The progressive increase in transmissibility and virulence of emerging SARS-CoV-2 variants could lead to a significantly more deadly pandemic

The emergence of new variants of concern (VOC) has slowed down progress against the COVID-19 pandemic in 3 ways: 1. by increasing the transmissibility of the virus and hence the reproduction number; 2. by increasing immune escape capabilities of the virus and decreasing effectiveness of available vaccines; and 3. by increasing the pathogenicity of the infection.

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. Although there have been reports of enhanced virulence of VOCs having the N501Y mutation, there is a lack of comprehensive analyses that demonstrate increased virulence of the delta variant.

Evaluating the virulence of N501Y-positive variants and the delta variant compared to earlier SARS-CoV-2 strains using Ontario’s COVID-19 case data

Researchers from Toronto University, Canada, recently showed that these emerging VOCs were linked to increased virulence, as determined by hospitalization risk, ICU admission, and mortality. This study is currently available on the medRxiv* preprint server.

They 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.

Results show that infection by VOCs with the N501Y mutation significantly elevated risk of hospitalization, ICU admission, and death in patients in Ontario

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 results show 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.

“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.”

Although 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. According to the authors, 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. 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.

Progressive increase in transmissibility and virulence of emerging VOCs could lead to a significantly more lethal pandemic

To summarize, the researchers 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 authors believe that the progressive increase in infectiousness and virulence of emerging SARS-CoV-2 variants could lead to a significantly larger and more lethal pandemic.

Combined with increased transmissibility and immune escape, these VOCs represent a significant escalation in risk to public health during the SARS-CoV-2 pandemic.”

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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