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Preparing for a Future COVID-19 Wave: Non-Pharmaceutical Interventions in Germany (Scientific Reports)

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A Scientific Reports article, Preparing for a future COVID-19 wave: insights and limitations from a data-driven evaluation of non-pharmaceutical interventions in Germany, by Ashwin Aravindakshan, Jörn Boehnke, Ehsan Gholami and Ashutosh Nayak. The abstract states that the authors measure the impact of non-pharmaceutical interventions on disease spread by exploiting variation in policy measures across the 16 states of Germany, adapting a Susceptible-Exposed-Infected-Recovered model. It states that contact restrictions, closure of educational institutions and retail outlet closures were associated with the sharpest drops in movement, and that contact restrictions appear most effective at lowering COVID-19 cases while border closures appear to have only minimal effects.

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Preparing For A Future Covid 19 Wave Insights And Limitations From A Data Driven Evaluation Of Non Pharmaceutical Interv

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“Preparing for a Future COVID-19 Wave: Non-Pharmaceutical Interventions in Germany (Scientific Reports).” Original at doi.org. Archived at Pandemic Darlings, https://pandemicdarlings.com/source-documents/preparing-for-a-future-covid-19-wave-insights-and-limitations-from-a-data-driven-evaluation-of-non-pharmaceutical-interv/, SHA-256 599d0a4db216db993c2db9593dbfb08e7f22d98282e4c0550fb7f0bde2bf304c.

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                OPEN             Preparing for a future COVID‑19
                                 wave: insights and limitations
                                 from a data‑driven evaluation
                                 of non‑pharmaceutical
                                 interventions in Germany
                                 Ashwin Aravindakshan*, Jörn Boehnke, Ehsan Gholami & Ashutosh Nayak

                                 To contain the COVID-19 pandemic, governments introduced strict Non-Pharmaceutical Interventions
                                 (NPI) that restricted movement, public gatherings, national and international travel, and shut down
                                 large parts of the economy. Yet, the impact of the enforcement and subsequent loosening of these
                                 policies on the spread of COVID-19 is not well understood. Accordingly, we measure the impact of NPIs
                                 on mitigating disease spread by exploiting the spatio-temporal variations in policy measures across
                                 the 16 states of Germany. While this quasi-experiment does not allow for causal identification, each
                                 policy’s effect on reducing disease spread provides meaningful insights. We adapt the Susceptible–
                                 Exposed–Infected–Recovered model for disease propagation to include data on daily confirmed
                                 cases, interstate movement, and social distancing. By combining the model with measures of policy
                                 contributions on mobility reduction, we forecast scenarios for relaxing various types of NPIs. Our
                                 model finds that in Germany policies that mandated contact restrictions (e.g., movement in public
                                 space limited to two persons or people co-living), closure of educational institutions (e.g., schools),
                                 and retail outlet closures are associated with the sharpest drops in movement within and across
                                 states. Contact restrictions appear to be most effective at lowering COVID-19 cases, while border
                                 closures appear to have only minimal effects at mitigating the spread of the disease, even though
                                 cross-border travel might have played a role in seeding the disease in the population. We believe that
                                 a deeper understanding of the policy effects on mitigating the spread of COVID-19 allows a more
                                 accurate forecast of disease spread when NPIs are partially loosened and gives policymakers better
                                 data for making informed decisions.


