A fascinating comment by Fontanet and others published in The Lancet February 11th 2021 discusses this issue.

COVID-19 pandemic has devastated healthcare systems, shutdown schools and communities, and plunged the world into an economic recession.  

While 2020 was a challenging year, 2021 looks to be difficult with the emergence of multiple variants of SARS-CoV-2. 

The race to vaccinate the world will need to respond to the pathogens constant evolution to evade immunity.  What marks the path to the end of this pandemic? 

2020 saw the successful development and testing of COVID-19 vaccines within timeframes not considered possible before. 

Two mRNA COVID-19 vaccines produce the first results, with impressive efficacy of 94-95%.

The disadvantage of these two vaccines is their low temperature storage requirements. Although other COVID-19 vaccines developed to date that use viral vectors, subunit particles, or inactivated viruses have comparatively lower levels of efficacy, with estimates of 70% for ChAdOx1 nCoV-19 and 92% for the Sputnik V Russian adenovirus vector vaccines, they do not have the ultra-cold storage temperature requirements of the mRNA vaccines and are therefore easier to deliver.  

Data available so far for COVID-19 vaccines have shown protection only against clinical forms of infection, with the exception of recent data showing reduction in the duration of viral shedding and viral load among recipients of the ChAdOx1 nCoV-19 vaccine compared with placebo, suggesting a potential impact on viral transmission as well.  

In December 2020, an unexpected rise in the reported COVID-19 cases was attributed to the emergence of the new SARS-CoV-2 variants in the UK and in South Africa.  

In South Africa, high transmission in the context of high population immunity may have favoured the emergence and subsequent spread of the variant.  Both variants had a mutation in the receptor binding domain of the spike protein that is reported to contribute to increased transmission.  The increased transmission rate was between 40 and 70%.  The South African variant had two additional mutations in the spike protein that conferred a potential immune escape to antibodies. 

In a concerning development, another set of mutations in a new lineage has been identified in Manaus Brazil.

A key issue is whether COVID-19 vaccines will be able to protect against infection of disease from these new SARS-CoV-2 variants. 

Preliminary research suggests serum from individuals immunised with the mRNA COVID-19 vaccines neutralised a 501 mutation pseudo virion but neutralised another variant to a lesser extent. 

Moreover, preliminary clinical trial results of the ChAdOx1 nCoV-19 showed 74% efficacy in UK but only 22% in South Africa whereas the NVX-CoV2373 protein based COVID-19 vaccine showed 89% efficacy in the UK but only 49% efficacy in South Africa where the South African variant predominates. 

Similarly, differences in vaccine efficacy in the USA and South Africa were reported for the Ad26.COV2.S COVID-19 vaccine.  More encouraging, 85% protection against severe COVID-19 has been reported for the Ad26.COV2.S vaccine in South Africa.  If this is confirmed, a vaccine strategy targeting first those at risk of severe COVID-19 might therefore still be effective even in the presence of these variants.  

The recent emergence of SARS-CoV-2 variants, after a period of relative viral genetic stability, is a cause for concern since multiple new escape variants could emerge in future and lead to severe epidemic rebound, as seen in South Africa. 

Increased viral transmission creates greater opportunities for the emergence of SARS-CoV-2 variants.  Hence the end of the pandemic is only possible when vaccines that are effective against circulating variants are distributed equitably across the world. 

As high income countries race to immunise their populations within months, they leave themselves vulnerable to SARS-CoV-2 evolving in other countries to a new lineage that vaccines might not protect well against.  Repeatedly formulating new vaccines may be needed to control some new SARS-CoV-2 variants.  With the increase in basic reproduction number of more transmissible SARS-CoV-2 variants, higher vaccine coverage will be required to achieve herd immunity, and vaccinating children might also be necessary to reach this coverage.  

The emergence of new SARS-CoV-2 variants calls for a number of important measures.  

First, fewer new infections means less viral replication, which in turn lowers the risk of new variants.  This situation can only be achieved by a combination of non-pharmaceutical inventions and scale up of vaccines, both being important, until population immunity is achieved.  Aiming for a COVID-19 elimination strategy is the preferred option in this context.  

Second, for surveillance of the circulation of SARS-CoV-2 variants, sharing of variant specific PCR primers could help to monitor their spread, particularly in resource limited countries. 

In addition, every country should include genomic sequence in the SARS-CoV-2 variants in their plans.  For resource limited countries, support from the WHO, the Africa Centre for Disease Control and Prevention, and other partner institutions will be necessary to help develop expertise and capacity as well as strengthen health systems.  All genetic sequences should be posted on an international platform.  Infections in people who were previously infected or vaccinated should be carefully examined for escape variants.  

Third, a central repository of samples of serum cells in individuals with passed infection or passed immunisation with available COVID-19 vaccines should be established for seroneutralisation and cellular immunity functional testing against newly discovered variants.  This repository could release regular advisories to provide guidance on minimum set of epitopes to be included in new COVID-19 vaccines.  

Fourth, the production of COVID-19 vaccine should be reactive and adaptive to newly emerging lineages.  This flexibility is likely to be easier to achieve with the new COVID-19 vaccine technologies currently being deployed and based on nucleic acid vaccines or viral vector vaccines.  

Finally, vaccines needed to be available, affordable and accessible at a global scale.  Several high income countries have purchased vaccine doses sometimes close to nine doses per person, while WHO has called for greater equity and stronger support for co-vaccine initiatives and its mandate of equitable vaccine access, especially for resource limited countries.  Of note, is an initiative of the African Union to independently purchase and distribute COVID-19 vaccines to countries over the continent to supplement the COVAX programme.  Whether vaccine delivery should be prioritised to the countries who have high SARS-CoV-2 prevalence and continued transmission e.g. South Africa, Brazil, Mexico, or India to prevent further emergence of new variants has to be considered.  

This pandemic is a reminder to high income countries with infectious diseases that the tremendous impact on economies and lives, and rapid development and implementation of effective vaccines against these diseases should remain priorities globally.  

Global cooperation to ensure equity and responsiveness to local context is essential on the difficult path ahead to end this COVID-19 pandemic.

Dr Paul Ettlinger
BM, DRCOG, FRCGP, FRIPH, DOccMed

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