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1.
JMIR Public Health Surveill ; 10: e53551, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38568186

ABSTRACT

BACKGROUND: In this study, we built upon our initial research published in 2020 by incorporating an additional 2 years of data for Europe. We assessed whether COVID-19 had shifted from the pandemic to endemic phase in the region when the World Health Organization (WHO) declared the end of the public health emergency of international concern on May 5, 2023. OBJECTIVE: We first aimed to measure whether there was an expansion or contraction in the pandemic in Europe at the time of the WHO declaration. Second, we used dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we provided the historical context for the course of the pandemic in Europe in terms of policy and disease burden at the country and region levels. METHODS: In addition to the updates of traditional surveillance data and dynamic panel estimates from the original study, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-tailed t test for whether regional weekly speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. RESULTS: Speed for the region had remained below the outbreak threshold for 4 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1-day and 7-day persistence coefficients remained statistically significant, the coefficients were moderate in magnitude (0.404 and 0.547, respectively; P<.001 for both). The shift parameters for the 2 weeks around the WHO declaration were small and insignificant, suggesting little change in the clustering effect of cases on future cases at the time. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 became insignificant for the first time in April 2023. CONCLUSIONS: While COVID-19 continues to circulate in Europe, the rate of transmission remained below the threshold of an outbreak for 4 months ahead of the WHO declaration. The region had previously been in a nearly continuous state of outbreak. The more recent trend suggested that COVID-19 was endemic in the region and no longer reached the threshold of the pandemic definition. However, several countries remained in a state of outbreak, and the conclusion that COVID-19 was no longer a pandemic in Europe at the time is unclear.


Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , Humans , Europe/epidemiology , Longitudinal Studies , SARS-CoV-2 , History, 21st Century , World Health Organization
2.
JMIR Public Health Surveill ; 10: e53219, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38568184

ABSTRACT

BACKGROUND: This study updates the COVID-19 pandemic surveillance in the Middle East and North Africa (MENA) we first conducted in 2020 with 2 additional years of data for the region. OBJECTIVE: The objective of this study is to determine whether the MENA region meets the criteria for moving from a pandemic to endemic. In doing so, this study considers pandemic trends, dynamic and genomic surveillance methods, and region-specific historical context for the pandemic. These considerations continue through the World Health Organization (WHO) declaration of the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. METHODS: In addition to updates to traditional surveillance data and dynamic panel estimates from the original study by Post et al, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional weekly speed of COVID-19 spread was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data from September 4, 2020, to May 12, 2023. RESULTS: The speed of COVID-19 spread for the region had remained below the outbreak threshold for 7 continuous months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant and positive, the weekly shift parameters suggested the coefficients had most recently turned negative, meaning the clustering effect of new COVID-19 cases became even smaller in the 2 weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of the speed of spread equal to 10 became entirely insignificant from October 2022 onward. CONCLUSIONS: The COVID-19 pandemic had far-reaching effects on MENA, impacting health care systems, economies, and social well-being. Although COVID-19 continues to circulate in the MENA region, the rate of transmission remained well below the threshold of an outbreak for over 1 year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had transitioned to endemic by the time of the WHO declaration.


Subject(s)
COVID-19 , Pandemics , SARS-CoV-2 , COVID-19/epidemiology , Humans , Africa, Northern/epidemiology , Middle East/epidemiology , Longitudinal Studies
3.
JMIR Public Health Surveill ; 10: e44398, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38568194

ABSTRACT

BACKGROUND: In May 2020, the World Health Organization (WHO) declared Latin America and the Caribbean (LAC) the epicenter of the COVID-19 pandemic, with over 40% of worldwide COVID-19-related deaths at the time. This high disease burden was a result of the unique circumstances in LAC. OBJECTIVE: This study aimed to (1) measure whether the pandemic was expanding or contracting in LAC when the WHO declared the end of COVID-19 as a public health emergency of international concern on May 5, 2023; (2) use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history; and (3) provide, with a focus on prevention policies, a historical context for the course of the pandemic in the region. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study, we used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern (VOCs). We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Additionally, we conducted a 1-sided t test for whether the regional weekly speed (rate of novel COVID-19 transmission) was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the period from August 2020 to May 2023. RESULTS: The speed of pandemic spread for the region had remained below the outbreak threshold for 6 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant for the 120-day period ending on the week of May 5, 2023, the coefficients were relatively modest in magnitude (0.457 and 0.491, respectively). Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, did not indicate any change in this clustering effect of cases on future cases. From December 2021 onward, Omicron was the predominant VOC in sequenced viral samples. The rolling t test of speed=10 became entirely insignificant from January 2023 onward. CONCLUSIONS: Although COVID-19 continues to circulate in LAC, surveillance data suggest COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. However, the region experienced a high COVID-19 burden in the early stages of the pandemic, and prevention policies should be an immediate focus in future pandemics. Ahead of vaccination development, these policies can include widespread testing of individuals and an epidemiological task force with a contact-tracing system.