                                 In response to the COVID-19 pandemic, governments around the world implemented varying degrees of non-
                                 pharmaceutical interventions (NPIs) to control the spread of the ­disease1–5. These policies severely restricted
                                 movement, public gatherings, national and international travel, and shut down large parts of the economy includ-
                                 ing schools and non-essential businesses. Multiple studies have investigated the role that these lockdowns played
                                 in delaying the spread and reducing the severity of the ­pandemic6,7–14. The lockdowns also created tremendous
                                 hardships for individuals and ­businesses15–17. As the spread of COVID-19 decelerated across countries, govern-
                                 ments began relaxing the NPIs to help balance the need for economic security against the risk of growing infec-
                                 tion ­numbers18. Nevertheless, beyond the knowledge of the possibility of a future ­wave19, there is still limited
                                 understanding of the association of loosening different policies with changes in mobility that eventually relate
                                 to the spread of the disease.
                                     In this study, we explore this association by estimating each NPI’s connection to social mobility and the
                                 resulting disease mitigation. The proposed methodology permits the forecasting of disease spread under dif-
                                 ferent policy scenarios of implementation and relaxation by associating a policy with a change in mobility. The
                                 presented model allows policymakers to forecast the impacts of removing different types of restrictions on
                                 mobility and disease mitigation.
                                     Initial analysis of the impact of policy restrictions in China suggests that NPIs that significantly affected
                                 human mobility (e.g., household quarantine) reduced the spread of the ­disease20,21, even more than restrictions


                                 University of California, Davis, Davis, CA, USA. *email: aaravind@ucdavis.edu


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                                            that limited national and international ­travel22. Additionally, simulations of NPIs in ­Wuhan13 show that main-
                                            taining restrictions helped delay the epidemic peak. The results also suggest that an early end to such interven-
                                            tions leads to an earlier secondary peak, which can be flattened by relaxing the social ­mixing13. To the best of
                                            our knowledge no study quantifies the effects of the types and timings of the implementation and relaxation of
                                            government policy interventions in reducing mobility, and in turn decreasing the spread of COVID-19. Our
                                            estimates allow for projections of the impact of easing individual interventions on the spread of the disease. These
                                            projections act as aids for policymakers to determine how lifting certain policies will change social mobility, and
                                            in turn affect the number of new COVID-19 cases.
                                                Using data from the 16 states of Germany, we explore the effectiveness of different NPIs in reducing social
                                            mobility, and in turn affecting the spread of the disease. Because German states enforced and relaxed policies to
                                            varying degrees at different points in time, the variations in implementation allow us to capture the incremental
                                            effectiveness of these policies at reducing social mobility in the general population. It is important to note that
                                            we cannot identify each policy’s causal effect on reducing disease spread. While each German state implemented
                                            their own COVID-19 interventions, the data do not offer sufficient variation in the sequencing of policies to
                                            uniquely identify the effect of each intervention. However, the existing variation allows for a necessary under-
                                            standing of the relative magnitude of each of the interventions and provides meaningful insights of each policy’s
                                            contribution in reducing disease spread.
                                                To determine how policy enforcement impacted mobility and disease spread, we associate the type and
                                            timing of the policy intervention to actual social mobility as recorded in the data released by ­Google23. Next,
                                            using our predictions of social mobility based on the policy interventions, we predict the spread of COVID-19
                                            by modifying the SEIR model presented ­in20 to include social distancing and other forms of mobility data (e.g.,
                                            travel by air, bus, rail, and road). Finally, we project the impact of relaxing a policy on the number of new cases
                                            across Germany and compare how differences in start times for policy relaxations alter the cumulative number
                                            of expected cases over a 90-day time span.
                                                Our findings suggest that not implementing social distancing in Germany is associated with a 24.6-fold (IQR:
                                            20 to 29-fold) increase in cumulative infected case counts as of May 7, 2020. In other words, social distancing
                                            appears to reduce case counts by about 96% (IQR: 95–96.6%). We also found that policies were not equal in their
                                            effectiveness at reducing new cases. Compared to keeping the restrictions in place, the lifting of contact restric-
                                            tions appear to be the most punitive with an associated 150% (IQR: 144–156%) increase in daily case numbers
                                            over a 90-day period. This is followed by the lifting educational facilities closure and the opening of retail outlets
                                            (46.1% IQR: 44.0–48.1%, and 33.9% IQR: 33.0–34.8%), respectively.

