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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

Our take —

In this preprint study which has not yet been peer-reviewed, researchers found that clinical specimens from persons infected with the Delta and Episilon variant had higher infectious viral titers (i.e., amount of replication competent virus) and infectivity (amount of replication competent virus per viral RNA copy) than clinical specimens from persons infected with the Alpha variant. This study provides biological rationale for increased transmission and spread of the Delta variant as compared to other SARS-CoV-2 variants. While this study used rigorous laboratory methods, it was limited by a lack of epidemiological data on specimens, which limits our understanding of how important factors like age or vaccination status may also impact viral RNA levels and infectious viral titer. 

Study design

Cross-Sectional

Study population and setting

This cross-sectional study used 165 clinical specimens (e.g., nasal swabs) identified to be positive for SARS-CoV-2 at the University of Washington Virology Laboratory on March 25, 2021, August 3, 2021, or August 25, 2021. Aliquots of all included specimens were frozen within two days of collection. RT-PCR was used to measure total and subgenomic E RNA levels of SARS-CoV-2. A micro-focus forming assay, which involves growing live virus, was used to measure infectious viral titers of SARS-CoV-2. 

Summary of Main Findings

For each variant, the amount of total and E subgenomic viral RNA levels (i.e., cycle threshold values) were positively correlated with the amount of replication competent virus. Compared to the Alpha variant, the Epsilon and Delta variants had a greater number of infectious units per quantity of total RNA (i.e., infectivity) and subgenomic E RNA. 

Study Strengths

The study measured infectious viral titers and total and subgenomic viral RNA levels, and compared these values across variants. 

Limitations

The major limitation of the study is the lack of clinical and epidemiological data that may impact viral titers (e.g., age, time since symptom onset and vaccination status). Additionally, since not all variants were widely circulating at the same time in the U.S., the included samples were not collected from the same population, nor would sample characteristics that may impact viral titers and culturable virus likely be the same across time when the samples were collected (ex: vaccination status).  

Value added

This novel investigation using a micro-focus forming assay demonstrated that the Delta and Epsilon variants of SARS-CoV-2 may be more biologically infectious than the Alpha variant. This information can be useful in understanding how interventions such as masking, ventilation, etc. may need to be increased in response to increased infectivity of specific variants.

This review was posted on: 8 December 2021