A few weeks back I wrote an article about an observational study published in Lancet that, among other things, looked at whether there was any correlation between stringency of lockdown and the number of people who died of covid. It didn’t find any correlation, which suggests that lockdowns don’t work. That study did have some major limitations however.
First of all, it was observational, based on analysis of statistics, and so can only show patterns (or lack of patterns), not cause and effect, and retrospective, meaning that the researchers based their analysis on existing data that had been produced for other purposes. This is a relatively low quality form of evidence. Second, the follow-up period was short, with data only being gathered until May 1st. It could be argued that this is too short a time period to see an effect of lockdown on mortality.
Now, however, we have some new data that addresses both of these limitations. The first comes in the form of a prospective cohort study that was published in the New England Journal of Medicine. A prospective cohort study is a study in which a group of people are recruited and then followed over time to see what happens to them. This is better than a retrospective study, because there is no way of looking at the end result before you begin, and thereby less scope for “cheating”. It’s not as good as a randomized controlled trial (the gold standard in terms of scientific methodology) because you’re not in control of all the variables, and you don’t have a control group, but it is a big step up from just looking at national statistics and trying to draw conclusions from them.
The study was funded by the US Defence Health Agency and DARPA (the Defence Advanced Research Projects Agency), and the purpose of the study was to see if quarantine rules that had been implemented in the US Marine Corps were effective at preventing spread of covid-19. The intervention involved many different parts, so we’re going to go through it in some detail. The group that was studied was new Marine Corps recruits, who were going through their initial training period.
The new recruits were asked to self-quarantine at home for the two weeks immediately prior to arriving at the base to begin their service in the Marine Corps. When they did arrive, they were placed in a further two week quarantine at a college campus that was being used exclusively for this purpose. During the second quarantine period, the recruits were required to wear face masks at all times except when eating and sleeping, to always be at least six feet apart, and they were prohibited from leaving the campus. They had to wash their hands regularly, and were not allowed access to electronics or other items that might contribute to surface transmission of the virus. Furthermore, they spent most of their time outdoors.
The campus was organized in such a way that all movement was unidirectional, and every building had separate entry and exit points, to keep people from getting too close to each other or bumping in to each other. During their time in campus, recruits only had direct contact with other members of their platoon and their instructors. They were not allowed to interact with any of the on-site support staff (cooks, cleaners, etc).
The recruits lived two to a room, ate together with their platoon in a communal eating area, and used shared bathrooms. They were required to disinfect the bathrooms with bleach between after each visit, and the dining hall was cleaned with bleach in between meals.
All recruits had their temperature taken daily and were asked on a daily basis about symptoms. At any sign of symptoms or a raised temperature, they were put in isolation and not allowed to return to their platoon until a PCR test came back negative.
A total of 1,848 marine recruits were enrolled in the study and the average age of the participants was 19. PCR tests for SARS-CoV-2 were carried out on arrival at the campus, and on days 7 and 14 of the two week on-campus quarantine. Anyone who tested positive at any of these time points was immediately placed in isolation. A further 1,619 recruits declined to participate in the study or were excluded because they were under 18. However, the 1,619 individuals who declined to participate in the study followed the exact same restrictions as the study group, except for the fact that they didn’t have PCR tests taken on arrival or on day 7. They therefore cannot be used as a control group, which is unfortunate.
So, what were the results?
16 out of 1,847 recruits (0,9%) tested positive for SARS-CoV-2 on arrival at the campus. All of them claimed to have quarantined at home for the full two weeks before arrival and had not been exposed to anyone with symptoms during that period. 5 of these 16 individuals had antibodies to covid, and were thus most likely not infectious (antibodies generally develop around two weeks after infection, at which point people usually are no longer infectious). Only one of the 16 had symptoms. All 16 were isolated from the rest of the recruits as soon as their results came back positive (within 48 hours).
On day 7, a new round of PCR testing was carried out and a further 24 recruits had become positive to SARS-CoV-2, of which three were symptomatic. On day 14, a final round of PCR testing was carried out, and 11 more recruits had become positive, of which one was symptomatic.
Overall, 1,9% of participants became PCR positive during the two week period, in spite of all the measures taken to prevent spread, although only four people developed symptomatic covid. It is important to note that the infected people were not spread evenly throughout the platoons. Some platoons had a lot of infections, and others had none.
The researchers followed up by looking at which specific covid strains were present among the recruits, in order to figure out where people became infected, and from whom. Not surprisingly, infection happened within platoons, and more specifically, to a large extent within shared bedrooms. In spite of the fact that different platoons were walking in the same corridors, using the same bathrooms, and eating in the same mess hall, no infection happened across platoons – all infections happened within platoons (with one exception, where two people from different platoons were sharing a bedroom).