                                            Method
                                            In this work, we build an epidemiology model (Susceptible–Exposed–Infectious–Recovered, SEIR) to under-
                                            stand the impact of Non-Pharmaceutical Interventions (NPIs) in the spread of COVID-19 across Germany.
                                            We postulate that introduction of NPIs led to increase in social distancing that helped in containing the spread
                                            of the virus. We use Community Movement as an indicator for social distancing. First, we build a SEIR model
                                            that includes social distancing as a parameter. Then we use a linear regression model to estimate the impact of
                                            different NPIs on social distancing. We include other covariates that could simultaneously impact social distanc-
                                            ing (e.g. awareness, weather, and state, week, day of week fixed effects). We use the coefficients from the linear
                                            regression model to simulate different scenarios and quantify the impact of NPIs using the SEIR model. We first
                                            discuss the data used in this work, followed by methods and results from our analysis.

                                            COVID‑19 case data. Interconnected air, land, and sea transportation networks led to the spread of
                                            COVID-19 from Wuhan, China to the rest of China, and eventually to most countries around the ­world24,25. To
                                            accurately model the spatial spread of the disease into Germany, we collected three types of daily mobility data:
                                            (1) daily air transportation data to capture the movement within and between Germany and 142 other countries;
                                            (2) daily ground transportation data between the nine countries that share borders with Germany; and (3) daily
                                            inter-state ground transportation. The daily COVID-19 case data were obtained from the Johns Hopkins Coro-
                                            navirus Resource ­Center26 and Robert Koch ­Institute27 for all countries in our dataset as well as the 16 German
                                            states. Figure 1 introduces the states and the cumulative case numbers for all states.

                                            Government policies. To encourage and enforce physical distancing, governments across all 16 German
                                            states introduced a variety of NPIs at different points in time. Figure 2 provides an overview of the timeline. Data
                                            for these policies were collected ­from28,29, and Table S2 in the Supplementary Materials describes those policies.
                                            To understand the impact of each policy in containing the spread of the disease, we analyze (1) what would have
                                            happened if individuals did not reduce their mobility (i.e., if social distancing norms were never introduced),
                                            and (2) what would happen if a policy (p) is relaxed in the future. While the former can help governments in
                                            the early implementation of critical policies in case of future epidemics, the latter can help governments during
                                            current and future epidemics to decide which policies to relax first.

                                            Community mobility.          Google’s COVID-19 Community Mobility ­Reports23 detail how movement trends
                                            change over time as public awareness increases and NPIs are introduced (Fig. 3). The report tracks movement
                                            trends over time by geography, across different categories such as retail and recreation, groceries and phar-
                                            macies, parks, transit stations, workplaces, and residential. We also consider Apple’s community movement
                                            ­reports30. As movement trends across locations are highly correlated (e.g., 0.92 between Apple’s “Driving” and
                                             Google’s “Retail and Recreation”), we only consider community mobility trends “Retail and Recreation” as a



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                                  Figure 1.  Map of Germany, Abbreviations of the 16 German states, and confirmed positive cases for COVID-
                                  19. Panel (a) shows a map of Germany and the abbreviations of the 16 German states (Figures generated using
                                  Tableau Software, Version 2020.2). Panel (b) shows the cumulative curves for the 16 states of Germany.


