UK: The Alpha variant rears its ugly head again

A big surprise in the latest UK sequencing figures show that the Alpha variant has made something of a comeback this week. Even though the percentage of Alpha cases is still tiny compared to that of Delta, the figure of more than 400 Alpha cases is the highest since mid-June 2021.

It’s unclear whether this is a localised outbreak (it may be part of the unfolding superspreader event of the Boardmasters festival in Cornwall for example), or whether these are cases scattered across the UK, but to see such a resurgence after so many weeks of Delta dominance is something of a shock as the Alpha variant was far less effective at breaking through vaccine protection than the Delta variant is.

After weeks of just a handful of Alpha cases in the UK, there is suddenly a spike of over 400 new cases:

 

Confirmation that the Delta variant has dipped recently:

Charts and data courtesy of CovSpectrum.org

 

 

 

Image by Josch13 from Pixabay

New C.1.2 variant mutating 41 times a year, twice as fast other known Sars-CoV-2 variants

Scientists first detected C.1.2 in May 2021, finding that it was descended from C.1, which scientists found surprising as C.1 had last been detected in January. The new variant has “mutated substantially” compared to C.1 and is more mutations away from the original virus detected in Wuhan than any other Variant of Concern or Variant of Interest detected so far worldwide.

The study also found that the C.1.2 lineage has a mutation rate of about 41.8 mutations per year, which is nearly twice as fast as the current global mutation rate of the other variants. The scientists stated that this short period of increased evolution was also seen with the Alpha, Beta and Gamma variants, suggesting that a single event, followed by a spike in cases, drove faster mutation rates.

Jerusalem Post report

Medrxiv preprint: The continuous evolution of SARS-CoV-2 in South Africa: a new lineage with rapid accumulation of mutations of concern and global detection

 

Delta attempting to brute-force its way past the human immune system

 

 

 

Photo by Abby Savage on Unsplash

The future of Sars-CoV-2: Multiple vaccine breakthrough infections in one patient

The patient had three RT-PCR confirmed SARS-CoV-2 infections. Two breakthrough infections occurred in quick succession with the first over 3 weeks after complete vaccination with COVISHIELD and despite post-vaccination seroconversion. The first breakthrough infection was due to the Alpha variant and the second due to the Delta variant. The Delta variant infection resulted in hypoxia, hospitalization, and illness lasting seven weeks. Serial serology, acute phase reactants, and chest imaging supported WGS in establishing distinct episodes of infection. WGS established a fully vaccinated family member as the index case.

Research article: Severe SARS-CoV-2 Breakthrough Reinfection With Delta Variant After Recovery From Breakthrough Infection by Alpha Variant in a Fully Vaccinated Health Worker

 

Preprint: Just three mutations for SARS-CoV-2 to escape from highly neutralizing convalescent plasma

Preprint: Just three mutations for SARS-CoV-2 to escape from highly neutralizing convalescent plasma

“Only three mutations were sufficient to generate this escape variant.”  This work shows that, under strong immune pressure, SARS-CoV-2 can use mutations in both the N-terminal domain and the receptor-binding domain to escape potent polyclonal neutralizing responses. Indeed, after a long period under immune selective pressure, SARS-CoV-2 evolved to evade the immunity of a potent polyclonal serum from a COVID-19 convalescent donor. Only three mutations were sufficient to generate this escape variant. The new virus was resistant to 70% of the neutralizing antibodies tested and had a decreased susceptibility to all convalescent sera.

Preprint: SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma

 

Delta attempting to brute-force its way past the human immune system

USA: Republican Mike McCaul’s final report into the origins of the Sars-CoV-2 pandemic

Mike McCaul’s final report on the origins of the pandemic can be downloaded here.

A House Republican lawmaker’s investigation into the origins of COVID-19 is raising concerns that the pandemic outbreak stemmed from a genetically modified virus which leaked from the Wuhan Institute of Virology, the Chinese city where the disease was first detected in December 2019.

The Hill article

Github: AY.3.1 – a new sub-lineage of AY.3 concentrated in Mississippi, USA

AY.3 is the main variant being sequenced weekly in Mississippi (>70% of all recent sequences), most falling within this sub-lineage of AY.3 that is distinguished by the mutations described below (>60% of all recent sequences). For example, of 91 Pangolin-typeable sequences generated on 13 July 2021 by Dr. Robinson’s team, from broad sampling across Mississippi, 68 are AY.3 and 13 are unclassified B.1.617.2. Of those 81 Delta sequences, 60 are this new sub-lineage (those sequences are not yet in GISAID and are thus not included in the counts above for the USA or MS). Thus, there is clear epidemiological relevance of this sub-lineage in a region of the USA.

Github: A new sub-lineage of AY.3 concentrated in Mississippi, US

 

USA: AY.3 genomes increasing faster than Delta B.1.617.2

 

Image by Mark Dawdy from Pixabay

UK SAGE Bombshell Report: The Long Term Evolution of Sars-CoV-2

Scenario One: A variant that causes severe disease in a greater proportion of the population than has occurred to date.  Scenario Two: A variant that evades current vaccines.  Scenario Three: Emergence of a drug resistant variant after anti-viral strategies.  Scenario Four: SARS-CoV-2 follows an evolutionary trajectory with decreased virulence.

 

Scenario One: A variant that causes severe disease in a greater proportion of the population than has occurred to date. For example, with similar morbidity/mortality to other zoonotic coronaviruses such as SARS-CoV (~10% case fatality) or MERS-CoV (~35% case fatality).

Likelihood of increased severity phenotype: Realistic possibility.

 

Scenario Two: A variant that evades current vaccines. This could be caused by: Antigenic ‘shift’: Natural recombination events that insert a different spike gene sequence (or partial sequence) from human CoVs MERS-CoV (highly unlikely due to the low frequency of MERS-CoV infections), or from currently circulating endemic human CoVs (more likely due to the prevalence of these viruses). This would recombine into the ‘body’ of SARS-CoV-2 that is capable of high replication in human cells. The consequence could be a virus that causes disease at a level similar to COVID-19 when it first emerged but against which our current battery of spike glycoprotein-based vaccines would not work. 

Likelihood: Realistic possibility.

 

Scenario Three: Emergence of a drug resistant variant after anti-viral strategies. This could be caused by: Emergence of new variants following the administration of directly acting antiviral therapies. As we begin to use directly acting antiviral drugs it is highly likely a variant will be selected that had resistance to individual agents. For example, drugs that target the viral 3C protease, drugs that target the polymerase, monoclonal antibodies that target the spike glycoprotein. If the drugs are used as a mono therapy, then resistant variants have a high probability of emerging. This may render all drugs in that category unusable.

Likelihood: Likely – unless the drugs are used correctly.

 

Scenario Four: SARS-CoV-2 follows an evolutionary trajectory with decreased virulence. This could be caused by: Variants arising with increased transmissibility but decreased pathogenesis/virulence as the virus becomes fully adapted to the human host becoming an endemic infection. Coupled with the likelihood of eventual high populations immunity the infection produces less disease. In other words, this virus will become like other human CoV that causes common colds, but with much less severe disease predominantly in the old or clinically vulnerable. 

Likelihood: Unlikely in the short term, realistic possibility in the long term.

 

Download the entire report here

GOV.UK SAGE Website Link

 

So what is Plan B if the vaccines fail with a new #coronavirus super-variant?