Subject(s)
COVID-19 , COVID-19/epidemiology , Humans , Caribbean Region/epidemiology , Latin America/epidemiology , Longitudinal Studies , Pandemics , SARS-CoV-2
5.
Sci Total Environ ; 824: 153802, 2022 Jun 10.
Article in English | MEDLINE | ID: mdl-35150681

ABSTRACT

Aboveground net primary productivity (ANPP) of an ecosystem is among the most important metrics of valued ecosystem services. Measuring the efficiency scores of ecological production (ESEP) based on ANPP using relevant variables is valuable for identifying inefficient sites. The efficiency scores computed by the Data Envelopment Analysis (DEA) may be influenced by the number of input variables incorporated into the models and two DEA settings-orientations and returns-to-scales (RTSs). Therefore, the objectives were threefold to: (1) identify soil-environmental variables relevant to ANPP, (2) assess the sensitivity of ESEP to the number of input variables and DEA settings, and (3) assess local management relations with ESEP. The ANPP rates were calculated for pine forests in the southeastern U.S. where 10 management types were used. This was followed by an all-relevant variable selection technique based on 696 variables that cover biotic, pedogenic, climatic, geological, and topographical factors. Five minimal-optimal variable selection techniques were further applied to create five parsimonious sets that contain a different number of variables used as DEA inputs. After setting ANPP as the output variable, two DEA orientations (input/output) and six RTS were applied to compute ESEP. The variable selection methods succeeded in objectively identifying the major factors relevant to ANPP variation. The site index showed the highest correlation with ANPP (r = 0.39), while various precipitation factors were negatively correlated (r = - 0.15~ - 0.29, p < 0.01). Parsimonious ESEP models observed a decrease in score variances as the number of input variables increased. Various RTS produced similar scores across orientations. Of the DEA settings, an output orientation with decreasing RTS produced the most progressive ESEP with large variation. Results also suggested that macro- and micronutrient fertilization is the best combination of management strategies to achieve high ESEP. This holistic benchmark approach can be applied to other ecological functions in diverse regions.


Subject(s)
Ecosystem , Soil , Forests , Southeastern United States
6.
JMIR Public Health Surveill ; 8(2): e28737, 2022 02 24.
Article in English | MEDLINE | ID: mdl-34882569

ABSTRACT

BACKGROUND: Despite the availability of vaccines, the US incidence of new COVID-19 cases per day nearly doubled from the beginning of July to the end of August 2021, fueled largely by the rapid spread of the Delta variant. While the "Delta wave" appears to have peaked nationally, some states and municipalities continue to see elevated numbers of new cases. Vigilant surveillance including at a metropolitan level can help identify any reignition and validate continued and strong public health policy responses in problem localities. OBJECTIVE: This surveillance report aimed to provide up-to-date information for the 25 largest US metropolitan areas about the rapidity of descent in the number of new cases following the Delta wave peak, as well as any potential reignition of the pandemic associated with declining vaccine effectiveness over time, new variants, or other factors. METHODS: COVID-19 pandemic dynamics for the 25 largest US metropolitan areas were analyzed through September 19, 2021, using novel metrics of speed, acceleration, jerk, and 7-day persistence, calculated from the observed data on the cumulative number of cases as reported by USAFacts. Statistical analysis was conducted using dynamic panel data models estimated with the Arellano-Bond regression techniques. The results are presented in tabular and graphic forms for visual interpretation. RESULTS: On average, speed in the 25 largest US metropolitan areas declined from 34 new cases per day per 100,000 population, during the week ending August 15, 2021, to 29 new cases per day per 100,000 population, during the week ending September 19, 2021. This average masks important differences across metropolitan areas. For example, Miami's speed decreased from 105 for the week ending August 15, 2021, to 40 for the week ending September 19, 2021. Los Angeles, San Francisco, Riverside, and San Diego had decreasing speed over the sample period and ended with single-digit speeds for the week ending September 19, 2021. However, Boston, Washington DC, Detroit, Minneapolis, Denver, and Charlotte all had their highest speed of the sample during the week ending September 19, 2021. These cities, as well as Houston and Baltimore, had positive acceleration for the week ending September 19, 2021. CONCLUSIONS: There is great variation in epidemiological curves across US metropolitan areas, including increasing numbers of new cases in 8 of the largest 25 metropolitan areas for the week ending September 19, 2021. These trends, including the possibility of waning vaccine effectiveness and the emergence of resistant variants, strongly indicate the need for continued surveillance and perhaps a return to more restrictive public health guidelines for some areas.


Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , Humans , Longitudinal Studies , Pandemics/prevention & control , Public Health Surveillance/methods , SARS-CoV-2
7.
JMIR Public Health Surveill ; 7(6): e24251, 2021 06 17.
Article in English | MEDLINE | ID: mdl-34081593

ABSTRACT

BACKGROUND: COVID-19 transmission rates in South Asia initially were under control when governments implemented health policies aimed at controlling the pandemic such as quarantines, travel bans, and border, business, and school closures. Governments have since relaxed public health restrictions, which resulted in significant outbreaks, shifting the global epicenter of COVID-19 to India. Ongoing systematic public health surveillance of the COVID-19 pandemic is needed to inform disease prevention policy to re-establish control over the pandemic within South Asia. OBJECTIVE: This study aimed to inform public health leaders about the state of the COVID-19 pandemic, how South Asia displays differences within and among countries and other global regions, and where immediate action is needed to control the outbreaks. METHODS: We extracted COVID-19 data spanning 62 days from public health registries and calculated traditional and enhanced surveillance metrics. We use an empirical difference equation to measure the daily number of cases in South Asia as a function of the prior number of cases, the level of testing, and weekly shifts in variables with a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: Traditional surveillance metrics indicate that South Asian countries have an alarming outbreak, with India leading the region with 310,310 new daily cases in accordance with the 7-day moving average. Enhanced surveillance indicates that while Pakistan and Bangladesh still have a high daily number of new COVID-19 cases (n=4819 and n=3878, respectively), their speed of new infections declined from April 12-25, 2021, from 2.28 to 2.18 and 3.15 to 2.35 daily new infections per 100,000 population, respectively, which suggests that their outbreaks are decreasing and that these countries are headed in the right direction. In contrast, India's speed of new infections per 100,000 population increased by 52% during the same period from 14.79 to 22.49 new cases per day per 100,000 population, which constitutes an increased outbreak. CONCLUSIONS: Relaxation of public health restrictions and the spread of novel variants fueled the second wave of the COVID-19 pandemic in South Asia. Public health surveillance indicates that shifts in policy and the spread of new variants correlate with a drastic expansion in the pandemic, requiring immediate action to mitigate the spread of COVID-19. Surveillance is needed to inform leaders whether policies help control the pandemic.


