We have come a long way since the start of the COVID-19 pandemic-from hoarding toilet paper and wiping down groceries to sending our children back to school and vaccinating billions. Over this ...period, the global community of epidemiologists and evolutionary biologists has also come a long way in understanding the complex and changing dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. In this Review, we retrace our steps through the questions that this community faced as the pandemic unfolded. We focus on the key roles that mathematical modeling and quantitative analyses of empirical data have played in allowing us to address these questions and ultimately to better understand and control the pandemic.
It is imperative to advance our understanding of heterogeneities in the transmission of SARS-CoV-2 such as age-specific infectiousness and superspreading. To this end, it is important to exploit ...multiple data streams that are becoming abundantly available during the pandemic. In this paper, we formulate an individual-level spatiotemporal mechanistic framework to integrate individual surveillance data with geolocation data and aggregate mobility data, enabling a more granular understanding of the transmission dynamics of SARS-CoV-2.We analyze reported cases, between March and early May 2020, in five (urban and rural) counties in the state of Georgia. First, our results show that the reproductive number reduced to below one in about 2 wk after the shelter-in-place order. Superspreading appears to be widespread across space and time, and it may have a particularly important role in driving the outbreak in rural areas and an increasing importance toward later stages of outbreaks in both urban and rural settings. Overall, about 2% of cases were directly responsible for 20% of all infections. We estimate that the infected nonelderly cases (<60 y) may be 2.78 2.10, 4.22 times more infectious than the elderly, and the former tend to be the main driver of superspreading. Our results improve our understanding of the natural history and transmission dynamics of SARS-CoV-2. More importantly, we reveal the roles of age-specific infectiousness and characterize systematic variations and associated risk factors of superspreading. These have important implications for the planning of relaxing social distancing and, more generally, designing optimal control measures.
Although recognized as the leading cause of epidemic acute gastroenteritis across all age groups, norovirus has remained poorly characterized with respect to its endemic disease incidence. Use of ...different methods, including attributable proportion extrapolation, population-based surveillance, and indirect modeling, in several recent studies has considerably improved norovirus disease incidence estimates for the United States. Norovirus causes an average of 570-800 deaths, 56,000-71,000 hospitalizations, 400,000 emergency department visits, 1.7-1.9 million outpatient visits, and 19-21 million total illnesses per year. Persons >65 years of age are at greatest risk for norovirus-associated death, and children <5 years of age have the highest rates of norovirus-associated medical care visits. Endemic norovirus disease occurs year round but exhibits a pronounced winter peak and increases by ≤ 50% during years in which pandemic strains emerge. These findings support continued development and targeting of appropriate interventions, including vaccines, for norovirus disease.
The duration of immunity to norovirus (NoV) gastroenteritis has been believed to be from 6 months to 2 years. However, several observations are inconsistent with this short period. To gain better ...estimates of the duration of immunity to NoV, we developed a mathematical model of community NoV transmission. The model was parameterized from the literature and also fit to age-specific incidence data from England and Wales by using maximum likelihood. We developed several scenarios to determine the effect of unknowns regarding transmission and immunity on estimates of the duration of immunity. In the various models, duration of immunity to NoV gastroenteritis was estimated at 4.1 (95% CI 3.2-5.1) to 8.7 (95% CI 6.8-11.3) years. Moreover, we calculated that children (<5 years) are much more infectious than older children and adults. If a vaccine can achieve protection for duration of natural immunity indicated by our results, its potential health and economic benefits could be substantial.
