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      Is Lockdown Effective in Limiting SARS-CoV-2 Epidemic Progression?—a Cross-Country Comparative Evaluation Using Epidemiokinetic Tools

      , MD, PhD , 1 , 2 , , PharmD, PhD 2 , 3 , , PharmD, PhD 2 , 3

      Journal of General Internal Medicine

      Springer International Publishing

      COVID-19, epidemic, lockdown, modeling, pharmacokinetics, SARS-CoV-2

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          Abstract

          Background

          To date, the risk/benefit balance of lockdown in controlling severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic is controversial.

          Objective

          We aimed to investigate the effectiveness of lockdown on SARS-CoV-2 epidemic progression in nine different countries (New Zealand, France, Spain, Germany, the Netherlands, Italy, the UK, Sweden, and the USA).

          Design

          We conducted a cross-country comparative evaluation using a susceptible-infected-recovered (SIR)-based model completed with pharmacokinetic approaches.

          Main Measures

          The rate of new daily SARS-CoV-2 cases in the nine countries was calculated from the World Health Organization’s published data. Using a SIR-based model, we determined the infection (β) and recovery (γ) rate constants; their corresponding half-lives ( t 1/2β and t 1/2γ); the basic reproduction numbers ( R 0 as β/γ); the rates of susceptible S(t), infected I(t), and recovered R(t) compartments; and the effectiveness of lockdown. Since this approach requires the epidemic termination to build the (I) compartment, we determined S(t) at an early epidemic stage using simple linear regressions.

          Key Results

          In New Zealand, France, Spain, Germany, the Netherlands, Italy, and the UK, early-onset stay-at-home orders and restrictions followed by gradual deconfinement allowed rapid reduction in SARS-CoV-2-infected individuals ( t 1/2β ≤ 14 days) with R 0 ≤ 1.5 and rapid recovery ( t 1/2γ ≤ 18 days). By contrast, in Sweden (no lockdown) and the USA (heterogeneous state-dependent lockdown followed by abrupt deconfinement scenarios), a prolonged plateau of SARS-CoV-2-infected individuals (terminal t 1/2β of 23 and 40 days, respectively) with elevated R 0 (4.9 and 4.4, respectively) and non-ending recovery (terminal t 1/2γ of 112 and 179 days, respectively) was observed.

          Conclusions

          Early-onset lockdown with gradual deconfinement allowed shortening the SARS-CoV-2 epidemic and reducing contaminations. Lockdown should be considered as an effective public health intervention to halt epidemic progression.

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          Most cited references 4

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          Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis

          Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings. Methods We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047. Findings Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] −10·2%, 95% CI −11·5 to −7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; p interaction=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD −14·3%, −15·9 to −10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; p interaction=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD −10·6%, 95% CI −12·5 to −7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings. Interpretation The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance. Funding World Health Organization.
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            Scientific and ethical basis for social-distancing interventions against COVID-19