Subject(s)
COVID-19/epidemiology , Communicable Disease Control/statistics & numerical data , Disease Outbreaks/statistics & numerical data , Health Policy , Public Health/statistics & numerical data , Adult , Aged , Aged, 80 and over , Asia/epidemiology , COVID-19/prevention & control , Communicable Disease Control/legislation & jurisprudence , Female , Humans , Longitudinal Studies , Male , Middle Aged , Public Health Surveillance , SARS-CoV-2
8.
JMIR Public Health Surveill ; 7(5): e25753, 2021 05 10.
Article in English | MEDLINE | ID: mdl-33852410

ABSTRACT

BACKGROUND: The COVID-19 global pandemic has disrupted structures and communities across the globe. Numerous regions of the world have had varying responses in their attempts to contain the spread of the virus. Factors such as public health policies, governance, and sociopolitical climate have led to differential levels of success at controlling the spread of SARS-CoV-2. Ultimately, a more advanced surveillance metric for COVID-19 transmission is necessary to help government systems and national leaders understand which responses have been effective and gauge where outbreaks occur. OBJECTIVE: The goal of this study is to provide advanced COVID-19 surveillance metrics for Canada at the country, province, and territory level that account for shifts in the pandemic including speed, acceleration, jerk, and persistence. Enhanced surveillance identifies risks for explosive growth and regions that have controlled outbreaks successfully. METHODS: Using a longitudinal trend analysis study design, we extracted 62 days of COVID-19 data from Canadian public health registries for 13 provinces and territories. We used an empirical difference equation to measure the daily number of cases in Canada as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: We compare the week of February 7-13, 2021, with the week of February 14-20, 2021. Canada, as a whole, had a decrease in speed from 8.4 daily new cases per 100,000 population to 7.5 daily new cases per 100,000 population. The persistence of new cases during the week of February 14-20 reported 7.5 cases that are a result of COVID-19 transmissions 7 days earlier. The two most populous provinces of Ontario and Quebec both experienced decreases in speed from 7.9 and 11.5 daily new cases per 100,000 population for the week of February 7-13 to speeds of 6.9 and 9.3 for the week of February 14-20, respectively. Nunavut experienced a significant increase in speed during this time, from 3.3 daily new cases per 100,000 population to 10.9 daily new cases per 100,000 population. CONCLUSIONS: Canada excelled at COVID-19 control early on in the pandemic, especially during the first COVID-19 shutdown. The second wave at the end of 2020 resulted in a resurgence of the outbreak, which has since been controlled. Enhanced surveillance identifies outbreaks and where there is the potential for explosive growth, which informs proactive health policy.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Public Health Surveillance/methods , Canada/epidemiology , Humans , Longitudinal Studies
9.
JMIR Public Health Surveill ; 7(4): e25728, 2021 04 27.
Article in English | MEDLINE | ID: mdl-33852413

ABSTRACT

BACKGROUND: The COVID-19 pandemic has placed unprecedented stress on economies, food systems, and health care resources in Latin America and the Caribbean (LAC). Existing surveillance provides a proxy of the COVID-19 caseload and mortalities; however, these measures make it difficult to identify the dynamics of the pandemic and places where outbreaks are likely to occur. Moreover, existing surveillance techniques have failed to measure the dynamics of the pandemic. OBJECTIVE: This study aimed to provide additional surveillance metrics for COVID-19 transmission to track changes in the speed, acceleration, jerk, and persistence in the transmission of the pandemic more accurately than existing metrics. METHODS: Through a longitudinal trend analysis, we extracted COVID-19 data over 45 days from public health registries. We used an empirical difference equation to monitor the daily number of cases in the LAC as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. COVID-19 transmission rates were tracked for the LAC between September 30 and October 6, 2020, and between October 7 and 13, 2020. RESULTS: The LAC saw a reduction in the speed, acceleration, and jerk for the week of October 13, 2020, compared to the week of October 6, 2020, accompanied by reductions in new cases and the 7-day moving average. For the week of October 6, 2020, Belize reported the highest acceleration and jerk, at 1.7 and 1.8, respectively, which is particularly concerning, given its high mortality rate. The Bahamas also had a high acceleration at 1.5. In total, 11 countries had a positive acceleration during the week of October 6, 2020, whereas only 6 countries had a positive acceleration for the week of October 13, 2020. The TAC displayed an overall positive trend, with a speed of 10.40, acceleration of 0.27, and jerk of -0.31, all of which decreased in the subsequent week to 9.04, -0.81, and -0.03, respectively. CONCLUSIONS: Metrics such as new cases, cumulative cases, deaths, and 7-day moving averages provide a static view of the pandemic but fail to identify where and the speed at which SARS-CoV-2 infects new individuals, the rate of acceleration or deceleration of the pandemic, and weekly comparison of the rate of acceleration of the pandemic indicate impending explosive growth or control of the pandemic. Enhanced surveillance will inform policymakers and leaders in the LAC about COVID-19 outbreaks.


