COVID Transmissions for 10-1-2020

A Tale of Two Pandemics

Oct 01, 2020

Good morning! It has been 319 days since the first documented human case of COVID-19. September is on its way out.

Welcome to October! Spooky.

Today I want to do an in-depth comparing pandemics.

As usual, bolded terms are linked to the running newsletter glossary.

Keep the newsletter growing by sharing it! I love talking about science and explaining important concepts in human health, but I rely on all of you to grow the audience for this:

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Now, let’s talk COVID.

Response to Moderna mRNA vaccine similar in older adults vs younger populations

In results published yesterday in The New England Journal of Medicine, researchers found that in a Phase 1 clinical trial, the immune response to the Moderna mRNA-1273 COVID-19 vaccine was similar in older adults to the previously-reported immune response seen in younger individuals: https://www.nejm.org/doi/full/10.1056/NEJMoa2028436

This is not proof of efficacy. That proof will come in the Phase 3 trial. However, it is a reassuring piece of evidence to suggest that if the vaccine does ultimately work, it may work just as well in at-risk older adults as it does in everyone else.

The idea that it might have worked differently is a legitimate concern; many vaccines are not as effective in aged immune systems, and special formulations need to be made. That’s still possible here, but this suggests that it may not be necessary.

Preventing COVID-19 transmission indoors

It appears that the indoor setting is highly dangerous for the spread of COVID-19. Recently the New York Times ran an article discussing strategies that might help to make indoor environments safer even as the weather begins to cool in the global north and winter sets in: https://www.nytimes.com/2020/09/27/health/coronavirus-transmission-indoors.html

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

Exercising again

While sick, I took a long break from working out because I was sick, but also because I was trying to isolate. Today I got back on the bike trail and got in a workout, which felt great.

A Tale of Two Pandemics

In this week’s “presidential” “debate” (I feel both words belong in scare quotes, yes), the topic of the US response to the 2009 swine-origin H1N1 influenza virus pandemic came up. I’ll skip the political rhetoric and instead cut right to the chase: In the US, 14,000 people died in the 2009 pandemic, while 204,000 people and counting have died during the COVID-19 pandemic. There were no nationwide lockdowns and there were no major disruptions to daily life in 2009. This is not meant as a comparison between the US political regimes at the time; it is simply what happened.

Several times during the COVID-19 pandemic I’ve been asked why this pandemic is having a bigger, more world-changing effect, and I want to revisit this here. I am going to try to avoid an explicit political opinion to what degree I can, but I need to be clear about something: public health is the application of political apparatus to health problems. Public health is political, and there’s no way around it. However it does not need to be politically extremist, and is best done when avoiding extremes. I will endeavor to do so.

I’d like to tell you the story of my experience during the 2009 pandemic, and contrast this with what has happened in 2020 at various points. This should help us to understand some of what happened to make these two events different.

The 2009 influenza virus pandemic was something with which I have direct experience. It began around the same time as my formal training as a virologist. I was still going through laboratory rotations, and had just begun a rotation in the lab that I would ultimately join to work on my thesis, when the pandemic began.

At first, I did not understand the gravity of what was happening. I received an email that CDC surveillance had detected a new strain of influenza virus in California. At the time I hadn’t completed my Medical Microbiology course, and I don’t think I fully appreciated that this was an unusual event.

While every year there is a new seasonal strain of influenza virus, these strains have limited changes relative to the previous year’s strain. These slight changes are called “antigenic drift,” and are quite subtle. When a pandemic strain appears, the change is referred to as an “antigenic shift,” and is substantially more extreme. What this CDC email was telling me was that there was a shifted virus in town, and it was potentially going to cause a pandemic. Of course, it did.

This was the first point of difference between the 2009 and 2020 pandemics. Specifically, the existence of a CDC surveillance network that detected the new virus almost immediately upon its emergence. We are very familiar with influenza viruses and have a national system that catalogs isolates of virus collected all around the United States. There are corresponding global networks for influenza surveillance and there is massive international collaboration.

None of this existed for COVID-19. By the time we realized that the virus could cause serious problems it was already essentially January. While the 2009 H1N1 influenza virus likely originated in Mexico some weeks before it was detected in the US, it was a shorter time—and we should also consider that influenza viruses are substantially less contagious than SARS-CoV-2, so there is a certain time dilation in their relative ability to spread.

