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Supplemental Digital Content is available in the text., Background: Serology tests can identify previous infections and facilitate estimation of the number of total infections. However, immunoglobulins targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to wane below the detectable level of serologic assays (which is not necessarily equivalent to the duration of protective immunity). We estimate the cumulative incidence of SARS-CoV-2 infection from serology studies, accounting for expected levels of antibody acquisition (seroconversion) and waning (seroreversion), and apply this framework using data from New York City and Connecticut. Methods: We estimated time from seroconversion to seroreversion and infection fatality ratio (IFR) using mortality data from March to October 2020 and population-level cross-sectional seroprevalence data from April to August 2020 in New York City and Connecticut. We then estimated the daily seroprevalence and cumulative incidence of SARS-CoV-2 infection. Results: The estimated average time from seroconversion to seroreversion was 3–4 months. The estimated IFR was 1.1% (95% credible interval, 1.0%, 1.2%) in New York City and 1.4% (1.1, 1.7%) in Connecticut. The estimated daily seroprevalence declined after a peak in the spring. The estimated cumulative incidence reached 26.8% (24.2%, 29.7%) at the end of September in New York City and 8.8% (7.1%, 11.3%) in Connecticut, higher than maximum seroprevalence measures (22.1% and 6.1%), respectively. Conclusions: The cumulative incidence of SARS-CoV-2 infection is underestimated using cross-sectional serology data without adjustment for waning antibodies. Our approach can help quantify the magnitude of underestimation and adjust estimates for waning antibodies.

Background Although live attenuated monovalent human rotavirus vaccine (Rotarix) efficacy has been characterized through randomized studies, its effectiveness, especially in non-clinical settings, is less clear. In this study, we estimate the impact of childhood Rotarix® vaccination on community rotavirus prevalence. Methods We analyse 10 years of serial population-based diarrhoea case-control study, which also included testing for rotavirus infection (n = 3430), and 29 months of all-cause diarrhoea active surveillance from a child cohort (n = 376) from rural Ecuador during a period in which Rotarix vaccination was introduced. We use weighted logistic regression from the case-control data to assess changes in community rotavirus prevalence (both symptomatic and asymptomatic) and all-cause diarrhoea after the vaccine was introduced. We also assess changes in all-cause diarrhoea rates in the child cohort (born 2008–13) using Cox regression, comparing time to first all-cause diarrhoea case by vaccine status. Results Overall, vaccine introduction among age-eligible children was associated with a 82.9% reduction [95% confidence interval (CI): 49.4%, 94.2%] in prevalence of rotavirus in participants without diarrhoea symptoms and a 46.0% reduction (95% CI: 6.2%, 68.9%) in prevalence of rotavirus infection among participants experiencing diarrhoea. Whereas all age groups benefited, this reduction was strongest among the youngest age groups. For young children, prevalence of symptomatic diarrhoea also decreased in the post-vaccine period in both the case-control study (reduction in prevalence for children Conclusions Rotarix vaccination may suppress transmission, including asymptomatic transmission, in low- and middle-income settings. It was highly effective among children in a rural community setting and provides population-level benefits through indirect protection among adults.

Serological testing remains a passive component of the public health response to the COVID-19 pandemic. Using a transmission model, we examine how serological testing could have enabled seropositive individuals to increase their relative levels of social interaction while offsetting transmission risks. We simulate widespread serological testing in New York City, South Florida, and Washington Puget Sound and assume seropositive individuals partially restore their social contacts. Compared to no intervention, our model suggests that widespread serological testing starting in late 2020 would have averted approximately 3300 deaths in New York City, 1400 deaths in South Florida and 11,000 deaths in Washington State by June 2021. In all sites, serological testing blunted subsequent waves of transmission. Findings demonstrate the potential benefit of widespread serological testing, had it been implemented in the pre-vaccine era, and remain relevant now amid the potential for emergence of new variants., Serological testing remains a passive component of the current public health response to the COVID-19 pandemic. Using a mathematical model, the authors examine how testing for antibodies could have enabled policies in which seropositive individuals increased their relative levels of social interaction while offsetting transmission risks

SummaryBackgroundCountries continue to debate the need for decontamination of cold-chain food packaging to reduce possible SARS-CoV-2 fomite transmission among workers. While laboratory-based studies demonstrate persistence of SARS-CoV-2 on surfaces, the likelihood of fomite-mediated transmission under real-life conditions is uncertain.MethodsUsing a quantitative risk assessment model, we simulated in a frozen food packaging facility 1) SARS-CoV-2 fomite-mediated infection risks following worker exposure to contaminated plastic packaging; and 2) reductions in these risks attributed to masking, handwashing, and vaccination.FindingsIn a representative facility with no specific interventions, SARS-CoV-2 infection risk to a susceptible worker from contact with contaminated packaging was 2·8 × 10−3per 1h-period (95%CI: 6·9 × 10−6, 2·4 × 10−2). Implementation of standard infection control measures, handwashing and masks (9·4 × 10−6risk per 1h-period, 95%CI: 2·3 × 10−8, 8·1 × 10−5), substantially reduced risk (99·7%). Vaccination of the susceptible worker (two doses Pfizer/Moderna, vaccine effectiveness: 86-99%) combined with handwashing and masking reduced risk to less than 1·0 × 10−6. Simulating increased infectiousness/transmissibility of new variants (2-, 10-fold viral shedding) among a fully vaccinated workforce, handwashing and masks continued to mitigate risk (2·0 × 10−6-1·1 × 10−5risk per 1h-period). Decontamination of packaging in addition to these interventions reduced infection risks to below the 1·0 × 10−6risk threshold.InterpretationFomite-mediated SARS-CoV-2 infection risks were very low under cold-chain conditions. Handwashing and masking provide significant protection to workers, especially when paired with vaccination.FundingU.S. Department of Agriculture

