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COVID-19: South African variant may be worse than UK variant

Daniel R. Lucey, MD, MPH, FIDSA
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A template is needed for the variants to come

Overshadowed by reporting about the UK variant virus “B.1.1.7,”  a separate but similar variant SARS-CoV-2 virus in South Africa “501.V2” is under appreciated and deserves more international attention.

Both variant viruses containing multiple mutations in the spike (S) protein, including in the receptor binding domain. One key mutation “N501Y” is present in both the UK and South African variants. It could increase binding to human cells via the “ACE2” receptor, and contribute to the apparent increased transmissibility of both variants.

A preliminary manuscript, pending peer review, is posted at KRISP.org (Kwazulu-Natal Research Innovation and Sequencing Platform), a site launched by a network of laboratories, scientists and academic institutions with the aim of sharing data for public health responses to COVID-19 in South Africa.

This manuscript is titled:  “Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa,” by Tegally H et al.

The Africa CDC website is also a good source for information on the South African variant.

This Africa Centre for Disease Control and Prevention website states that studies are underway to see if “higher viral loads” are associated with this variant, as well as “whether it causes more severe illness” (as only anecdotally reported so far), and if there is any impact on vaccine efficacy, antibody efficacy, or diagnostic test sensitivity. If any of these concerns are proven to be true in the coming days, then this variant could be worse than the UK variant. Some nations have already halted air traffic to and from South Africa, although fewer nations so far than have done so than for the UK.

Slide presentations are also posted on the above link to the African CDC website by the renowned South African Professor Salim S. Abdool Karim and Professor Tulio de Oliveira (on behalf of the NGS-SA -- Network for Genomic Surveillance: South Africa).

The latter has one slide that focuses on concern about resistance to neutralizing antibodies (“Nabs”). This slide illustrates the 3 mutations in the Receptor Binding Domain, N501Y, E484K (“enhances binding affinity to ACE2 and confers resistance to class 2 Nabs”) and K417N (that “would abolish key interactions with class 1 Nabs, and likely contributes towards immune evasion at this site”).

This “501.V2” variant was first recognized in Nelson Mandela Bay then spread across other parts of the Eastern Cape to the Western Cape, along the Garden coastal route and into KwaZulu Natal in the southeast. Since early November it has been spreading rapidly as the 2nd major wave in the country now starting its southern hemisphere summertime.

More generally what these two variants in the UK and South Africa teach us is that there will be more variants and we need a standard TEMPLATE to recognize, assess, and respond comprehensively  to these and future virus variants.

Perhaps more variants already exist somewhere in the world, but we have not yet recognized them due to inadequate surveillance and sequencing of SARS-CoV-2 from around the world. The United States is an arrival point for direct flights from UK, South Africa and around  the world; however, our surveillance and sequencing Is not as robust as is needed to identify such variants as early as we should.

The last thing the United States needs now is more transmissible SARS-CoV-2 variants that would increase the total number of infections, and corresponding further increase in the number of hospitalizations, ICU admissions, and deaths.

In addition, imagine how much worse the situation would become if either or both of these variants conferred even partial resistance to monoclonal antibodies, convalescent plasma, vaccines, or diagnostic tests.  

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