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1. Contact tracing efficiency, transmission heterogeneity, and accelerating COVID-19 epidemics

   https://doi.org/10.1371/journal.pcbi.1009122  

   Gardner, Billy J. ; Kilpatrick, A. Marm ( June 2021 , PLOS Computational Biology)

   Funk, Sebastian (Ed.)

   Simultaneously controlling COVID-19 epidemics and limiting economic and societal impacts presents a difficult challenge, especially with limited public health budgets. Testing, contact tracing, and isolating/quarantining is a key strategy that has been used to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 and other pathogens. However, manual contact tracing is a time-consuming process and as case numbers increase a smaller fraction of cases’ contacts can be traced, leading to additional virus spread. Delays between symptom onset and being tested (and receiving results), and a low fraction of symptomatic cases being tested and traced can also reduce the impact of contact tracing on transmission. We examined the relationship between increasing cases and delays and the pathogen reproductive number R t , and the implications for infection dynamics using deterministic and stochastic compartmental models of SARS-CoV-2. We found that R t increased sigmoidally with the number of cases due to decreasing contact tracing efficacy. This relationship results in accelerating epidemics because R t initially increases, rather than declines, as infections increase. Shifting contact tracers from locations with high and low case burdens relative to capacity to locations with intermediate case burdens maximizes their impact in reducing R t (but minimizing total infections may be more complicated). Contact tracing efficacy decreased sharply with increasing delays between symptom onset and tracing and with lower fraction of symptomatic infections being tested. Finally, testing and tracing reductions in R t can sometimes greatly delay epidemics due to the highly heterogeneous transmission dynamics of SARS-CoV-2. These results demonstrate the importance of having an expandable or mobile team of contact tracers that can be used to control surges in cases. They also highlight the synergistic value of high capacity, easy access testing and rapid turn-around of testing results, and outreach efforts to encourage symptomatic cases to be tested immediately after symptom onset. 

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2. Severe Acute Respiratory Syndrome Coronavirus 2 Delta Vaccine Breakthrough Transmissibility in Alachua County, Florida

   https://doi.org/10.1093/cid/ciac197  

   Rife Magalis, Brittany ; Rich, Shannan ; Tagliamonte, Massimiliano S. ; Mavian, Carla ; Cash, Melanie N. ; Riva, Alberto ; Marini, Simone ; Amador, David Moraga ; Zhang, Yanping ; Shapiro, Jerne ; et al ( March 2022 , Clinical Infectious Diseases)

   Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant has caused a dramatic resurgence in infections in the United Sates, raising questions regarding potential transmissibility among vaccinated individuals.

   Between October 2020 and July 2021, we sequenced 4439 SARS-CoV-2 full genomes, 23% of all known infections in Alachua County, Florida, including 109 vaccine breakthrough cases. Univariate and multivariate regression analyses were conducted to evaluate associations between viral RNA burden and patient characteristics. Contact tracing and phylogenetic analysis were used to investigate direct transmissions involving vaccinated individuals.

   The majority of breakthrough sequences with lineage assignment were classified as Delta variants (74.6%) and occurred, on average, about 3 months (104 ± 57.5 days) after full vaccination, at the same time (June-July 2021) of Delta variant exponential spread within the county. Six Delta variant transmission pairs between fully vaccinated individuals were identified through contact tracing, 3 of which were confirmed by phylogenetic analysis. Delta breakthroughs exhibited broad viral RNA copy number values during acute infection (interquartile range, 1.2-8.64 Log copies/mL), on average 38% lower than matched unvaccinated patients (3.29-10.81 Log copies/mL, P < .00001). Nevertheless, 49% to 50% of all breakthroughs, and 56% to 60% of Delta-infected breakthroughs exhibited viral RNA levels above the transmissibility threshold (4 Log copies/mL) irrespective of time after vaccination.

   Delta infection transmissibility and general viral RNA quantification patterns in vaccinated individuals suggest limited levels of sterilizing immunity that need to be considered by public health policies. In particular, ongoing evaluation of vaccine boosters should specifically address whether extra vaccine doses curb breakthrough contribution to epidemic spread.

    

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3. Ensemble machine learning of factors influencing COVID-19 across US counties

   https://doi.org/10.1038/s41598-021-90827-x  

   McCoy, David ; Mgbara, Whitney ; Horvitz, Nir ; Getz, Wayne M. ; Hubbard, Alan ( December 2021 , Scientific Reports)

   Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the causal agent for COVID-19, is a communicable disease spread through close contact. It is known to disproportionately impact certain communities due to both biological susceptibility and inequitable exposure. In this study, we investigate the most important health, social, and environmental factors impacting the early phases (before July, 2020) of per capita COVID-19 transmission and per capita all-cause mortality in US counties. We aggregate county-level physical and mental health, environmental pollution, access to health care, demographic characteristics, vulnerable population scores, and other epidemiological data to create a large feature set to analyze per capita COVID-19 outcomes. Because of the high-dimensionality, multicollinearity, and unknown interactions of the data, we use ensemble machine learning and marginal prediction methods to identify the most salient factors associated with several COVID-19 outbreak measure. Our variable importance results show that measures of ethnicity, public transportation and preventable diseases are the strongest predictors for both per capita COVID-19 incidence and mortality. Specifically, the CDC measures for minority populations, CDC measures for limited English, and proportion of Black- and/or African-American individuals in a county were the most important features for per capita COVID-19 cases within a month after the pandemic started in a county and also at the latest date examined. For per capita all-cause mortality at day 100 and total to date, we find that public transportation use and proportion of Black- and/or African-American individuals in a county are the strongest predictors. The methods predict that, keeping all other factors fixed, a 10% increase in public transportation use, all other factors remaining fixed at the observed values, is associated with increases mortality at day 100 of 2012 individuals (95% CI [1972, 2356]) and likewise a 10% increase in the proportion of Black- and/or African-American individuals in a county is associated with increases total deaths at end of study of 2067 (95% CI [1189, 2654]). Using data until the end of study, the same metric suggests ethnicity has double the association as the next most important factors, which are location, disease prevalence, and transit factors. Our findings shed light on societal patterns that have been reported and experienced in the U.S. by using robust methods to understand the features most responsible for transmission and sectors of society most vulnerable to infection and mortality. In particular, our results provide evidence of the disproportionate impact of the COVID-19 pandemic on minority populations. Our results suggest that mitigation measures, including how vaccines are distributed, could have the greatest impact if they are given with priority to the highest risk communities. 

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4. The unintended consequences of inconsistent closure policies and mobility restrictions during epidemics

   https://doi.org/10.1186/s44263-023-00028-z  

   Althouse, Benjamin M. ; Wallace, Brendan ; Case, B. K. M. ; Scarpino, Samuel V. ; Allard, Antoine ; Berdahl, Andrew M. ; White, Easton R. ; Hébert-Dufresne, Laurent ( December 2023 , BMC Global and Public Health)

   Controlling the spread of infectious diseases―even when safe, transmission-blocking vaccines are available―may require the effective use of non-pharmaceutical interventions (NPIs), e.g., mask wearing, testing, limits on group sizes, venue closure. During the SARS-CoV-2 pandemic, many countries implemented NPIs inconsistently in space and time. This inconsistency was especially pronounced for policies in the United States of America (US) related to venue closure.

   Here, we investigate the impact of inconsistent policies associated with venue closure using mathematical modeling and high-resolution human mobility, Google search, and county-level SARS-CoV-2 incidence data from the USA. Specifically, we look at high-resolution location data and perform a US-county-level analysis of nearly 8 million SARS-CoV-2 cases and 150 million location visits, including 120 million church visitors across 184,677 churches, 14 million grocery visitors across 7662 grocery stores, and 13.5 million gym visitors across 5483 gyms.

   Analyzing the interaction between venue closure and changing mobility using a mathematical model shows that, across a broad range of model parameters, inconsistent or partial closure can be worse in terms of disease transmission as compared to scenarios with no closures at all. Importantly, changes in mobility patterns due to epidemic control measures can lead to increase in the future number of cases. In the most severe cases, individuals traveling to neighboring jurisdictions with different closure policies can result in an outbreak that would otherwise have been contained. To motivate our mathematical models, we turn to mobility data and find that while stay-at-home orders and closures decreased contacts in most areas of the USA, some specific activities and venues saw an increase in attendance and an increase in the distance visitors traveled to attend. We support this finding using search query data, which clearly shows a shift in information seeking behavior concurrent with the changing mobility patterns.

   While coarse-grained observations are not sufficient to validate our models, taken together, they highlight the potential unintended consequences of inconsistent epidemic control policies related to venue closure and stress the importance of balancing the societal needs of a population with the risk of an outbreak growing into a large epidemic.

    

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5. Symptom and Age Homophilies in SARS-CoV-2 Transmission Networks during the Early Phase of the Pandemic in Japan

   https://doi.org/10.3390/biology10060499  

   Andalibi, Ali ; Koizumi, Naoru ; Li, Meng-Hao ; Siddique, Abu Bakkar ( June 2021 , Biology)

   null (Ed.)

   Kanagawa and Hokkaido were affected by COVID-19 in the early stage of the pandemic. Japan’s initial response included contact tracing and PCR analysis on anyone who was suspected of having been exposed to SARS-CoV-2. In this retrospective study, we analyzed publicly available COVID-19 registry data from Kanagawa and Hokkaido (n = 4392). Exponential random graph model (ERGM) network analysis was performed to examine demographic and symptomological homophilies. Age, symptomatic, and asymptomatic status homophilies were seen in both prefectures. Symptom homophilies suggest that nuanced genetic differences in the virus may affect its epithelial cell type range and can result in the diversity of symptoms seen in individuals infected by SARS-CoV-2. Environmental variables such as temperature and humidity may also play a role in the overall pathogenesis of the virus. A higher level of asymptomatic transmission was observed in Kanagawa. Moreover, patients who contracted the virus through secondary or tertiary contacts were shown to be asymptomatic more frequently than those who contracted it from primary cases. Additionally, most of the transmissions stopped at the primary and secondary levels. As expected, significant viral transmission was seen in healthcare settings. 

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