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2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334252

ABSTRACT

In a paper recently published in  Nature Medicine , Fukumoto et al. tried to assess the government-led school closure policy during the early phase of the COVID-19 pandemic in Japan. They compared the reported incidence rates between municipalities that had and had not implemented school closure in selected periods from March–May 2020, where they matched for various potential confounders, and claimed that there was no causal effect on the incidence rates of COVID-19. However, the effective sample size (ESS) of their dataset had been substantially reduced in the process of matching due to imbalanced covariates between the treatment (i.e. with closure) and control (without closure) municipalities, which led to the wide uncertainty in the estimates. Despite the study title starting with "No causal effect of school closures", their results are insufficient to exclude the possibility of a strong mitigating effect of school closure on incidence of COVID-19. In this replication/reanalysis study, we showed that the confidence intervals of the effect estimates from Fukumoto et al. included a 100% relative reduction in COVID-19 incidence. Simulations of a hypothetical 50% or 80% mitigating effect hardly yielded statistical significance with the same study design and sample size. We also showed that matching of variables that had large influence on propensity scores (e.g. prefecture dummy variables) may have been incomplete.

3.
Elife ; 112022 Feb 09.
Article in English | MEDLINE | ID: covidwho-1742929

ABSTRACT

The distribution of the generation time (the interval between individuals becoming infected and transmitting the virus) characterises changes in the transmission risk during SARS-CoV-2 infections. Inferring the generation time distribution is essential to plan and assess public health measures. We previously developed a mechanistic approach for estimating the generation time, which provided an improved fit to data from the early months of the COVID-19 pandemic (December 2019-March 2020) compared to existing models (Hart et al., 2021). However, few estimates of the generation time exist based on data from later in the pandemic. Here, using data from a household study conducted from March to November 2020 in the UK, we provide updated estimates of the generation time. We considered both a commonly used approach in which the transmission risk is assumed to be independent of when symptoms develop, and our mechanistic model in which transmission and symptoms are linked explicitly. Assuming independent transmission and symptoms, we estimated a mean generation time (4.2 days, 95% credible interval 3.3-5.3 days) similar to previous estimates from other countries, but with a higher standard deviation (4.9 days, 3.0-8.3 days). Using our mechanistic approach, we estimated a longer mean generation time (5.9 days, 5.2-7.0 days) and a similar standard deviation (4.8 days, 4.0-6.3 days). As well as estimating the generation time using data from the entire study period, we also considered whether the generation time varied temporally. Both models suggest a shorter mean generation time in September-November 2020 compared to earlier months. Since the SARS-CoV-2 generation time appears to be changing, further data collection and analysis is necessary to continue to monitor ongoing transmission and inform future public health policy decisions.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Humans , Pandemics , Public Health , United Kingdom/epidemiology
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322412

ABSTRACT

Introduction: Patients with severe coronavirus disease 2019 (COVID-19) pneumonia often have the complications of coagulopathy and thrombotic phenomena, which lead to high mortality. Whether administering systematic anticoagulant therapy is beneficial remains unclear. We report our experience using systemic anticoagulation with unfractionated heparin to treat severe COVID-19. Methods: : We conducted a retrospective historical control study of severe COVID-19 patients requiring mechanical ventilation who received prophylactic-dose anticoagulation (April 1–May 20) or therapeutic-dose anticoagulation (May 21–August 20) in the intensive care unit (ICU) of the tertiary emergency critical care medical center in Japan. The primary endpoints were in-hospital mortality and anticoagulation therapy-related adverse events. The secondary endpoints included the administration of veno-venous extracorporeal membrane oxygenation (ECMO), ventilator-free days (VFD), ICU-free days, and the development of multiple organ dysfunction syndrome. Results: : Twenty-one patients were in the prophylactic-dose group and 26 patients were in the therapeutic-dose group. Background characteristics between the groups were not significantly different, although the therapeutic-dose group had a lower in-hospital mortality rate [0 (0.0%) patients vs. 4 (19.0%) patients;p = 0.063] and significantly longer ICU-free days (median [interquartile range (IQR)]: 15 days [13-18] vs. 5 days [0-13];p = 0.014). Hemorrhagic events did not occur during the study period. Compared to the prophylactic-dose group, the therapeutic-dose group tended to have a longer VFD, were not treated with ECMO, and did not experience multiple organ dysfunction syndrome;however, the difference was not statistically significant. Conclusions: : Therapeutic-dose anticoagulation may be beneficial for patients with severe COVID-19 pneumonia requiring mechanical ventilation.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310014

