COVID Transmissions for 8-11-2021

Does a spoonful of sugar cause severe COVID-19?

Aug 11, 2021

Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.

It has been 633 days since the first documented human case of COVID-19. We missed 632, the year that Mohammed died. This was a watershed event in Muslim history, leading to the creation of a Caliphate that in 633 succeeded in uniting the Arabian peninsula under the rule of Caliph Abu Bakr.

Today we cover some advice on protecting yourself from the third wave of COVID-19, and then I dive into a study that suggests blood glucose level may be connected to COVID-19 severity.

Bolded terms are linked to the running newsletter glossary.

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Now, let’s talk COVID.

Situation in the US: >100,000 new cases per day

The situation in the US as it currently stands is extremely bad. There are 6.3 million cases currently active, representing more than 1 in 100 people—it’s closer to 1 in 50, in fact. Yesterday, more than 101,000 people were registered as new infections.

The situation around the world is also indicative of a third global wave, but I don’t want to speak too sweepingly here.

I do want to review a few things, however, that I shared earlier in the pandemic and that I was hopeful I would never need to share again:

You must assume that you are a danger to others because you could have COVID-19 and not realize it; this is particularly true if you are not vaccinated
You should also assume that everyone else is a danger to you for the above reason
The current infection numbers are not a realistic representation of the current dynamics of the outbreak, and are probably an underestimate
- Testing is not rapid turnaround; even at its best, it can take 1-2 days to get a test result—you should assume that today’s testing numbers are reflective of tests performed between 1 and 3 days prior
- Realization of symptoms is not immediate, and can take between 2 days and 14 days; typically it is 4-5 days
- The above two points combine to suggest that today’s numbers reflect cases that began roughly 1 week ago; we should assume that without mitigation measures being taken, the outbreak has continued to grow in that time
- Vaccinated people may not realize they are infected with COVID-19 and may be less likely to test
- Even unvaccinated people with mild or asymptomatic disease may not be getting tested
- All of this comes together to suggest that it is extremely dangerous to be in public in the US right now without taking measures to protect yourself

So how do you protect yourself?

Take the advice of Linsey Marr, a world expert on aerosolization of infectious diseases:

Linsey Marr @linseymarr

Fully agree with @ashishkjha. He says 1. Vaccinate 2. Ventilate 3. Masks 3. Tests 5. Avoid indoor crowding Each adds protection. None alone enough in high transmission areas. Don’t have to do all, but the more you do, the more you keep folks safe & ensure safe in-person learning.

Ashish K. Jha, MD, MPH @ashishkjha

My kids' schools open in a month Have been talking to school leaders (unions, superintendents) across the US about how to keep schools safe We have 5 tools And if we use some combination of them, we can get all kids back to school safely, full-time So what are they? Thread

I recognize Dr. Marr used “3” twice, yes. Whatever. Her advice is just as good. I want to address each of these:

Vaccinate: vaccination reduces your risk of becoming ill by about 85%; it reduces your risk of hospitalization by more than 90%, and your risk of death by >97%—it is the single best self-protective measure you can take. It is unfortunately no longer enough to control this pandemic with vaccination alone, however, because not enough people are getting vaccinated fast enough. We need the other items on the list.
Ventilate: COVID-19 spreads when infected people breathe in the faces of people who are not adequately protected. If we keep airflow high, and filter that air indoors, we reduce the exposure of people to exhaled virus particles. This means if you’re seeing people outside your household, try to see them outdoors. If you must be indoors, try to be in a well-ventilated indoor space, potentially one with HEPA filtration or similar.
Masks: masks reduce spread of COVID-19 by as much as 80%. They’re nearly as good as vaccines, but neither is good enough on its own. Masking and vaccination together can get this thing under control, however. Mask up!
Tests: this is more population-level advice, but if every individual makes a decision to test regularly, then we’re a population. Get tested if you feel sick. Consider getting tested if you have been in public. Consider getting tested if you were around someone from outside your household. If you test positive, isolate yourself for 10 days or until you have received a negative test.
Avoid indoor crowding: This partly goes with ventilate. Look, the more people who are inside a place with you, the higher the chance is that one has COVID-19, and thus the higher the chance that you will get it too. Like I said, we’re close to 1 in 50 people in the US being currently sick with this thing. There are local variations, but on average, every time you are indoors with a stranger, you’re rolling the dice. The more strangers you’re indoors with, the more dice you’re rolling. Don’t get into indoor public spaces where there are large crowds. Don’t tempt fate.

The most important here on an individual level are vaccination and masking. The others are ideal conditions that you should also try to follow.

