Progress against the COVID pandemic has been impeded by the emergence of new variants of concern (VOC), and new ones may further worsen and prolong it.
VOCs increase the transmissibility of the SARS-CoV-2 virus and hence raise the reproduction number. Furthermore, they enhance the immune escape capabilities of the virus and blunt the effectiveness of available vaccines. Finally, they increase the pathogenicity of the infection.
Alpha, Beta, and Gamma VOCs with the N501Y mutation replaced the initial wild-type SARS-CoV-2 strains in Ontario, Canada, and then the Delta variant dominated during the period between February to June 2021. While enhanced virulence of VOCs having the N501Y mutation has been reported, there is a lack of comprehensive analyses that demonstrate increased virulence of the Delta variant.
Researchers from Toronto University, Canada, recently showed that these emerging VOCs were linked to increased virulence, as determined by hospitalisation risk, ICU admission, and mortality. This study is currently available on the medRxiv preprint server.
The researchers created a retrospective cohort of patients testing positive for SARS-CoV-2 in Ontario and screening 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 hospitalisation; 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 hospitalisation; and 121% (57-211%) for death.
VOCs with the N501Y mutation were found to be associated with a significantly higher risk of hospitalisation, ICU admission, and death in infected individuals in Ontario, Canada. They also reveal that the Delta variant, becoming dominant 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 hospitalisation and ICU admission,” the authors found.
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 vaccination rates has certainly mitigated the impact of these VOCs.
In summary, the researchers showed that despite excellent vaccination rates in Ontario, Canada, and VOCs infecting predominantly younger and healthier individuals, these VOCs are associated with an increase in virulence and risk of death. In particular, the Delta variant is more virulent compared to previously dominant VOCs possessing the N501Y mutation. It is the authors’ view that the progressive increase in transmissibility, immune escape and virulence of emerging VOCs could result in the pandemic being more drawn out and deadly.