ABSTRACT

Schools can play a central role in driving infectious disease transmission. Strategies for safe operation of schools during pandemics therefore need to carefully consider both the efficiency of measures for infection control and the impact on children through lost face-to face schooling time. Heterogeneous social contact patterns associated with the social structures of schools (i.e. classes/grades) are likely to influence the within-school transmission dynamics;however, empirical evidence on the fine-scale transmission patterns between students has been limited. Using a mathematical model, we analysed a large-scale dataset of seasonal influenza outbreaks in Matsumoto city, Japan to infer social interactions within and between classes/grades from observed transmission patterns. The overall within-school reproduction number, which determines the initial growth of cases and the risk of sustained transmission, was only minimally associated with class sizes and the number of classes per grade. We then used these patterns in a model parameterised separately to COVID-19 and pandemic influenza, and simulated school outbreaks under multiple strategies for minimising the risk of within-school transmission. Simulations suggested that with such transmission patterns, interventions changing class structures (e.g. reduced class sizes) may not be effective in reducing the risk of major school outbreaks upon introduction of a case and that other precautionary measures (e.g. screening and isolation) need to be employed. Class-level closures in response to detection of a case were suggested to be effective in reducing the size of an outbreak when regular screening tests for students are not available.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310013

ABSTRACT

Introduction: Contact tracing has the potential to control outbreaks without the need for stringent physical distancing policies, e.g. civil lockdowns. Unlike forward contact tracing, backward contact tracing identifies the source of newly detected cases. This approach is particularly valuable when there is high individual-level variation in the number of secondary transmissions (overdispersion). Methods: By using a simple branching process model, we explored the potential of combining backward contact tracing with more conventional forward contact tracing for control of COVID-19. We estimated the typical size of clusters that can be reached by backward tracing and simulated the incremental effectiveness of combining backward tracing with conventional forward tracing. Results: Across ranges of parameter values consistent with dynamics of SARS-CoV-2, backward tracing is expected to identify a primary case generating 3-10 times more infections than a randomly chosen case, typically increasing the proportion of subsequent cases averted by a factor of 2-3. The estimated number of cases averted by backward tracing became greater with a higher degree of overdispersion. Conclusion: Backward contact tracing can be an effective tool for outbreak control, especially in the presence of overdispersion as is observed with SARS-CoV-2.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310012

ABSTRACT

Background: A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic reproduction number R 0 , variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others. Methods: We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution. Results: Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of R 0 (2-3), the overdispersion parameter k of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1;95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for R 0 and k (95% CrIs: R 0 1.4-12;k 0.04-0.2);however, the upper bound of R 0 was not well informed by the model and data, which did not notably differ from that of the prior distribution. Conclusions: Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294656

ABSTRACT

In a paper recently published in Nature Medicine , Fukumoto et al. tried to assess the government-led school closure policy during the early phase of the COVID-19 pandemic in Japan. They compared the reported incidence rates between municipalities that had and had not implemented school closure in selected periods from March–May 2020, where they rigorously matched for potential confounders, and claimed that they found no causal effect on the incidence rates of COVID-19. However, the effective sample size (ESS) of their dataset had been substantially reduced in the process of matching due to imbalanced covariates between the treatment (i.e. with closure) and control (without) municipalities, which led to the wide uncertainty in the estimates. That said, the study title "No causal effect…" is a rather strong statement because the results are also consistent with a strong mitigating effect of school closure on incidence of COVID-19.