Summary Background Concerns exist about whether monovalent (RV1) and pentavalent (RV5) rotavirus vaccines provide adequate protection against diverse strains and whether vaccine introduction will ...lead to selective pressure. We aimed to investigate the distribution of rotavirus strains and strain-specific rotavirus vaccine effectiveness after vaccine introduction. Methods We did a systematic review of published work to assess the strain-specific effectiveness of RV1 and RV5 rotavirus vaccines. We classified strains as homotypic, partly heterotypic, and fully heterotypic based on the amount of antigen-matching between strain and vaccine. When studies reported vaccine effectiveness against single antigens (G-type or P-type), we categorised them as either single-antigen vaccine type or single-antigen non-vaccine type. Our primary outcome was strain-specific vaccine effectiveness, comparing effectiveness of homotypic strains with fully or partly heterotypic strains. A secondary outcome was the prevalence of rotavirus strains after vaccine introduction. We estimated pooled odds ratios using random-effect regression models, stratified by country income level and vaccine type, and tested for differences in strain-specific vaccine effectiveness. We assessed strain distribution trends from surveillance reports. Findings In high-income countries, RV1 pooled vaccine effectiveness was 94% (95% CI 80–98) against homotypic strains, 71% (39–86) against partly heterotypic strains, and 87% (76–93) against fully heterotypic strains. In middle-income settings, respective pooled data were 59% (36–73), 72% (58–81), and 47% (28–61). In high-income countries, RV5 vaccine effectiveness was 83% (78–87) against homotypic strains, 82% (70–89) against single-antigen vaccine type strains, 82% (70–89) against partly heterotypic strains, and 75% (47–88) against single-antigen non-vaccine type strains. In middle-income settings, RV5 vaccine effectiveness was 70% (58–78) against single-antigen vaccine type strains, 37% (10–56) against partly heterotypic strains, and 87% (38–97) against single-antigen non-vaccine type strains. No difference was noted in vaccine effectiveness for either RV1 or RV5 in any setting (all p>0·05). Prevalent strains in countries using RV1 were G2P4 (2198 of 4428, 50%) and G1P8 (953, 22%), and those in countries using RV5 were G1P8 (1280 of 3875, 33%) and G2P4 (1169, 30%). Sustained predominance of a single strain was not recorded. Interpretation RV1 and RV5 exert similar effectiveness against homotypic and heterotypic rotavirus strains. Persistence of specific strains was not recorded, suggesting vaccine-induced selective pressure did not occur. Expansion of rotavirus surveillance efforts to low-income countries and ongoing surveillance are crucial to identify emergence of new strains and to assess strain-specific vaccine effectiveness in various settings. Funding None.
Background. Globally, gastroenteritis is recognized as an important contributor to mortality among children, but population-based data on gastroenteritis deaths among adults and the contributions of ...specific pathogens are limited. We aimed to describe trends in gastroenteritis deaths across all ages in the United States and specifically estimate the contributions of Clostridium difficile and norovirus. Methods. Gastroenteritis-associated deaths in the United States during 1999-2007 were identified from the National Center for Health Statistics multiple-cause-of-death mortality data. All deaths in which the underlying cause or any of the contributing causes listed gastroenteritis were included. Time-series regression models were used to identify cause-unspecified gastroenteritis deaths that were probably due to specific causes; seasonality of model residuals was analyzed to estimate norovirus-associated deaths. Results. Gastroenteritis mortality averaged 39/1 000 000 person-years (11 255 deaths per year) during the study period, increasing from 25/1 000 000 person-years in 1999-2000 to 57/1 000 000 person-years in 2006-2007 (P < .001). Adults aged ≥65 years accounted for 83% of gastroenteritis deaths (258/1 000 000 person-years). C. difficile mortality increased 5-fold from 10/1 000 000 person-years in 1999-2000 to 48/1 000 000 person-years in 2006-2007 (P (P < .001). Norovirus contributed to an estimated 797 deaths annually (3/1 000 000 person-years), with surges by up to 50% during epidemic seasons associated with emergent viral strains. Conclusions. Gastroenteritis-associated mortality has more than doubled during the past decade, primarily affecting the elderly. C. difficile is the main contributor to gastroenteritis-associated deaths, largely accounting for the increasing trend, and norovirus is probably the second leading infectious cause. These findings can help guide appropriate clinical management strategies and vaccine development.
