The United Kingdom's COVID-19 epidemic during early 2020 was one of world's largest and was unusually well represented by virus genomic sampling. We determined the fine-scale genetic lineage ...structure of this epidemic through analysis of 50,887 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes, including 26,181 from the UK sampled throughout the country's first wave of infection. Using large-scale phylogenetic analyses combined with epidemiological and travel data, we quantified the size, spatiotemporal origins, and persistence of genetically distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, whereas lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.
Acute respiratory infections (ARIs) impose a major public health burden on fragile healthcare systems of developing Southeast Asian countries such as Vietnam. The epidemiology, genetic diversity and ...transmission patterns of respiratory viral pathogens that circulate in this region are not well characterized. We used RT-PCR to screen for 14 common respiratory viruses in nasal/throat samples from 4326 ARI patients from 5 sites in Vietnam during 2012-2016. 64% of patients tested positive for viruses; 14% tested positive multiple co-infecting viruses. The most frequently detected viruses were
(RSV, 23%),
(HRV, 13%),
(IAV, 11%) and
(HBoV, 7%). RSV infections peaked in July to October, were relatively more common in children <1 year and in the northernmost hospital. IAV infections peaked in December to February and were relatively more common in patients >5 years in the central region. Coinfection with IAV or RSV was associated with increased disease severity compared with patients only infected with HBoV or HRV. Over a hundred genomes belonging to 13 families and 24 genera were obtained via metagenomic sequencing, including novel viruses and viruses less commonly associated with ARIs. Phylogenetic and phylogeographic analyses further indicated that neighboring countries were the most likely source of many virus lineages causing ARIs in Vietnam and estimated the period that specific lineages have been circulating. Our study illustrates the value of applying the state-of-the-art virus diagnostic methods (multiplex RT-PCR and metagenomic sequencing) and phylodynamic analyses at a national level to generate an integrated picture of viral ARI epidemiology.
Hospital-based and community-based 'high-risk cohort' studies investigating humans at risk of zoonotic infection due to occupational or residential exposure to animals were conducted in Vietnam, with ...diverse viruses identified from faecal samples collected from humans, domestic and wild animals. In this study, we focus on the positive-sense RNA virus family
, investigating the prevalence, diversity, and potential for cross-species transmission. Through metagenomic sequencing, we found picornavirus contigs in 23% of samples, belonging to 15 picornavirus genera. Prevalence was highest in bats (67%) while diversity was highest in rats (nine genera). In addition, 22% of the contigs were derived from novel viruses: Twelve phylogenetically distinct clusters were observed in rats of which seven belong to novel species or types in the genera
and
; four distinct clusters were found in bats, belonging to one novel parechovirus species and one related to an unclassified picornavirus. There was no evidence for zoonotic transmission in our data. Our study provides an improved knowledge of the diversity and prevalence of picornaviruses, including a variety of novel picornaviruses in rats and bats. We highlight the importance of monitoring the human-animal interface for possible spill-over events.
The reagents for the PCR diagnostic test were designed using the full spectrum of the SARS-CoV-2 reference genome collected on 5 January 2020, in Wuhan.1 A recent analysis has shown that the majority ...of current PCR diagnostic targets have undergone mutations with the nucleocapsid (N) gene primers and probes having undergone the most mutations.2 In Africa, analysing virus genome sequences revealed transmission patterns within individual countries. ...a recent study in Singapore comparing the clinical and immunological indicators in patients infected with the wild-type SARS-CoV-2 and those infected with the Δ382 variant of SARS-CoV-2 which has a deletion in its ORF8 of 382-nucleotide showed that the ∆382 variant of SARS-CoV-2 was associated with a milder infection.6 The state of genome sequences available publicly from WHO AFRO countries Overall, there has been a much-increased global effort and speed in pathogen sequencing and availing the data in public depositories during this SARS CoV-2 pandemic. The launch of a network of laboratories in September 2020 to reinforce genome sequencing of SARS-CoV-2 in Africa by the WHO World and the Africa Centres for Disease Control and Prevention (Africa CDC) is a welcome development.11 This strengthens the capacity of the member states already provided by other partners on the continent including the African Center of Excellence for Genomics of Infectious Diseases (ACEGID), Nigerian Center for Disease Control (Nigeria CDC) and Tackling Infections to Benefit Africa (TIBA).12 There is also need to ensure that the sequencing is science-led or purpose-led so that limited resources are not wasted on sequencing for the sake of sequencing. ...there is need to ensure that supporting data are collected and well curated so that patient meta-data including clinical, immunological and prognosis can easily be related to the sequence data.
SARS-CoV-2 infections and deaths have been lower in Africa than in other continents, which could be attributed to previous exposure to other pathogens that induce protective cross-immunity or modify ...the immune phenotype. We aimed to identify and characterise pre-existing cross-reactive immune responses to SARS-CoV-2 in an African population.
