Overview
When we last spoke to our contact - Chair of Immunology & Molecular Biology at one of the nation’s top academic institutions - at the end of December, he was generally optimistic about our ability to "crush the curve" by mid-1Q21, which happened. Today, he's more cautious because: "Something happened toward the end of February; cases stopped going down and curled back up. That should not have happened, period." It remains to be seen if additional hot spots will emerge or if the fire burns out from here. This summer may not be as "normal" as it could have been; however, the vaccines are working and it looks like masks help to prevent the flu, which may not be as contagious as we all previously thought. Given recent COVID-19 case trends and 1Q21 earnings commentary thus far, we think we're seeing signs that the return to in-person care and reopening theses are playing out.
Highlights
- Something happened at the end of February: The combination of relaxed attitudes and variants helps explain only some of the increase in COVID-19 cases that started back in February. We should be at 1k per day by now. There is something we don't understand about the biology of the virus.
- It’s a numbers game: Vaccines have been highly effective so far with minimal breakthrough cases, but the high and rising case numbers globally give the virus increasing odds of generating a significant new variant.
- Treatment options have improved but remain misunderstood due to bad media coverage. Research is improving and plasma is effective at early disease stages, for example, but this is not widely accepted and more research is needed.
CALL NOTES
Background information:
- Our contact is a professor of medicine and chair of molecular biology and immunology at a large academic institution. His experience researching how microbes - bacteria, fungi, and viruses - cause disease and how our immune systems defend us spans decades.
What do you think is going on with elevated COVID-19 cases?
- To blame people is hard, but half the country wasn’t taking this seriously. Every day, more people are vaccinated and more are recovering from COVID - there should be fewer hosts. So, I don't know.
- One [likely] possibility is a combination of relaxed attitudes and variants. If the variants are more contagious and replace the prior, then there will be more cases (i.e., another curve on top of a declining curve).
- The more ominous explanation is that the variants defeat immunity. The CDC updated the breakthrough cases and as of mid-April there were ~5,800 fully vaccinated but infected people. That's a very, very small number, and shows tremendous vaccine efficacy; however, if the virus replicated w/ in those people and the new variant becomes contagious - i.e., it's more fit - then we're back to square one. We'd be dealing with a new virus.
- That's why I look at the number of new cases every morning - it's the "fire" or number of people that can infect others, and it's been hovering around 70k.
What about the fatality rate in Michigan? The volume of cases is about the same YoY but the death ratio has plummeted...
- Yes, that's the good thing - you have to adjust for the younger demographic, but the majority of 65+ have been vaccinated so naturally there are fewer deaths.
Is the variant playing a role or is it just age and stupidity?
- It's hard to know. Whatever happened at the end of February - or two weeks earlier - was way before Spring Break. Something with the biology of the virus is going on in the background that we don't fully understand. It’s possible that we know the population of variants has been replaced in some cities. It's good that mortality much lower.
Could mortality spike?
- Yes. In the worst-case scenario (above), the new virus becomes a problem. The likelihood of that is reduced by the number of vaccinated people. We need to get that "fire" down to 1k or less to reduce the probability of nightmare scenarios.
- Most of the fully vaccinated people are well-covered/protected, but there could be some people with antibody defects. That's a likely issue - even with the most effective vaccines - Hep B comes to mind - 10% of people don’t make antibodies.
- The mRNA vaccines are much more effective, so I think that probability is lower, but it's always a probability distribution and the selection of a new strain can happen in those people. If that happens, we’re also potentially back to square one.
The death rate remains depressed relative to past waves/spikes, per the "Michigan chart" we published ~1 week ago:
The global scenario?
- It's worse - look at India. The probability of someone being reintroduced is high. We won’t beat this with travel restrictions - have to crush the curves. Each one is an event and the way to think about variants -> SARS-CoV-3. It's just different.
- The virus doesn’t have infinite choices - it still has to make a protein, something with a shape. The neutralizing titer we measure is only a fraction of the immune response. T cell recognition, for example. There’s a layer of defense and that’s why these vaccines are working so well.
What about kids and teens? Is there something about the ACE receptor/ACE inhibitors or something unique about immunity in adults vs. kids?
- We have been spared thus far. In most pandemics, the kids and elderly are most susceptible. In this one, it's clearly been the elderly - we've been lucky. However, it's worrisome that the variants seem to be spreading in kids/youth.
We've been tracking cases, new coronavirus-like illness (CLI) presenting at EDs, and hospitalizations closely. It's remarkable how low/stable sub-18 has been, and it looks like the data are rolling over, again:
- It's the immune system that kills w/ COVID-19. If a patient's immune system doesn't respond well, e.g., people with B cell defects, for example, or if someone is on immunosuppressants, they don't get too sick or end up in the ICU, but they also can't clear the virus.
- Children may have less robust immune systems or we can speculate about passing other coronaviruses around, prior immunity, or how as you get older you accumulate more memory and respond differently. All the data can be interpreted multiple ways.
Coronavirus-like illness in Michigan looks like it's rolling over in the CDC data - what will make you feel better?
- The CDC data is very noisy and the media does not help when it could - it feels like the media wants to push hopeless, negative stories.
- The US deployed plasma and there was an inverse correlation (use of plasma and mortality) at the population level - that's difficult to explain unless plasma was helping. That's just one example, but the media could publish a sentence saying, "Work has shown that plasma works." You can send people home w/ COVID-19 with a unit of plasma - if we get into trouble with variants, we might only have variant plasma. What will the headlines say? Will negative or no headlines influence a physician's willingness to try something?
- Regeneron has done a good job, but they don’t have production capacity if we’re dealing w/ a variant. Some progress or positive press there would make me feel better because that new case volume curve should not look how it does - it should have gone straight down. It just doesn't look right - again, there's a variable we don't understand here, and the lags in the CDC data are an issue.
What's your biggest takeaway/message that you'd like to get across?
- This is not going to be over until we deal with it globally. Countries that don’t deal will "export" the problem. The problem with that is: the alternative is to lock down, but then economic growth problem.
- We're missing something - there are no new antivirals, but the vaccine(s) came early. Antibody therapy works if people are treated early, but we need small molecule antivirals like we now have for HIV (there were hundreds being researched for HIV, there are none for SARS-CoV-2 now - it's one area that our response has not been strong).
What do you think about COVID-19 testing?
- With endemic COVID, there will be a lot of testing. I think rapid testing will come. The problem is not the variants. Rather, there's a lot of “human meat” out there. We're doing once per week here - it's hard to do it more than that w/ PCR capacity - rapid tests will be helpful in containing COVID-19..
Long-COVID - any updates? We've heard estimates ranging from 10-30% of people w/ COVID-19 end up with lingering symptoms...
- It's a big number. Medicine is really good at diseases you can find a cause. It's terrible with diseases like this where a patient shows up with symptoms that you can’t put together - chronic fatigue, long-COVID, Brain Fog (what is that?) or low energy. We’ll have millions of people with these soft symptoms and medicine must come up with a different way to deal with them.
Please reach out to with any feedback or inquiries, questions for future field checks, or requests for underlying data.
Thomas Tobin
Managing Director
Twitter
LinkedIn
