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The SARS-CoV-2 Transmission Riddle - Part 5
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The SARS-CoV-2 Transmission Riddle - Part 5
Poor methods lead to waste, misleading research and failure to address uncertainties.(revised February 2024)
This is the fifth post of a re-run of our Transmission Riddle series, originally posted in 2022. Each post has been updated and reworked with what new evidence we could find. The serial numbers of the original posts may not correspond as we expand, merge, edit and add, like a concertina.
As the panic and hysteria have assuaged, some are noticing the problem. The BMJ said the pandemic “turbocharged scientific publishing,” and covid bolstered an already perverse publishing system. Alas, things have changed little apart from the vast majority of authors who inundated the airwaves in 2020-22 and have now moved on to more topical areas.
Asymptomatics were the invisible spreaders, requiring mass testing to identify and isolate them because they had no outward sign of infection. Test, test, test was the WHO message, and we will catch the unseen spreaders, quarantine them and contain the pandemic: only ‘two weeks to flatten the curve.’
Several authors outdid each other in providing point estimates of the prevalence of asymptomatics, leading those in charge to claim asymptomatics had a significant role in driving the pandemic.
“Senior people did not understand, well enough, the problem of asymptomatic transmission," said Dominic Cummings. In evidence to the Science and Health Joint Committee, Matt Hancock said ‘he “bitterly” regrets not overruling the scientific advice at the start and proceeding on the basis that there is asymptomatic transmission until we know there is not.’
On Jan 28 2020, the UK Government’s advisors SAGE minutes reported, ‘there is limited evidence of asymptomatic transmission,’ and ‘it would not be useful to test asymptomatic individuals, as a negative test result could not be interpreted with certainty.’
On Feb 4, SAGE minutes reported a PHE review that concluded the data is inadequate to provide evidence for major asymptomatic/subclinical transmission of “2019nCoV”. SAGE reported to ministers that “asymptomatic transmission cannot be ruled out, and transmission from mildly symptomatic individuals is likely." A further meeting on Apr 30 stated a study amongst asymptomatic NHS healthcare workers indicated the positivity was 5 to 6 percent.
Not for the first time, we were confused; therefore, we did a bit of digging and reported that the proportion of asymptomatic across 21 studies was between 5 and 80 percent. Our post surprised us with the unusually high number of citations it has so far received (141).
We also learned there wasn’t a reliable study to determine the number of asymptomatics.
The studies had several flaws. Authors had not followed positives long enough for symptoms to appear, or as in several studies, had someone test and not follow up with the individual. Also, most studies did not properly take a history and recognise signs such as confusion in older adults. Confusion may be a sign of infection from anything between a simple urinary tract infection and COVID-19.
An example of the problem is highlighted by different studies' assessment of temperature thresholds - symptomatic could be a temperature above 37.5, 37.8 or 38°C. Such variation contributes to the wild differing estimates of prevalence. Timing also matters.
In Surie et al., participants in a nursing home were followed for 42 days from enrolment. At the first PCR-positive test, 11 (65%) participants were asymptomatic, but all became symptomatic (one on day 25).
Given the problem in assessing the evidence, we applied our framework to identify those studies on asymptomatics that used serial PCR cycle threshold readings along with viral culture and/or gene sequencing with adequate follow-up.
From a starting grid of 444 studies, we ended up with 18 reliable pieces of work that we included in our systematic review - 96 percent of the studies were unreliable, highlighting the research waste during the pandemic.
The quality of the 18 studies was underlined by the response rate of the corresponding authors to requests for clarification or further data: 100 percent replied. This is a very unusual situation in epidemiology and reassured us that all the authors did have access to their data and were willing to collaborate.
So what did we find?
True asymptomatics are a lower proportion of symptomatic cases; they vary by setting and population - and yes - they can be infectious.
Some, especially older people and immunosuppressed can remain asymptomatic with infectious viral shedders for weeks. Others, like children, clear the bug in a few days. Single aggregate estimates cannot be calculated, given this diversity.
Still, some, like the elderly, are more likely than not to be infectious for a long time, especially with low Cts. Spot tests and amateurish history-taking should not be made. At least two PCRs are necessary, and a dip in the cycle threshold is likely to spell an infectious phase. Hence, the importance of serial measurements.
The differences in the proportion of asymptomatic cases occur due to single point-in-time testing (with no follow-up) and the use of various signs/symptoms definitions.
