If you haven't noticed already, the game has moved on, subtly but surely. Countries are moving on from lock downs, even as cases are at best stable or slowly declining (UK, USA, Italy, Spain), or even surging in some (Brazil, India, Russia). There is now a tacit acceptance that the price of continued and total lock down is too steep, and that nations may have to accept some new cases, in order that society and economy as a whole, can reopen.
It is not a question of if but when. Cases will surge in many places. The pandemic hasn't peaked in the last 3 nations, and is hardly under control in the first group. Some countries have rolled out a "track and trace" mobile app, based on using bluetooth signal to inform if the phone in question has been in the vicinity of one owned by a COVID sufferer. For this, you have to download a track and trace app. If your phone data shows you are at risk, a "track and tracer" (25000 strong in the UK) will contact you, and ask you to self-isolate for 14 days. If you develop the disease, you self isolate for 7 days.
However, there is another way- something that makes the track and trace much, much more effective. This is the power of genomic screening of the COVID19 strains. RNA viruses undergo many more mutations than DNA viruses. One reason for this is the spontaneous deamination of cytosine to uracil. When this happens in DNA virus, this is quickly detected by the virus, and the base is corrected back to cytosine, as uracil is not normally present in DNA. However, this cannot happen in RNA viruses, as uracil is not a "foreign base", and will therefore not be "corrected". C to U mutations will therefore accumulate.
In fact, RNA viruses have over 10 times the rate of mutations as DNA viruses. This does not increase or decrease the pathogenicity of the virus appreciably, but it does mean that within a community or a nation, there might be several "strains" (with differing genome sequences) of the virus in circulation. As this usually affects only a single nucleotide, rather than blocks, it is called "intra-host single nucleotide variation", or simply iSNV. And this presents an opportunity for those seeking to track the spread of the virus.
Consider this. With a limited number of cases, you have the power to sequence the genome of the virus in every documented case within a matter of hours. Each cluster of cases will have a "signature" viral genome, because of the fact that the index case will have a viral strain with its own unique mutations. Thus, once the pandemic is stable and reasonably contained, scientists have within their power to look at the viral genome of a new case, and from a database of existing patients, pinpoint exactly from whom the infection was acquired. Thus, self isolation, instead of being a non-selective and disruptive tool, can be applied selectively and in a limited fashion, to maximum effect. The rest of the population can get on with their lives.
Some examples of common viral mutations might make this easier to understand. During the Zaire Ebola epidemic, it became clear that within the incorporated viral genome in host DNA, a disproportionately high number of mutations were thymine to cytosine (T>C). (Thymine does not appear in RNA, so this is referring to the host DNA that has incorporated the complementary sequence of the viral RNA). It turns out that the preponderance of T>C in virus infected cells is due to the action of an interferon inducible enzyme called "Adenosine deaminase acting in RNA 1", or simply ADAR1. (Interferons, as you know, are produced by the host in response to viral infections).
ADAR1 deaminates adenosine to inosine. Inosine is not a natural nucleotide, and is read as guanosine by the cell. Since the complementary base of guanine is cytosine, the thymine bases complementary to adenine are "corrected" to cytosine by single nucleotide excision and repair. Hence T>C.
This is not a pipe dream. Scientists in NZ, Australia and UK have an extensive database of viral genomes circulating in their respective nations. While the database is virtually 100% complete in NZ and Aus, the UK has data on 20% of viral genomes in circulation, given the very large number of cases. But they are getting there.
This, IMO, presents the only realistic way of opening up the society while continuing to promptly identify and isolate cases and their contacts.
It is not a question of if but when. Cases will surge in many places. The pandemic hasn't peaked in the last 3 nations, and is hardly under control in the first group. Some countries have rolled out a "track and trace" mobile app, based on using bluetooth signal to inform if the phone in question has been in the vicinity of one owned by a COVID sufferer. For this, you have to download a track and trace app. If your phone data shows you are at risk, a "track and tracer" (25000 strong in the UK) will contact you, and ask you to self-isolate for 14 days. If you develop the disease, you self isolate for 7 days.
However, there is another way- something that makes the track and trace much, much more effective. This is the power of genomic screening of the COVID19 strains. RNA viruses undergo many more mutations than DNA viruses. One reason for this is the spontaneous deamination of cytosine to uracil. When this happens in DNA virus, this is quickly detected by the virus, and the base is corrected back to cytosine, as uracil is not normally present in DNA. However, this cannot happen in RNA viruses, as uracil is not a "foreign base", and will therefore not be "corrected". C to U mutations will therefore accumulate.
In fact, RNA viruses have over 10 times the rate of mutations as DNA viruses. This does not increase or decrease the pathogenicity of the virus appreciably, but it does mean that within a community or a nation, there might be several "strains" (with differing genome sequences) of the virus in circulation. As this usually affects only a single nucleotide, rather than blocks, it is called "intra-host single nucleotide variation", or simply iSNV. And this presents an opportunity for those seeking to track the spread of the virus.
Consider this. With a limited number of cases, you have the power to sequence the genome of the virus in every documented case within a matter of hours. Each cluster of cases will have a "signature" viral genome, because of the fact that the index case will have a viral strain with its own unique mutations. Thus, once the pandemic is stable and reasonably contained, scientists have within their power to look at the viral genome of a new case, and from a database of existing patients, pinpoint exactly from whom the infection was acquired. Thus, self isolation, instead of being a non-selective and disruptive tool, can be applied selectively and in a limited fashion, to maximum effect. The rest of the population can get on with their lives.
Some examples of common viral mutations might make this easier to understand. During the Zaire Ebola epidemic, it became clear that within the incorporated viral genome in host DNA, a disproportionately high number of mutations were thymine to cytosine (T>C). (Thymine does not appear in RNA, so this is referring to the host DNA that has incorporated the complementary sequence of the viral RNA). It turns out that the preponderance of T>C in virus infected cells is due to the action of an interferon inducible enzyme called "Adenosine deaminase acting in RNA 1", or simply ADAR1. (Interferons, as you know, are produced by the host in response to viral infections).
ADAR1 deaminates adenosine to inosine. Inosine is not a natural nucleotide, and is read as guanosine by the cell. Since the complementary base of guanine is cytosine, the thymine bases complementary to adenine are "corrected" to cytosine by single nucleotide excision and repair. Hence T>C.
This is not a pipe dream. Scientists in NZ, Australia and UK have an extensive database of viral genomes circulating in their respective nations. While the database is virtually 100% complete in NZ and Aus, the UK has data on 20% of viral genomes in circulation, given the very large number of cases. But they are getting there.
This, IMO, presents the only realistic way of opening up the society while continuing to promptly identify and isolate cases and their contacts.
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