Another interesting result from the viral genome mapping is how many people a single infected person could go on to infect, in spite of all the measures in place to prevent spread. In two separate platoons, one person brought the virus in from outside, and spread the infection to eight other individuals within their platoon over the course of the two week period.
In some ways I find this the most interesting result of the whole study. The fact that you can go from a single infected person to nine infected people in one platoon over the course of a two week period, in spite of the use of extraordinarily stringent methods to prevent spread, shows how unbelievably infectious SARS-CoV-2 can be.
What can we conclude from all this?
First of all, it is important to note that this study has one problematic aspect, and that is the use of PCR without some kind of follow-up to confirm that a positive result really is a true positive (for example with a viral culture). A second problem is that there is no control group, so it’s impossible to say what would have happened had there been no lockdown-like restrictions.
That being said, this study clearly shows how effectively the virus spreads even when extremely repressive methods are being used to contain it. In spite of strict physical distancing, rigorous hand and surface hygiene, face masks, PCR based screening, daily symptom checks, and two weeks of quarantine before even arriving at campus, the virus still snuck in and was still able to spread effectively among the recruits. The stringency of the measures that were put in place among the recruits was far more extreme than anything that could be accomplished in a civilian setting. And yet, in two of the platoons, the virus still spread like wildfire.
Having said that, it would have been nice to have had a control group to compare with. Hopefully a proper randomized controlled trial will come out at some point that clarifies the remaining question marks, and gives a more definitive answer to the question of what effect, if any, stringent lockdowns have in terms of stopping the spread of covid-19.
There are three other aspects of this study that I find interesting. The first is that it suggests that pre-symptomatic and asymptomatic spread does happen with covid, since anyone showing the slightest symptoms was immediately isolated, and in spite of this, the virus still spread. And the two individuals who were thought to be the index patients for the two big clusters never developed any symptoms themselves
The second is that it gives further credence to the idea that most people with covid are not very infectious, while a small number of people are “super spreaders”. If we presume that the five people who were both PCR and antibody positive on arrival no longer had active infections, then that means 11 people had active covid infections on arrival at the campus. Two weeks later, an additional 38 people had been infected. Of those, 16 were infected by just two people, which means that the remaining 22 were infected by some combination of the other nine. So, two individuals were clearly far more infectious than the rest.
The third aspect that is interesting is that infection only happened within platoons, not between them. That is in spite of the fact that different platoons were using the same spaces, only at different times. To me this suggests that SARS-CoV-2 doesn’t hang around in the air and maintain the ability to infect people who come in to the same space at a later time point, as some people have been suggesting (one recent Swedish study had found evidence of SARS-CoV-2 in a hospital attic and this led to fear-mongering articles in the Swedish media). Rather, it seems from this study that covid-19 only spreads through close and immediate personal contact.
Next up, we have a study that was recently published in Frontiers in Public Health. The authors received no specific funding for the study and reported no conflicts of interest. Like the Lancet study I wrote about a few weeks back, this was an analysis of global statistics. The difference between this study and the previous one is that this one looked at a lot more countries (every country that had at least 10 covid deaths at the end of August was included, which means that 160 countries were included in total), and looked at a much longer time frame. While the earlier study only gathered data up to May 1st, this one gathered data until the end of August. If lockdowns do affect mortality, there should certainly be a visible effect by that time.
So, what were the results?
The was no correlation between the stringency of lockdown and the number of covid deaths. Strong positive correlations with covid deaths were seen with the proportion of the population that is obese, and with the level of sedentary behavior in the population. In other words, the results are perfectly in line with the earlier study published in Lancet. Other factors that were found to correlate positively with covid mortality were age, proportion of the population with cardiovascular disease, and proportion of the population with cancer.
Two factors that showed a strong negative correlation with covid mortality were the general prevalence of infectious diseases in a population, and the average Gross Domestic Product (GDP). This makes sense to me, since poorer countries have more infectious diseases generally, and they also have younger, less obese populations, that are less likely to succumb to covid if infected.
Two other factors that correlated negatively with covid mortality were average temperature and average level of sunlight. Given that covid seemed to disappear in many countries during the summer, and now seems to have returned in autumn, the virus appears to act in a highly seasonal manner, so it makes sense that these correlations would exist. No correlation was seen, however, between humidity and death rate from covid.
What can we conclude from these two studies?
I would say that these studies strengthen the conclusions from my previous article. Lockdown appears to be largely ineffective. Ensuring good overall population health by encouraging a healthy diet and regular exercise does appear to be effective.
But if it is the case that lockdown is ineffective, how come Sweden had so many more covid deaths than other nordic countries?
That is a topic I will come back to in the near future.