Background:Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000–2030 across 112 countries.Methods:Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios.Results:We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000–2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases.Conclusions:This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future.Funding:VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium’s modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Severe acute respiratory syndrome coronavirus 2 can persist on surfaces, suggesting possible surface-mediated transmission of this pathogen. We found that fomites might be a substantial source of transmission risk, particularly in schools and child daycares. Combining surface cleaning and decontamination with mask wearing can help mitigate this risk.

The SARS-CoV-2 global pandemic poses significant health risks to workers who are essential to maintaining the food supply chain. Using a quantitative risk assessment model, this study characterized the impact of risk reduction strategies for controlling SARS-CoV-2 transmission (droplet, aerosol, fomite-mediated) among front-line workers in a representative enclosed food manufacturing facility. We simulated: 1) individual and cumulative SARS-CoV-2 infection risks from close contact (droplet and aerosols at 1-3m), aerosol, and fomite-mediated exposures to a susceptible worker following exposure to an infected worker during an 8h-shift; and 2) the relative reduction in SARS-CoV-2 infection risk attributed to infection control interventions (physical distancing, mask use, ventilation, surface disinfection, hand hygiene). Without mitigation measures, the SARS-CoV-2 infection risk was largest for close contact (droplet and aerosol) at 1m (0.96, 95%CI: 0.67–1.0). In comparison, risk associated with fomite (0.26, 95%CI: 0.10–0.56) or aerosol exposure alone (0.05, 95%CI: 0.01–0.13) at 1m distance was substantially lower (73-95%). At 1m, droplet transmission predominated over aerosol and fomite-mediated transmission, however, this changed by 3m, with aerosols comprising the majority of the exposure dose. Increasing physical distancing reduced risk by 84% (1 to 2m) and 91% (1 to 3m). Universal mask use reduced infection risk by 52-88%, depending on mask type. Increasing ventilation (from 0.1 to 2-8 air changes/hour) resulted in risk reductions of 14-54% (1m) and 55-85% (2m). Combining these strategies, together with handwashing and surface disinfection, resulted in Significance StatementUsing mathematical modeling, we find that workers in enclosed food manufacturing facilities are at higher risk of SARS-CoV-2 infection from close contact transmission (exposure to large droplets and small aerosol particles) than fomite transmission. Thus, strategies protecting workers should prioritize close contact transmission pathways, such as physical distancing, universal mask use, and room air changes, with surface disinfection (reducing fomite transmission) and handwashing of secondary importance. Our work supports current international (EU-OSHA), domestic (FDA, OSHA), and food industry-standard guidance for managing COVID-19 transmission in essential workers in the food manufacturing sector. Although our model was designed for an indoor food manufacturing setting, it can be readily adapted to other indoor environments and infectious respiratory pathogens.

In April 2020, the incidence of norovirus outbreaks reported to the National Outbreak Reporting System dramatically declined. We used regression models to determine if this decline was best explained by underreporting, seasonal trends, or reduced exposure due to nonpharmaceutical interventions (NPIs) implemented for severe acute respiratory syndrome coronavirus 2 using data from 9 states from July 2012 to July 2020. The decline in norovirus outbreaks was significant for all 9 states, and underreporting and/or seasonality are unlikely to be the primary explanation for these findings. These patterns were similar across a variety of settings. NPIs appear to have reduced incidence of norovirus, a nonrespiratory pathogen.

Background: Projected increases in extreme weather may change relationships between rain-related climate exposures and diarrheal disease. Whether rainfall increases or decreases diarrhea rates is unclear based on prior literature. The concentration-dilution hypothesis suggests that these conflicting results are explained by the background level of rain: Rainfall following dry periods can flush pathogens into surface water, increasing diarrhea incidence, whereas rainfall following wet periods can dilute pathogen concentrations in surface water, thereby decreasing diarrhea incidence. Objectives: In this analysis, we explored the extent to which the concentration-dilution hypothesis is supported by published literature. Methods: To this end, we conducted a systematic search for articles assessing the relationship between rain, extreme rain, flood, drought, and season (rainy vs. dry) and diarrheal illness. Results: A total of 111 articles met our inclusion criteria. Overall, the literature largely supports the concentration-dilution hypothesis. In particular, extreme rain was associated with increased diarrhea when it followed a dry period [incidence rate ratio (IRR)=1.26; 95% confidence interval (CI): 1.05, 1.51], with a tendency toward an inverse association for extreme rain following wet periods, albeit nonsignificant, with one of four relevant studies showing a significant inverse association (IRR=0.911; 95% CI: 0.771, 1.08). Incidences of bacterial and parasitic diarrhea were more common during rainy seasons, providing pathogen-specific support for a concentration mechanism, but rotavirus diarrhea showed the opposite association. Information on timing of cases within the rainy season (e.g., early vs. late) was lacking, limiting further analysis. We did not find a linear association between nonextreme rain exposures and diarrheal disease, but several studies found a nonlinear association with low and high rain both being associated with diarrhea. Discussion: Our meta-analysis suggests that the effect of rainfall depends on the antecedent conditions. Future studies should use standard, clearly defined exposure variables to strengthen understanding of the relationship between rainfall and diarrheal illness. https://doi.org/10.1289/EHP6181

