The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-triggered coronavirus disease 2019 (COVID-19) pandemic has so far caused over 200 million documented infections worldwide. This is likely a monumental undercount in view of the asymptomatic or very mild phenotype of most infections. The perplexing range of disease severity has been among the biggest barriers to tracing and isolating all infectious cases.
A new study traces the degree to which the Beta variant of this virus is associated with severe, critical or fatal disease, using a case-control model.
The researchers carried out their work in Qatar, where the first wave of the pandemic peaked in early March 2021, caused by the Alpha B.1.1.7 variant, followed immediately by another wave of infections caused by the Beta B.1.351.
This scenario allowed a direct comparison between the two variants regarding their severity, criticality and fatality. The investigators applied the results of eight case-control studies that used data from the complete national database related to SARS-CoV-2 infections in the country.
The researchers retrieved data on the polymerase chain reaction (PCR) testing, serology, vaccinations and clinical characteristics. The presence of a positive PCR test with hospital admission was the criterion for assessment of the patient every three days until death or discharge. The worst outcome was used to grade the patient.
The cases in this study, available as a preprint on the medRxiv* server, were those who developed severe, critical or fatal outcomes following COVID-19. They were matched against controls, namely, asymptomatic or mild infections, at a ratio of 1:3. The guidelines of the World Health Organization were applied for severity grading using patient charts.
Alpha and beta variants cause severe disease
The researchers found that the Alpha variant, which rapidly became dominant in most of the world during the first quarter of 2021, had 48% higher odds of causing severe disease than the wildtype variants. The Alpha variant also showed a trend towards causing more critical disease, but deaths due to this or the wildtype variant were too few to assess its fatality characteristics.
Conversely, patients with the Beta variant had 24% higher odds of progressing to severe disease relative to the Alpha variant. The odds of developing critical COVID-19 were 50% higher, and of death due to COVID-19, higher by 57%.
The higher severity of the clinical phenotype of infection caused by the Alpha variant was confirmed, while the beta variant was observed to be associated with still more serious illness.
What are the implications?
The scientists concluded that the Beta variant, B.1.351, is associated with slightly higher odds of severe disease, but 50% higher odds of critical, and almost 60% higher odds of fatal disease. The findings underline the risks posed by this variant to the healthcare system, especially with regard to those patients who require intensive care facilities and sophisticated resources.
These results also provide an explanation for why the number of hospitalizations and deaths surged during the wave of beta infection compared to the earlier wave. In fact, the number of admissions to acute care facilities doubled with the beta infection wave.
Even worse, admissions to the intensive care unit (ICU), and COVID-19 deaths, went up fourfold, indicating that the Beta variant is more prone to cause critical and fatal outcomes following SARS-CoV-2 infection.
The current study includes smaller numbers of Alpha-variant-caused critical and fatal outcomes, relative to the Beta infections. This is due to the low numbers of critical cases and deaths in this mostly young working-age population. The case-control design allowed for matching of comorbidities in both cohorts, since they were not specifically adjusted for these conditions. Moreover, a high incidence of comorbidities is unlikely in a young population such as this.
The findings may not be easy to extrapolate to older populations, however. Despite these limitations, the study demonstrates that healthcare systems may be stressed by a global increase in the prevalence of the Beta variant.
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.