                                  measure of social distancing (details in Supplement Section S3.1). We define social distancing as sdi = − Ci/100
                                  where Ci is the community mobility trend in state i.
                                      While the community mobility data provides information on changes in local movement, it does not provide
                                  information on inter-state movement. Ground transportation accounts for the vast majority of movement, with
                                  cars accounting for 85% of total ground transportation in ­Germany31. We collected detailed traffic data from
                                  Jan 1, 2013 to Dec 31, 2018 from the German Bundesanstalt für Straßenwesen (Federal Institute for Roadways).
                                  The dataset contains the hourly count of the number of vehicles crossing different checkpoints along highways
                                  across Germany. The institute used sensors to identify the type of vehicle, which we include in our analysis to
                                  estimate the number of individuals. We construct correction factors to extrapolate hourly traffic for Jan 1, 2020
                                  to April 30, 2020 (details in Supplementary Material), and the model includes public holidays, day of the week,
                                  and state population as control variables. According to a survey, 61% of people in Germany use cars to commute
                                  to their ­workplace32. So, to control for changes in car movement during the period of the study, we adjust the
                                  predicted daily car movement between states using Google’s community mobility data for workplaces (Fig. 4).
                                      We used Deutsche Bahn’s timetables (www.bahn.com) for all major train stations in Germany to estimate the
                                  number of daily rail travelers moving across states and arriving from neighboring countries. To account for the
                                  changes in movement due to COVID-19 and cancelations of several trains, we adjust the number of passengers
                                  moving across states by using the community mobility data for transit stations (Fig. 5).
                                      We obtained the search history of a large European bus and train comparison platform to estimate the number
                                  of passengers moving across cities and states in Germany, and passengers traveling to Germany from neighboring
                                  countries. We set bus transport to zero after March 16, 2020 as all bus movement in Germany stopped on that day.
                                      We also obtained flight transportation information from the Opensky ­Network33, whose database utilizes
                                  Automatic Dependent Surveillance Broadcast (ADS-B) flight trajectories to identify the departure and arrival
                                  airport of flights (Fig. 6).
                                      We also use additional controls to isolate the effect of individual policies. We use Google Trends data for
                                  the search term “COVID-19” to control for awareness over time (Fig. 7a). Severe movement restrictions due to
                                  increased enforcement of these policy restrictions led to a greater sense of unease and dissatisfaction amongst
                                  some sections of the population (e.g.34, and while such protests are small, prolonged enforcement of restrictions
                                  could increase dissatisfaction). We use weather data (maximum daily temperature) from wetterkontor.de as a
                                  control to account for the propensity of the population to leave their homes as the weather improves (Fig. 7b).
                                  Finally, to account for unobserved heterogeneity across states and over time, we include state, week and day of
                                  week fixed effects. This allows us to control for variations that are not explicitly included in the model.

                                  Models
                                  Susceptible–exposed–infected–recovered (SEIR) model. The SEIR compartmental model is a
                                  transmission model of an infectious disease. The model includes a set of evolutionary equations that describes
                                  the spread of the disease in each subpopulation as follows:




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                                            Figure 2.  Timeline for implementation of NPIs across states. The policies are visualized in the same order from
                                            top to bottom for each state. These policies include, in this order, contact restrictions (movement in public space
                                            is limited to two persons or people co-living), initial business closures (e.g. restaurants), retail outlet closures,
                                            stay at home orders, non-essential business closures (e.g. trade shows), closure of educational institutes (e.g.
                                            schools and universities), and border closures (closing international borders). Border closures apply to 10 states
                                            sharing international borders. We use data from February 18, 2020 to May 7, 2020 in our study. Not every policy
                                            was implemented by each state as of April 20, 2020, and none of the implemented policies were relaxed until
                                            April 20. State governments started relaxing these policies after April 20, 2020.


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traffic in different locations as compared to baseline from historical data. Panel (a) shows the movement trend
across different categories of places for Bavaria. Similar movement trends for all the other states are shown in the
Supplementary Material. Panel (b) shows the community mobility and social distancing in Bavaria.

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Figure 4. Ground transportation using cars and trucks in Germany. Panel (a) shows the number of passengers
arriving in different states by car. Panel (b) shows the number of passengers arriving in different states. During
the period of this study, there was no restriction on truck movement.

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Figure 5. Ground transportation using trains in Germany. Panel (a) shows part of the train timetable available
in all German train stations. More specifically, the sample snippet displayed in Panel (a) lists the departure
times of trains leaving Berlin Hbf (Berlin Central Station). We parsed 538 timetable files to obtain the train
schedule for all of Germany. We combine information from the arrival and departure timetables to construct the
complete route of a train. Panel (b) shows the number of passengers arriving to different states by train.
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Figure 6. Transportation data in Germany. Panel (a) shows the number of air passengers arriving in different
states in Germany. We assume 200 passengers for domestic and 500 passengers for international flights.