Following the introduction of rotavirus vaccination in the United States, rotavirus and cause-unspecified gastroenteritis discharges significantly decreased in 2008 in the 0-4, 5-14, and 15-24-year ...age groups, with significant reductions observed in March, the historic peak rotavirus month, in all age groups. We estimate that 15% of the total 66 000 averted hospitalizations and 20% of the $204 million in averted direct medical costs attributable to the vaccination program were among unvaccinated 5-24 year-olds. This study demonstrates a previously unrecognized burden of severe rotavirus in the population > 5 years and the primacy of very young children in the transmission of rotavirus.
University administrators face decisions about how to safely return and maintain students, staff and faculty on campus throughout the 2020-21 school year. We developed a ...susceptible-exposed-infectious-recovered (SEIR) deterministic compartmental transmission model of SARS-CoV-2 among university students, staff, and faculty. Our goals were to inform planning at our own university, Emory University, a medium-sized university with around 15,000 students and 15,000 faculty and staff, and to provide a flexible modeling framework to inform the planning efforts at similar academic institutions. Control strategies of isolation and quarantine are initiated by screening (regardless of symptoms) or testing (of symptomatic individuals). We explored a range of screening and testing frequencies and performed a probabilistic sensitivity analysis. We found that among students, monthly and weekly screening can reduce cumulative incidence by 59% and 87%, respectively, while testing with a 2-, 4- and 7-day delay between onset of infectiousness and testing results in an 84%, 74% and 55% reduction in cumulative incidence. Smaller reductions were observed among staff and faculty. Community-introduction of SARS-CoV-2 onto campus may be controlled with testing, isolation, contract tracing and quarantine. Screening would need to be performed at least weekly to have substantial reductions beyond disease surveillance. This model can also inform resource requirements of diagnostic capacity and isolation/quarantine facilities associated with different strategies.
Noroviruses are the leading cause of foodborne illness in the United States. To better guide interventions, we analyzed 2,922 foodborne disease outbreaks for which norovirus was the suspected or ...confirmed cause, which had been reported to the Foodborne Disease Outbreak Surveillance System of the Centers for Disease Control and Prevention during 2001-2008. On average, 365 foodborne norovirus outbreaks were reported annually, resulting in an estimated 10,324 illnesses, 1,247 health care provider visits, 156 hospitalizations, and 1 death. In 364 outbreaks attributed to a single commodity, leafy vegetables (33%), fruits/nuts (16%), and mollusks (13%) were implicated most commonly. Infected food handlers were the source of 53% of outbreaks and may have contributed to 82% of outbreaks. Most foods were likely contaminated during preparation and service, except for mollusks, and occasionally, produce was contaminated during production and processing. Interventions to reduce the frequency of foodborne norovirus outbreaks should focus on food workers and production of produce and shellfish.
Background. Diarrhea remains an important cause of morbidity, but until the mid 1990s, hospital admissions for diarrhea in the US adult population were declining. We aimed to describe recent trends ...in gastroenteritis hospitalizations and to determine the contribution of norovirus. Methods. We analyzed all gastroenteritis-associated hospital discharges during 1996-2007 from a nationally representative data set of hospital inpatient stays. Annual rates of discharges by age were calculated. Time-series regression models were fitted using cause-specified discharges as explanatory variables; model residuals were analyzed to estimate norovirus- and rotavirus-associated discharges. We then calculated the annual hospital charges for norovirus-associated discharges. Results. Sixty-nine percent of all gastroenteritis discharges were cause-unspecified and rates increased by ≥50% in all adult and elderly age groups (≥18 years of age) from 1996 through 2007. We estimate an annual mean of 71,000 norovirus-associated hospitalizations, costing $493 million per year, with surges to nearly 110,000 hospitalizations per year in epidemic seasons. We also estimate 24,000 rotavirus hospitalizations annually among individuals aged ≥5 years. Conclusions. Gastroenteritis hospitalizations are increasing, and we estimate that norovirus is the cause of 10% of cause-unspecified and 7% of all-cause gastroenteritis discharges. Norovirus should be routinely considered as a cause of gastroenteritis hospitalization.
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