a dangerous virus for a small proportion of the population, for the vast majority it is a non-event. It is a serious public health concern, but actions taken to mitigate the epidemic can have equally or more serious health consequences. This is a tough and persistent virus, and few actions taken to mitigate spread seem to have any real or lasting effect. Unless you are willing to lock and isolate people in their homes for an indefinite period, which isn’t economically or socially feasible, it isn’t going to be possible to completely suppress the virus or its spread. We need to accept that and accept that for the population as a whole, this is a very low risk pathogen. The responses should take that into account.
One of the things that has really struck me about the response to this epidemic is the failure of the experts to use the knowledge they supposedly have in their own fields of expertise. One example is the immune response. I have been spending a fair amount of time with my immunology textbook and some general material on the immune system. The experts got everyone so hung up on antibodies, and in particular, on “neutralizing” antibodies, which in the case of this virus they said meant antibodies that blocked the activity of the portion of the virus that was used to gain entry into human cells, the so-called spike protein. And the antibodies had to be circulating in the blood. Of course, the immune system is so much more complex and versatile than that.
The few open-minded and broadly thinking researchers remembered that T cells can be equally important, whether fighting off an acute infection or providing the adaptive response against reinfection. In hindsight it seems obvious that the routine encounter with seasonal coronaviruses would have left some immune response, I recall wondering in regard to the cruise ship numbers if that could have anything to do with the low numbers of infected persons and the asymptomatic cases. So now it seems clear that there is a T cell adaptive effect against the current strain in many people and that this response may occur in the mucosal tissues of the upper respiratory system as well as the blood, and that there likely is some pre-existing B cell based response as well.
And in regard to antibodies, produced by the B cell complexes, some antibodies that bind have a role in directing other parts of the immune system to fight invading pathogens. And neutralization may also occur by interfering with the virus’ ability to replicate. So even though the spike protein and the receptor binding domain may be relatively unique and not well recognized by the preexisting circulating antibodies and B memory cells, other parts of the current strain are, and binding in some of those epitopes, or regions, that are recognized, can also inhibit the work of the virus. Current antibody assays that are used for either measuring response to recent acute infection, or to the presence of cross-reactive responses from prior seasonal coronavirus infections, are likely to miss the whole picture. Several recent papers have critiqued antibody assays for these weaknesses.
So I have come to be skeptical of many antibody surveys as being incomplete and probably missing the full immune response. The more comprehensive approaches seem to pick up this full response. I am very encouraged that much of the population has pre-existing immune responses that quickly dispatch the virus if they encounter it. And most people who have any degree of illness develop a strong, lasting and diverse response to the current coronavirus strain. This is very, very positive.
The epidemiologists and their modeling compatriots have also been dreadful. They completely overlooked the basics about variability in susceptibility and infectiousness and they minimized the impossibility of accurately building forecasting models. The scarcity of dependable data should have been emphasized and these supposed experts should have strongly warned that any projections should not have been used for developing the policy responses. The traditional epidemic model may be too simplistic. I have come to think of “infection” in more complex terms as, it doesn’t likely mean exposed people aren’t “infected” in some way, just that they don’t become “infectious”. So back to the standard model, it makes me think “susceptible” doesn’t mean much, but “infectious” is really important, and my schema of the progress of the epidemic would have a lot of focus on what happens when a given individual encounters the virus, because we all likely will encounter it at some point. It appears that for many people, the encounter ends quickly at a superficial level, by that I mean at the interface of the mucosal tissues of the upper respiratory system, and the virus never gets a chance to start replicating, or does so at such a low level that the person is not shedding an infectious dose. So an accurate model would be focussed on what percent of people who encounter the virus become infectious. And among those who become infected and infectious, what percent impose any burden on the health system. It appears to me that less than 1% of patients actually need hospitalization. And the fatality rate is going to end up being very low as well.
But the complexity of what it means to be infected and infectious also makes the modeling, and the public health response, more complex, because what does it mean to be recovered? If you quickly fought off a normal dose of virus, would you fight off a much higher one? Could some aspect of your immune system wane to the point of leaving you more vulnerable? Does not becoming infectious even though you encountered the virus still lead to development of more specific immune system responses, B cell and T cell ones, against this strain? So there are interesting and important unanswered questions about the nature of the infection and the human response to it, although we have a pretty good directional sense.
The public policy response to the epidemic can only be characterized as disastrous in most countries. With no analysis or thought to the consequences, economies were just shut down. We will be living with the results for a long time. People have been terrorized far beyond the actual threat the virus poses. People are missing needed health care. People feel even more isolated, lonely and anxious. Children are harmed in their social development and prolonged isolation will weaken their immune systems and make them more vulnerable to both the current virus and other infectious agents. It was completely unnecessary, as a couple of brave countries have shown, to approach the epidemic like this. Hopefully people will eventually recognize this, because we can’t make the same mistakes again.