Panel (b) shows the number of bus passengers arriving to different states from other states in Germany and
neighboring countries. We assume 20 passengers per trip.

Ni=Ni+)>0) (a4 - Mi) (5)

where S;, E;, and Nj represent the susceptible, exposed, and the total population of state i, respectively. I? rep-
resents the documented infected individuals which is the subset of the infected population that have symptoms
severe enough to be diagnosed with the illness. I/’ is the rest of the infected population known as the undocu-
mented infected individuals. We consider values for SEIR metapopulation state variables on day t. Additionally,
the variable sd; (sd; < 1) defines the daily change in social mobility (or degree of social distancing) in the state
i. We also control for the potential of spillovers between states by accounting for interstate travel. Specifically,
the number of interstate travelers from state j to state i via transportation network v, is Mj on a given day. We
assume documented infected patients do not travel between states, while the asymptomatic undocumented
infected individuals may move from one state to another. Finally, we note that the SEIR model works under the
assumption that the incubation and infectious times are exponentially distributed and the relative change in the
total population is negligible for the time period of the disease spread.

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Figure 7. Covariates in Linear Regression Model. Panel (a) shows the Google Trends for the search term
“COVID-19” for Bavaria. Google Trends numbers indicate search interest of a topic over time as a proportion of
all other searches at the same time. We use Google Trends to account for increased awareness over time. Panel
(b) shows the maximum temperature recorded in a day for Bavaria. We show the Google Trends and Maximum
Daily Temperature for other states in the Supplementary Material (Figs. $8, S9 respectively).

We estimate the parameters of this model via Ensemble Adjustment Kalman Filter (EAKF) which is suitable
for models with a high number of parameters. We also adjust for various delays (e.g. the latency period from the
onset of symptoms to diagnosis, the time between the exposure and becoming contagious, and the incubation
period). Further details are provided in Supplement S1 and Table S1.

The parameters estimated from the SEIR model are used to predict the number of new case counts under the
different scenarios we consider for policy (NPIs) easing.

Linear regression: NPls and social mobility. We use a linear regression model to estimate the associa-
tion of NPIs with community mobility (Cj,;) as shown in Eq. (6) where K is a constant. We use a binary variable
Xjpt = lif policy p is active in state j on day ft, trendj, is the exponentially smoothed Google Trends number
for search term “COVID-19,” and temp, , is the daily maximum temperature in degree Celsius in state j on day t.
To account for state-level unobserved heterogeneity, we use state fixed effects (state;). In addition to state-level
differences, we also control for week-based differences and day of week-based differences by incorporating week
fixed effects (week;) and day of week fixed effects (day;). For stable parameter estimation, we consider state
Thuringia as our base state (0 state fixed effects), week 9 as our base week (0 week fixed effect) and Monday as
our base day (0 day of week fixed effect). Fixed effects in Eq. (6) are modeled as indicator functions. (details in
Supplement Section $3).

Cut = KES Bo, FB Mend. +Bm™” temp "BS" statet pret week ty. Ba day te,

(6)

This specification models states to be independent, which may lead to failure of the SEIR model in capturing
spillovers across states. To address spillovers from different states, we use movement across states in the SEIR
model (car, bus, train, truck, and flight) and state fixed effects. We assume that Google Trends might be able to
capture spillover effects (if cases increase in one state, population in neighboring states will be more self-aware).
Further details are presented in Supplement S3.3.