Subject(s)
COVID-19/epidemiology , Public Health Surveillance , Caribbean Region/epidemiology , Humans , Latin America/epidemiology , Longitudinal Studies
10.
JMIR Public Health Surveill ; 7(4): e25695, 2021 04 28.
Article in English | MEDLINE | ID: mdl-33818391

ABSTRACT

BACKGROUND: The COVID-19 pandemic has severely impacted Europe, resulting in a high caseload and deaths that varied by country. The second wave of the COVID-19 pandemic has breached the borders of Europe. Public health surveillance is necessary to inform policy and guide leaders. OBJECTIVE: This study aimed to provide advanced surveillance metrics for COVID-19 transmission that account for weekly shifts in the pandemic, speed, acceleration, jerk, and persistence, to better understand countries at risk for explosive growth and those that are managing the pandemic effectively. METHODS: We performed a longitudinal trend analysis and extracted 62 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in Europe as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: New COVID-19 cases slightly decreased from 158,741 (week 1, January 4-10, 2021) to 152,064 (week 2, January 11-17, 2021), and cumulative cases increased from 22,507,271 (week 1) to 23,890,761 (week 2), with a weekly increase of 1,383,490 between January 10 and January 17. France, Germany, Italy, Spain, and the United Kingdom had the largest 7-day moving averages for new cases during week 1. During week 2, the 7-day moving average for France and Spain increased. From week 1 to week 2, the speed decreased (37.72 to 33.02 per 100,000), acceleration decreased (0.39 to -0.16 per 100,000), and jerk increased (-1.30 to 1.37 per 100,000). CONCLUSIONS: The United Kingdom, Spain, and Portugal, in particular, are at risk for a rapid expansion in COVID-19 transmission. An examination of the European region suggests that there was a decrease in the COVID-19 caseload between January 4 and January 17, 2021. Unfortunately, the rates of jerk, which were negative for Europe at the beginning of the month, reversed course and became positive, despite decreases in speed and acceleration. Finally, the 7-day persistence rate was higher during week 2 than during week 1. These measures indicate that the second wave of the pandemic may be subsiding, but some countries remain at risk for new outbreaks and increased transmission in the absence of rapid policy responses.


Subject(s)
COVID-19/epidemiology , Public Health Surveillance , Europe/epidemiology , Humans , Longitudinal Studies
11.
JMIR Public Health Surveill ; 7(4): e26042, 2021 04 22.
Article in English | MEDLINE | ID: mdl-33783360

ABSTRACT

BACKGROUND: Public mass shootings are a significant public health problem that require ongoing systematic surveillance to test and inform policies that combat gun injuries. Although there is widespread agreement that something needs to be done to stop public mass shootings, opinions on exactly which policies that entails vary, such as the prohibition of assault weapons and large-capacity magazines. OBJECTIVE: The aim of this study was to determine if the Federal Assault Weapons Ban (FAWB) (1994-2004) reduced the number of public mass shootings while it was in place. METHODS: We extracted public mass shooting surveillance data from the Violence Project that matched our inclusion criteria of 4 or more fatalities in a public space during a single event. We performed regression discontinuity analysis, taking advantage of the imposition of the FAWB, which included a prohibition on large-capacity magazines in addition to assault weapons. We estimated a regression model of the 5-year moving average number of public mass shootings per year for the period of 1966 to 2019 controlling for population growth and homicides in general, introduced regression discontinuities in the intercept and a time trend for years coincident with the federal legislation (ie, 1994-2004), and also allowed for a differential effect of the homicide rate during this period. We introduced a second set of trend and intercept discontinuities for post-FAWB years to capture the effects of termination of the policy. We used the regression results to predict what would have happened from 1995 to 2019 had there been no FAWB and also to project what would have happened from 2005 onward had it remained in place. RESULTS: The FAWB resulted in a significant decrease in public mass shootings, number of gun deaths, and number of gun injuries. We estimate that the FAWB prevented 11 public mass shootings during the decade the ban was in place. A continuation of the FAWB would have prevented 30 public mass shootings that killed 339 people and injured an additional 1139 people. CONCLUSIONS: This study demonstrates the utility of public health surveillance on gun violence. Surveillance informs policy on whether a ban on assault weapons and large-capacity magazines reduces public mass shootings. As society searches for effective policies to prevent the next mass shooting, we must consider the overwhelming evidence that bans on assault weapons and/or large-capacity magazines work.


Subject(s)
Firearms/legislation & jurisprudence , Mass Casualty Incidents/prevention & control , Policy , Public Health Surveillance , Wounds, Gunshot/prevention & control , Humans , Mass Casualty Incidents/statistics & numerical data , Regression Analysis , United States/epidemiology , Wounds, Gunshot/epidemiology
12.
J Med Internet Res ; 23(2): e26081, 2021 02 09.
Article in English | MEDLINE | ID: mdl-33481757

ABSTRACT

BACKGROUND: The COVID-19 pandemic has had profound and differential impacts on metropolitan areas across the United States and around the world. Within the United States, metropolitan areas that were hit earliest with the pandemic and reacted with scientifically based health policy were able to contain the virus by late spring. For other areas that kept businesses open, the first wave in the United States hit in mid-summer. As the weather turns colder, universities resume classes, and people tire of lockdowns, a second wave is ascending in both metropolitan and rural areas. It becomes more obvious that additional SARS-CoV-2 surveillance is needed at the local level to track recent shifts in the pandemic, rates of increase, and persistence. OBJECTIVE: The goal of this study is to provide advanced surveillance metrics for COVID-19 transmission that account for speed, acceleration, jerk and persistence, and weekly shifts, to better understand and manage risk in metropolitan areas. Existing surveillance measures coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until, and after, an effective vaccine is developed. Here, we provide values for novel indicators to measure COVID-19 transmission at the metropolitan area level. METHODS: Using a longitudinal trend analysis study design, we extracted 260 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in the 25 largest US metropolitan areas as a function of the prior number of cases and weekly shift variables based on a dynamic panel data model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: Minneapolis and Chicago have the greatest average number of daily new positive results per standardized 100,000 population (which we refer to as speed). Extreme behavior in Minneapolis showed an increase in speed from 17 to 30 (67%) in 1 week. The jerk and acceleration calculated for these areas also showed extreme behavior. The dynamic panel data model shows that Minneapolis, Chicago, and Detroit have the largest persistence effects, meaning that new cases pertaining to a specific week are statistically attributable to new cases from the prior week. CONCLUSIONS: Three of the metropolitan areas with historically early and harsh winters have the highest persistence effects out of the top 25 most populous metropolitan areas in the United States at the beginning of their cold weather season. With these persistence effects, and with indoor activities becoming more popular as the weather gets colder, stringent COVID-19 regulations will be more important than ever to flatten the second wave of the pandemic. As colder weather grips more of the nation, southern metropolitan areas may also see large spikes in the number of cases.