Vaccination is still how we’re going to end the pandemic, but that tactic can’t be used alone for right now.

Is blood glucose at the heart of COVID-19 severity?

I was recently sent a paper that suggests—quite strongly—that blood glucose levels explain why some people get very sick with COVID-19 while others do not.

This paper has an interesting methodology. It crunched through a large database of other papers, and using some machine processing, arranged their topics into broad categories, and built a network showing what topics were most frequently discussed alongside COVID-19. From this work, the authors were able to determine that blood glucose level is very frequently mentioned alongside COVID-19, and that it is often connected somehow with severity.

This methodology is not direct science, so I wanted to share this paper largely to put guardrails on it. When you look at a research database, and try to come to conclusions based on the aggregation of the research in the database, you have a very specific problem. As Tom Lehrer put it, “Life is like a sewer; what you get out of it depends on what you put into it.” If the research in the database is low-quality, then the conclusions from aggregating it will also be low-quality. However, if it is high-quality…then you could learn something interesting.

The authors of the paper go on to demonstrate quite a few correlations between blood glucose levels and COVID-19 severity. These correlations are largely demographic in nature, and I’m not impressed with their methodology as a way to show a definitive link between higher blood glucose and more severe COVID-19. However! I do think it suggests a testable hypothesis linking elevated blood glucose with more severe COVID-19.

That’s one thing that I think this sort of work is very good at doing—identifying hypotheses for future research. This study looked at other papers, and gives us a sense of what the general trend in research in COVID-19 severity may be suggesting. In other words, it gave us a sense of what this field of research “thinks” is connected to COVID-19 severity. The field itself may not have made this connection as fully yet, but through this work, we find the hypothesis sitting there.

Now the hard work begins of testing this hypothesis. A study should be designed that looks specifically at blood glucose and its connection with COVID-19 severity in a prospective fashion. While blood glucose may not be causally linked with COVID-19, it may be what we call an effective prognostic biomarker, something which can be used to assess the course of the disease before it has set in.

I happen to work on biomarkers as part of my day job. Validating them is a well-established formal process, and the path forward from here is exceptionally clear. There are a few possibilities for study design, but for most of them, you need a population of people with blood glucose level measurements, at least some of whom went on to get COVID-19. Several key performance characteristics would then be measured. One basic thing would be looking at the false positive rate (the number of times the marker predicted a severe case but it didn’t happen) and the false negative rate (the number of times the marker didn’t predict a severe case, but one happened anyway), and use these for further analyses that would help assess the value of blood glucose as a prognostic biomarker. That could be very valuable, because it could help to identify those patients who need the most medical attention before their COVID-19 has escalated to irretrievable severity. Giving these patients monoclonal antibodies, for example, could make a real dent in COVID-19 mortality.

We could do more, as well. I am skeptical that blood glucose levels are the sole cause of COVID-19 severity, but if they are even a contributor, we could try using drugs that lower blood glucose to treat COVID-19. A randomized controlled trial of such drugs in COVID-19 would be relatively straightforward to design. A small trial with a small number of participants, focusing on hospitalized patients who have elevated blood glucose, could help us understand just how important blood glucose may be to COVID-19 pathogenesis.

In other words, there are a lot of options for what we could do with this hypothesis. I think it’s worth considering. But I wouldn’t say that this research shows any kind of definitive connection. More work is needed.

The paper is found here, published in Frontiers in Public Health: https://www.frontiersin.org/articles/10.3389/fpubh.2021.695139/full

What am I doing to cope with the pandemic? This:

Working on a systematic review

Work has been eating a lot of my time lately. I have been assigned a big research project that begins with what’s called a “systematic review.” Using a predetermined search strategy, I am collecting all research related to a specific topic. I have also developed inclusion and exclusion criteria for adding the papers I find to my review, all of which I have to specify in advance in order for the work to be considered unbiased. I’m finding it pretty fun! But, I might be unusual in this.

Carl Fink commented regarding the chances of a 2-dose Johnson and Johnson regimen:

You knew I would comment, right?
I'm just waiting for the result of the "two doses of Janssen" study that's in Phase 3 right now. Might it be as effective as Pfizer and Moderna? Moreso?

I’ve been waiting for those results for a long time, too. I’m not sure we will ever see them:

I'm no longer holding out hope that we will see results of the ENSEMBLE 2 trial of the 2-dose J&J regimen. It should have read out some results months ago. I wonder if it ran into trouble because too many patients in the placebo arm went on to get actual vaccines. Either way I don't think it will read out.

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