Limitations: association as opposed to identification. Our approach rests on spatial-temporal vari-
ations in NPIs contributing to variations in social distancing, which in turn is linked to variations in COVID-19
case numbers. We do not claim causality when analyzing this chain of events, as there are ways in which causal
identification may fail. For example, if the data do not provide adequate variation in the sequencing of policy
interventions, then our estimates cannot uniquely identify the effect of each intervention. Figure 3 shows for
example that Contact Restriction never occurred first in any state, and thus our associative effect estimate likely
contains bias. Combinatorically, for the seven NPIs observed, there exist 13,700 possible sequences (i.e., there
are )-,_97Pk = 13,700 possible orders/permutations in which the seven NPIs are implemented in each state).
However, in real world settings, most countries adopted similar sets of policies within a short span of time
despite these vast sets of possibilities. For example, Sebhatu et al.° note that “almost 80% of OECD countries
adopted the same COVID-19 NPIs within a span of 2 w[ee]k[s].” They find that rather than accounting for
country specific characteristics, policymakers set policies based on “...the number of earlier adopters in the
same region.” Due to the homogeneity of policies despite the heterogeneity of country and state characteristics,
all policy level analyses suffer from estimation biases due to the lack of variation in the adoption and implemen-

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                                            Figure 8.  Linear regression model for estimating the marginal contribution of different NPIs on social
                                            distancing. Panel (a) shows the linear regression coefficients for different NPIs. The vertical bars show the 95%
                                            confidence interval bounds for coefficients. Our regression model has an R-square value of 0.976. Panel (b)
                                            shows the smoothed social distancing (red dots) and predicted social distancing (blue line) in Bavaria. The blue
                                            shade shows the 95% confidence bounds around prediction for social distancing. The plots for all other states
                                            are included in the Supplementary Material (Fig. S11).


                                            tation of policies. Even though we observe temporal and sequencing differences across states, the variation is
                                            not sufficient to attribute causality to these interventions. Ultimately, we would like to examine interventions at
                                            a more granular, perhaps even individual level (e.g., assess the probability of a person contracting COVID-19
                                            when certain NPIs are enacted) to obtain a greater variation in the sequencing of interventions. Unfortunately,
                                            this is not how policy decisions are made: they cover wider jurisdictions, and their historical sequence is limited.
                                                A second thread to identification are spillover effects across states that may result in biased estimates. We try
                                            our best to account for spillovers between states in the following ways: (1) implementing most interstate move-
                                            ment in the SEIR model (car, flight, bus, train, and truck), (2) include Google Trends in the linear regression
                                            model (people in a state would be more cautious and search for “COVID-19” more frequently if case numbers
                                            rise in neighboring states), and (3) include state fixed effects to account for state level heterogeneity (to help
                                            alleviate potential spillover of a particular state from its neighbors). Moreover, Supplement S3.3 addresses the
                                            issue of potential spillover across states in more detail by evaluating two alternative specifications. However, we
                                            still cannot completely rule out the possibility of spillovers.
                                                Due to the data-imposed inability to identify the causal impact of NPIs on COVID-19 cases, this study only
                                            proposes associative effects for each NPI.