Subject(s)
COVID-19/epidemiology , Communicable Disease Control , COVID-19/prevention & control , COVID-19/transmission , Health Policy , Humans , Longitudinal Studies , Models, Statistical , Pandemics , Public Health , Public Health Surveillance , Registries , SARS-CoV-2 , United States/epidemiology
13.
J Med Internet Res ; 23(2): e25799, 2021 02 03.
Article in English | MEDLINE | ID: mdl-33475513

ABSTRACT

BACKGROUND: SARS-CoV-2, the virus that caused the global COVID-19 pandemic, has severely impacted Central Asia; in spring 2020, high numbers of cases and deaths were reported in this region. The second wave of the COVID-19 pandemic is currently breaching the borders of Central Asia. Public health surveillance is necessary to inform policy and guide leaders; however, existing surveillance explains past transmissions while obscuring shifts in the pandemic, increases in infection rates, and the persistence of the transmission of COVID-19. OBJECTIVE: The goal of this study is to provide enhanced surveillance metrics for SARS-CoV-2 transmission that account for weekly shifts in the pandemic, including speed, acceleration, jerk, and persistence, to better understand the risk of explosive growth in each country and which countries are managing the pandemic successfully. METHODS: Using a longitudinal trend analysis study design, we extracted 60 days of COVID-19-related data from public health registries. We used an empirical difference equation to measure the daily number of cases in the Central Asia region as a function of the prior number of cases, level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: COVID-19 transmission rates were tracked for the weeks of September 30 to October 6 and October 7-13, 2020, in Central Asia. The region averaged 11,730 new cases per day for the first week and 14,514 for the second week. Infection rates increased across the region from 4.74 per 100,000 persons to 5.66. Russia and Turkey had the highest 7-day moving averages in the region, with 9836 and 1469, respectively, for the week of October 6 and 12,501 and 1603, respectively, for the week of October 13. Russia has the fourth highest speed in the region and continues to have positive acceleration, driving the negative trend for the entire region as the largest country by population. Armenia is experiencing explosive growth of COVID-19; its infection rate of 13.73 for the week of October 6 quickly jumped to 25.19, the highest in the region, the following week. The region overall is experiencing increases in its 7-day moving average of new cases, infection, rate, and speed, with continued positive acceleration and no sign of a reversal in sight. CONCLUSIONS: The rapidly evolving COVID-19 pandemic requires novel dynamic surveillance metrics in addition to static metrics to effectively analyze the pandemic trajectory and control spread. Policy makers need to know the magnitude of transmission rates, how quickly they are accelerating, and how previous cases are impacting current caseload due to a lag effect. These metrics applied to Central Asia suggest that the region is trending negatively, primarily due to minimal restrictions in Russia.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Administrative Personnel , Armenia/epidemiology , Asia, Central/epidemiology , Azerbaijan/epidemiology , Benchmarking , Cyprus/epidemiology , Denmark/epidemiology , Food Insecurity , Georgia (Republic)/epidemiology , Gibraltar/epidemiology , Humans , Kosovo/epidemiology , Longitudinal Studies , Pandemics/prevention & control , Public Health , Public Health Surveillance/methods , Registries , Republic of North Macedonia/epidemiology , Russia/epidemiology , SARS-CoV-2 , Turkey/epidemiology , Water Insecurity
14.
J Med Internet Res ; 23(2): e25454, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33464207

ABSTRACT

BACKGROUND: The COVID-19 pandemic has had a profound global impact on governments, health care systems, economies, and populations around the world. Within the East Asia and Pacific region, some countries have mitigated the spread of the novel coronavirus effectively and largely avoided severe negative consequences, while others still struggle with containment. As the second wave reaches East Asia and the Pacific, it becomes more evident that additional SARS-CoV-2 surveillance is needed to track recent shifts, rates of increase, and persistence associated with the pandemic. OBJECTIVE: The goal of this study is to provide advanced surveillance metrics for COVID-19 transmission that account for speed, acceleration, jerk, persistence, and weekly shifts, to better understand country risk for explosive growth and those countries who are managing the pandemic successfully. Existing surveillance coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until an effective vaccine is developed. We provide novel indicators to measure disease transmission. METHODS: Using a longitudinal trend analysis study design, we extracted 330 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in East Asia and the Pacific as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: The standard surveillance metrics for Indonesia, the Philippines, and Myanmar were concerning as they had the largest new caseloads at 4301, 2588, and 1387, respectively. When looking at the acceleration of new COVID-19 infections, we found that French Polynesia, Malaysia, and the Philippines had rates at 3.17, 0.22, and 0.06 per 100,000. These three countries also ranked highest in terms of jerk at 15.45, 0.10, and 0.04, respectively. CONCLUSIONS: Two of the most populous countries in East Asia and the Pacific, Indonesia and the Philippines, have alarming surveillance metrics. These two countries rank highest in new infections in the region. The highest rates of speed, acceleration, and positive upwards jerk belong to French Polynesia, Malaysia, and the Philippines, and may result in explosive growth. While all countries in East Asia and the Pacific need to be cautious about reopening their countries since outbreaks are likely to occur in the second wave of COVID-19, the country of greatest concern is the Philippines. Based on standard and enhanced surveillance, the Philippines has not gained control of the COVID-19 epidemic, which is particularly troubling because the country ranks 4th in population in the region. Without extreme and rigid social distancing, quarantines, hygiene, and masking to reverse trends, the Philippines will remain on the global top 5 list of worst COVID-19 outbreaks resulting in high morbidity and mortality. The second wave will only exacerbate existing conditions and increase COVID-19 transmissions.


