No, the vaccinated are not 5x more likely to be contagious compared to unvaccinated
We need more reading; less reporting.
Recently a few reports have come out touting the notion that the vaccinated are spreading COVID more than the unvaccinated, with reports being derived from this paper in the New England Journal of Medicine (NEJM)1.
More specifically, the main claim is that the vaccinated are 5x more contagious than the unvaccinated 10 days after SARS-COV2 infection.
Unfortunately, this study is another case of poor analysis with widespread reporting.
The purpose of this study was to examine whether the CDC’s modified isolation guidelines fit with clinical data. The CDC changed their isolation period from 10 days to 5 days, and so this study was intended to examine whether people were still infectious after a set period of days.
The study looked at both unvaccinated and vaccinated individuals during the Delta and Omicron wave, taking periodic nasal swabs and conducting both PCR tests and cell culture analyses of samples.
PCR tests detect for the virus, yet don’t provide any indication to the replication capacity (i.e. is the virus still active). Cell cultures are used to determine whether a virus is still able to replicate.
In microbiology labs you may have conducted a bacteriophage study, in which you took a petri dish with bacteria, inoculated it with a bacteriophage (“bacteria eating”- viruses that target bacteria) and watched for empty regions of the petri dish which would insinuate bacteria lysis caused by the bacteriophage. The concept is no different with SARS-COV2 culturing.
Here, the culturing of SARS-COV2 is a way of determining how long the virus remains replication-competent, and it’s this measure that is used to determine for how long a virus can remain contagious.
With that being said, let’s look at this “5x contagious” reporting.
It appears that one reporting came from TrialSiteNews, and it’s here where many people have likely derived their assumptions of this study.
Geert Vanden Bossche appears to have reported on TSN’s reporting and provided this excerpt in his Substack:
“Published recently in the prestigious New England Journal of Medicine (NEJM), a study led by Massachusetts-based physician-scientists leads to a disturbing discovery: individuals fully vaccinated and boosted against COVID-19 actually recover markedly more slowly from the illness and surprisingly, even remain contagious for lengthier periods of time as compared to unvaccinated persons.”
I should make it clear that I am unsure of the veracity of this statement being tied to the remarks within the TSN post, as the TSN post has been redacted (we’ll see why). So note that this quote could be entirely misattributed, and if so I’ll exclude it if a correction is needed.
Upon first looking at the study title you’ll realize the study doesn’t directly mention this “5x contagious” claim. So where did it come from?
It likely came from this graph from the Results:
Simple math would argue that 26 is about 5 times greater than 5, which is likely where the “vaccinated are 5x greater than unvaccinated to be contagious at the 10 day mark” comment came from.
Sounds pretty alarming, but we can see why there are many issues with this interpretation.
We can forego many of the problems with the small sample size and the matching of cohorts, but note that this graph looks at time for PCR conversion. Note that PCR conversion here is in regards to a conversion from a positive test to a negative test, so this graph is measuring at what point participants start testing negative.
In no ways can a PCR test actually measure “infectivity” because PCR tests don’t provide any measure of whether the virus is still replication-competent; that’s what cell culture studies are for.
Instead, reporters probably should have looked at this graph which shows time to culture conversion (i.e. when the virus appears to stop replicating):
Sure, maybe you can make a comment that this graph may show a 3x more contagious rate among the vaccinated (or maybe 7 if we decide to add the vaccinated and boosted cohorts), but we’re dealing with so few individuals here that it’s hard to really gain anything significantly meaningful here. This graph also doesn’t tell us exactly who got infected with what (hint: the supplemental material tells us that only one boosted person out of the 13 got infected during Delta- Table S1).
The researchers make this remark in regards to their findings:
There were no appreciable between-group differences in the time to PCR conversion or culture conversion according to vaccination status, although the sample size was quite small, which led to imprecision in the estimates (Figure 1D and 1E).
Even if we are highly critical of the researchers remarks in downplaying infectivity, I still find it rather difficult to draw such conclusions from this study specifically. This is another case of people extrapolating too far from the studies and making conclusions that are either not warranted or not founded.
But what’s really strange here is that all indications should have told us that the PCR graph is probably not the thing we should be looking at.
The researchers explain that in their final paragraph:
Although culture positivity has been proposed as a possible proxy for infectiousness,5 additional studies are needed to correlate viral-culture positivity with confirmed transmission in order to inform isolation periods.
And within the TSN redaction they make mention of this remark, which makes it a bit confusing as to what graph was being looked at specifically, as the 5x interpretation could only have come from the PCR graph. Now, I could be completely wrong in my assumption, and I’d like to hear of other interpretations/possibilities.
There are a few additional issues with this interpretation. Note that cell culture studies may not actually rely on daily collection of swabs and daily incubation to measure cell lysis. Cell culture studies may take samples at the initial point of infection, inoculate and incubate Vero E6 cells, and take measurements every few days. This creates a few limitations in interpreting cell culture results.
For example, one of the studies cited by this NEJM article is a study from North, et. al.2 which provides this methodology in their Supplemental Material3:
Vero-E6 cells (ATCC, USA) were prepared in D10+ media (Dulbeco’s modified Eagle’s media (DMEM, Fisher, USA) supplemented with HEPES buffer (Fisher, USA), 1x Penicillin/Streptomycin (Fisher, USA), 1x Glutamine (Glutamax, Thermo, USA) and 10% fetal bovine serum (FBS) (Sigma, USA)]. Cells were seeded one day prior to inoculation. Plates were centrifuged for 1 hour at 2000 x g at 37oC, then placed in an incubator. Plates were observed at 3- and 6-days post-infection with a light microscope and wells showing CPE were counted. Supernatant of wells displaying CPE was harvested 10-14 days postinfection, and RNA was isolated using a QIAamp Viral RNA Mini kit (QIAGEN, USA) for sequence confirmation. The SARS-CoV-2 isolate USA-WA1/2020 strain (BEI Resources, USA) was used as a positive control for all experiments.