In this cross-sectional study, we determined the prevalence of SARS-CoV-2 serological cross-reactivity of 339 previously collected pre-pandemic (2000–19) serum samples from adults living in four villages in Zimbabwe (Mupfure, Mutoko, Chiredzi, and Murewa). We tested samples with a COVID-19 rapid diagnostic test then screened for cross-reactivity with peptides from the proteomes of seven human coronaviruses. We compared peptide location, coverage, and intensity and matched peptides predicted to be B-cell epitopes to the Human Immune Epitope Database (HIED).
Pre-SARS-CoV-2 serum samples from Mupfure and Murewa showed an overall prevalence of cross-reactivity with the SARS-CoV-2 rapid diagnostic test of 31·9% (95% CI 26·93–37·11). Peptide analysis of samples from all four villages highlighted complex IgM and IgG response profiles against peptides in the spike, nucleocapsid, and polyprotein 1AB proteins across all coronaviruses. Interrogating SARS-CoV-2 peptides recognised by IgG and IgM from the Zimbabwean serum samples against the HIED showed that most were either unique to SARS-CoV-2 or shared only with other betacoronaviruses. However, some SARS-CoV-2 peptides shared motifs with antigens from pathogens endemic to Zimbabwe, including Trypanosoma spp and Plasmodium spp, plant and food immunogens, and human autoantigens.
The effect of these cross-reactive antibodies on SARS-CoV-2 infection or COVID-19 is unknown; however, these antibodies should be considered when interpreting SARS-CoV-2 seroepidemiology studies and evaluating outcomes of COVID-19 vaccine trials in Africa. This study also calls for further characterisation of SARs-CoV-2 immune phenotypes and responses in African populations.
Scottish Funding Council Global Challenges Research Fund Grant at the University of Edinburgh; UK National Institute for Health Research.
This study demonstrates that an adoption of a segmenting and shielding strategy could increase the scope to partially exit COVID-19 lockdown while limiting the risk of an overwhelming second wave of ...infection. We illustrate this using a mathematical model that segments the vulnerable population and their closest contacts, the ‘shielders’. Effects of extending the duration of lockdown and faster or slower transition to post-lockdown conditions and, most importantly, the trade-off between increased protection of the vulnerable segment and fewer restrictions on the general population are explored. Our study shows that the most important determinants of outcome are: (i) post-lockdown transmission rates within the general and between the general and vulnerable segments; (ii) fractions of the population in the vulnerable and shielder segments; (iii) adherence to protective measures; and (iv) build-up of population immunity. Additionally, we found that effective measures in the shielder segment, e.g. intensive routine screening, allow further relaxations in the general population. We find that the outcome of any future policy is strongly influenced by the contact matrix between segments and the relationships between physical distancing measures and transmission rates. This strategy has potential applications for any infectious disease for which there are defined proportions of the population who cannot be treated or who are at risk of severe outcomes.
This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
Despite ∼60 % of human pathogens being of zoonotic origin, the diversity of viruses in non-human hosts remains understudied. To investigate the viral diversity present in Vietnam, the Vietnam ...Initiative on Zoonotic Infections (VIZIONS) collected 2100 rectal swabs and faecal samples from several non-human hosts (including pigs, rats and bats) as well enteric hospital patients and individuals with high animal contact. Samples underwent metagenomic sequencing (Illumina HiSeq), assembly (MetaSPAdes) and screening for viral sequences (Blastn and DIAMOND Blastp). The majority (87.5%) of viral sequences identified in humans shared high nucleotide identity (>95 %) to previously described viral species, with the exception of sequences assigned to Anelloviridae and Picobirnaviridae. Approximately half (46.5%) of viral sequences identified in non-human hosts shared between 60 to 80% nucleotide identity to its closest match in GenBank. For all hosts other from rats the family with the highest frequency of low identity hits was Picobirnaviridae. Sources of diversity at a viral family level were mostly host specific, with pigs having diverse astrovirus and smacovirus sequences, rats for rotavirus and adenovirus and bats for coronavirus and parvovirus. These results highlight the historic bias of sequencing viruses from human hosts and the need to shift focus to non-human hosts. Pig, bats and rats in Vietnam harbor a large diversity of potentially novel viruses that may be threats to animal and human health.
There is still limited information on the diversity of viruses co-circulating in humans and animals. Here, we report data obtained from a large field collection of enteric samples taken from humans, ...pigs, rodents and other mammal hosts in Vietnam between 2012 and 2016. Each of 2100 stool or rectal swab samples was subjected to virally-enriched agnostic metagenomic sequencing; the short read sequence data are accessible from the European Nucleotide Archive (ENA). We link the sequence data to metadata on host type and demography and geographic location, distinguishing hospital patients, members of a cohort identified as a high risk of zoonotic infections (e.g. abattoir workers, rat traders) and animals. These data are suitable for further studies of virus diversity and virus discovery in humans and animals from Vietnam and to identify viruses found in multiple hosts that are potentially zoonotic.
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