Subject(s)
COVID-19/epidemiology , Asia, Southeastern/epidemiology , Australasia/epidemiology , COVID-19/transmission , Asia, Eastern/epidemiology , Health Policy , Humans , Indonesia/epidemiology , Longitudinal Studies , Malaysia/epidemiology , Pandemics , Philippines/epidemiology , Polynesia/epidemiology , Public Health , Public Health Surveillance , Registries , SARS-CoV-2
15.
J Med Internet Res ; 23(1): e25830, 2021 01 15.
Article in English | MEDLINE | ID: mdl-33302252

ABSTRACT

BACKGROUND: The COVID-19 pandemic has disrupted the lives of millions and forced countries to devise public health policies to reduce the pace of transmission. In the Middle East and North Africa (MENA), falling oil prices, disparities in wealth and public health infrastructure, and large refugee populations have significantly increased the disease burden of COVID-19. In light of these exacerbating factors, public health surveillance is particularly necessary to help leaders understand and implement effective disease control policies to reduce SARS-CoV-2 persistence and transmission. OBJECTIVE: The goal of this study is to provide advanced surveillance metrics, in combination with traditional surveillance, for COVID-19 transmission that account for weekly shifts in the pandemic speed, acceleration, jerk, and persistence to better understand a country's risk for explosive growth and to better inform those who are managing the pandemic. Existing surveillance coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until an effective vaccine is developed. METHODS: Using a longitudinal trend analysis study design, we extracted 30 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in MENA as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel data model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: The regression Wald statistic was significant (χ25=859.5, P<.001). The Sargan test was not significant, failing to reject the validity of overidentifying restrictions (χ2294=16, P=.99). Countries with the highest cumulative caseload of the novel coronavirus include Iran, Iraq, Saudi Arabia, and Israel with 530,380, 426,634, 342,202, and 303,109 cases, respectively. Many of the smaller countries in MENA have higher infection rates than those countries with the highest caseloads. Oman has 33.3 new infections per 100,000 population while Bahrain has 12.1, Libya has 14, and Lebanon has 14.6 per 100,000 people. In order of largest to smallest number of cumulative deaths since January 2020, Iran, Iraq, Egypt, and Saudi Arabia have 30,375, 10,254, 6120, and 5185, respectively. Israel, Bahrain, Lebanon, and Oman had the highest rates of COVID-19 persistence, which is the number of new infections statistically related to new infections in the prior week. Bahrain had positive speed, acceleration, and jerk, signaling the potential for explosive growth. CONCLUSIONS: Static and dynamic public health surveillance metrics provide a more complete picture of pandemic progression across countries in MENA. Static measures capture data at a given point in time such as infection rates and death rates. By including speed, acceleration, jerk, and 7-day persistence, public health officials may design policies with an eye to the future. Iran, Iraq, Saudi Arabia, and Israel all demonstrated the highest rate of infections, acceleration, jerk, and 7-day persistence, prompting public health leaders to increase prevention efforts.


Subject(s)
COVID-19/epidemiology , Africa, Northern/epidemiology , Humans , Longitudinal Studies , Middle East/epidemiology , Pandemics , Public Health Surveillance/methods , SARS-CoV-2/isolation & purification
16.
J Med Internet Res ; 22(11): e24248, 2020 11 19.
Article in English | MEDLINE | ID: mdl-33211026

ABSTRACT

BACKGROUND: Since the novel coronavirus emerged in late 2019, the scientific and public health community around the world have sought to better understand, surveil, treat, and prevent the disease, COVID-19. In sub-Saharan Africa (SSA), many countries responded aggressively and decisively with lockdown measures and border closures. Such actions may have helped prevent large outbreaks throughout much of the region, though there is substantial variation in caseloads and mortality between nations. Additionally, the health system infrastructure remains a concern throughout much of SSA, and the lockdown measures threaten to increase poverty and food insecurity for the subcontinent's poorest residents. The lack of sufficient testing, asymptomatic infections, and poor reporting practices in many countries limit our understanding of the virus's impact, creating a need for better and more accurate surveillance metrics that account for underreporting and data contamination. OBJECTIVE: The goal of this study is to improve infectious disease surveillance by complementing standardized metrics with new and decomposable surveillance metrics of COVID-19 that overcome data limitations and contamination inherent in public health surveillance systems. In addition to prevalence of observed daily and cumulative testing, testing positivity rates, morbidity, and mortality, we derived COVID-19 transmission in terms of speed, acceleration or deceleration, change in acceleration or deceleration (jerk), and 7-day transmission rate persistence, which explains where and how rapidly COVID-19 is transmitting and quantifies shifts in the rate of acceleration or deceleration to inform policies to mitigate and prevent COVID-19 and food insecurity in SSA. METHODS: We extracted 60 days of COVID-19 data from public health registries and employed an empirical difference equation to measure daily case numbers in 47 sub-Saharan countries as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: Kenya, Ghana, Nigeria, Ethiopia, and South Africa have the most observed cases of COVID-19, and the Seychelles, Eritrea, Mauritius, Comoros, and Burundi have the fewest. In contrast, the speed, acceleration, jerk, and 7-day persistence indicate rates of COVID-19 transmissions differ from observed cases. In September 2020, Cape Verde, Namibia, Eswatini, and South Africa had the highest speed of COVID-19 transmissions at 13.1, 7.1, 3.6, and 3 infections per 100,0000, respectively; Zimbabwe had an acceleration rate of transmission, while Zambia had the largest rate of deceleration this week compared to last week, referred to as a jerk. Finally, the 7-day persistence rate indicates the number of cases on September 15, 2020, which are a function of new infections from September 8, 2020, decreased in South Africa from 216.7 to 173.2 and Ethiopia from 136.7 to 106.3 per 100,000. The statistical approach was validated based on the regression results; they determined recent changes in the pattern of infection, and during the weeks of September 1-8 and September 9-15, there were substantial country differences in the evolution of the SSA pandemic. This change represents a decrease in the transmission model R value for that week and is consistent with a de-escalation in the pandemic for the sub-Saharan African continent in general. CONCLUSIONS: Standard surveillance metrics such as daily observed new COVID-19 cases or deaths are necessary but insufficient to mitigate and prevent COVID-19 transmission. Public health leaders also need to know where COVID-19 transmission rates are accelerating or decelerating, whether those rates increase or decrease over short time frames because the pandemic can quickly escalate, and how many cases today are a function of new infections 7 days ago. Even though SSA is home to some of the poorest countries in the world, development and population size are not necessarily predictive of COVID-19 transmission, meaning higher income countries like the United States can learn from African countries on how best to implement mitigation and prevention efforts. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/21955.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Health Policy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Public Health Surveillance , Africa South of the Sahara/epidemiology , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/virology , Female , Humans , Male , Models, Biological , Pandemics , Pneumonia, Viral/virology , Registries , SARS-CoV-2
17.
J Med Internet Res ; 22(12): e24286, 2020 12 03.
Article in English | MEDLINE | ID: mdl-33216726

