Intrinsic host susceptibility among multiple species to intranasal SARS-CoV-2 identifies diverse virological, biodistribution and pathological outcomes.

SARS-CoV-2 exhibits a diverse host species range with variable outcomes, enabling differential host susceptibility studies to assess suitability for pre-clinical countermeasure and pathogenesis studies. Baseline virological, molecular and pathological outcomes were determined among multiple species-one Old World non-human primate (NHP) species (cynomolgus macaques), two New World NHP species (red-bellied tamarins; common marmosets) and Syrian hamsters-following single-dose, atraumatic intranasal administration of SARS-CoV-2/Victoria-01. After serial sacrifice 2, 10 and 28-days post-infection (dpi), hamsters and cynomolgus macaques displayed differential virus biodistribution across respiratory, gastrointestinal and cardiovascular systems. Uniquely, New World tamarins, unlike marmosets, exhibited high levels of acute upper airway infection, infectious virus recovery associated with mild lung pathology representing a host previously unrecognized as susceptible to SARS-CoV-2. Across all species, lung pathology was identified post-clearance of virus shedding (antigen/RNA), with an association of virus particles within replication organelles in lung sections analysed by electron microscopy. Disrupted cell ultrastructure and lung architecture, including abnormal morphology of mitochondria 10-28 dpi, represented on-going pathophysiological consequences of SARS-CoV-2 in predominantly asymptomatic hosts. Infection kinetics and host pathology comparators using standardized methodologies enables model selection to bridge differential outcomes within upper and lower respiratory tracts and elucidate longer-term consequences of asymptomatic SARS-CoV-2 infection.

Detection of Enterovirus D68 in Wastewater Samples from the UK between July and November 2021.

Infection with enterovirus D68 (EV-D68) has been linked with severe neurological disease such as acute flaccid myelitis (AFM) in recent years. However, active surveillance for EV-D68 is lacking, which makes full assessment of this association difficult. Although a high number of EV-D68 infections were expected in 2020 based on the EV-D68's known biannual circulation patterns, no apparent increase in EV-D68 detections or AFM cases was observed during 2020. We describe an upsurge of EV-D68 detections in wastewater samples from the United Kingdom between July and November 2021 mirroring the recently reported rise in EV-D68 detections in clinical samples from various European countries. We provide the first publicly available 2021 EV-D68 sequences showing co-circulation of EV-D68 strains from genetic clade D and sub-clade B3 as in previous years. Our results show the value of environmental surveillance (ES) for the early detection of circulating and clinically relevant human viruses. The use of a next-generation sequencing (NGS) approach helped us to estimate the prevalence of EV-D68 viruses among EV strains from other EV serotypes and to detect EV-D68 minor variants. The utility of ES at reducing gaps in virus surveillance for EV-D68 and the possible impact of nonpharmaceutical interventions introduced to control the COVID-19 pandemic on EV-D68 transmission dynamics are discussed.

Changing composition of SARS-CoV-2 lineages and rise of Delta variant in England.

BACKGROUND: Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 (WHO label Alpha) rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. METHODS: We examine trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spans from 31st January 2021 to 15th May 2021. FINDINGS: Across data sources, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label Delta) spread rapidly, becoming the dominant variant in England by late May. INTERPRETATION: The outcome of competition between variants depends on a wide range of factors such as intrinsic transmissibility, evasion of prior immunity, demographic specificities and interactions with non-pharmaceutical interventions. The presence and rise of non-B.1.1.7 variants in March likely was driven by importations and some community transmission. There was competition between non-B.1.17 variants which resulted in B.1.617.2 becoming dominant in April and May with considerable community transmission. Our results underscore that early detection of new variants requires a diverse array of data sources in community surveillance. Continued real-time information on the highly dynamic composition and trajectory of different SARS-CoV-2 lineages is essential to future control efforts. FUNDING: National Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open Philanthropy, Academy of Medical Sciences Bill,Melinda Gates Foundation, Imperial College Healthcare NHS Trust, The Novo Nordisk Foundation, MRC Centre for Global Infectious Disease Analysis, Community Jameel, Cancer Research UK, Imperial College COVID-19 Research Fund, Medical Research Council, Wellcome Sanger Institute.