11.
Front Cardiovasc Med ; 8: 767074, 2021.
Article in English | MEDLINE | ID: covidwho-1555880

ABSTRACT

Background: Thrombosis is a characteristic complication in coronavirus disease 2019 (COVID-19). Since coagulopathy has been observed over the entire clinical course, thrombosis might be a clue to understanding the specific pathology in COVID-19. Currently, there is limited epidemiological data of COVID-19-associated thrombosis in the Japanese population and none regarding variant strains of SARS-CoV-2. Here, we elucidate the risk factors and the pattern of thrombosis in COVID-19 patients. Methods: The patients consecutively admitted to Tokyo Medical and Dental University Hospital with COVID-19 were retrospectively analyzed. SARS-CoV-2 variants of concern/interest (VOC/VOI) carrying the spike protein mutants E484K, N501Y, or L452R were identified by PCR-based analysis. All thrombotic events were diagnosed by clinical symptoms, ultrasonography, and/or radiological tests. Results: Among the 516 patients, 32 patients experienced 42 thromboembolic events. Advanced age, severe respiratory conditions, and several abnormal laboratory markers were associated with the development of thrombosis. While thrombotic events occurred in 13% of the patients with a severe respiratory condition, those events still occurred in 2.5% of the patients who did not require oxygen therapy. Elevated D-dimer and ferritin levels on admission were independent risk factors of thrombosis (adjusted odds ratio 9.39 and 3.11, 95% confidence interval 2.08-42.3, and 1.06-9.17, respectively). Of the thrombotic events, 22 were venous, whereas 20 were arterial. While patients with thrombosis received anticoagulation and antiinflammatory therapies with a higher proportion, the mortality rate, organ dysfunctions, and bleeding complications in these patients were higher than those without thrombosis. The incidence of thrombosis in COVID-19 became less frequent over time, such as during the replacement of the earlier strains of SARS-CoV-2 by VOC/VOI and during increased use of anticoagulatory therapeutics. Conclusion: This study elucidated that elevated D-dimer and ferritin levels are useful biomarkers of thrombosis in COVID-19 patients. The comparable incidence of arterial thrombosis with venous thrombosis and the development of thrombosis in less severe patients required further considerations for the management of Japanese patients with COVID-19. Further studies would be required to identify high-risk populations and establish appropriate interventions for thrombotic complications in COVID-19.

12.
Int J Infect Dis ; 113: 47-54, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1458656

ABSTRACT

OBJECTIVES: The effective reproduction number (Rt) has been critical for assessing the effectiveness of countermeasures during the coronavirus disease 2019 (COVID-19) pandemic. Conventional methods using reported incidences are unable to provide timely Rt data due to the delay from infection to reporting. Our study aimed to develop a framework for predicting Rt in real time, using timely accessible data - i.e. human mobility, temperature, and risk awareness. METHODS: A linear regression model to predict Rt was designed and embedded in the renewal process. Four prefectures of Japan with high incidences in the first wave were selected for model fitting and validation. Predictive performance was assessed by comparing the observed and predicted incidences using cross-validation, and by testing on a separate dataset in two other prefectures with distinct geographical settings from the four studied prefectures. RESULTS: The predicted mean values of Rt and 95% uncertainty intervals followed the overall trends for incidence, while predictive performance was diminished when Rt changed abruptly, potentially due to superspreading events or when stringent countermeasures were implemented. CONCLUSIONS: The described model can potentially be used for monitoring the transmission dynamics of COVID-19 ahead of the formal estimates, subject to delay, providing essential information for timely planning and assessment of countermeasures.


Subject(s)
COVID-19 , Basic Reproduction Number , Humans , Pandemics , SARS-CoV-2 , Temperature
13.
Euro Surveill ; 26(39)2021 09.
Article in English | MEDLINE | ID: covidwho-1448678

ABSTRACT

BackgroundTo mitigate SARS-CoV-2 transmission risks from international air travellers, many countries implemented a combination of up to 14 days of self-quarantine upon arrival plus PCR testing in the early stages of the COVID-19 pandemic in 2020.AimTo assess the effectiveness of quarantine and testing of international travellers to reduce risk of onward SARS-CoV-2 transmission into a destination country in the pre-COVID-19 vaccination era.MethodsWe used a simulation model of air travellers arriving in the United Kingdom from the European Union or the United States, incorporating timing of infection stages while varying quarantine duration and timing and number of PCR tests.ResultsQuarantine upon arrival with a PCR test on day 7 plus a 1-day delay for results can reduce the number of infectious arriving travellers released into the community by a median 94% (95% uncertainty interval (UI): 89-98) compared with a no quarantine/no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median > 99%; 95% UI: 98-100). Even shorter quarantine periods can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (mean incubation period) in quarantine and have at least one negative test before release are highly effective (median reduction 89%; 95% UI: 83-95)).ConclusionThe effect of different screening strategies impacts asymptomatic and symptomatic individuals differently. The choice of an optimal quarantine and testing strategy for unvaccinated air travellers may vary based on the number of possible imported infections relative to domestic incidence.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Vaccines , Humans , Pandemics , Quarantine , United Kingdom/epidemiology
14.
Surg Case Rep ; 7(1): 175, 2021 Aug 04.
Article in English | MEDLINE | ID: covidwho-1341471

