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expert reaction to comments made by Paul Tambyah (president-elect of the International Society of Infectious Diseases) about the SARS-CoV-2 virus, suggesting the D614G mutation may explain a reduced death rate from COVID-19 in some parts of the world

Reuters have reported* that Paul Tambyah, the president-elect of the International Society of Infectious Diseases, has suggested that the D614G mutation of the SARS-CoV-2 virus may explain the reduced death rate from COVID-19 in some parts of the world.


Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:

“It is certainly plausible that a SARS-CoV-2 subtype would become more infectious and less deadly, but it is not clear what real evidence is behind this statement or whether it is simply a suggestion.

“It is certainly the case that the case fatality rate is falling across the world. There are however, other very good explanations for this decline. Firstly disease does seem to be spreading in younger people more now than was the case in March, April and May and as we all know the case fatality rate is substantially lower in younger people that in older people. This is the case within Europe and also the case globally with the disease now spreading in countries with much younger populations.  Second, as with all epidemics, as doctors’ experience at managing the disease increase they are become better at keeping patients alive. This is particularly the case with the finding that dexamethasone, a readily available drug, can cut the death rate in the most severely ill patients by about 20%. Finally as testing becomes more readily available we are now diagnosing a higher proportion of cases that a few months ago. In March and April we were generally only diagnosing the more seriously ill and, therefore, the people most likely to die. Just being able to add the numbers of mild illnesses to now being diagnosed to total figure will drop the case fatality rate.

“As already accepted the suggestion of the appearance of a less lethal strain is possible. However, proving that the declining case-fatality rate is because of this new strain and not due the factors discussed above will need more much more careful analysis.”


Prof Brendan Wren, Professor of Medical Microbiology, London School of Hygiene & Tropical Medicine, said:

“The drop in death rates due to COVID-19 infection could be attributed to many factors such as (i) improved awareness and treatment of the disease, (ii) a more robust human population as the most susceptible die and (iii) changes in human practices such as improved hygiene and physical distancing would often make the infectious dose lower than in the pre-lockdown scenario, resulting in less severe disease. Without undertaking comparative analyses in appropriate infection models between the mutant D614G and the parent strain, it is not possible to correlate the emergence of this mutant with less disease severity.”


Dr Julian Tang, Honorary Associate Professor in Respiratory Sciences, University of Leicester, said:

“This SARS-CoV-2 D614G mutation has been emerging for some time now – as shown in  earlier papers1 which show the global distribution of this D614G mutation up till the end of June 2020. It is likely now the predominant SARS-CoV-2 genotype in most parts of the world.

“The D614G mutation in the SARS-CoV-2 spike (S) protein increases SARS-CoV-2 infectivity by stabilising and increasing the number of S proteins on the virus surface available to bind the human ACE2 enzyme receptor. This increases its ability to infect host cells and therefore its infectivity and transmissibility. Fortunately, this mutation does not appear to increase the severity of COVID-192.

“Convalescent plasma containing SARS-CoV-2 antibodies can still bind and neutralise the new D614G SARS-CoV-2, so vaccines based on the previous form of the virus should still be effective – though further mutations may well occur by the time these vaccines are licensed for general use.

“Such mutations are not unusual as a virus adapts to a new host. SARS-CoV-2 has moved from bats to humans, so some form of adaptive mutation was inevitable. A more transmissible virus will increase the R0 but if this does not result in more severe disease or deaths, the case-fatality rates (CFR) are likely to drop, as more people will become infected with a milder form of the virus without dying.

“Exactly how protective and how long any convalescent antibodies will last after infection with this emerging D614G SARS-CoV-2 is still unclear, but this will impact on the degree and duration of herd immunity acquired by populations infected by this new form of the virus.”

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