Canadian Study Warns That COVID-19 Pandemic Likely To Become More Deadly As Emerging Variants Have Increased Transmissibility And Virulence
Study findings of a new research by scientists from the University of Toronto alarmingly indicates that the current COVID-19 pandemic is likely to become more deadly and lethal as more emerging SARS-CoV-2 variants
are manifesting progressive increase in transmissibility and virulence.
The study team said that the period from February to June 2021 was one during which initial wild-type SARS-CoV-2 strains were supplanted in Ontario, Canada, first by variants of concern (VOC) with the N501Y mutation (Alpha/B1.1.17, Beta/B.1.351 and Gamma/P.1 variants), and then by the Delta/B.1.617 variant.
Although the increased transmissibility of these VOCs has been documented, data for increased virulence is limited.
The study team used Ontario’s COVID-19 case data to evaluate the virulence of these VOCs compared to non-VOC SARS-CoV-2 infections, as measured by risk of hospitalization, intensive care unit (ICU) admission, and death.
The team created a retrospective cohort of people in Ontario testing positive for SARSCoV-2 and screened for VOCs, with dates of test report between February 7 and June 22, 2021 (n=211,197).
They constructed mixed effects logistic regression models with hospitalization, ICU admission, and death as outcome variables. Models were adjusted for age, sex, time, comorbidities, and pregnancy status. Health units were included as random intercepts.
The study findings showed that when compared to non-VOC SARS-CoV-2 strains, the adjusted elevation in risk associated with N501Y-positive variants was 59% (49-69%) for hospitalization; 105% (82-134%) for ICU admission; and 61% (40-87%) for death.
Even worse, Increases with Delta variant were more pronounced: 120% (93-153%) for hospitalization; 287% (198-399%) for ICU admission; and 137% (50- 230%) for death. Interpretation: The progressive increase in transmissibility and virulence of SARS-CoV-2 VOCs will result in a significantly larger, and more deadly, pandemic than would have occurred in the absence of VOC emergence.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2021.07.05.21260050v2
The surprised emergence of new variants of concern (VOC) has slowed down progress against the COVID-19 pandemic in 3 ways:
- by increasing the transmissibility of the virus and hence the reproduction number;
- by increasing immune escape capabilities of the virus and decreasing effectiveness of available vaccines;
- by increasing the pathogenicity of the infection.
It has been shown that the initial wild-type SARS-CoV-2 strains in Ontario, Canada, was first replaced by alpha, beta, and gamma VOCs with the N501Y mutation and then by the delta variant during the period between February to June 2021.
Though there have been reports of enhanced virulence of VOCs having the N501Y mutation, there is a lack of proper comprehensive analyses that demonstrate increased virulence of the delta variant.
The study team recently showed that these emerging VOCs were linked to
increased virulence, as determined by hospitalization risk, ICU admission, and mortality.
The study team created a retrospective cohort of patients testing positive for SARS-CoV-2 in Ontario and screened for VOCs between February 3 and July 1, 2021. Case data was gathered from the Ontario provincial Case and Contact Management (CCM) database. All PCR positive COVID-19 specimens with a cycle threshold (Ct) ≤ 35 were screened for the N501Y mutation using the real-time PCR assay from the Public Health Ontario Laboratory. Whole genome sequencing (WGS) was performed on 5% of specimens regardless of the presence of mutations.
Most significantly, when compared to non-VOC strains of SARS-CoV-2, the increase in risk associated with N501Y-positive variants was 138% (105-176%) for ICU admission; 74% (62-86%) for hospitalization; and 83% (57-114%) for death, after adjusting for age, sex, and comorbidity. Increase in risks associated with the delta variant was even higher- 241% (163-344%) for ICU admission; 105% (80-133%) for hospitalization; and 121% (57-211%) for death.
These study findings showed that VOCs with the N501Y mutation were associated with a significantly elevated risk of hospitalization, ICU admission, and death in infected individuals in Ontario, Canada. They also reveal that the delta variant, which is now superseding the other VOCs in Ontario, has increased these risks even further.
Dr David N. Fisman MD MPH from Dalla Lana School of Public Health, University of Toronto told Thailand Medical News, “Individuals infected with VOCs were, on average, younger and less likely to have comorbid conditions than those infected with non-VOC, but nonetheless had higher crude risks of hospitalization and ICU admission.”
Though patients infected with the VOCs were younger and less likely to have comorbidities than those infected with non-VOC strains, they had higher risks of hospitalization as well as ICU admission.
The study team said that the clear and significant elevation of risks of even delayed outcomes such as death visible in their analysis is remarkable given the relatively small number of delta variant infections in the time period of this study.
More importantly the fact that Canada is one of the leading countries in the world in terms of COVID-19 vaccination rates has definitely mitigated the impact of these VOCs.
The study team demonstrated that despite a very good vaccination rate in Ontario, Canada, and VOCs infecting predominantly younger and healthier individuals, these VOCs are associated with an increase in virulence and risk of death.
The emerging delta variant is more virulent compared to previously dominant VOCs with the N501Y mutation. The team believes that the progressive increase in infectiousness and virulence of emerging SARS-CoV-2 variants could lead to a significantly larger and more lethal pandemic.
Dr Fisman concluded, “Combined with increased transmissibility and immune escape, these VOCs represent a significant escalation in risk to public health during the SARS-CoV-2 pandemic.”
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