ABSTRACT

BACKGROUND: The emergence of SARS-CoV-2, the virus that causes COVID-19, has led to a global pandemic. The United States has been severely affected, accounting for the most COVID-19 cases and deaths worldwide. Without a coordinated national public health plan informed by surveillance with actionable metrics, the United States has been ineffective at preventing and mitigating the escalating COVID-19 pandemic. Existing surveillance has incomplete ascertainment and is limited by the use of standard surveillance metrics. Although many COVID-19 data sources track infection rates, informing prevention requires capturing the relevant dynamics of the pandemic. OBJECTIVE: The aim of this study is to develop dynamic metrics for public health surveillance that can inform worldwide COVID-19 prevention efforts. Advanced surveillance techniques are essential to inform public health decision making and to identify where and when corrective action is required to prevent outbreaks. METHODS: Using a longitudinal trend analysis study design, we extracted COVID-19 data from global public health registries. We used an empirical difference equation to measure daily case numbers for our use case in 50 US states and the District of Colombia as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: Examination of the United States and state data demonstrated that most US states are experiencing outbreaks as measured by these new metrics of speed, acceleration, jerk, and persistence. Larger US states have high COVID-19 caseloads as a function of population size, density, and deficits in adherence to public health guidelines early in the epidemic, and other states have alarming rates of speed, acceleration, jerk, and 7-day persistence in novel infections. North and South Dakota have had the highest rates of COVID-19 transmission combined with positive acceleration, jerk, and 7-day persistence. Wisconsin and Illinois also have alarming indicators and already lead the nation in daily new COVID-19 infections. As the United States enters its third wave of COVID-19, all 50 states and the District of Colombia have positive rates of speed between 7.58 (Hawaii) and 175.01 (North Dakota), and persistence, ranging from 4.44 (Vermont) to 195.35 (North Dakota) new infections per 100,000 people. CONCLUSIONS: Standard surveillance techniques such as daily and cumulative infections and deaths are helpful but only provide a static view of what has already occurred in the pandemic and are less helpful in prevention. Public health policy that is informed by dynamic surveillance can shift the country from reacting to COVID-19 transmissions to being proactive and taking corrective action when indicators of speed, acceleration, jerk, and persistence remain positive week over week. Implicit within our dynamic surveillance is an early warning system that indicates when there is problematic growth in COVID-19 transmissions as well as signals when growth will become explosive without action. A public health approach that focuses on prevention can prevent major outbreaks in addition to endorsing effective public health policies. Moreover, subnational analyses on the dynamics of the pandemic allow us to zero in on where transmissions are increasing, meaning corrective action can be applied with precision in problematic areas. Dynamic public health surveillance can inform specific geographies where quarantines are necessary while preserving the economy in other US areas.


Subject(s)
COVID-19/prevention & control , COVID-19/transmission , Public Health Surveillance , COVID-19/epidemiology , COVID-19/mortality , Humans , Longitudinal Studies , Pandemics/prevention & control , Pandemics/statistics & numerical data , Public Health , Registries , SARS-CoV-2 , United States/epidemiology
18.
J Med Internet Res ; 22(10): e21955, 2020 10 05.
Article in English | MEDLINE | ID: mdl-32924962

ABSTRACT

BACKGROUND: The Great COVID-19 Shutdown aimed to eliminate or slow the spread of SARS-CoV-2, the virus that causes COVID-19. The United States has no national policy, leaving states to independently implement public health guidelines that are predicated on a sustained decline in COVID-19 cases. Operationalization of "sustained decline" varies by state and county. Existing models of COVID-19 transmission rely on parameters such as case estimates or R0 and are dependent on intensive data collection efforts. Static statistical models do not capture all of the relevant dynamics required to measure sustained declines. Moreover, existing COVID-19 models use data that are subject to significant measurement error and contamination. OBJECTIVE: This study will generate novel metrics of speed, acceleration, jerk, and 7-day lag in the speed of COVID-19 transmission using state government tallies of SARS-CoV-2 infections, including state-level dynamics of SARS-CoV-2 infections. This study provides the prototype for a global surveillance system to inform public health practice, including novel standardized metrics of COVID-19 transmission, for use in combination with traditional surveillance tools. METHODS: Dynamic panel data models were estimated with the Arellano-Bond estimator using the generalized method of moments. This statistical technique allows for the control of a variety of deficiencies in the existing data. Tests of the validity of the model and statistical techniques were applied. RESULTS: The statistical approach was validated based on the regression results, which determined recent changes in the pattern of infection. During the weeks of August 17-23 and August 24-30, 2020, there were substantial regional differences in the evolution of the US pandemic. Census regions 1 and 2 were relatively quiet with a small but significant persistence effect that remained relatively unchanged from the prior 2 weeks. Census region 3 was sensitive to the number of tests administered, with a high constant rate of cases. A weekly special analysis showed that these results were driven by states with a high number of positive test reports from universities. Census region 4 had a high constant number of cases and a significantly increased persistence effect during the week of August 24-30. This change represents an increase in the transmission model R value for that week and is consistent with a re-emergence of the pandemic. CONCLUSIONS: Reopening the United States comes with three certainties: (1) the "social" end of the pandemic and reopening are going to occur before the "medical" end even while the pandemic is growing. We need improved standardized surveillance techniques to inform leaders when it is safe to open sections of the country; (2) varying public health policies and guidelines unnecessarily result in varying degrees of transmission and outbreaks; and (3) even those states most successful in containing the pandemic continue to see a small but constant stream of new cases daily.


