Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing future zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports, but later this conclusion became controversial. We show here that the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2–susceptible mammals were sold at the market in late 2019 and that within the market, SARS-CoV-2–positive environmental samples were spatially associated with vendors selling live mammals. Although there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred through the live wildlife trade in China and show that the Huanan market was the epicenter of the COVID-19 pandemic. Description Pandemic epicenter As 2019 turned into 2020, a coronavirus spilled over from wild animals into people, sparking what has become one of the best documented pandemics to afflict humans. However, the origins of the pandemic in December 2019 are controversial. Worobey et al. amassed the variety of evidence from the City of Wuhan, China, where the first human infections were reported. These reports confirm that most of the earliest human cases centered around the Huanan Seafood Wholesale Market. Within the market, the data statistically located the earliest human cases to one section where vendors of live wild animals congregated and where virus-positive environmental samples concentrated. In a related report, Pekar et al. found that genomic diversity before February 2020 comprised two distinct viral lineages, A and B, which were the result of at least two separate cross-species transmission events into humans (see the Perspective by Jiang and Wang). The precise events surrounding virus spillover will always be clouded, but all of the circumstantial evidence so far points to more than one zoonotic event occurring in Huanan market in Wuhan, China, likely during November–December 2019. —CA Spatial distributions of early cases and environmental samples show that SARS-CoV-2 emergence was associated with the wildlife trade.

/pdf/the-huanan-seafood-wholesale-market-in-wuhan-was-the-early-ojtb0hsx.pdf

The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic

Understanding the circumstances that lead to pandemics is important for their prevention. We analyzed the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted “A” and “B.” Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October to 8 December), and the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans before November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events. Description Pandemic epicenter As 2019 turned into 2020, a coronavirus spilled over from wild animals into people, sparking what has become one of the best documented pandemics to afflict humans. However, the origins of the pandemic in December 2019 are controversial. Worobey et al. amassed the variety of evidence from the City of Wuhan, China, where the first human infections were reported. These reports confirm that most of the earliest human cases centered around the Huanan Seafood Wholesale Market. Within the market, the data statistically located the earliest human cases to one section where vendors of live wild animals congregated and where virus-positive environmental samples concentrated. In a related report, Pekar et al. found that genomic diversity before February 2020 comprised two distinct viral lineages, A and B, which were the result of at least two separate cross-species transmission events into humans (see the Perspective by Jiang and Wang). The precise events surrounding virus spillover will always be clouded, but all of the circumstantial evidence so far points to more than one zoonotic event occurring in Huanan market in Wuhan, China, likely during November–December 2019. —CA SARS-CoV-2 genomic diversity early in the COVID-19 pandemic points to emergence involving at least two zoonotic events.

/pdf/the-molecular-epidemiology-of-multiple-zoonotic-origins-of-1kqrpp9t.pdf

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

Abstract Wildlife reservoirs of broad-host-range viruses have the potential to enable evolution of viral variants that can emerge to infect humans. In North America, there is phylogenomic evidence of continual transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to white-tailed deer ( Odocoileus virginianus ) through unknown means, but no evidence of transmission from deer to humans. We carried out an observational surveillance study in Ontario, Canada during November and December 2021 ( n = 300 deer) and identified a highly divergent lineage of SARS-CoV-2 in white-tailed deer (B.1.641). This lineage is one of the most divergent SARS-CoV-2 lineages identified so far, with 76 mutations (including 37 previously associated with non-human mammalian hosts). From a set of five complete and two partial deer-derived viral genomes we applied phylogenomic, recombination, selection and mutation spectrum analyses, which provided evidence for evolution and transmission in deer and a shared ancestry with mink-derived virus. Our analysis also revealed an epidemiologically linked human infection. Taken together, our findings provide evidence for sustained evolution of SARS-CoV-2 in white-tailed deer and of deer-to-human transmission. 

/pdf/divergent-sars-cov-2-variant-emerges-in-white-tailed-deer-25rvznj5.pdf

Divergent SARS-CoV-2 variant emerges in white-tailed deer with deer-to-human transmission

The biological DMARD (bDMARD) abatacept (Orencia®), a recombinant fusion protein, selectively modulates a co-stimulatory signal necessary for T-cell activation. In the EU, abatacept is approved for use in patients with highly active and progressive rheumatoid arthritis (RA) not previously treated with methotrexate. Abatacept is also approved for the treatment of moderate to severe active RA in patients with an inadequate response to previous therapy with at least one conventional DMARD (cDMARD), including methotrexate or a TNF inhibitor. In phase III trials, beneficial effects on RA signs and symptoms, disease activity, structural damage progression and physical function were seen with intravenous (IV) or subcutaneous (SC) abatacept regimens, including abatacept plus methotrexate in methotrexate-naive patients with early RA and poor prognostic factors, and abatacept plus methotrexate or other cDMARDs in patients with inadequate response to methotrexate or TNF inhibitors. Benefits were generally maintained during longer-term follow-up. Absolute drug-free remission rates following withdrawal of all RA treatments were significantly higher with abatacept plus methotrexate than with methotrexate alone. Both IV and SC abatacept were generally well tolerated, with low rates of immunogenicity. Current evidence therefore suggests that abatacept is a useful treatment option for patients with RA.

