New SARSCoV-2 variants: A third wave after the calm?

by Dr. Rey Pagtakhan

On February 19, the Public Health Agency of Canada released its report, Update on COVID-19 in Canada: Epidemiology and Modelling, which contained this warning:

“Variants of concern increase the threat for a spring resurgence, but a strong collective effort can see us through. With a combination of strong public health measures and strict adherence to individual precautions, we can prevent a resurgence.”

The report gives the following projections:

1. If public health measures are prematurely lifted, the variants of concern would trigger a pan-Canadian resurgence so rapid as to create a third wave akin to the most lethal pandemic curve of the Spanish flu a century ago;
2. If public health measures are kept at the same level or loosen, variants of concern would also cause a third-wave resurgence, although not as rapid, before more intense rapid mass vaccination starts in April; and
3. If public health measures and individual compliance are combined and made more stringent and stricter, resurgence would be prevented and control of the epidemic would be achieved. That is, the country will avoid a third wave.

Based on the average daily new case counts of 2,886 the week preceding the report, Canada’s top public health expert, Dr. Theresa Tam, elaborated on the modelling projections, using actual numbers and assuming the new variants of concern are 50 per-cent more transmissible than the current dominant form of the COVID-19 virus in Canada:

1. If the current restrictions remain in place, Canada could see 10,000 cases a day by the end of March;
2. If these restrictions are lifted, Canada could be on track for more than 20,000 daily new cases by mid-March.

Using the same assumption for transmissibility, the U.S. Centers for Disease Control and Prevention conveyed a similar message with its own forecast published five days later.

One shudders at the likelihood of a pandemic third wave. This is particularly gnawing in light of the decline seen over the last couple of months of new cases, hospitalizations and deaths around the world. While the downward trend could be due to mass vaccination that started in December 2020, better adherence to stricter public health measures, supportive and coordinated political leadership, or to any combination of these factors, the flattening of the curve may reflect the adverse influence of the new virus variants. If so, the earlier progress that has been made is once more under threat.

Are we seeing the early signs of pandemic resurgence? To not make it inevitable, we are well advised to follow public health guidance and do our individual best to have “the fewest interactions, with the fewest people, for the shortest time, at greatest distance possible, while wearing the best-fitting facemask.”

SARSCoV-2 variants of concern

To date, Canada has identified 976 cases of COVID-19 with a SARSCoV-2 variant of concern across all 10 provinces.

1. B.1.1.7 – First detected in the UK, it has the mutation N501Y in the spike protein plus 22 other mutations. It is associated with increased transmissibility and risk of death.
2. B.1.351 – First detected in South Africa, it has multiple mutations in the spike protein, including N501Y. It may affect neutralization by monoclonal antibodies. It has no known impact on disease severity.
3. P.1 – First detected in travelers from Brazil, it contains three mutations in the spike protein receptor binding domain, including the N501Y. It is associated with increased transmissibility and it affects the ability of antibodies to recognize and neutralize the virus.

Theses three variants each have the N501Y mutation. They have one or more mutations that differentiate them from the wild-type or predominant virus variants already circulating among the general population, which contain no major mutation. A common characteristic among the variants of concern is the role of international travel in transmission. Three of the five cases recently detected in Manitoba were related to international travel.

In the U.S., more than 1,900 of the three major variants as seen in Canada have also been identified, almost all of which belong to the B.1.1.7 lineage. Two forthcoming reports from California on new variants, B.1.427 and B.1.429, which are associated with severe infectiousness and severity, are soon to be published.

What are the concerns about the new variants?

1. Ability to evade natural or vaccine-induced immunity – Both natural infection with and vaccination against SARS-CoV-2 produce a “polyclonal” antibody response that targets several parts of the spike protein. The virus could accumulate significant mutations in the spike protein to evade immunity induced. This is the most worrisome concern since Canada and the other countries have only begun their vaccination drive barely two months ago and the proportion of the population that had been fully vaccinated is nowhere near the level required to establish herd immunity.
2. Ability to spread more quickly in people – One study has shown transmissibility increased by about 50 per cent, which would most certainly increase the number of cases in the community.
3. Ability to cause either milder or more severe disease in people – If the increase in caseload is accompanied by serious cases requiring oxygen therapy and ventilator-assisted breathing, the acute care burden can overwhelm the health system once more. Preliminary studies have shown a predisposition of some variants to cause more severe disease requiring oxygen therapy.
4. Ability to evade detection by specific diagnostic tests – Many diagnostic tests use multiple targets to detect the virus, hence, would still work even if a mutation impacts one of the targets. Tests that rely on only one target may fail in their diagnostic capability. This is being closely monitored.
5. Decreased susceptibility to therapeutics that employ monoclonal antibodies – These treatments are more specific than natural immune response-generated antibodies; hence, they may be less effective against variants that emerge.

