SARS-CoV-2 transmission bottleneck is in the order of one to three virions

Previous research conducted by two researchers at Emory University to characterize the transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), found that the size of the virus transmission bottleneck was important , that is to say of the order of 1000 virions. Now a new study, published on the bioRxiv * preprint from the same researchers, focusing on the Austrian region, found that the SARS-CoV-2 transmission bottlenecks were much tighter than previously thought.

A new computational analysis using more than 500 deep sequences has been performed. A combination of genetic and epidemiological data from a wide range of viruses was analyzed to characterize the transmission dynamics of SARS-CoV-2 in Austria between February and April 2020. In addition, the researchers studied the patterns of low-grade variants. frequency shared between transmission pairs where a de novo genetic mutation was present in the recipient.

After a thorough reanalysis, the researchers obtained a contradictory result from the previous article. They found that SARS-CoV-2 transmission bottlenecks are extremely small and tight, that is, in the order of 1 to 3 virions. The most significant aspect of this result is that it shed light on how the virus evolves between hosts. In addition, it has also helped to understand the process or pattern by which genetic mutation occurs within the population.

The reason for re-analyzing the data was the presence of some questionable items. Previous research estimated the size of the bottleneck (using a 3% variant) to be bimodal, with 14 of 39 transmission pairs having an inferred size. To better understand the above result, the scientists reanalyzed the deep sequencing data (sizes of transmission bottlenecks at 1% and 3%) and found similarities between the result obtained and previous research. However, upon further analysis, they found a decrease in the size of the bottleneck. This decrease was estimated over a cutoff of 1% to a cutoff of 3% for each of the 13 transmission pairs that had donors with a peak frequency of intrahost mononucleotide variants (iSNVs)> 6%.

Scientists reported that increasing the variant call threshold removes iSNVs from the analysis. In addition, a constant decrease in inferred bottleneck size may occur if low frequency donor iSNVs represent large bottleneck sizes and high frequency donor iSNVs represent small neck sizes. ‘strangulation. The current investigation has shown the presence of low frequency iSNV on the donor-recipient transmission pairs, indicating significant congruence between their frequencies, revealing a large transmission bottleneck. However, high-frequency donor iSNVs, which were rarely present for donor-recipient transmission, would suggest a tight transmission bottleneck.

To understand the conflicting patterns, the scientists looked at the genetic mutations present, from the start, in the recipient hosts. The genetic variations were present in the “tv traces” because the iSNVs were absent from a donor and present in the corresponding recipient.

The scientists explained that in a de novo variant having a constant or fixed factor in a sample of recipients, no sharing of iSNV should be observed between a donor and a recipient. Their presence in the recipient can only be observed at subclonal frequencies where rapid intra-host recombination occurs, or the fixed de novo variant occurs multiple times in different genetic backgrounds. However, the previous study showed subclonal iSNVs shared at remarkably similar frequencies between the transmission pairs and a fixed de novo variant present in the recipient. This result was reanalyzed because shared low frequency iSNVs are very unlikely to be a transmitted genetic variation. Low-frequency iSNVs shared between donor-recipient pairs occurred either spuriously or independently in the recipient (homoplasias). The scientists further stressed that these factors should be omitted from any analysis of transmission bottlenecks involving a transmission pair.

In the re-estimation study, the scientists used the beta-binomial method at a conservative variant call threshold of 6%. 13 transmission pairs with one or more iSNV donors were found at a threshold of 6%, indicating that the size of the bottlenecks can only be estimated for these pairs. Increasing the variant call threshold is irrelevant in estimating the size of the bottlenecks. The current study found that an estimate of an average bottleneck size of 1.21, such that 99% of transmissions are successful, should result from 3 virions or less.

Therefore, this analysis indicates that SARS-CoV-2 has a narrow transmission bottleneck, which is similar in size to influenza A viruses. A small bottleneck size also suggests that infections are generally introduced to a very low viral genetic diversity. Scientists believe their research would add substantially value to existing information on the course of SARS-CoV-2 between and within infected individuals.

*Important Notice

bioRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behaviors, or treated as established information.