Testing for SARS-CoV-2 antibodiesBMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3325 (Published 08 September 2020) Cite this as: BMJ 2020;370:m3325
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
This article never explicitly refers to predictive values, positive or negative. Predictive values depend on the underlying disease prevalence, but sensitivity and specificity do not.
Sensitivity and specificity could be seen as theoretical and abstract. They won't tell you the chances of actually having Covid if you test positive. You may be a false positive.
Likelihood ratios perform a similar role to predictive values, but are more complicated, indeed cumbersome.
It is no surprise that a high sensitivity corresponds with a low specificity, and vice versa. As the Pearson-Neyman lemma tells us, specificity and sensitivity, the same as type I and type II errors, are inversely related.
There is regrettably no mention of the ROC (Receiver Operating Characteristic) curve. This trades off sensitivity against specificity for various cut-off points. The farther apart disease and non-disease functions are, the more accurate any diagnostic test would appear to be.
A GP in a stretched and stressed local practice hasn't the time for odds calculations and 'nomograms'. Positive and negative predictive values would seem the ticket here.
The Covid kits are very difficult to use for a pensioner such as me. It's a shame that easier serology tests don't yet exist..
Now, why hasn't there been an educational article on the terribly fascinating and dreadfully complicated 'r-number'?
During this ugliest of crises that is Covid, we aren't getting the number-crunching properly explained.
This piece lacking any trace of Predictive Values in diagnostic tests is short-changing us.
Competing interests: No competing interests
When dealing with SARS-CoV-2 antibodies and, more in general, with anti-SARS-CoV-2 immune response, adequate attention should be also paid to animal species, both domestic/domesticated (such as cats, ferrets and, to a lesser extent, dogs) and wild (such as lions, tigers, non-human primates and minks kept in captivity), which have been reported to be susceptible, at various degrees, to the Coronavirus pathogen responsible for CoViD-19 in mankind (1). Notably, a SARS-CoV-2 spillover from humans to farmed minks, coupled with a viral spillback from minks to humans, has been also described in the Netherlands (2).
Social distancing, hand washing and correct wearing of face masks have been clearly shown to confer strong protection against SARS-CoV-2 spread among people. In this respect, growing concern exists about the "environmental fate" of the aforementioned (disposable) masks, with marine (and terrestrial) contamination/pollution by millions (if not billions, provided that we are dealing with a pandemic!) of face masks being an absolutely realistic possibility. Indeed, a dramatically increasing marine pollution by plastic debris is already taking place across the entire Planet, with the "fish-to-plastic ratio", currently estimated to be 5:1, being expected to reach 1:1 by the year 2050 (3). This alarming context is made even more so by the fact that micro/nanoplastics are known to act as "attractors and concentrators" for a huge number of "persistent environmental contaminants" (like "heavy metals", PCBs, dioxins, "flame retardants", etc.), with Cetaceans (especially Odontocete Cetaceans like dolphins) being able to "accumulate" high levels of the aforementioned chemical pollutants inside their body tissues, given their position of "top predators" within the marine foodweb (4).
Obviously, this contaminant "transfer" through the alimentary chain may be consistently enhanced by micro/nanoplastics, following their acquirement on behalf of Cetaceans through ingestion of (plastic debris harbouring) prey. It has been additionally suggested that micro/nanoplastics could serve as "attractors and concentrators" also for infectious agents like Toxoplasma gondii, a protozoan pathogen of concern for free-ranging dolphins and whales (5). It is currently unknown, in fact, how "pelagic" or "offshore" cetacean species may acquire T. gondii infection, given the "dilution effect" plausibly exerted by the sea water towards this parasite (as well as, most likely, towards other protozoan and non-protozoan agents).
Coming back to SARS-CoV-2, is it biologically plausible that the "scenario" depicted above for T. gondii could also apply to the "new" human beta-coronavirus, which has now caused more than 1 million deaths worldwide? When viewed from a "biological plausibility standpoint", coupled with an appropriate use of the "principle of precaution" and of the "One Health concept", my answer would be "yes, it is". My "affirmative" reply to such a relevant issue results from the (presumably) "large scale contamination" of marine (and terrestrial) ecosystems (not equally across the Planet, most likely) on behalf of "not adequately disposed face masks", an unknown number/percentage of which could also harbour SARS-CoV-2 (which could be subsequently "attracted and concentrated" by micro/nanoplastics).
Furthermore, based upon the data of an interesting article recently published in PNAS, bottlenose dolphins (Tursiops truncatus) and grey whales (Echrichtius robustus) would rank among the mammalian species with the highest similarity/homology level of their ACE-2 SARS-CoV-2 viral receptor with the human one.
Of course, we don't know yet if "dolphins and whales" are truly susceptible to SARS-CoV-2 infection, with much more work being needed before we can conclude if this is or is not the case.
Nevertheless, as already recommended for SARS-CoV-2-susceptible "synanthropic" species (like cats and dogs), an "ad hoc" search for SARS-CoV-2 antibodies should be carried out also on "stranded" Cetaceans, in a similar manner to what is "routinely" done for a number of infectious pathogens of documented concern for the marine Cetofauna (such as Morbillivirus, Herpesvirus, Brucella ceti and the previously mentioned T. gondii).
1) Di Guardo G. (2020) - Journal of Comparative Pathology.
2) Di Guardo G. (2020) - Drug Target Review.
3) World Economic Forum Report (2016).
4) Di Guardo G., Mazzariol S. (2017) - Science.
5) Di Guardo G. (2020) - Protistology.
Competing interests: No competing interests
Reading the article and numerous other publications as well as the pronouncements of the Government, I request:
1. Please give up all serology for attempting to control the spread of the Virus.
2. If you are just carrying out research of no use to the public today - then tell us that this is merely a research exercise.
3. By all means establish the existence of the virus in Individual unwell humans by taking swabs competently.
4. Establish spread of the virus in defined communities by testing sewage.
I acknowledge I am fallible.
Would welcome corrections.
Competing interests: Citizen
Guesstimates in, guesstimates out.
In the case of Covid-19, the pre-test probability is a guesstimate, meaning interpreting the result of any test, positive or negative, is no better than a guesstimate. Why, therefore, are the experts encouraging the govt to spend vast sums of public money on widespread testing? Is this really a PR exercise on behalf of both the experts and the govt to be seen to be doing something based on science in their response to the pandemic?
The only predictable result of widespread testing will be to create a bonanza for the manufacturers of the tests Better, and far cheaper, to stick to traditional methods of dealing with pandemics, ie social distancing, and isolation of those with symptoms.
Competing interests: No competing interests