Errors in Tracing Coronavirus SARS-CoV-2 Transmission Using a Maximum Likelihood Tree. Comment on “A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis”

Authors' Reply to: Errors in Tracing Coronavirus SARS-CoV-2 Transmission Using a Maximum Likelihood Tree. Comment on “A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis”

“…Yet, epidemiological tracing and surveillance by other means was not the focus of our work [7], which discusses only the unreliability of using SARS-CoV-2 sequence data, without the aid of other contact tracing methods, to infer virus dissemination during the early phase of the pandemic. Therefore, one of the major points raised by Forster and Forster [1] in their commentary is irrelevant since it is not pertinent to our work or the interpretation of our findings.…”

“…Forster and Forster [1] misinterpret the message of our paper, based on targeted sentences/paragraphs taken out of context. There was no trivial or other oversight in our analysis.…”

“…conceptual and theoretical mistakes, in the commentary by Forster and Forster [1], we would like to emphasize the following points. First, very recent work by Morel and colleagues [2] has confirmed and further extended our original observation of a lack of a phylogenetic signal in SARS-CoV-2 sequences from the early phase of the pandemic, which is in line with our main criticism that Forster et al's work [3] was based on a superficial analysis of biased and noisy sequence data, resulting at best in misleading conclusions.…”

“…If anything, the subsequent isolation of sequences of patients from Portugal, Brazil, Wales, and the Netherlands, which were identical to the pre-existing Italian sequence, illustrates our point precisely: "it is not possible with the present data to decide which branching pattern (and, therefore, which phylogeographic reconstruction) most likely represents actual dissemination routes among European countries." Forster and Forster [1] go on to discuss how the Welsh, both Dutch, and Brazilian patients had all visited Italy a few days before falling ill. This is interesting information that may suggest such patients were infected in Italy; after all, contact tracing is presently considered the golden standard for tracking SARS-CoV-2 dissemination, but it has very little to do with the central problem raised in our paper [7]: branching patterns in the phylogeny alone, especially when based on several identical sequences from different geographic areas (one of the very definitions of a lack of a phylogenetic signal in any basic textbook [11], which Forster and Forster [1] seem to ignore) cannot distinguish among different and equally likely dissemination scenarios.…”

“…Forster and Forster [1] go on to discuss how the Welsh, both Dutch, and Brazilian patients had all visited Italy a few days before falling ill. This is interesting information that may suggest such patients were infected in Italy; after all, contact tracing is presently considered the golden standard for tracking SARS-CoV-2 dissemination, but it has very little to do with the central problem raised in our paper [7]: branching patterns in the phylogeny alone, especially when based on several identical sequences from different geographic areas (one of the very definitions of a lack of a phylogenetic signal in any basic textbook [11], which Forster and Forster [1] seem to ignore) cannot distinguish among different and equally likely dissemination scenarios. In fact, Table 1 in our manuscript shows, as expected given the presence of several identical sequences sampled over a short time interval in different countries, that alternative topologies underlying alternative dissemination scenarios are equally likely.…”