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1.
Nat Rev Phys ; 2(6): 279-281, 2020.
Article in English | MEDLINE | ID: covidwho-1684119

ABSTRACT

As the COVID-19 pandemic continues, mathematical epidemiologists share their views on what models reveal about how the disease has spread, the current state of play and what work still needs to be done.

3.
[Unspecified Source]; 2020.
Preprint in English | [Unspecified Source] | ID: ppcovidwho-292763

ABSTRACT

Decontamination of objects and surfaces can limit transmission of infectious agents via fomites or biological samples. It is required for the safe re-use of potentially contaminated personal protective equipment and medical and laboratory equipment. Heat treatment is widely used for the inactivation of various infectious agents, notably viruses. We show that for liquid specimens (here suspension of SARS-CoV-2 in cell culture medium), virus inactivation rate under heat treatment at 70°C can vary by almost two orders of magnitude depending on the treatment procedure, from a half-life of 0.86 min (95% credible interval: [0.09, 1.77]) in closed vials in a heat block to 37.0 min ([12.65, 869.82]) in uncovered plates in a dry oven. These findings suggest a critical role of evaporation in virus inactivation using dry heat. Placing samples in open or uncovered containers may dramatically reduce the speed and efficacy of heat treatment for virus inactivation. Heating procedures must be carefully specified when reporting experimental studies to facilitate result interpretation and reproducibility, and carefully considered when designing decontamination guidelines.

4.
Nat Rev Microbiol ; 20(5): 299-314, 2022 May.
Article in English | MEDLINE | ID: covidwho-1526083

ABSTRACT

In the past two decades, three coronaviruses with ancestral origins in bats have emerged and caused widespread outbreaks in humans, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first SARS epidemic in 2002-2003, the appreciation of bats as key hosts of zoonotic coronaviruses has advanced rapidly. More than 4,000 coronavirus sequences from 14 bat families have been identified, yet the true diversity of bat coronaviruses is probably much greater. Given that bats are the likely evolutionary source for several human coronaviruses, including strains that cause mild upper respiratory tract disease, their role in historic and future pandemics requires ongoing investigation. We review and integrate information on bat-coronavirus interactions at the molecular, tissue, host and population levels. We identify critical gaps in knowledge of bat coronaviruses, which relate to spillover and pandemic risk, including the pathways to zoonotic spillover, the infection dynamics within bat reservoir hosts, the role of prior adaptation in intermediate hosts for zoonotic transmission and the viral genotypes or traits that predict zoonotic capacity and pandemic potential. Filling these knowledge gaps may help prevent the next pandemic.


Subject(s)
COVID-19 , Chiroptera , Animals , Evolution, Molecular , Humans , Phylogeny , SARS-CoV-2/genetics
5.
Elife ; 102021 07 13.
Article in English | MEDLINE | ID: covidwho-1389776

ABSTRACT

Ambient temperature and humidity strongly affect inactivation rates of enveloped viruses, but a mechanistic, quantitative theory of these effects has been elusive. We measure the stability of SARS-CoV-2 on an inert surface at nine temperature and humidity conditions and develop a mechanistic model to explain and predict how temperature and humidity alter virus inactivation. We find SARS-CoV-2 survives longest at low temperatures and extreme relative humidities (RH); median estimated virus half-life is >24 hr at 10°C and 40% RH, but ∼1.5 hr at 27°C and 65% RH. Our mechanistic model uses fundamental chemistry to explain why inactivation rate increases with increased temperature and shows a U-shaped dependence on RH. The model accurately predicts existing measurements of five different human coronaviruses, suggesting that shared mechanisms may affect stability for many viruses. The results indicate scenarios of high transmission risk, point to mitigation strategies, and advance the mechanistic study of virus transmission.


Subject(s)
Hot Temperature , Humidity , Models, Biological , SARS-CoV-2/growth & development , Virus Inactivation , COVID-19 , Humans
7.
Elife ; 92020 02 24.
Article in English | MEDLINE | ID: covidwho-1344521

ABSTRACT

Traveller screening is being used to limit further spread of COVID-19 following its recent emergence, and symptom screening has become a ubiquitous tool in the global response. Previously, we developed a mathematical model to understand factors governing the effectiveness of traveller screening to prevent spread of emerging pathogens (Gostic et al., 2015). Here, we estimate the impact of different screening programs given current knowledge of key COVID-19 life history and epidemiological parameters. Even under best-case assumptions, we estimate that screening will miss more than half of infected people. Breaking down the factors leading to screening successes and failures, we find that most cases missed by screening are fundamentally undetectable, because they have not yet developed symptoms and are unaware they were exposed. Our work underscores the need for measures to limit transmission by individuals who become ill after being missed by a screening program. These findings can support evidence-based policy to combat the spread of COVID-19, and prospective planning to mitigate future emerging pathogens.