The study also conflates symptom onset with first day of a positive PCR test, using whichever one came first. In a study that is intended to measure specific times for conversion the use of either symptom onset or a positive PCR test doesn’t provide for an accurate starting point for the infection.
Overall, it’s a bit disheartening to think that the reporting going on right now may be plagued by improper reading of the material. It feels as if the need to report precedes the actual reading of studies in several circumstances, and this just feels like a growing issue among COVID skeptics. Take, for instance, the reporting on the Icelandic study which is still being cited by several people now:
We can’t call ourselves more critical thinkers or more intelligent when it appears that we aren’t doing the due diligence to read studies properly. Instead of focusing on clickbait titles and rushing to publish, how about we take some time and make sure that our interpretations of studies are sound.
Take a precautionary approach, especially given the fact that many people are reading people’s interpretations of studies rather than reading the studies themselves.
It’s rather compelling that the few votes on the Icelandic study suggest that most people didn’t read the study that they were commenting on. This may be what’s happening here as well, as several commenters have commented on the interpretation of the study rather than the actual study.
As stated, TSN has provided a redaction to their article. It’s a rather critical move, yet at the same time one wonders whether a redaction would be necessary if the study was assessed properly from the start.
It’s once again a reminder that we should stop and read studies before we report on them. The truth is far more important than the hysteria, and more of us should bear in mind the ramifications our reporting can have on the general public.
Note: Right now I’m working on Part III of my Catecholamine post, however I’m going down quite a few rabbit holes so I’m not sure when I will be able to post this part. I will hope by the end of the week, although there are a few posts I intend on posting this week as well. Apologies for the inconsistencies, but please look forward to the post in the future.
If you enjoyed this post and other works please consider supporting me through a paid Substack subscription or through my Ko-fi. Any bit helps, and it encourages independent creators and journalists outside the mainstream.
Boucau, J., Marino, C., Regan, J., Uddin, R., Choudhary, M. C., Flynn, J. P., Chen, G., Stuckwisch, A. M., Mathews, J., Liew, M. Y., Singh, A., Lipiner, T., Kittilson, A., Melberg, M., Li, Y., Gilbert, R. F., Reynolds, Z., Iyer, S. L., Chamberlin, G. C., Vyas, T. D., … Barczak, A. K. (2022). Duration of Shedding of Culturable Virus in SARS-CoV-2 Omicron (BA.1) Infection. The New England journal of medicine, 387(3), 275–277. https://doi.org/10.1056/NEJMc2202092
The title of this post may be misleading as it builds off of the researchers prior work with Delta. As such, this research is a combination of the researchers’ Delta and Omicron research.
North, C. M., Barczak, A., Goldstein, R. H., Healy, B. C., Finkelstein, D. M., Ding, D. D., Kim, A., Boucau, J., Shaw, B., Gilbert, R. F., Vyas, T., Reynolds, Z., Siddle, K. J., MacInnis, B. L., Regan, J., Flynn, J. P., Choudhary, M. C., Vyas, J. M., Laskowski, K., Dighe, A. S., … Sacks, C. A. (2022). Determining the Incidence of Asymptomatic SARS-CoV-2 Among Early Recipients of COVID-19 Vaccines (DISCOVER-COVID-19): A Prospective Cohort Study of Healthcare Workers Before, During and After Vaccination. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 74(7), 1275–1278. https://doi.org/10.1093/cid/ciab643
CPE= Cytopathic effects, which are structural changes to cells after viral infection, including the lysing of infected cells.
So I've seen a few comments and I would like to make a few points of clarification.
First off, this post shouldn't be seen as casting any aspersions towards TSN, but it should be an example that we study reports should be a bit careful in jumping to conclusions, especially ones which may cause people to runaway with conclusions.
Also, this post wasn't intended to provide a robust analysis, but moreso to critique the assumption that was made from this study. Of note, it was the GvB article where I found this study, and at the time of his posting he may not have been aware of TSN's redaction.
As to the title, I definitely understand why it is seen as clickbait, and I probably should have come up with a different title. The title here was in response to the original title, which can be seen on TSN's website.
As a quick note, for websites you can edit titles or anything within the article's content, but after publishing the URL generally remains the same. This is how mainstream media tends to run afoul with stealth edits on their stories post-publication.
You can see TSN's original title in their URL, and it's that title that I was mostly responding to.
https://www.trialsitenews.com/a/bombshell-study-vaccinated-5x-more-contagious-than-the-unvaccinated-10-days-after-sars-cov-2-infection-ae391446
And so it was that title that I was responding to with my title.
Lastly, Brian Mowrey below provided some commentary, and it appears Igor mentioned this study specifically in regards to reduced viral clearance. I won't make any remarks in regards to that interpretation unless I look through the supplemental data, but keep in mind that my post should not undermine the study, but merely some of the interpretations floating around in regards to the 5x remark.
I used to subscribe to TSN and now I only get their daily headlines. I was very disappointed when I read the original study referenced by the salacious TSN headline, only to find out that that the study stated that there were no appreciable differences between the two groups -- like you highlight in your analysis. We have a lot of other evidence showing shortcomings with the vaccine -- why then play the same ideological game the mainstream media plays and lose credibility in the process?