There are a few reasons for this difference. First, we had never seen this virus before, while we have been fighting influenza viruses for a very long time. Our ability to detect viruses is directly related to our knowledge about them, and we had a longer head start in getting that knowledge against the 2009 influenza virus. With SARS-CoV-2, we have been playing catchup in developing accurate detection and testing and deploying that nationally.

This had a clear impact on our ability to contain the virus early on. Unfortunately we did not catch up well and we are only now beginning to develop a national testing infrastructure. I believe the reasons for this were due to political missteps based on a mistaken strategy, but we also cannot deny that this began with our country’s infrastructure on the back foot. However, one would expect the wealthiest nation in the history of the world to be able to ramp up a little more quickly than it has.

The next major events of the 2009 pandemic surrounded identification of the at-risk populations. Normal seasonal influenza has a familiar set of at-risk individuals: children, pregnant women, and older individuals. These formed the core of the recommendations that came from the CDC. Interestingly, as time went on, we started to find that older individuals were not impacted as severely as we might have expected. This was a phenomenon that took some time to understand.

As it turns out, the 2009 H1N1 influenza virus was descended from a similar lineage as the 1918 H1N1 influenza virus. That virus circulated in human populations for many years after the initial pandemic, drifting and mutating with us seasonally as previous pandemic strains tend to do. It took until 1957 for a new influenza pandemic to occur, when H2N2 influenza viruses became dominant and essentially wiped out the 1918 strains.

What this means is that anyone who was under the age of 52 in 2009 would not have been exposed to a 1918-lineage influenza virus. Anyone over this age, however, very likely could have been exposed to such a virus. The older a person was, the more likely that their immune system had experience with this lineage.

This is important because the similarities in lineage led to cross-reactivity between the 2009 virus and antibodies generated to respond to the 1918 influenza virus lineage. While this cross-reactivity was not perfect, it was apparently sufficient to lessen disease in individuals who had them. These individuals all happened to be older.

Unfortunately, in the COVID-19 pandemic, we do not have a past global circulation of a highly similar virus. There has been some conversation about cross-reactive T-cells resulting from human coronavirus infections, but it is not clear if these are helpful or harmful in combating disease.

This is a problem that no political entity could have dealt with, but it is nonetheless a problem. However, where we did not have preexisting immunity protecting our older population, in the COVID-19 pandemic we have been extremely lucky that children have been largely spared. This is not universally true, of course—some children have become seriously ill or died, but then again it was not universally true that older individuals were protected from 2009 H1N1 influenza virus either.

At any rate, the initial CDC recommendations on the risk groups during the 2009 pandemic encompassed more people than were at risk from that virus, and were otherwise quite accurate. With COVID-19, there has been more guesswork and we still do not fully understand what makes the disease more severe in certain individuals as compared to others. This guesswork makes it complicated to try to create interventions that will help to save lives.

Additionally, as I’ve touched on before, we understand very well that influenza viruses are not generally spread long distances in airborne aerosols. Instead, influenza viruses spread easily through close contact and droplets. There are possibilities for aerosolization of influenza viruses, but these happen under unusual circumstances. Also, the presence of preexisting cross-reactive immunity may have had an impact on the ability of the novel influenza virus to spread through the population. Perhaps as a consequence of these facts, influenza is meaningfully less contagious than COVID-19. What’s even more important is that we understood how to contain the virus and could design key interventions for preventing its spread. Simply put, a combination of public health knowledge and features of the disease meant that it just couldn’t spread as quickly as COVID-19 could.

Continuing on the theme of “we understand influenza better than we understand SARS-CoV-2,” we also happen to have a large number of antiviral medications that can be used to combat influenza virus infections. While these are not always very effective at saving lives from influenza, they can sometimes shorten disease and can certainly be used in a preventative fashion. For COVID-19, we had no such tools at the beginning of the pandemic, and it has taken an unprecedented and colossal international effort to conduct clinical trials to determine interventions that can help to save lives. The fact that it took months to realize the potential value of corticosteroid treatments against COVID-19, combined with the other facts that I have shared, translates directly to additional deaths.