Abatacept: A Review in Rheumatoid Arthritis.

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is more typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK, and the imposition of new restrictions, in particular the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages which preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically-infected individual. We conclude that the last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that the individual need not be immunocompromised, as persistently-infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs to each other, and identify that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations, and its lack of rapid evolutionary rate on the ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms) it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.

/pdf/the-origins-and-molecular-evolution-of-sars-cov-2-lineage-b-2qev2da7.pdf

The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK

Transmission of SARS-CoV-2 (Variant Delta) from Pet Hamsters to Humans and Onward Human Propagation of the Adapted Strain: A Case Study

Introduction
The purpose of the present study was to determine whether the abatacept autoinjector can be used by the intended population without patterns of preventable use errors, and is acceptable when assessed against key user needs.

/pdf/usability-and-acceptability-of-the-abatacept-pre-filled-3new3bp194.pdf

Usability and Acceptability of the Abatacept Pre-Filled Autoinjector for the Subcutaneous Treatment of Rheumatoid Arthritis

Surveillance of Coronaviruses in Wild Aquatic Birds in Hong Kong: Expanded Genetic Diversity and Discovery of Novel Subgenus in the Deltacoronavirus

Background Transmission of SARS-CoV-2 from humans to other mammals, including pet animals, has been reported. However, with the exception of farmed mink, there is no previous evidence that these infected animals can infect humans, resulting in sustained human-to-human transmission. Following a confirmed SARS-CoV-2 infection of a pet shop worker, animals in the shop and the warehouse supplying it were tested for evidence of SARS-CoV-2 infection. Methods In this case study, viral swabs and blood samples were collected from animals in a pet shop and its corresponding warehouse in Hong Kong. Nasal swab or saliva samples from human COVID-19 patients epidemiologically linked to the pet shop and from subsequent local cases confirmed to be infected by SARS-CoV-2 delta variant were collected. Oral swabs were tested by quantitative RT-PCR (RT-qPCR) for SARS-CoV-2 and blood samples were serologically tested by a surrogate virus neutralisation test and plaque reduction neutralisation test. The SARS-CoV-2 RT-qPCR positive samples were sequenced by next generation viral full genome sequencing using the ISeq sequencing platform (Illumina), and the viral genomes were phylogenetically analysed. Findings Eight (50%) of 16 individually tested Syrian hamsters in the pet shop and seven (58%) of 12 Syrian hamsters in the corresponding warehouse were positive for SARS-CoV-2 infection in RT-qPCR or serological tests. None of the dwarf hamsters (n=75), rabbits (n=246), guinea pigs (n=66), chinchillas (n=116), and mice (n=2) were confirmed positive for SARS-CoV-2 in RT-qPCR tests. SARS-CoV-2 viral genomes deduced from human and hamster cases in this incident all belong to the delta variant of concern (AY.127) that had not been circulating locally before this outbreak. The viral genomes obtained from hamsters were phylogenetically related with some sequence heterogeneity. Phylogenetic dating suggests infection in these hamsters occurred around Oct 14, 2021 (95% CI Sept 15 to Nov 9, 2021). Multiple zoonotic transmission events to humans were detected, leading to onward human-to-human transmission. Interpretation Pet hamsters can be naturally infected with SARS-CoV-2. The virus can circulate among hamsters and lead to human infections. Both genetic and epidemiological results strongly suggest that there was more than one hamster-to-human transmission event in this study. This incident also led to onward human transmission. Importation of SARS-CoV-2-infected hamsters was a likely source of this outbreak. Funding US National Institutes of Health, Research Grants Council of Hong Kong, Food and Health Bureau, and InnoHK.

http://www.thelancet.com/article/S0140673622003269/pdf

Transmission of SARS-CoV-2 delta variant (AY.127) from pet hamsters to humans, leading to onward human-to-human transmission: a case study

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Transmission of SARS-CoV-2 (Variant Delta) from Pet Hamsters to Humans and Onward Human Propagation of the Adapted Strain: A Case Study

Usability and Acceptability of the Abatacept Pre-Filled Autoinjector for the Subcutaneous Treatment of Rheumatoid Arthritis

Surveillance of Coronaviruses in Wild Aquatic Birds in Hong Kong: Expanded Genetic Diversity and Discovery of Novel Subgenus in the Deltacoronavirus

Transmission of SARS-CoV-2 delta variant (AY.127) from pet hamsters to humans, leading to onward human-to-human transmission: a case study