It has been a few weeks since my latest attempt to step back, take a look at everything we think we have learned and know about coronavirus and issue a status report, with a very abbreviated look forward. I will do the look forward first. I have no idea what will happen next. All the research I have read on seasonality and other factors potentially bearing on why the epidemic seems to surge in one place and then another, but not in some, provides no clear guidance or answers. I don’t think anyone knows. I think attempts to suppress the virus or even mitigate spread are futile. It is here to stay, we have to and we will adapt. We will adapt in large part because, among the realm of potential pathogens, it is not particularly lethal, rarely causing serious disease or death, particularly to the great bulk of the population. Will it re-emerge in northern temperate latitudes as weather turns cooler? Is that what is happening in Europe? Why doesn’t it seem to be happening in the US? Have some areas seen a combination of enough infections and enough pre-existing immunity to substantially slow any possible transmission? I don’t think anyone knows. More important is that we recognize the need to adapt, not make futile attempts to suppress, and that we balance all the costs and harms inflicted by both the virus and our actions in response to it, and act in the interest of the greatest good for the most people, not being obsessed with preventing every possible CV-19 case or death, no matter what the damage to the population’s health and its economic, social and educational well-being.
Otherwise, the status is pretty much as of the last similar post, with the exception of the PCR testing issues. A lot of unanswered questions remain. This is an interesting coronavirus strain; nothing really noticeable for almost everyone who is exposed to it, very deadly for a few–the frail elderly, the morbidly obese, some with other serious illnesses. How is it transmitted–mostly in larger droplets, is there some extensive transmission by smaller aerosol particles, how long does the virus remain viable in such particles, can be picked up off of surfaces on which is has been deposited? Why is there less transmission outdoors–sunlight, air flow and currents? We don’t have definitive answers to such basic questions, particularly in regard to the quantification of method of transmission.
How much virus does it take to infect a person, how wide is the range of potential dose, what variables affect the dose needed to start an infection? How much virus shedding does a person need to do to become infectious, how long do they remain infectious, does infectiousness vary with severity of infection and disease? The evidence is not conclusive but it appears that asymptomatic and mild infections lead to a lower viral loads and shedding and a shorter period of infectiousness. The peak of infectiousness appears to coincide with the day of symptom onset, and decline somewhat rapidly after a few days. Again, important unresolved issues.
Are we using adequate tests to detect infection and assess the presence or level of infectiousness. The gold standard would be to culture samples from everyone tested, but that is more expensive, and more importantly, too slow for practical use, when it is crucial to identify truly infectious persons and isolate them and identify others they may have transmitted to. We know with some certainty now that many labs are calling very marginal results a positive result (according to the New York Times story, up to 90% of all “cases”), and are ignoring fairly well-established research correlating cycle number with culture positivity. Once again, I am baffled by the ignorance, incompetence or willful disregard of the science by our supposed public health experts. This is a critical issue for people to understand if they are to have an accurate picture of how widespread the epidemic actually is, and it has direct, very serious ramifications for the individuals receiving a positive result. Businesses and schools face the threat of shutdown due to the presence of cases, which may well not be cases. How could public officials not have proactively brought this issue to the attention of the public and addressed it by full transparency about the cycle number being used to call a result positive? How could they not have insisted on retests of marginal results? Unfortunately, these failures contribute to conspiratorial thinking. It leads to an appearance of trying to frighten the public with an excessive number of non-existent cases and justify extreme mitigation actions directed toward a spread that isn’t really occurring. But why should we be surprised given what we have witnessed from government to date?
We can say with increasing confidence that almost all patients who survive develop a robust and durable adaptive immune response, both B cell (antibodies) and/or T cell ones. This includes people with symptomatic or mild infections and disease. Antibody surveys alone will not identify all persons who have been infected nor will many antibody assays be sensitive enough to pick up the presence of antibodies in all previously infected persons.
This epidemic should have shaken up the obvious complacency of the epidemiologists and infectious disease specialists, who were completely incapable of understanding the epidemic other than through the lens of a textbook model, and even then forgot basic first principles. Human heterogeneity, variability is the key, and understanding and incorporating that variability into our view of the epidemic is the most critical task. Instead we got simplistic models which largely treated the entire population as homogenous. God bless Gabriela Gomes and her associated authors for sparking a different approach to modeling, one that incorporates variability along crucial dimensions of susceptibility and infectiousness, resulting in model outputs that look more like what has actually happened. And where were the immunologists to warn us early on that given the almost universal prevalence of infection with seasonal coronaviruses, people might have pre-existing immune responses to this strain, responses which could be a primary factor in the variability in susceptibility and infectiousness.
What happens at the individual level is collectively reflected in the population level course of the epidemic. At the individual level, the likelihood of infection, most importantly, of an infection serious enough to make the person infectious, is dependent on a myriad of factors: the age and sex of the person, health status, population density of where they live or work, number of contacts and who those contacts are with, the strength of their general immune system, the potential of cross-reactive adaptive immunity, the number of virus particles to which a person is exposed, and so on. When those factors are properly analyzed and fed into modeling formulas, you get a more accurate projection of the shape of the epidemic.
An epidemic slows when the virus no longer easily finds unexposed humans which it can infect and whose cells will be vehicles for replication and transmission to other humans. That spread can be influenced by a variety of factors and actions, but the most reliable and least costly in many dimensions, is having a sufficient number of people with adaptive immune responses that limit infection, either from being infected by this strain, or because they have the pre-existing cross-reactive response. Because of heterogeneity in contacts, in dose needed to spark an infection, in immune and health status, and other factors, a smaller fraction of the population than traditionally assumed may need to be infection resistant to cause a substantial slowing of the rate of transmission. A vaccine can also help create this population-level slowing of transmission.
I am not going to dwell on the disastrous governmental responses to the epidemic to date. Fed by media hysteria and an obsession with risk aversion, but only to one limited risk, enormous damage has been done. Our approach to quantifying the epidemic has been irresponsible and also fed the hysteria. Massive testing with no regard for false positives or marginal results leads to the appearance of large numbers of cases and surges in case growth. The unprecedented treatment of every death of every person who happened to have, or be suspected of having, some CV-19 in them at some time prior to death, leads to a death number that really is absurdly exaggerated.
There has been much debate about the comparison to flu. I keep pointing out that if we tested for influenza like we do for CV, if we counted deaths with flu virus like we do those with CV-19 virus, and if we had no vaccine for flu, influenza would account for far more cases and deaths than CV-19 has, and across a much wider range of the population. Does anyone actually believe that the response was justified by the threat?