                                            Results
                                            Quantifying policy contributions. To determine the impact of different state policies, we use a linear
                                            regression model to predict changes in mobility (Cj,t) due to policy p. Coefficients from the linear regression
                                            model are shown in Fig. 8a. We calculate social distancing (sdj,t) from mobility in Fig. 8b. As explained above,
                                            we cannot identify each policy’s causal effect on reducing disease spread. However, we are still able to provide
                                            meaningful insights of each policy’s contribution in reducing the disease spread.
                                                 Figure 8a shows the parameter estimates of various NPIs on social mobility. The complete list of parameter
                                            estimates are provided in the Supplement (Table S3). The estimates capture the average incremental effect of
                                            these policies across Germany’s 16 states in reducing mobility. From the graph, we see that contact restrictions
                                            have a very large negative effect on mobility (10.3 percentage point drop in mobility, 95% Confidence Inter-
                                            val (CI): 8.2 to 12.5). COVID-19 is mainly spread through airborne transmission among individuals in close
                                            proximity. The policy of contact restrictions limits the number of people that may congregate and requires all
                                            people to stay a minimum of 6 feet apart from one another to ensure social. Educational Facilities Closure also
                                            precipitates a significant drop in mobility (5 percentage point drop; CI: 3.1–6.9). A significant drop is possible as
                                            it indirectly leads to decrease in mobility (for example, children staying home without care givers forces parents
                                            to work from home). The other policies listed in order of impact on mobility (estimate of percentage point drop
                                            in mobility from the regression and 95% Confidence Interval in parenthesis) are: Retail Outlets Closures (3.1,
                                            CI: 2.1–4.1), Initial Business Closures (3.4; CI: 1.2–3.7), Border Closures (0.03, CI: − 1 to 1), Non-essential Ser-
                                            vices Closures (0.62; CI: − 0.5 to 1.7), and Stay at Home Orders (− 0.01; CI: − 1.9 to 1.8). It can be observed that
                                            parameter estimates for Border Closures, Non-essential Services Closure, and Stay at Home Orders are statisti-
                                            cally insignificant (confidence intervals include 0). However, it does not conclude that these NPIs had no effect.
                                            For example, international travel might have played a significant role in seeding the disease. However, once the
                                            Borders were closed, the Border Closure NPI played a minimal role in mitigating the spread of the disease. As
                                            discussed in the previous section (“Limitations: Association as opposed to Identification”), we estimate associa-
                                            tions as opposed to causal effects.



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                                  Predicting disease spread. We use the predicted mobility from the linear regression to predict new case
                                  counts. We investigate the contribution of each policy to the mitigation of disease spread by determining the role
                                  of social distancing in the estimation of the number of susceptible and exposed individuals in a given popula-
                                  tion. We modify the SEIR model used ­in20 to include different transportation networks and predicted mobility
                                  for each state (Eqs. 1–5). Using the estimation procedure ­in20, we find the model parameters to predict disease
                                  spread for all 16 states in Germany—the model accounts for documented as well as undocumented infected
                                  cases. As shown in Supplementary Material Fig. S20, the proportion of documented infected ( I d ) as a function
                                  of total cases increases over time. This finding aligns with expectations because of the rapid increase in testing
                                  across ­Germany35.
                                      Figure 9a shows the actual disease progression in Germany; the disease spread as predicted by our model
                                  in the presence of predicted social distancing, as well as disease spread as predicted by our model when mobil-
                                  ity remained unchanged with no social distancing measures. Similar predictions for the states are provided in
                                  Fig. 9c. We use the time period of Feb 18, 2020–Apr 20, 2020 to infer model parameters. This period includes
                                  early stages of the COVID-19 epidemic in Germany and the time that state policies are enacted. We use these
                                  parameters to estimate the number of daily documented cases during the time interval of Feb 18, 2020–May 7,
                                  2020, which corresponds to 17 days out of sample forecasts. The model finds 172,922 (IQR: 140,301–204,952)
                                  cumulative documented cases in Germany as of May 7, 2020 (actual reported cases: 166,069) with the estimated
                                  average error rate of 4%. Figure 9b shows the amount of expected increase in the number of cases across the
                                  states of Germany and the nation, if no social distancing was practiced. Across Germany one would expect a
                                  24.6-fold (IQR: 20–29) increase in the number of cases without any social distancing (i.e., sdi = 0), the effect
                                  varying significantly by states from a low of 16-fold (IQR:12.2–19.7) in Hamburg to a high of 86-fold (IQR:
                                  66.3–107.3) in Mecklenburg-Vorpommern.

                                  Lifting of restrictions. We simulate what-if scenarios to determine the impact of lifting restrictions on new
                                  cases in each state. Under the scenario that a restriction has been relaxed while others remained operational, we
                                  forecast mobility using Eq. (6), and we subsequently project the new case count using the predicted mobility.
                                  This step is repeated across all restrictions, each relaxed individually.
                                       In Scenario 1, we project all changes from April 21, 2020 to July 19, 2020, assuming that the restriction was
                                  relaxed on April 21, 2020. