Sleuthing the Sludge

Further refinement in waste water investigations answers important question about COVID evolution.

Early on in the Pandemic, waste water analysis proved that it was a highly useful tool for monitoring the level of COVID disease in communities. This was key at a stage when we had limited availability for testing individuals. It also demonstrated its ability to predict sudden surges in disease activity, prior to increased clinical cases; and finally waste water testing was able to alert us to the arrival of new variants of concern. Back in January 2022 we learned of “cryptic COVID sequences” being identified in the waste stream of New York City. These were viral lineages not seen in specimens from any humans at the time, and it was hypothesized that they were the result of animal infection, possibly city rats. This phenomenon was later reported from other ares of the country. Word on the street is that New York’s Pizza Rat has hired the same attorney as Tucker Carlson and Don Lemmon, claiming character defamation.

DOI: https://doi.org/10.1128/mbio.03621-22

Fast forward to last month when researchers from the New York Department of Public Health published results showing that indeed 16% of rats from several locations in the city were infected with COVID strains long gone from the human population. That seemed to clinch the possibility that COVID had established ongoing rat to rat transmission. (The other possibility being chronic infection of individual rats.) Now researchers from Wisconsin have used waste water testing and some detective work to further our understanding of COVID and its evolution in the human population. They detected waste water samples with very high concentrations of an unusual COVID lineage, which persisted unchanged for many months, and was not being found in any clinical specimens. By tracing the viral RNA backwards through the waste stream at each sewer junction, they were able to isolate the source to one half of a single building and a few restrooms. They did not do any clinical testing of people utilizing those restrooms; but it’s a pretty solid bet that the source is one or more chronically infected humans—unless Wisconsin rats have incredibly sophisticated toiletting behavior. This dovetails nicely with the case reports of Paxlovid treatment of chronically infected COVID patients discussed in last week’s post.

https://www.medrxiv.org/content/10.1101/2022.10.28.22281553v1. Tracing the origin of SARS-CoV-2 Omicron-like Spike sequences detected in wastewater Martin M. Shaffer, et al.

Other instances of waste water testing being able to identify a single building as the source of infection have been almost exclusively limited to college dormitories—to accomplish this in a general community of 100,000 people is quite a feat. Beyond that it also gives us further important clues to the evolution of the virus and the role of chronic infection.

When Omicron first appeared in South Africa in November of 2021, it was able to rate a brand new Greek letter by possessing a unique ensemble of 10 mutations in the RBD (receptor binding domain). That was a huge evolutionary shift, and it was hypothesized that this virus had likely originated during chronic infection of an immunocompromised host. In 2017 South Africa had an almost incomprehensible HIV prevalence of 14% in the overall population (and higher in some age groups), which translates into 8 million immunocompromised individuals. Quite a few of theses people are significantly compromised, since only 62% are on anti-retroviral drugs, and in the 15-24 year old group only 40% are on treatment. That is an enormous opportunity for COVID to experiment with chronic infection, and select for a wide variety of immune evasive mutations.

Let’s get back to Wisconsin now. The unusual viral RNA sequence persisting for months in the waste water was a COVID lineage that had briefly been present in that area in early 2021, before the appearance of Omicron—but it also had the signature Omicron mutations present in the RBD. The most parsimonious explanation is that the virus underwent convergent evolution over time in a chronically infected person. Convergent evolution means that in the presence of an inadequate immune response, the virus will eventually accumulate a series of the most favorable mutations as a response to the suboptimal immune pressure. In other words, the critical mutations which defined the incredible infectiousness of South Africa’s original Omicron, very likely arose independently in a chronically infected person in Wisconsin. That has important implications for our continuing need to widely monitor waste water, here and around the world, looking for novel combinations of mutations with known (and unknown) immune escape potential. Similarly, we should be looking for mutations we suspect can increase disease severity.

The next topic is another issue I have discussed in the past, and that is the fragility of trust in Public Health authorities. This is frequently viewed through the lens of political affiliation (everything seems reduced to that these days), but the issue is much more complex and nuanced. There is a current measles outbreak in American Samoa with 32 suspected cases. In 2019 there was an epidemic of measles in the South Pacific region with the near by, larger nation of Samoa recording 5700 cases and 83 deaths, almost all under age 5. This obviously is a vastly more lethal virus than SARS2-COV19 for children. Of interest is the fact that between 2017 and 2019 the percentage of eligible children in American Samoa who received MMR vaccine cratered from 73% to 34%. Changes like that don’t usually happen overnight. The cause was very clearly a terrible event in which two children received improperly reconstituted vaccine, and died as a direct consequence. The effect on the population’s psyche was tremendous, and is having serious consequences now. Throughout the Pandemic, public pronouncements by our own national Public Health officials have at times been confusing, contradictory or just obviously untrue. I am not referring to situations where scientific information changed down the road, invalidating an earlier judgement, but rather, wrong in real time. Apparently you don’t get many free passes to be incorrect or misleading in the court of public trust, especially when you are ordering people’s lives, mandating that they take a new vaccine, closing their children’s schools for a year, and dramatically affecting their livelihood. For those of you who have not read it I recommend this week’s article in the New York Times:

Dr. Fauci Looks Back on the Pandemic and What Went Wrong - The New York Times, April, 24,2023

Some may see it as a giant Mea non culpa, and in fact the last section is precisely that. Overall, I find it a genuine attempt to sum up and understand the many things that could have been done better. Fauci highlights the one thing we did, better than any other nation, and the one response that truly made a titanic difference—the development of multiple highly effective vaccines in world record time. Certain people will object to this characterization on the basis of COVID breakthrough infections. That perception is understandable, but entirely the result of clumsy, ill informed messaging on the part of the government. Vaccines against respiratory viruses, especially RNA viruses which mutate rapidly, are not typically 95% effective in preventing disease. Think of Influenza vaccine or Pneumococcal vaccine. That reality should have been anticipated and factored into public messaging right from the start with the emphasis on: “This vaccine will dramatically lower your risk severe disease death”. When the inevitable breakthrough infections became apparent to everyone, the initial government response was to down play them, and pretend they were rare events, another effort guaranteed to foster mistrust. Fauci acknowledges that vaccine mandates were another serious mistake. Leaving questions of individual rights aside, in this particular case vaccine mandates made no sense scientifically, and they hardened the resolve of some people, who as Fauci says, “Were on the fence”. The vaccines provided very substantial protection from severe disease and death—that is a fact. Of course there is the cottage industry of people who draw attention to themselves by criticizing everything possible about the vaccines; they inevitably would exist, but the CDC and FDA made their role easier.

It is obvious that Fauci with his medical and scientific perspective finds it impossible to understand the seemingly illogical influences at work undermining many people’s trust in Science. I think their mistrust is really not about Science per se, but directed at the government and its functionaries who interpret scientific data. Fauci repeatedly refers to vaccine hesitancy as a Republican verses Democrat division. It takes the Times interviewer to point out that the issue is far more complex with race, rural verses urban, educational and income levels also playing prominent roles. People are sensitive to an official narrative that belittles them, and it clearly does nothing to encourage co-operation. In a politically polarized era, if government gets into the realm of presenting itself as The Science, it skates on thin ice. Will we do better with the next Pandemic? I’m not optimistic. Resentment towards certain Public Health policies, which are now increasingly felt to have been ineffectual, mis-guided over-reaches, has caused the pendulum to swing so far in the opposite direction that it may have a significant negative impact on our ability to respond effectively to future challenges.

That’s it for this week. Peri and I came to New Jersey packing shorts and T-shirts, only to find it’s not a whole lot warmer than Telluride, where we had over 11 inches of snow on Tuesday. If you find these Infectious Disease updates interesting, forward them to your circle of friends and associates. Your comments are welcome, and the like button at the top floods the dopamine receptors.