            On Dec 31, 2019, the WHO China Country Office received notice of a cluster of pneumonia cases of unknown aetiology in the Chinese city of Wuhan, Hubei province. 1 The incidence of coronavirus disease 2019 (COVID-19; caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) has since risen exponentially, now affecting all WHO regions. The number of cases reported to date is likely to represent an underestimation of the true burden as a result of shortcomings in surveillance and diagnostic capacity affecting case ascertainment in both high-resource and low-resource settings. 2 By all scientifically meaningful criteria, the world is undergoing a COVID-19 pandemic. In the absence of any pharmaceutical intervention, the only strategy against COVID-19 is to reduce mixing of susceptible and infectious people through early ascertainment of cases or reduction of contact. In The Lancet Infectious Diseases, Joel Koo and colleagues 3 assessed the potential effect of such social distancing interventions on SARS-CoV-2 spread and COVID-19 burden in Singapore. The context is worthy of study, since Singapore was among the first settings to report imported cases, and has so far succeeded in preventing community spread. During the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak in Singapore, numerous non-pharmaceutical interventions were implemented successfully, including effective triage and infection control measures in health-care settings, isolation and quarantine of patients with SARS and their contacts, and mass screening of school-aged children for febrile illness. 4 Each of these measures represented an escalation of typical public health action. However, the scale and disruptive impact of these interventions were small compared with the measures that have been implemented in China in response to COVID-19, including closure of schools, workplaces, roads, and transit systems; cancellation of public gatherings; mandatory quarantine of uninfected people without known exposure to SARS-CoV-2; and large-scale electronic surveillance.5, 6 Although these actions have been praised by WHO, 5 the possibility of imposing similar measures in other countries raises important questions. Populations for whom social-distancing interventions have been implemented require and deserve assurance that the decision to enact these measures is informed by the best attainable evidence. For a novel pathogen such as SARS-CoV-2, mathematical modelling of transmission under differing scenarios is the only viable and timely method to generate such evidence. Koo and colleagues 3 adapted an existing influenza epidemic simulation model 7 using granular data on the composition and behaviour of the population of Singapore to assess the potential consequences of specific social-distancing interventions on the transmission dynamics of SARS-CoV-2. The authors considered three infectivity scenarios (basic reproduction number [R 0] of 1·5, 2·0, or 2·5) and assumed between 7·5% and 50·0% of infections were asymptomatic. The interventions were quarantine with or without school closure and workplace distancing (whereby 50% of workers telecommute). Although the complexity of the model makes it difficult to understand the impact of each parameter, the primary conclusions were robust to sensitivity analyses. The combined intervention, in which quarantine, school closure, and workplace distancing were implemented, was the most effective: compared with the baseline scenario of no interventions, the combined intervention reduced the estimated median number of infections by 99·3% (IQR 92·6–99·9) when R 0 was 1·5, by 93·0% (81·5–99·7) when R 0 was 2·0, and by 78·2% (59·0–94·4) when R 0 was 2·5. The observation that the greatest reduction in COVID-19 cases was achieved under the combined intervention is not surprising. However, the assessment of the additional benefit of each intervention, when implemented in combination, offers valuable insight. Since each approach individually will result in considerable societal disruption, it is important to understand the extent of intervention needed to reduce transmission and disease burden. New findings emerge daily about transmission routes and the clinical profile of SARS-CoV-2, including the substantially underestimated rate of infection among children. 8 The implications of such findings with regard to the authors' conclusions about school closure remain unclear. Additionally, reproductive number estimates for Singapore are not yet available. The authors estimated that 7·5% of infections are clinically asymptomatic, although data on the proportion of infections that are asymptomatic are scarce; as shown by Koo and colleagues in sensitivity analyses with higher asymptomatic proportions, this value will influence the effectiveness of social-distancing interventions. Additionally, the analysis assumes high compliance of the general population, which is not guaranteed. Although the scientific basis for these interventions might be robust, ethical considerations are multifaceted. 9 Importantly, political leaders must enact quarantine and social-distancing policies that do not bias against any population group. The legacies of social and economic injustices perpetrated in the name of public health have lasting repercussions. 10 Interventions might pose risks of reduced income and even job loss, disproportionately affecting the most disadvantaged populations: policies to lessen such risks are urgently needed. Special attention should be given to protections for vulnerable populations, such as homeless, incarcerated, older, or disabled individuals, and undocumented migrants. Similarly, exceptions might be necessary for certain groups, including people who are reliant on ongoing medical treatment. The effectiveness and societal impact of quarantine and social distancing will depend on the credibility of public health authorities, political leaders, and institutions. It is important that policy makers maintain the public's trust through use of evidence-based interventions and fully transparent, fact-based communication. © 2020 Caia Image/Science Photo Library 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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              Comparison of Estimated Rates of Coronavirus Disease 2019 (COVID-19) in Border Counties in Iowa Without a Stay-at-Home Order and Border Counties in Illinois With a Stay-at-Home Order

              Key Points Question Was the stay-at-home order in Illinois associated with different rates of coronavirus disease 2019 (COVID-19) compared with Iowa, which did not issue a stay-at-home order? Findings This cross-sectional study of border counties in Iowa and Illinois used difference-in-differences design and found an increase in estimated rates of COVID-19 cases per 10 000 residents in the border counties in Iowa compared with the border counties in Illinois after a stay-at-home order was implemented in Illinois but not in Iowa. Meaning The results of this study suggest that issuing a stay-at-home order in Iowa may have helped limit the spread of COVID-19 cases in that state.
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                Author and article information

                Contributors
                bruno.megarbane@lrb.aphp.fr
                Journal
                J Gen Intern Med
                J Gen Intern Med
                Journal of General Internal Medicine
                Springer International Publishing (Cham )
                0884-8734
                1525-1497
                13 January 2021
                : 1-7
                Affiliations
                [1 ]GRID grid.411296.9, ISNI 0000 0000 9725 279X, Department of Medical and Toxicological Critical Care, , Lariboisière Hospital, Federation of Toxicology, APHP, , ; Paris, France
                [2 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, University of Paris, INSERM UMRS-1144, , ; Paris, France
                [3 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, Laboratory of Pharmacokinetics, Faculty of Pharmacy, , ; Paris, France
                Article
                6345
                10.1007/s11606-020-06345-5
                7806254
                33442818
                © Society of General Internal Medicine 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                Categories
                Original Research

                Internal medicine

                covid-19, epidemic, lockdown, modeling, pharmacokinetics, sars-cov-2

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