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Posts Tagged ‘virology

the science of Covid19: testing

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filched from the excellent JAMA website

So here in South Australia we have fairly drastic social distancing rules with pubs and restaurants and many businesses closed and so on, though in terms of case numbers we’re doing better than other states, and Australia in general is doing a lot better than other countries with comparable populations. Our crude case fatality rates (deaths per million) are smaller than any country ahead of us in number of cases in general – we’re currently ranked twentieth in case numbers. All of this is based on worldometer figures, which we can only hope are as reliable as they can be.

Our relative success has been attributed by some to our testing system. Worldometer has recently added a couple of new lines to their country-by-country statistics, ‘total tests’ and ‘tests per million’, which gives some idea of the testing rate, though little idea of the testing criteria, or the spread of testing throughout the country. According to these figures, the testing rate here is impressive compared to any other country of similar or larger population. Of course, there are just too many variables to make a direct connection between testing and fatality rates, but all experts agree that high rates of testing are beneficial. Worldometer also allows us to make some telling comparisons. For example, neighbours Sweden and Norway are recording a similar number of Covid-19 cases, 6400 and 5500 respectively, though Sweden has almost twice the population. That looks bad for Norway. But Sweden has had 373 fatalities compared to only 62 for Norway. That looks very bad for Sweden. And when we compare the testing, we find that, for half the population, Norway has carried out almost three times the number of tests that Sweden has. That’s almost 6 times the rate of testing. In fact Norway has the highest testing rate in Europe (apart from those with much smaller populations such as Iceland and Luxembourg). Other countries that appear to have greatly reduced fatality rates through comprehensive testing include Germany and South Korea. Clearly, large scale testing is working to keep fatalities down. It’s not unreasonable to attribute the escalating rate of infections in the US to the lack of a co-ordinated and comprehensive testing system, though the fatality rate there is relatively low. It’s clear that, with testing as well as with other responses, the states have failed to unite, largely due to a complete absence of federal governance.

The essential test for Covid-19 is polymerase chain reaction (PCR), and the detection process is well explained in the illustration above, and a little more fully on the JAMA (Journal of the American Medical Association) website. Or, at least, I assume so, as a non-scientific person. But in order to fully understand the process I need to capture it in my own words.

So SARS CoV-2 infects humans by binding to their ACE2 receptors by means of their spike proteins, one of four types of structural proteins pertaining to the virus. Studies have found that SARS CoV-2 has ‘a higher affinity to human ACE2 than the original SARS virus strain’, which presumably goes some way to explain its greater infectiousness. A PCR test is able to detect specific genetic material within the virus. A swab sample is taken from the throat or the nose or the lower respiratory tract or the stool, depending on test type. The JAMA website puts it this way:

After a sample is collected, RNA, which is part of the virus particle, is extracted and converted to complementary DNA for testing. The PCR test involves binding sequences on the DNA that only are found in the virus and repeatedly copying everything in between. This process is repeated many times, with doubling of the target region with each cycle. A fluorescent signal is created when amplification occurs, and once the signal reaches a threshold, the test result is considered positive. If no viral sequence is present, amplification will not occur, resulting in a negative result.

Australia’s Department of Health describes two types of test for the presence of SARS-CoV-2, nucleic acid/PCR tests (as above) and serology antibody tests, but the department sounds a warning:

The reliability of COVID-19 tests is uncertain due to the limited evidence base. Available evidence mainly comes from symptomatic patients, and their clinical role in detecting asymptomatic carriers is unclear.

This statement is dated March 27, and with the fast-moving situation, may no longer be relevant. And speaking of fast-moving situations, here in South Australia we’ve had our first recorded death from the virus, while I’ve been writing this. There’s also news overnight that a tiger from the Bronx zoo has tested positive. This has been confirmed by further testing. Other cats there are showing milder versions of the same symptoms but haven’t been tested. The tiger is described as being in a stable condition, and authorities are claiming that there’s no evidence of transmission from zoo or domestic animals to humans, but this kind of news may well lead to a public panic. And after all, absence of evidence doesn’t necessarily mean evidence of absence. There’s no doubt that the tiger’s infection raises a host of worrisome questions. Was the tiger infected by humans, as seems likely? If not, where did it get the virus from? And if the other cats are positive (they haven’t been tested due to problems with anaesthetics), then where will it end?

Antibody tests look not at infection but immunity. An effective test will show whether a person’s immune system has detected and neutralised the virus. Demand for these types of tests is extremely high, as immunity would mean that these people would be able to return to normal activity., with all the attendant economic benefits. Antibody detection would be of particular importance for current health workers. Such tests would show that the workers have already been infected by SARS-CoV-2 (perhaps without symptoms), and have developed immunity. Widespread use of the tests would also reveal the number of asymptomatic cases. Currently the number of people infected can only be an estimate based on current testing (the worldometer figures tell of confirmed cases, which can only be confirmed by testing). Children, for example, may be infected (and infectious) but asymptomatic, but the extent of this is pure guesswork. Getting real data would be useful in determining schools’ operations.

However, there are difficulties with antibody tests. According to The Lancet,

the technology behind antibody tests is fundamentally distinct and generally harder to get right. “If you have a sequence today, you have a PCR tomorrow”, says Linfa Wang, director of Duke-NUS Medical School’s programme in emerging infectious diseases, in Singapore. “Whether the sensitivity [of PCR] will be enough is another thing, but usually in the first round, it will give you data that you can use. Serology is different.”

One of the issues is knowing which protein, or antigen, on the virus to target. The spike protein is seen as the obvious target, as it’s the means of entering the host cell. Virologists in China have been using the spike protein (due to its specificity) and the nucleocapsid protein (due to its abundance). At least ten antibody test types have already been used throughout China. Specificity is important because, according to The Lancet, ‘the more unique [the protein] is, the lower the odds of cross-reactivity with other coronaviruses—false positives resulting from immunity to other coronaviruses’. These include those that cause the common cold, as well as SARS-CoV.

So that’s enough for now, I’ll continue to try and inform myself, having nothing better to do, and post some more results from that process next time. Keep well!


Written by stewart henderson

April 7, 2020 at 12:34 pm