What we can and cannot learn from SARS-CoV-2 and animals in metagenomic samples from the Huanan market.

While the exact context of the emergence of SARS-CoV-2 remains uncertain, data accumulated since 2020 have provided an increasingly more precise picture of Wuhan's Huanan Seafood Wholesale Market, to which the earliest clusters of human cases of Covid-19 were linked. After the market closed on January 1st 2020, teams from the Chinese Center for Disease Control and Prevention collected environmental samples, and sequenced them. Metagenomic sequencing data from these samples were shared in early 2023. These data confirmed that non-human animals susceptible to SARS-CoV-2 were present in the market before it closed, but also that these animals were located in the side of the market with most human cases, and in a corner with comparatively more SARS-CoV-2-positive environmental samples. The environmental samples were however collected after abundant human-to-human transmission had taken place in the market, precluding any identification of a non-human animal host. Jesse Bloom recently investigated associations between SARS-CoV-2 and non-human animals, concluding that the data failed to indicate whether non-human animals were infected by SARS-CoV-2, despite this being an already acknowledged limitation of the data. Here I explain why a correlation analysis could not confidently conclude which hosts(s) may have shed SARS-CoV-2 in the market, and I rebut the suggestion that such analyses had been encouraged. I show that Bloom's investigation ignores the temporal and spatial structure of the data, which led to incorrect interpretations. Finally, I show that criteria put forward by Bloom to identify the host(s) that shed environmental SARS-CoV-2 would also exclude humans. Progress on the topic of SARS-CoV-2's origin requires a clear distinction between scientific studies and news articles (mis)interpreting them.

[What do we know about the origin of COVID-19 three years later?] / ¿Qué sabemos del origen del COVID-19 tres años después?

More than three years have passed since the first case of a new coronavirus infection (SARS-CoV-2) in the city of Wuhan (Hubei, China). The Wuhan Institute of Virology was founded in that city in 1956 and the country's first biosafety level 4 laboratory opened within that center in 2015. The coincidence that the first cases of infection emerged in the city where the virology institute's headquarters is located, the failure to 100% identify the virus' RNA in any of the coronaviruses isolated in bats, and the lack of evidence on a possible intermediate animal host in the contagion's transmission make it so that at present, there are doubts about the real origin of SARS-CoV-2. This article will review two theories: SARS-CoV-2 as a virus of zoonotic origin or as a leak from the high-level biosafety laboratory in Wuhan.

¿Qué sabemos del origen del COVID-19 tres años después? / What do we know about the origin of COVID-19 three years later?

More than three years have passed since the first case of a new coronavirus infection (SARS-CoV-2) in the city of Wuhan (Hubei, China). The Wuhan Institute of Virology was founded in that city in 1956 and the country’s first biosafety level 4 laboratory opened within that center in 2015. The coincidence that the first cases of infection emerged in the city where the virology institute’s headquarters is located, the failure to 100% identify the virus’ RNA in any of the coronaviruses isolated in bats, and the lack of evidence on a possible intermediate animal host in the contagion’s transmission make it so that at present, there are doubts about the real origin of SARS-CoV-2. This article will review two theories: SARS-CoV-2 as a virus of zoonotic origin or as a leak from the high-level biosafety laboratory in Wuhan (AU)

Han pasado más de tres años desde el primer caso de infección por un nuevo coronavirus (SARS-CoV-2) en la ciudad de Wuhan (Hubei, China). En esta misma ciudad se fundó en 1956 el Instituto de Virología de Wuhan y en 2015 abrieron en este centro el primer laboratorio de bioseguridad de nivel 4 del país. La coincidencia de ciudad entre los primeros casos de infección y la sede del instituto de virología, sumados a la fallida identificación del RNA del virus al 100% en ninguno de los coronavirus aislados en murciélagos, junto con la falta de evidencia sobre el posible animal intermediario en la transmisión de contagio, hacen que a fecha de hoy surjan dudas sobre el origen real del SARS-CoV-2. En este artículo revisaremos dos teorías, el SARS-CoV-2 como origen zoonótico o como escape del laboratorio de alta bioseguridad en Wuhan (AU)

What do we know about the origin of COVID-19 three years later?

More than three years have passed since the first case of a new coronavirus infection (SARS-CoV-2) in the city of Wuhan (Hubei, China). The Wuhan Institute of Virology was founded in that city in 1956 and the country's first biosafety level 4 laboratory opened within that center in 2015. The coincidence that the first cases of infection emerged in the city where the virology institute's headquarters is located, the failure to 100% identify the virus' RNA in any of the coronaviruses isolated in bats, and the lack of evidence on a possible intermediate animal host in the contagion's transmission make it so that at present, there are doubts about the real origin of SARS-CoV-2. This article will review two theories: SARS-CoV-2 as a virus of zoonotic origin or as a leak from the high-level biosafety laboratory in Wuhan.

Genomic Bootstrap Barcodes and Their Application to Study the Evolution of Sarbecoviruses.

Recombination creates mosaic genomes containing regions with mixed ancestry, and the accumulation of such events over time can complicate greatly many aspects of evolutionary inference. Here, we developed a sliding window bootstrap (SWB) method to generate genomic bootstrap (GB) barcodes to highlight the regions supporting phylogenetic relationships. The method was applied to an alignment of 56 sarbecoviruses, including SARS-CoV and SARS-CoV-2, responsible for the SARS epidemic and COVID-19 pandemic, respectively. The SWB analyses were also used to construct a consensus tree showing the most reliable relationships and better interpret hidden phylogenetic signals. Our results revealed that most relationships were supported by just a few genomic regions and confirmed that three divergent lineages could be found in bats from Yunnan: SCoVrC, which groups SARS-CoV related coronaviruses from China; SCoV2rC, which includes SARS-CoV-2 related coronaviruses from Southeast Asia and Yunnan; and YunSar, which contains a few highly divergent viruses recently described in Yunnan. The GB barcodes showed evidence for ancient recombination between SCoV2rC and YunSar genomes, as well as more recent recombination events between SCoVrC and SCoV2rC genomes. The recombination and phylogeographic patterns suggest a strong host-dependent selection of the viral RNA-dependent RNA polymerase. In addition, SARS-CoV-2 appears as a mosaic genome composed of regions sharing recent ancestry with three bat SCoV2rCs from Yunnan (RmYN02, RpYN06, and RaTG13) or related to more ancient ancestors in bats from Yunnan and Southeast Asia. Finally, our results suggest that viral circular RNAs may be key molecules for the mechanism of recombination.

The SARS-CoV-2 origin dilemma: Zoonotic transfer or laboratory leak?

The COVID-19 pandemic is responsible for millions of deaths worldwide yet its origin remains unclear. Two potential scenarios of how infection of humans initially occurred include zoonotic transfer from wild animals and a leak of the pathogen from a research laboratory. The Wuhan wet markets where wild animals are sold represent a strong scenario for zoonotic transfer. However, isolation of SARS-CoV-2 or its immediate predecessor from wild animals in their natural environment has yet to be documented. Due to incomplete evidence for a zoonotic origin, a laboratory origin is plausible. The Wuhan Institute of Virology is at the epicenter of the pandemic and their work has included manipulation of wild-type coronavirus to enable infection of human cells. Although stronger evidence supports the zoonotic transfer, inconclusive reports maintain the laboratory leak hypothesis alive. It is imperative to reach a factual conclusion to prevent future pandemics.