How do variants occur?

Basically, a virus variant is the natural consequence of replication that occurs in a virus’ life history in the human host over time.

Viruses such as SARS-CoV-2, which causes COVID-19, are constantly changing. The virus genome packed inside an envelope contains proteins and instructions to build parts of the virus, such as the spike protein, which allows the virus to attach to human cells during an infection. This section of the genome serves as a key region for monitoring mutations. Mutations are changes in the genetic code of a virus that naturally occur over time when a person is infected. A certain amount of genetic variation is expected to occur over time. While many mutations do not affect the virus’s ability to spread or cause disease, it is crucial to monitor circulating viruses for key mutations that happen that are more beneficial for the virus.

Dr. Alyson Kelvin, a Canadian virologist and researcher in vaccine development, said in a recent CBC News interview, “Each virus has a singular goal of replicating itself. With tens of millions of people helping move the coronavirus back and forth between hosts, that means countless replications. Some of those contain random, insignificant mistakes. And when the mistakes prove beneficial to the virus, helping it produce more copies, those errors can become a new normal of sorts – a variant.”

Understanding the singular goal of a virus

Last month’s edition of the National Geographic magazine (February 2021) featured the article, “How Viruses Shape Our World” by David Quammen. His essay clarifies a couple of the basics in virology: 1. a virus is inanimate, which means it is destitute of life, and 2. a virus wants to replicate – to copy itself – which means it is animated and implies the presence of activity. This teaching, when presented simply in this manner, seems puzzling.

Virions and virocells – Delineating the inanimate and animated parts of a virus

It is this seeming conundrum that Quammen’s exposition led me to focus on the behaviour of a virus when residing inside the human host or outside, suspended in the air as aerosol or lying on surfaces as fomites. He quoted the scientist Patrick Forterre of the Pasteur Institute in Paris, France who explained: “Scientists were confusing the viral particles known as virions (the bits of genome or genetic material enclosed in a protein coat or shell or envelope) with the totality of a virus, and was as wrong as confusing a seed with a plant.”

The French scientist went on to further explain that the virions, which are inanimate, are only a part of the totality of a virus. “The real wholeness of the virus,” he continued, “also includes its presence within a cell, once it has seized the cell’s machinery to replicate more virions, more seeds of itself.” When that has happened, “the cell has become part of the virus’s life history.”

For this combined entity, he coined the new term, “virocell.” In this stage when a virus infects a person, the wholeness of the virus is expressed and active, not inanimate, and obeys the official viral mandate, that is, “reading the viral genome and replicating it.” That is the wholeness of the virus complying with its inherent domain or natural property – to replicate itself.

The pathogenic virus SARSCoV-2 that causes COVID-19 is a single-stranded RNA virus. As such, its RNA genome is prone to undergo, over time, mutations or variations as the virus replicates to make more viruses. The opportunity to replicate its genome occurs whenever the virus infects people and resides in their cells. And every time it replicates its genome, chances for “skips, staggers, and mistakes” – errors or mutations – are bound to happen, notwithstanding it has proofreading enzymes to correct most of the mutations.

For a little over a year now since it first infected a cluster of citizens in Wuhan, China in early December 2019, SARSCoV-2 has been globe-trotting in the comfort of its human hosts. The human cell has become part and parcel of its life history and travels. In the first few human hosts infected, we have learned the virus replicated in abundance, harmed organs, primarily the lungs, and soon managed to spread – human to human – across the country and across continents. Until now, it continues to encircle the world, leaving in its path the misery of illness and death for millions of the world citizens. It needs little imagination to acknowledge that the viral genome has been replicated billions of times. During this period of time, errors must have been incorporated, resulting in many new variants with mutations on certain regions of the viral genome of the original, wild type of circulating SARSCoV-2, which had very few mutations and none major.

As of February 25, 2021, the Johns Hopkins University Coronavirus Tracker, has tallied 112,999,297 cases and 2,507,444 deaths worldwide. In Canada, the count is 863,495 cases and 21,868 deaths. The U.S.A.: 28,411,273 cases and 508,127 deaths. The Philippines: 568,680 cases and 12,207 deaths.

Rey D. Pagtakhan, P.C., O.M., LL.D., Sc.D., M.Sc., M.D. is a former cabinet minister and Parliamentary Secretary to Canada’s Prime Minister. He is also a retired lung specialist and professor from the University of Manitoba Faculty of Medicine. He graduated from the University of the Philippines and did postgraduate studies at the Washington University, University of Manitoba, and University of Arizona medical centres. He spoke on the “Global Threat of Infectious Diseases” at the 2003 G-8 Science Ministers and Advisors Carnegie Group Meeting in Berlin. reypagtakhan@gmail.com.

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