Subject(s)
Asymptomatic Infections , Betacoronavirus , Coronavirus Infections/diagnosis , Mass Screening , Pneumonia, Viral/diagnosis , Travel , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Outbreaks , Humans , Infection Control , Mass Screening/methods , Mass Screening/standards , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Risk Assessment , SARS-CoV-2
8.
Appl Environ Microbiol ; 87(19): e0031421, 2021 09 10.
Article in English | MEDLINE | ID: covidwho-1319372

ABSTRACT

Decontamination helps limit environmental transmission of infectious agents. It is required for the safe reuse of contaminated medical, laboratory, and personal protective equipment, and for the safe handling of biological samples. Heat treatment is a common decontamination method, notably used for viruses. We show that for liquid specimens (here, solution of SARS-CoV-2 in cell culture medium), the virus inactivation rate under heat treatment at 70°C can vary by almost two orders of magnitude depending on the treatment procedure, from a half-life of 0.86 min (95% credible interval [CI] 0.09, 1.77) in closed vials in a heat block to 37.04 min (95% CI 12.64, 869.82) in uncovered plates in a dry oven. These findings suggest a critical role of evaporation in virus inactivation via dry heat. Placing samples in open or uncovered containers may dramatically reduce the speed and efficacy of heat treatment for virus inactivation. Given these findings, we reviewed the literature on temperature-dependent coronavirus stability and found that specimen container types, along with whether they are closed, covered, or uncovered, are rarely reported in the scientific literature. Heat-treatment procedures must be fully specified when reporting experimental studies to facilitate result interpretation and reproducibility, and must be carefully considered when developing decontamination guidelines. IMPORTANCE Heat is a powerful weapon against most infectious agents. It is widely used for decontamination of medical, laboratory, and personal protective equipment, and for biological samples. There are many methods of heat treatment, and methodological details can affect speed and efficacy of decontamination. We applied four different heat-treatment procedures to liquid specimens containing SARS-CoV-2. Our results show that the container used to store specimens during decontamination can substantially affect inactivation rate; for a given initial level of contamination, decontamination time can vary from a few minutes in closed vials to several hours in uncovered plates. Reviewing the literature, we found that container choices and heat treatment methods are only rarely reported explicitly in methods sections. Our study shows that careful consideration of heat-treatment procedure-in particular the choice of specimen container and whether it is covered-can make results more consistent across studies, improve decontamination practice, and provide insight into the mechanisms of virus inactivation.


Subject(s)
Decontamination/methods , Hot Temperature , Personal Protective Equipment/statistics & numerical data , SARS-CoV-2/physiology , Specimen Handling/methods , Virus Inactivation , Decontamination/instrumentation , Reproducibility of Results , Specimen Handling/instrumentation
9.
mSystems ; 6(2)2021 Apr 13.
Article in English | MEDLINE | ID: covidwho-1183288

ABSTRACT

RNA viruses, such as hepatitis C virus (HCV), influenza virus, and SARS-CoV-2, are notorious for their ability to evolve rapidly under selection in novel environments. It is known that the high mutation rate of RNA viruses can generate huge genetic diversity to facilitate viral adaptation. However, less attention has been paid to the underlying fitness landscape that represents the selection forces on viral genomes, especially under different selection conditions. Here, we systematically quantified the distribution of fitness effects of about 1,600 single amino acid substitutions in the drug-targeted region of NS5A protein of HCV. We found that the majority of nonsynonymous substitutions incur large fitness costs, suggesting that NS5A protein is highly optimized. The replication fitness of viruses is correlated with the pattern of sequence conservation in nature, and viral evolution is constrained by the need to maintain protein stability. We characterized the adaptive potential of HCV by subjecting the mutant viruses to selection by the antiviral drug daclatasvir at multiple concentrations. Both the relative fitness values and the number of beneficial mutations were found to increase with the increasing concentrations of daclatasvir. The changes in the spectrum of beneficial mutations in NS5A protein can be explained by a pharmacodynamics model describing viral fitness as a function of drug concentration. Overall, our results show that the distribution of fitness effects of mutations is modulated by both the constraints on the biophysical properties of proteins (i.e., selection pressure for protein stability) and the level of environmental stress (i.e., selection pressure for drug resistance).IMPORTANCE Many viruses adapt rapidly to novel selection pressures, such as antiviral drugs. Understanding how pathogens evolve under drug selection is critical for the success of antiviral therapy against human pathogens. By combining deep sequencing with selection experiments in cell culture, we have quantified the distribution of fitness effects of mutations in hepatitis C virus (HCV) NS5A protein. Our results indicate that the majority of single amino acid substitutions in NS5A protein incur large fitness costs. Simulation of protein stability suggests viral evolution is constrained by the need to maintain protein stability. By subjecting the mutant viruses to selection under an antiviral drug, we find that the adaptive potential of viral proteins in a novel environment is modulated by the level of environmental stress, which can be explained by a pharmacodynamics model. Our comprehensive characterization of the fitness landscapes of NS5A can potentially guide the design of effective strategies to limit viral evolution.