Subject(s)
Communicable Disease Control/legislation & jurisprudence , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Health Policy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Public Health Informatics/methods , Betacoronavirus , COVID-19 , Communicable Disease Control/methods , Humans , Models, Statistical , Pandemics , Public Health , Reference Standards , Regression Analysis , SARS-CoV-2 , United States
19.
Front Physiol ; 7: 65, 2016.
Article in English | MEDLINE | ID: mdl-26973533

ABSTRACT

Transient receptor potential vanilloid receptor 4 (TRPV4) is a calcium-permeable non-selective cation channel implicated in numerous physiological and pathological functions. This study aimed to investigate the effect of TRPV4 activation on respiration and to explore the potential involvement of bronchopulmonary sensory neurons. Potent TRPV4 agonist GSK1016790A was injected into right atrium in anesthetized spontaneously breathing rats and the changes in breathing were measured. Patch-clamp recording was performed to investigate the effect of GSK1016790A or another TRPV4 activator 4α-PDD on cultured rat vagal bronchopulmonary sensory neurons. Immunohistochemistry was carried out to determine the TRPV4-expressing cells in lung slices obtained from TRPV4-EGFP mice. Our results showed, that right-atrial injection of GSK1016790A evoked a slow-developing, long-lasting rapid shallow breathing in anesthetized rats. Activation of TRPV4 also significantly potentiated capsaicin-evoked chemoreflex responses. The alteration in ventilation induced by GSK1016790A was abolished by cutting or perineural capsaicin treatment of both vagi, indicating the involvement of bronchopulmonary afferent neurons. The stimulating and sensitizing effects of GSK1016790A were abolished by a selective TRPV4 antagonist GSK2193874 and also by inhibiting cyclooxygenase with indomethacin. Surprising, GSK1016790A or 4α-PDD did not activate isolated bronchopulmonary sensory neurons, nor did they modulate capsaicin-induced inward currents in these neurons. Furthermore, TRPV4 expression was found in alveolar macrophages, alveolar epithelial, and vascular endothelial cells. Collectively, our results suggest that GSK1016790A regulates the respiration through an indirect activation of bronchopulmonary sensory neurons, likely via its stimulation of other TRPV4-expressing cells in the lungs and airways.

20.
J Virol ; 89(15): 7465-77, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25948750

ABSTRACT

UNLABELLED: As a herpesvirus, Epstein-Barr virus (EBV) establishes a latent infection that can periodically undergo reactivation, resulting in lytic replication and the production of new infectious virus. Latent membrane protein-1 (LMP1), the principal viral oncoprotein, is a latency-associated protein implicated in regulating viral reactivation and the maintenance of latency. We recently found that LMP1 hijacks the SUMO-conjugating enzyme Ubc9 via its C-terminal activating region-3 (CTAR3) and induces the sumoylation of cellular proteins. Because protein sumoylation can promote transcriptional repression, we hypothesized that LMP1-induced protein sumoylation induces the repression of EBV lytic promoters and helps maintain the viral genome in its latent state. We now show that with inhibition of LMP1-induced protein sumoylation, the latent state becomes less stable or leakier in EBV-transformed lymphoblastoid cell lines. The cells are also more sensitive to viral reactivation induced by irradiation, which results in the increased production and release of infectious virus, as well as increased susceptibility to ganciclovir treatment. We have identified a target of LMP1-mediated sumoylation that contributes to the maintenance of latency in this context: KRAB-associated protein-1 (KAP1). LMP1 CTAR3-mediated sumoylation regulates the function of KAP1. KAP1 also binds to EBV OriLyt and immediate early promoters in a CTAR3-dependent manner, and inhibition of sumoylation processes abrogates the binding of KAP1 to these promoters. These data provide an additional line of evidence that supports our findings that CTAR3 is a distinct functioning regulatory region of LMP1 and confirm that LMP1-induced sumoylation may help stabilize the maintenance of EBV latency. IMPORTANCE: Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) plays an important role in the maintenance of viral latency. Previously, we documented that LMP1 targets cellular proteins to be modified by a ubiquitin-like protein (SUMO). We have now identified a function for this LMP1-induced modification of cellular proteins in the maintenance of EBV latency. Because latently infected cells have to undergo viral reactivation in order to be vulnerable to antiviral drugs, these findings identify a new way to increase the rate of EBV reactivation, which increases cell susceptibility to antiviral therapies.


Subject(s)
Epstein-Barr Virus Infections/metabolism , Herpesvirus 4, Human/physiology , Repressor Proteins/metabolism , Viral Matrix Proteins/metabolism , Virus Latency , Cell Line , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Infections/virology , Gene Expression Regulation, Viral , Herpesvirus 4, Human/genetics , Humans , Promoter Regions, Genetic , Protein Binding , Repressor Proteins/genetics , Sumoylation , Tripartite Motif-Containing Protein 28 , Viral Matrix Proteins/genetics
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