ABSTRACT

BACKGROUND: Coagulopathy induced by COVID-19 has received much attention. Arterial and venous thrombosis of multiple organs due to COVID-19-related coagulopathy is associated with a poor outcome. CASE PRESENTATION: A 67-year-female was transferred to our hospital in need of intensive care for severe COVID-19 pneumonia. On day 7 after admission, despite the treatments, her respiratory and hemodynamic status deteriorated. Computed tomography revealed massive ascites and free air as well as wall defects of the transverse colon. An emergency laparotomy was undertaken in the intensive-care unit, and 17 cm of the transverse colon was resected. Histopathological findings revealed two perforation sites of 25 and 7 mm in diameter, necrosis of the intestinal mucosa around the perforation sites, and the microcirculatory thrombosis in the mesentery vessels which was suspected of having been induced by COVID-19-related coagulopathy. CONCLUSIONS: The case highlights the risk of intestinal ischemia and perforation induced by COVID-19 coagulopathy. Physicians treating COVID-19 should recognize the risk and evaluate patients carefully.

15.
Acute Med Surg ; 8(1): e679, 2021.
Article in English | MEDLINE | ID: covidwho-1287317

ABSTRACT

AIM: Patients with severe coronavirus disease 2019 (COVID-19) pneumonia often have complications of coagulopathy and thrombotic phenomena, which lead to high mortality. Whether administering systematic anticoagulant therapy is beneficial remains unclear. We report our experience using systemic anticoagulation with unfractionated heparin to treat severe COVID-19. METHODS: We conducted a retrospective historical control study of severe COVID-19 patients requiring mechanical ventilation who received prophylactic-dose anticoagulation (April 1-May 25) or therapeutic-dose anticoagulation (May 26-August 31) in the intensive care unit (ICU) of a tertiary emergency critical care medical center in Japan. The primary endpoints were in-hospital mortality and anticoagulation therapy-related adverse events. The secondary endpoints included thromboembolic events, administration of venovenous extracorporeal membrane oxygenation (ECMO), ventilator-free days (VFDs), ICU-free days, and the development of multiple organ dysfunction syndrome. RESULTS: A total of 29 and 33 patients were in the prophylactic-dose and therapeutic-dose groups, respectively. Background characteristics between the groups were not significantly different, although the therapeutic-dose group had a significantly lower in-hospital mortality rate [5 (17.2%) patients versus 0 (0.0%) patients; P = 0.033] and longer ICU-free days (median [interquartile range]: 15 days [13-18] versus 5 days [0-13]; P = 0.008). Hemorrhagic-events did not occur during the study period. Compared with the prophylactic-dose group, the therapeutic-dose group tended to have longer VFDs, was not treated with ECMO, and did not experience thromboembolic events and multiple organ dysfunction syndrome; however, the difference was not statistically significant. CONCLUSIONS: Therapeutic-dose anticoagulation may be beneficial for patients with severe COVID-19 pneumonia requiring mechanical ventilation.

