With the rise of many mutations and variants, the questions arise: 1) will the current vaccines protect and stem the tide of the pandemic? 2) Will the vaccines drive, by selection pressure, the establishment of new more resistant, transmissible and/or pathogenic variants? 3) Will masks and social distancing still be required after vaccination? Variants which emerged in Brazil (known as P.1.), Britain (known as 20I/501Y.V1 or B.1.1.7) and South Africa (known as 20I/501Y.V2 or B.1.351) are now the globally dominant strains because of their apparently enhanced infectivity and transmissibility.
Current vaccines work against the UK B.1.1.7 variant without the E484K mutation. However, recent clinical trials by Novavax and Johnson & Johnson showed that their new vaccines were less effective in South Africa compared with the UK or US, probably because of the high level of virus carrying the E484K mutation. However, Novavax vaccine was reported to have a 60% efficacy in South Africa which is a good response, when compared to influenza vaccine responses of from 40-60 %. Studies have shown that people who have been infected with SARS-CoV-2 generate T cells that target at least 15–20 different fragments of coronavirus proteins. Because of natural variability, a population will generate a large variety of T cells that could attack the virus (https://reader.elsevier.com/reader/sd/pii/S1074761320305379?token=3775A68CFC8B8609E4A6753EF03F560FAF6F4B30D3B821B81F3A1CBF077E6DB8C53232C5B16ACCA1E569F0AE6C5368F3). As I mentioned in an earlier post, it is very hard for the CoVID variant viruses to mutate to escape cell recognition because of this T cell variation, The specificity of antibodies works in favor of variants. A recent pre-print shows a single mutation can defeat monoclonal antibodies against the spike protein of the virus and increased cell receptor binding, unfortunately a rare converging of properties in a single mutation. The mutation has been observed in a recent variant in California, CAL.20C viral variant from clade 20C, lineage B.1.429, that since November 2020 has generated multiple outbreaks and is undergoing massive expansion in California. This L452R mutation allows SARS-CoV-2 positive selection toward strong viral adaptation against containment measures that work on less contagious variants and against increasing population immunity against previous forms. The L452R mutation is at the leucine-452 position in the receptor-binding area of RBD (receptor binding domain) at the interface with the ACE2 receptor. Replacing it with arginine is anticipated to result in both a much stronger receptor binding and escape from neutralizing antibodies https://www.biorxiv.org/content/10.1101/2021.02.22.432189v1.full.pdf. Escape from two monoclonal antibodies has been predicted in a recent Science article https://science.sciencemag.org/content/sci/371/6531/850.full.pdf.
In a preprint published on 9 February, researchers found most T-cell responses to coronavirus vaccination or previous infection do not target regions mutated in two recently discovered variants, including 501Y.V2 (https://www.researchsquare.com/article/rs-226857/v1). Also, the vaccine made by Novavax of Gaithersburg, Maryland, a single-shot vaccine made by Johnson & Johnson of New Brunswick, New Jersey, and a vaccine made by AstraZeneca of Cambridge, UK, and the University of Oxford, UK are less effective at protecting against mild COVID-19 in South Africa, where the 501Y.V2 variant dominates, than in countries where it is now less common. AstraZeneca’s vaccine was only 22% effective against mild COVID-19 in a study of 2,000 people in South Africa, but the trial was too small and participants too young to draw any conclusions about any loss of benefit in protecting against severe disease. However, another recent paper compared the vaccine – induced neutralization of a less contagious version of the SARS-CoV-2 virus from last year (USA-WA1/2020), to the new variants Brazilian P1 and UK variant B.1.1.7 which gave results “roughly equivalent.” Geometric mean titers (GMT) of neutralizing antibodies against the USA-WA1/2020 virus, the UK B.1.1.7 variant, and the P1 variant were 532, 633, and 437, respectively. The GMT against three versions of the South African B.1.3.5 variant were less at 195, 485, and 331, respectively (https://www.medscape.com/viewarticle/947064).
A recent, yet to be peer-reviewed, study of men from 70-84 years of age, who died from COVID-19, increased from 5% of those who tested positive for the older variant, to more than 6%, if confirmed positive for variant B.1.1.7. For men 85 years or older, the risk of dying increased from 17% to 22% of those confirmed positive for the new variant. Therefore, the apparent increase in severity of this new variant has been limited in scope. It may reflect an increased viral load rather than a normalized increase in pathogenicity. There is little evolutionary advantage for a virus to become more pathogenic in a host in preference to transmissibility. This may happen only if there is a maintenance reservoir host in which the pathogenicity is less and from which the virus periodically emerges entering the host more vulnerable to lethality.
As to the third question, until the pandemic has subsided, even vaccinated people, including those who may have gotten upgraded vaccine for new variants, should continue to use masks, social distance, and, of course, continue to use good hand washing practices. Another early treatment to block viral replication has been discovered; a single pill of the investigational drug molnupiravir, when taken twice a day for 5 days, has been shown to eliminate SARS-CoV-2 from the nasopharynx of 49 participants in a new study (https://www.medscape.com/viewarticle/947061). Phase 2/3 efficacy and safety studies of the drug have started. The drug creates viral error catastrophe by inducing replication and mutations until the virus can’t effectively produce viable copies. This new early treatment and the non-pharmaceutical practices are necessary to decrease the total number of viruses in circulation, to greatly decrease the probability of establishing new variants even if they are more transmissible, and especially if those infected shed larger amounts of virus asymptomatically or symptomatically.
Global Biosurveillance 