In this issue of Cell, Korber et al. found that a SARS-CoV-2 variant in the spike protein D614G rapidly became dominant around the world. Although clinical and in vitro data suggest that D614G ...changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.
In this issue of Cell, Korber et al. found that a SARS-CoV-2 variant in the spike protein D614G rapidly became dominant around the world. Although clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.
The COVID‐19 pandemic has spread to many countries around the world, but the infection and death rates vary widely. One country that appeared to have kept the infection under control despite limited ...societal restrictions is Japan. This commentary explores why Japan may have, up to now, been spared an escalation of the SARS‐CoV‐2 infections.
Epidemiological synergy between outbreaks of viruses transmitted by Aedes aegypti mosquitoes, such as chikungunya, dengue, and Zika viruses, has resulted in coinfection of humans with multiple ...viruses. Despite the potential impact on public health, we know only little about the occurrence and consequences of such coinfections. Here, we review the impact of coinfection on clinical disease in humans, discuss the possibility for co-transmission from mosquito to human, and describe a role for modeling transmission dynamics at various levels of co-transmission. Solving the mystery of virus coinfections will reveal whether they should be viewed as a serious concern for public health.
As the SARS-CoV-2 pandemic evolves, new variants continue to emerge. Some highly transmissible variants, such as Delta, also raised concerns about the effectiveness provided by current vaccines. ...Understanding immunological correlates of protection and how laboratory findings correspond to clinical effectiveness is imperative to shape future vaccination strategies.
As the SARS-CoV-2 epidemic evolves, new variants continue to emerge. Some highly transmissible variants, such as Delta, also raised concerns about the effectiveness provided by current vaccines. Understanding immunological correlates of protection and how laboratory findings correspond to clinical effectiveness is imperative to shape future vaccination strategies.
We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA concentrations in primary sewage sludge in the New Haven, Connecticut, USA, metropolitan area during the Coronavirus ...Disease 2019 (COVID-19) outbreak in Spring 2020. SARS-CoV-2 RNA was detected throughout the more than 10-week study and, when adjusted for time lags, tracked the rise and fall of cases seen in SARS-CoV-2 clinical test results and local COVID-19 hospital admissions. Relative to these indicators, SARS-CoV-2 RNA concentrations in sludge were 0-2 d ahead of SARS-CoV-2 positive test results by date of specimen collection, 0-2 d ahead of the percentage of positive tests by date of specimen collection, 1-4 d ahead of local hospital admissions and 6-8 d ahead of SARS-CoV-2 positive test results by reporting date. Our data show the utility of viral RNA monitoring in municipal wastewater for SARS-CoV-2 infection surveillance at a population-wide level. In communities facing a delay between specimen collection and the reporting of test results, immediate wastewater results can provide considerable advance notice of infection dynamics.
SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, ...particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found that viral RNA concentrations peaked an average of 3.3 days (95% credible interval CI 2.5, 4.2) after first possible detectability at a cycle threshold value of 22.3 (95% CI 20.5, 23.9). The viral clearance phase lasted longer for symptomatic individuals (10.9 days 95% CI 7.9, 14.4) than for asymptomatic individuals (7.8 days 95% CI 6.1, 9.7). A second test within 2 days after an initial positive PCR test substantially improves certainty about a patient's infection stage. The effective sensitivity of a test intended to identify infectious individuals declines substantially with test turnaround time. These findings indicate that SARS-CoV-2 viral concentrations peak rapidly regardless of symptoms. Sequential tests can help reveal a patient's progress through infection stages. Frequent, rapid-turnaround testing is needed to effectively screen individuals before they become infectious.
6 years ago, I published a Cell Host and Microbe paper that described randomization of virus genetic populations during mosquito infection. From within the evolutionary chaos, however, there is an ...order that can reveal a virus' past. Using these insights, I forged a career harnessing virus evolution to understand epidemiological patterns.
How viruses evolve within hosts can dictate infection outcomes; however, reconstructing this process is challenging. We evaluate our multiplexed amplicon approach, PrimalSeq, to demonstrate how virus ...concentration, sequencing coverage, primer mismatches, and replicates influence the accuracy of measuring intrahost virus diversity. We develop an experimental protocol and computational tool, iVar, for using PrimalSeq to measure virus diversity using Illumina and compare the results to Oxford Nanopore sequencing. We demonstrate the utility of PrimalSeq by measuring Zika and West Nile virus diversity from varied sample types and show that the accumulation of genetic diversity is influenced by experimental and biological systems.
Genome sequencing has become a powerful tool for studying emerging infectious diseases; however, genome sequencing directly from clinical samples (i.e., without isolation and culture) remains ...challenging for viruses such as Zika, for which metagenomic sequencing methods may generate insufficient numbers of viral reads. Here we present a protocol for generating coding-sequence-complete genomes, comprising an online primer design tool, a novel multiplex PCR enrichment protocol, optimized library preparation methods for the portable MinION sequencer (Oxford Nanopore Technologies) and the Illumina range of instruments, and a bioinformatics pipeline for generating consensus sequences. The MinION protocol does not require an Internet connection for analysis, making it suitable for field applications with limited connectivity. Our method relies on multiplex PCR for targeted enrichment of viral genomes from samples containing as few as 50 genome copies per reaction. Viral consensus sequences can be achieved in 1-2 d by starting with clinical samples and following a simple laboratory workflow. This method has been successfully used by several groups studying Zika virus evolution and is facilitating an understanding of the spread of the virus in the Americas. The protocol can be used to sequence other viral genomes using the online Primal Scheme primer designer software. It is suitable for sequencing either RNA or DNA viruses in the field during outbreaks or as an inexpensive, convenient method for use in the lab.
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