16.
R Soc Open Sci ; 8(3): 202169, 2021 Mar 31.
Article in English | MEDLINE | ID: covidwho-1199604

ABSTRACT

An initial set of interventions, including the closure of host and hostess clubs and voluntary limitation of non-household contact, probably greatly contributed to reducing the disease incidence of coronavirus disease (COVID-19) in Japan, but this approach must eventually be replaced by a more sustainable strategy. To characterize such a possible exit strategy from the restrictive guidelines, we quantified the next-generation matrix, accounting for high- and low-risk transmission settings. This matrix was used to project the future incidence in Tokyo and Osaka after the state of emergency is lifted, presenting multiple 'post-emergency' scenarios with different levels of restriction. The effective reproduction numbers (R) for the increasing phase, the transition phase and the state-of-emergency phase in the first wave of the disease were estimated as 1.78 (95% credible interval (CrI): 1.73-1.82), 0.74 (95% CrI: 0.71-0.78) and 0.63 (95% CrI: 0.61-0.65), respectively, in Tokyo and as 1.58 (95% CrI: 1.51-1.64), 1.20 (95% CrI: 1.15-1.25) and 0.48 (95% CrI: 0.44-0.51), respectively, in Osaka. Projections showed that a 50% decrease in the high-risk transmission is required to keep R less than 1 in both locations-a level necessary to maintain control of the epidemic and minimize the risk of resurgence.

17.
Nat Commun ; 12(1): 1942, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-1157906

ABSTRACT

In early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.


Subject(s)
COVID-19/transmission , Family Characteristics , Schools/organization & administration , Adolescent , COVID-19/epidemiology , COVID-19/virology , Child , Child, Preschool , Disease Transmission, Infectious/prevention & control , England/epidemiology , Humans , Pandemics , Risk Assessment , Risk Factors , SARS-CoV-2/isolation & purification , Schools/statistics & numerical data
18.
Wellcome Open Res ; 5: 67, 2020.
Article in English | MEDLINE | ID: covidwho-1024785

ABSTRACT

Background: A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic reproduction number R 0, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others. Methods: We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution. Results: Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of R 0 (2-3), the overdispersion parameter k of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for R 0 and k (95% CrIs: R 0 1.4-12; k 0.04-0.2); however, the upper bound of R 0 was not well informed by the model and data, which did not notably differ from that of the prior distribution. Conclusions: Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.

19.
Proc Natl Acad Sci U S A ; 117(48): 30285-30294, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-920651

ABSTRACT

Sustaining economic activities while curbing the number of new coronavirus disease 2019 (COVID-19) cases until effective vaccines or treatments become available is a major public health and policy challenge. In this paper, we use agent-based simulations of a network-based susceptible-exposed-infectious-recovered (SEIR) model to investigate two network intervention strategies for mitigating the spread of transmission while maintaining economic activities. In the simulations, we assume that people engage in group activities in multiple sectors (e.g., going to work, going to a local grocery store), where they interact with others in the same group and potentially become infected. In the first strategy, each group is divided into two subgroups (e.g., a group of customers can only go to the grocery store in the morning, while another separate group of customers can only go in the afternoon). In the second strategy, we balance the number of group members across different groups within the same sector (e.g., every grocery store has the same number of customers). The simulation results show that the dividing groups strategy substantially reduces transmission, and the joint implementation of the two strategies could effectively bring the spread of transmission under control (i.e., effective reproduction number ≈ 1.0).


Subject(s)
COVID-19/economics , COVID-19/prevention & control , Pandemics/economics , Pandemics/prevention & control , Social Networking , Computer Simulation , Humans , Systems Analysis
20.
Wellcome Open Res ; 5: 239, 2020.
Article in English | MEDLINE | ID: covidwho-914801

ABSTRACT

Introduction: Contact tracing has the potential to control outbreaks without the need for stringent physical distancing policies, e.g. civil lockdowns. Unlike forward contact tracing, backward contact tracing identifies the source of newly detected cases. This approach is particularly valuable when there is high individual-level variation in the number of secondary transmissions (overdispersion). Methods: By using a simple branching process model, we explored the potential of combining backward contact tracing with more conventional forward contact tracing for control of COVID-19. We estimated the typical size of clusters that can be reached by backward tracing and simulated the incremental effectiveness of combining backward tracing with conventional forward tracing. Results: Across ranges of parameter values consistent with dynamics of SARS-CoV-2, backward tracing is expected to identify a primary case generating 3-10 times more infections than average, typically increasing the proportion of subsequent cases averted by a factor of 2-3. The estimated number of cases averted by backward tracing became greater with a higher degree of overdispersion. Conclusion: Backward contact tracing can be an effective tool for outbreak control, especially in the presence of overdispersion as was observed with SARS-CoV-2.

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