SARS-CoV-2 delta variant has higher viral RNA levels and increased infectivity, suggests study

Researchers in the United States have warned that the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first detected in India appears to be significantly more infectious than the B.1.1.7 (alpha) that first emerged in the UK.

Study: Quantitative measurement of infectious virus in SARS-CoV-2 Alpha, Delta and Epsilon variants reveals higher infectivity (viral titer:RNA ratio) in clinical samples containing the Delta and Epsilon variants. Image Credit: Corona Borealis Studio/ Shutterstock

The SARS-CoV-2 virus is the agent responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic that threatens global public health and the worldwide economy.

“Previous studies indicate that clinical samples collected from individuals infected with the delta variant may contain higher levels of RNA than previous variants, but the relationship between viral RNA and infectious virus for individual variants is unknown,” said the researchers from the University of Vermont in Burlington, the University of Washington in Seattle, and Faraday, Inc. in Burlington

Now, Emily Bruce and colleagues have measured both viral RNA and infectious virus levels in 165 clinical samples containing the B.1.1.7 (alpha), B.1.617.2 (delta), and B.1.429/B.1.427 (epsilon) variants of SARS-CoV-2.

The study found that the delta and epsilon variants exhibited significantly higher infectivity than alpha, with delta containing approximately six times as much infectious virus for the same amount of RNA.

“This increase in infectivity suggests increased measures (vaccination, masking, distancing, ventilation) are needed to control delta compared to alpha,” writes the team.

A pre-print version of the research paper is available on the medRxiv* server while the article undergoes peer review.

Emerging variants pose a threat to controlling the COVID-19 pandemic

Despite the rapid development of several effective COVID-19 vaccines, the emergence of novel, genetically distinct SARS-CoV-2 variants represents a threat to controlling the pandemic.

Mutations acquired in the viral genome can result in lineages with increased transmissibility and immune escape capabilities.

In the fall of 2020, the alpha variant that emerged in the UK was associated with increased transmission and subsequently designated a variant of concern (VOC) by December 2020.

Similarly, the epsilon lineage that emerged in California by late November 2020 exhibited increased transmissibility and signs of partial immune escape, resulting in its classification as a variant of interest (VOI) by March 2021.

What about the delta variant?

Since then, the delta lineage, first detected in India in the spring of 2021, appears to have outcompeted both of these variants and now accounts for approximately 90% of viral sequences globally.

This increase in global spread, combined with a possible increase in disease severity compared with alpha, led to the delta lineage being classified as a VOI in April 2021 and then a VOC the following month.

Studies have reported that the viral RNA levels in clinical samples infected with the delta variant are higher than those infected with previous variants.

However, “one difficulty in interpreting viral infectivity lies in the widespread use of viral RNA levels as measurements of viral load. While it is logical to assume a relationship between RNA and infectious viral levels, it is unlikely this is a fixed ratio in all scenarios,” writes Bruce and colleagues.

“Quantitative measurement of replication competent virus by plaque or focus assay would improve the ability to determine and interpret infectious viral loads for current and future variants, including VOI and VOC,” they say.

What did the researchers do?

To investigate the relationship between replication competent virus and viral RNA, the team measured infectious viral titer (using micro-focus forming assays) as well as total and subgenomic viral RNA levels (by reverse transcriptase quantitative polymerase chain reaction [RT-PCR]) in 165 clinical specimens containing the alpha, epsilon or delta variants.

The study revealed a high level of variability in the ratio of RNA to viral titer, particularly in delta.

As well as the variability observed for individual samples, trends of overall infectivity differed between the three variants.

Compared with the alpha variant, delta and epsilon had 5.9 and 4.3 times as much infectious virus, respectively, for samples with the same total viral RNA. A similar trend was observed when comparing infectious titers to subgenomic RNA levels.

Increased measures needed to control delta variant

The researchers say the finding that the delta variant shows increased infectivity compared with alpha is in line with the increased transmission and spread observed for this variant. It is also in line with reports indicating that live virus is more likely to be isolated from clinical specimens containing delta, they add.

“The increased infectivity we observe in delta clinical samples underscores the need for increased measures to prevent transmission to those who remain vulnerable, such as widespread vaccination, masking, distancing, and improved ventilation,” concludes the team.

*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.

Journal reference:

  • Despres, H. et al. (2021) “Quantitative measurement of infectious virus in SARS-CoV-2 Alpha, Delta and Epsilon variants reveals higher infectivity (viral titer:RNA ratio) in clinical samples containing the Delta and Epsilon variants.”. medRxiv. doi: 10.1101/2021.09.07.21263229.
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