During the influenza virus pandemic in 2009, development of a vaccine began almost immediately, and took approximately 5 months from the first emergence of the virus. 5 months from the first emergence of COVID-19 would have given us a vaccine by May 2020. This was, of course, impossible.

The 2009 influenza virus vaccine was possible because there is already an extensive pipeline for influenza vaccine development. We already know the immune correlates of protection for influenza viruses, and we understand the mechanisms that generate those correlates. Every year, we redevelop the previous year’s vaccine into a new seasonal vaccine for use against the new seasonal strains. We know the safety and efficacy parameters of these vaccine designs and they have been extensively tested in clinical trials with lots of long-term followup. Therefore, we were ready to develop a new influenza vaccine that year, in time for the fall in the Northern Hemisphere. We are always ready to do that. It just so happened that we needed to develop a vaccine against a pandemic strain—and we did.

Matters are much more complicated for SARS-CoV-2. We do not have a ready-made option for vaccination against this virus. We cannot simply take a preexisting vaccine and change the antigens that are used in order to match this new virus. We do not know that such an approach would work, or that it would be safe. A robust clinical trial program has therefore been required for each vaccine candidate, and many vaccine candidates have been required because there is no preexisting path to success.

It is a lot easier to pass a test if you know the questions and the answers in advance.

For this reason, there is a part of the 2009 pandemic that I experienced that we haven’t yet gotten to—vaccine deployment. The US has an infrastructure for national deployment of seasonal influenza vaccines. We are working, through Operation Warp Speed, on an infrastructure for the deployment of a COVID-19 vaccine, but since it is currently unclear what vaccine candidate will be the “winner,” there are necessary logistical steps that it may not be possible to take in advance. I expect deployment of a COVID-19 vaccine to be slower, therefore, than the deployment of the vaccine against the 2009 H1N1 influenza virus ended up being.

Speaking of a vaccine, I want to be clear what a tremendous impact this has on our ability to contain influenza virus outbreaks. Given the existence of an influenza virus vaccine and the low contagiousness of influenza viruses, we can say for certain that every influenza death results from a chain of individuals that includes at least one person who simply couldn’t be bothered to get the vaccine. Consider this the next time you put off getting your vaccination. Everyone who gets sick with influenza has the potential to kill someone else who is unable to get the vaccine, or whose immune response to the vaccine isn’t sufficient. Every death traces back to someone who just chose not to be vaccinated. I don’t personally want to be responsible for something like that, and I also don’t want to get influenza, so I get the vaccine. If you can, you should too.

All in all, we had some tremendous structural advantages in the 2009 pandemic. 14,000 people still died, but tens of thousands of people die annually from influenza virus infections in the US. It is always tragic, but it does not compare to the 204,000 deaths (so far) that have occurred in the US as a result of COVID-19.

Something that I have not mentioned, though, is that in the 2009 pandemic, the government got out of scientists’ and public health officials’ way. The CDC was allowed to operate without interference to run their surveillance network, detect the disease, issue recommendations, and coordinate a response. Research funding was allocated efficiently and effectively to explore the properties of the novel virus. Treatment recommendations were delivered to the general public by the CDC and personal physicians primarily, rather than via press conferences or in YouTube videos.

This was not a structural advantage. This was a conscious political choice that paid off for the ability of the United States to respond to the novel virus. I cannot dance around that fact. The emergence of the virus was taken seriously as a scientific and medical problem, and was addressed as one. It was neither downplayed nor ignored. Resources were made available as needed. A response was mounted with coordination rather than disorganization. This allowed us to capitalize on the structural advantages that existed from the initial emergence of the virus.

The reality is that these pandemics have been very different both for biological as well as sociological reasons. The 2009 influenza pandemic, however, could potentially be seen as a rehearsal for what has happened in 2020. It seems that perhaps we did not make the lessons of that pandemic permanent for our society, and ensure that we would have a rapid and adequate response to this type of global disaster. As an emerging disease virologist, I must therefore wonder: if 2009 was a rehearsal for this pandemic, is there a future event coming that might make 2020 look like a rehearsal? If so, when it comes, will we still remember the lessons that we should have learned?

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