Significant progress has already been made in development and testing of SARS-CoV-2 vaccines, and Phase III clinical trials have begun for 6 novel vaccine candidates to date. These Phase III trials seek to demonstrate direct benefits of a vaccine on vaccine recipients. However, vaccination is also known to bring about indirect benefits to a population through the reduction of virus circulation. The indirect effects of SARS-CoV-2 vaccination can play a key role in reducing case counts and COVID-19 deaths. To illustrate this point, we show through simulation that a vaccine with strong indirect effects has the potential to reduce SARS-CoV-2 circulation and COVID-19 deaths to a greater extent than an alternative vaccine with stronger direct effects but weaker indirect effects. Protection via indirect effects may be of particular importance in the context of this virus, because elderly individuals are at an elevated risk of death but are also less likely to be directly protected by vaccination due to immune senescence. We therefore encourage ongoing data collection and model development aimed at evaluating the indirect effects of forthcoming SARS-CoV-2 vaccines.

Significant progress has already been made in development and testing of SARS-CoV-2 vaccines, and Phase III clinical trials have begun for 6 novel vaccine candidates to date. These Phase III trials seek to demonstrate direct benefits of a vaccine on vaccine recipients. However, vaccination is also known to bring about indirect benefits to a population through the reduction of virus circulation. The indirect effects of SARS-CoV-2 vaccination can play a key role in reducing case counts and COVID-19 deaths. To illustrate this point, we show through simulation that a vaccine with strong indirect effects has the potential to reduce SARS-CoV-2 circulation and COVID-19 deaths to a greater extent than an alternative vaccine with stronger direct effects but weaker indirect effects. Protection via indirect effects may be of particular importance in the context of this virus, because elderly individuals are at an elevated risk of death but are also less likely to be directly protected by vaccination due to immune senescence. We therefore encourage ongoing data collection and model development aimed at evaluating the indirect effects of forthcoming SARS-CoV-2 vaccines.

Background Fomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities. The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs. Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues. Methods We developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces. We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites). We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types. To parameterize the model for each pathogen we conducted a thorough literature search. Results Based on parameter estimates from the literature the reproductive number (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\mathcal {R}_{0}$\end{document}R0) for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission. For influenza, on the other hand, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\mathcal {R}_{0}$\end{document}R0 for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission. Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus. The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands. Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding. Conclusions Fomite-mediated transmission is an important pathway for the three pathogens examined. The effectiveness of environmental interventions differs significantly both by pathogen and venue. While fomite-based interventions may be able to lower \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\mathcal {R}_{0}$\end{document}R0 for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\mathcal {R}_{0}>>1$\end{document}R0>>1) that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens. Electronic supplementary material The online version of this article (10.1186/s12879-018-3425-x) contains supplementary material, which is available to authorized users.

Rotavirus is considered a directly transmitted disease due to its high infectivity. Environmental pathways have, therefore, largely been ignored. Rotavirus, however, persists in water sources, and both its surface water concentrations and infection incidence vary with temperature. Here, we examine the potential for waterborne rotavirus transmission. We use a mechanistic model that incorporates both direct and waterborne transmission pathways, coupled with a hydrological model, and we simulate rotavirus transmission between two communities with interconnected water sources. To parameterize temperature dependency, we estimated temperature-dependent decay rates in water through a meta-analysis. Our meta-analysis suggests that rotavirus decay rates are positively associated with temperature (n = 39, P [Formula: see text] 0.001). This association is stronger at higher temperatures (over 20 °C), consistent with tropical climate conditions. Our model analysis demonstrates that water could disseminate rotavirus between the two communities for all modeled temperatures. While direct transmission was important for disease amplification within communities, waterborne transmission could also amplify transmission. In standing-water systems, the modeled increase in decay led to decreased disease, with every 1 °C increase in temperature leading to up to a 2.4% decrease in incidence. These effect sizes are consistent with prior meta-analyses, suggesting that environmental transmission through water sources may partially explain the observed associations between temperature and rotavirus incidence. Waterborne rotavirus transmission is likely most important in cooler seasons and in communities that use slow-moving or stagnant water sources. Even when indirect transmission through water cannot sustain outbreaks, it can seed outbreaks that are maintained by high direct transmission rates.