Rapid Increase of SARS-CoV-2 Variant B.1.1.7 Detected in Sewage Samples from England between October 2020 and January 2021.

SARS-CoV-2 variants with multiple amino acid mutations in the spike protein are emerging in different parts of the world, raising concerns regarding their possible impact on human immune response and vaccine efficacy against the virus. Recently, a variant named lineage B.1.1.7 was detected and shown to be rapidly spreading across the UK since November 2020. As surveillance for these SARS-CoV-2 variants of concern (VOCs) becomes critical, we have investigated the use of environmental surveillance (ES) for the rapid detection and quantification of B.1.1.7 viruses in sewage as a way of monitoring its expansion that is independent on the investigation of identified clinical cases. Next-generation sequencing analysis of amplicons synthesized from sewage concentrates revealed the presence of B.1.1.7 mutations in viral sequences, first identified in a sample collected in London on 10 November 2020 and shown to rapidly increase in frequency to >95% in January 2021, in agreement with clinical data over the same period. We show that ES can provide an early warning of VOCs becoming prevalent in the population and that, as well as B.1.1.7, our method can detect VOCs B.1.351 and P.1, first identified in South Africa and Brazil, respectively, and other viruses carrying critical spike mutation E484K, known to have an effect on virus antigenicity. Although we did not detect such mutation in viral RNAs from sewage, we did detect mutations at amino acids 478, 490, and 494, located close to amino acid 484 in the spike protein structure and known to also have an effect on antigenicity. IMPORTANCE The recent appearance and growth of new SARS-CoV-2 variants represent a major challenge for the control of the COVID-19 pandemic. These variants of concern contain mutations affecting antigenicity, which raises concerns on their possible impact on human immune response to the virus and vaccine efficacy against them. Here, we show how environmental surveillance for SARS-CoV-2 can be used to help us understand virus transmission patterns and provide an early warning of variants becoming prevalent in the population. We describe the detection and quantification of variant B.1.1.7, first identified in southeast England in sewage samples from London (UK) before widespread transmission of this variant was obvious from clinical cases. Variant B.1.1.7 was first detected in a sample from early November 2020, with the frequency of B.1.1.7 mutations detected in sewage rapidly increasing to >95% in January 2021, in agreement with increasing SARS-CoV-2 infections associated with B.1.1.7 viruses.

Tracking SARS-CoV-2 in Sewage: Evidence of Changes in Virus Variant Predominance during COVID-19 Pandemic.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the ongoing coronavirus disease (COVID-19) pandemic, is frequently shed in faeces during infection, and viral RNA has recently been detected in sewage in some countries. We have investigated the presence of SARS-CoV-2 RNA in wastewater samples from South-East England between 14th January and 12th May 2020. A novel nested RT-PCR approach targeting five different regions of the viral genome improved the sensitivity of RT-qPCR assays and generated nucleotide sequences at sites with known sequence polymorphisms among SARS-CoV-2 isolates. We were able to detect co-circulating virus variants, some specifically prevalent in England, and to identify changes in viral RNA sequences with time consistent with the recently reported increasing global dominance of Spike protein G614 pandemic variant. Low levels of viral RNA were detected in a sample from 11th February, 3 days before the first case was reported in the sewage plant catchment area. SARS-CoV-2 RNA concentration increased in March and April, and a sharp reduction was observed in May, showing the effects of lockdown measures. We conclude that viral RNA sequences found in sewage closely resemble those from clinical samples and that environmental surveillance can be used to monitor SARS-CoV-2 transmission, tracing virus variants and detecting virus importations.