10.
Trends Microbiol ; 29(7): 593-605, 2021 07.
Article in English | MEDLINE | ID: covidwho-1157752

ABSTRACT

Ecological and evolutionary processes govern the fitness, propagation, and interactions of organisms through space and time, and viruses are no exception. While coronavirus disease 2019 (COVID-19) research has primarily emphasized virological, clinical, and epidemiological perspectives, crucial aspects of the pandemic are fundamentally ecological or evolutionary. Here, we highlight five conceptual domains of ecology and evolution - invasion, consumer-resource interactions, spatial ecology, diversity, and adaptation - that illuminate (sometimes unexpectedly) the emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the applications of these concepts across levels of biological organization and spatial scales, including within individual hosts, host populations, and multispecies communities. Together, these perspectives illustrate the integrative power of ecological and evolutionary ideas and highlight the benefits of interdisciplinary thinking for understanding emerging viruses.


Subject(s)
COVID-19/virology , Disease Reservoirs/veterinary , Ecology , Evolution, Molecular , SARS-CoV-2/genetics , Animals , COVID-19/epidemiology , Chiroptera/virology , Disease Reservoirs/virology , Humans , Zoonoses/virology
11.
One Health Outlook ; 2(1): 17, 2020.
Article in English | MEDLINE | ID: covidwho-774760

ABSTRACT

BACKGROUND: For many emerging or re-emerging pathogens, cases in humans arise from a mixture of introductions (via zoonotic spillover from animal reservoirs or geographic spillover from endemic regions) and secondary human-to-human transmission. Interventions aiming to reduce incidence of these infections can be focused on preventing spillover or reducing human-to-human transmission, or sometimes both at once, and typically are governed by resource constraints that require policymakers to make choices. Despite increasing emphasis on using mathematical models to inform disease control policies, little attention has been paid to guiding rational disease control at the animal-human interface. METHODS: We introduce a modeling framework to analyze the impacts of different disease control policies, focusing on pathogens exhibiting subcritical transmission among humans (i.e. pathogens that cannot establish sustained human-to-human transmission). We quantify the relative effectiveness of measures to reduce spillover (e.g. reducing contact with animal hosts), human-to-human transmission (e.g. case isolation), or both at once (e.g. vaccination), across a range of epidemiological contexts. RESULTS: We provide guidelines for choosing which mode of control to prioritize in different epidemiological scenarios and considering different levels of resource and relative costs. We contextualize our analysis with current zoonotic pathogens and other subcritical pathogens, such as post-elimination measles, and control policies that have been applied. CONCLUSIONS: Our work provides a model-based, theoretical foundation to understand and guide policy for subcritical zoonoses, integrating across disciplinary and species boundaries in a manner consistent with One Health principles.

12.
Elife ; 92020 09 07.
Article in English | MEDLINE | ID: covidwho-745648

ABSTRACT

Understanding and mitigating SARS-CoV-2 transmission hinges on antibody and viral RNA data that inform exposure and shedding, but extensive variation in assays, study group demographics and laboratory protocols across published studies confounds inference of true biological patterns. Our meta-analysis leverages 3214 datapoints from 516 individuals in 21 studies to reveal that seroconversion of both IgG and IgM occurs around 12 days post-symptom onset (range 1-40), with extensive individual variation that is not significantly associated with disease severity. IgG and IgM detection probabilities increase from roughly 10% at symptom onset to 98-100% by day 22, after which IgM wanes while IgG remains reliably detectable. RNA detection probability decreases from roughly 90% to zero by day 30, and is highest in feces and lower respiratory tract samples. Our findings provide a coherent evidence base for interpreting clinical diagnostics, and for the mathematical models and serological surveys that underpin public health policies.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Immunoglobulin G/blood , Immunoglobulin M/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , RNA, Viral/analysis , Antibodies, Viral/blood , Antibodies, Viral/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G/isolation & purification , Immunoglobulin M/isolation & purification , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , RNA, Viral/isolation & purification , SARS-CoV-2
13.
Emerg Infect Dis ; 26(9)2020 09.
Article in English | MEDLINE | ID: covidwho-574540

ABSTRACT

We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Mucus/virology , Pneumonia, Viral/virology , RNA, Viral/analysis , Sputum/virology , COVID-19 , Hot Temperature , Humans , Humidity , Nasal Cavity/virology , Pandemics , RNA Stability , SARS-CoV-2
14.
Emerg Infect Dis ; 26(9)2020 09.
Article in English | MEDLINE | ID: covidwho-505770

ABSTRACT

The coronavirus pandemic has created worldwide shortages of N95 respirators. We analyzed 4 decontamination methods for effectiveness in deactivating severe acute respiratory syndrome coronavirus 2 virus and effect on respirator function. Our results indicate that N95 respirators can be decontaminated and reused, but the integrity of respirator fit and seal must be maintained.


Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Decontamination/methods , Equipment Reuse , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Ventilators, Mechanical/virology , COVID-19 , Coronavirus Infections/virology , Humans , Pneumonia, Viral/virology , SARS-CoV-2
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