Presymptomatic behave similarly but should be identified in situations of spread in institutions like nursing homes with repeated testing and medical examination. In some cases, presymptomatic can be highly infectious before the appearance of symptoms, partly explaining the introduction of SARS-CoV-2 into nursing homes.
Gene sequencing, which was used in the studies we reviewed, is a powerful but costly technique that can exclude contamination of co-infection with other microbes and elucidate the provenance of the isolate if related to its peers circulating in the surrounding community. It is possible to trace the viral lineage, but it cannot prove viral replicability. For this, you need a viral culture or a dipping Ct, perhaps coupled with a deterioration of the clinical picture.
To assign the likelihood of transmission (certain, probable/likely, possible, unlikely or unclear), we used the WHO Uppsala Monitoring Centre framework for standardised case causality assessment, which we adapted for viral transmission.
By now, you might consider that estimating the prevalence of asymptomatic and their role in the spread isn't an overnight undertaking.
We concluded that ‘high-quality studies provide PROBABLE evidence of SARS-CoV-2 transmission from presymptomatic and asymptomatic individuals.’
Thus, a dipping Ct indicates an increase in viral load in the individual, and that only comes from active viral replication.
We did an update a year later and found only one eligible study - which tells a tale in itself.
In December 2023, Matt Hancock gave evidence to the Covid Inquiry. He said there were concerns people could transmit the virus without symptoms. He also said his “single biggest regret” was that he didn’t push back over assumptions that covid could not be transmitted asymptomatically.
“In your witness statement, you say: "The global scientific consensus, reflected in the global scientific advice from the [World Health Organisation] until April 2020, was that there was no asymptomatic transmission." That's what you say in your statement, isn't it?”
However, in his 2022 book, Hancock alleged he had been told someone without symptoms could not pass on Covid.
“It is correct to say that in your book, for Apr 3, you note the publication by the World Health Organisation of a report dated Apr 2 in which there is reference to evidence of documented asymptomatic transmission.”
If you are feeling confused, bear with us.
The KC Hugo Keith said, “So your regret appears to be that you were told -and certainly did not understand, because you weren't told -- that there was likely to be or there may have been asymptomatic transmission, at an early enough stage when it really, really mattered. Is that the nub of it?
“Yes,” said Hancock.
As Hugo Keith KC pointed out, there is a contradiction in these two positions: They "cannot live together."
“In your book, you repeatedly state you were told that the coronavirus can't be passed on by somebody without symptoms.” However, “In evidence, today, you have acknowledged that there were concerns that there may be asymptomatic transmission.”
“The two cannot live together. Either you were told and you didn't understand -- to the contrary, you were told there is no asymptomatic transmission, or you were told of concerns that there may be asymptomatic transmission and those concerns crystallised over time.
Which is it?” Asked Hugo Keith.
Hancock didn't know whether he was coming or going.
However, those who don’t account for the cycle threshold and the quality of the symptom reporting will be equally bamboozled when they talk about asymptomatic infections.
Access the full Transmission Riddle Series.
References
Jefferson T, Spencer EA, Brassey J, Onakpoya IJ, Rosca EC, Plüddemann A, Evans DH, Conly JM, Heneghan CJ. Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) from pre and asymptomatic infected individuals: a systematic review. Clin Microbiol Infect. 2022 Feb;28(2):178-189. doi: 10.1016/j.cmi.2021.10.015. Epub 2021 Oct 29.
Jefferson T, Spencer EA, Onakpoya IJ, Plu Ddemann A, Conly JM, Heneghan CJ. Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) from pre and asymptomatic infected individuals: a systematic review update. Clin Microbiol Infect. 2022 Jun 28:S1198-743X(22)00329-9. doi: 10.1016/j.cmi.2022.06.016.
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The SARS-CoV-2 Transmission Riddle - Part 5
The really depressing thing about this whole tragic catastrophic worldwide event is that so very few people in power had any real understanding about a disease bought about by a respiratory virus (which was highly like man-made) and made decisions which damaged every single human on the planet with so little personal scientific knowledge. And those who did have a modicum of understanding went ahead with the 'rush' to ruin everyone's lives anyway regardless of the consequences. And now they admit they didn't have a clue.
Doesn't anyone feel ashamed? Or is that an old fashioned concept?
Hi Nigel,
Thanks that’s interesting, I didn’t know that - do you have reference where this issue has been shown to be the case? If so well look at the early pandemic Chinese studies that refer to asymptomatic to see if it is also the case.