Michael Coston
Editor, Senior Moderator
COG-UK: A Cautionary Tale On COVID Escape Mutants Generated In Patient Receiving Plasma Therapy
#15,633
While touted as a `breakthrough' treatment for COVID-19 over the summer, the use of convalescent plasma has returned decidedly mixed reviews (see BMJ: Clinical Trial On Convalescent Plasma Showed Little Benefit For COVID-19), although there have been some indications it may benefit severely ill patients.
As we've discussed previously, as a greater percentage of the population develops post-infection immunity to COVID-19 - and more people are immunized over time - it may help force the virus to mutate in order to survive.
We've seen escape mutations with avian flu in areas where incomplete or poorly matched poultry vaccines have been employed (see EID Journal: Subclinical HPAI In Vaccinated Poultry – China), and last summer in Scripps Research: Study Suggests Some Flu Viruses May Be Less Susceptible To A `Universal' Flu Vaccine, we saw similar concerns expressed over a universal flu vaccine.
A week ago, a pre-print article appeared on medRxiv with the intriguing title:
Neutralising antibodies drive Spike mediated SARS-CoV-2 evasion
SA Kemp, DA Collier, R Datir, S Gayed, A Jahun, M Hosmillo, IATM Ferreira, C Rees-Spear, P Mlcochova, Ines Ushiro Lumb, David Roberts, Anita Chandra, N Temperton, The CITIID-NIHR BioResource COVID-19 Collaboration, The COVID-19 Genomics UK (COG-UK) Consortium, K Sharrocks, E Blane, JAG Briggs, MJ van Gils, KGC Smith, JR Bradley, C Smith, RA Goldstein, IG Goodfellow, A Smielewska, JP Skittrall, T Gouliouris, E Gkrania-Klotsas, CJR Illingworth, LE McCoy, View ORCID ProfileRK Gupta
doi: https://doi.org/10.1101/2020.12.05.20241927
(EXCERPT)
Here we report fatal SARS-CoV-2 escape from neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences by both short and long read technologies over 23 time points spanning 101 days. Little evolutionary change was observed in the viral population over the first 65 days despite two courses of remdesivir.
However, following convalescent plasma we observed dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 NTD of the Spike protein. As serum neutralisation waned, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma.
(Continue . . . )
The 26-page PDF is detailed (and highly technical), and many will want to download and read the report in its entirety.
For those with less time, or who desire a less challenging read, the COVID-19 Genomics UK (COG-UK) Consortium has published an easy to digest but nonetheless eye-opening explainer which describes the generation of multiple escape mutants in an immune compromised patient receiving convalescent plasma.
The potential for seeing this happen was discussed at some length in a study published in eLife last October (see Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants) and again in December (see Viruses: Neutralizing SARS-CoV-2).
Follow the link to read COG-UK report. Highly Recommended.
Explainer
Persistent SARS-CoV-2 infection and viral evolution tracked in an immunocompromised patient
Alessandro M Carabelli, David L Robertson and Sharon Peacock 18 Dec 2020
In recent work from COG-UK consortium investigators, released as a pre-print, Professor Ravindra Gupta and colleagues investigated SARS-CoV-2 evolution in a single immunosuppressed individual treated with convalescent plasma. Here, we explain the results of the study and what they could mean for the COVID-19 pandemic.
(Continue . . . )
All of which serves to remind us that viruses haven't been around for millions of years without being able to adapt as needed to an ever changing environment.
https://afludiary.blogspot.com/2020/...id-escape.html
#15,633
While touted as a `breakthrough' treatment for COVID-19 over the summer, the use of convalescent plasma has returned decidedly mixed reviews (see BMJ: Clinical Trial On Convalescent Plasma Showed Little Benefit For COVID-19), although there have been some indications it may benefit severely ill patients.
As we've discussed previously, as a greater percentage of the population develops post-infection immunity to COVID-19 - and more people are immunized over time - it may help force the virus to mutate in order to survive.
We've seen escape mutations with avian flu in areas where incomplete or poorly matched poultry vaccines have been employed (see EID Journal: Subclinical HPAI In Vaccinated Poultry – China), and last summer in Scripps Research: Study Suggests Some Flu Viruses May Be Less Susceptible To A `Universal' Flu Vaccine, we saw similar concerns expressed over a universal flu vaccine.
A week ago, a pre-print article appeared on medRxiv with the intriguing title:
Neutralising antibodies drive Spike mediated SARS-CoV-2 evasion
SA Kemp, DA Collier, R Datir, S Gayed, A Jahun, M Hosmillo, IATM Ferreira, C Rees-Spear, P Mlcochova, Ines Ushiro Lumb, David Roberts, Anita Chandra, N Temperton, The CITIID-NIHR BioResource COVID-19 Collaboration, The COVID-19 Genomics UK (COG-UK) Consortium, K Sharrocks, E Blane, JAG Briggs, MJ van Gils, KGC Smith, JR Bradley, C Smith, RA Goldstein, IG Goodfellow, A Smielewska, JP Skittrall, T Gouliouris, E Gkrania-Klotsas, CJR Illingworth, LE McCoy, View ORCID ProfileRK Gupta
doi: https://doi.org/10.1101/2020.12.05.20241927
(EXCERPT)
Here we report fatal SARS-CoV-2 escape from neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences by both short and long read technologies over 23 time points spanning 101 days. Little evolutionary change was observed in the viral population over the first 65 days despite two courses of remdesivir.
However, following convalescent plasma we observed dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 NTD of the Spike protein. As serum neutralisation waned, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma.
(Continue . . . )
The 26-page PDF is detailed (and highly technical), and many will want to download and read the report in its entirety.
For those with less time, or who desire a less challenging read, the COVID-19 Genomics UK (COG-UK) Consortium has published an easy to digest but nonetheless eye-opening explainer which describes the generation of multiple escape mutants in an immune compromised patient receiving convalescent plasma.
The potential for seeing this happen was discussed at some length in a study published in eLife last October (see Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants) and again in December (see Viruses: Neutralizing SARS-CoV-2).
Follow the link to read COG-UK report. Highly Recommended.
Explainer
Persistent SARS-CoV-2 infection and viral evolution tracked in an immunocompromised patient
Alessandro M Carabelli, David L Robertson and Sharon Peacock 18 Dec 2020
In recent work from COG-UK consortium investigators, released as a pre-print, Professor Ravindra Gupta and colleagues investigated SARS-CoV-2 evolution in a single immunosuppressed individual treated with convalescent plasma. Here, we explain the results of the study and what they could mean for the COVID-19 pandemic.
(Continue . . . )
All of which serves to remind us that viruses haven't been around for millions of years without being able to adapt as needed to an ever changing environment.
https://afludiary.blogspot.com/2020/...id-escape.html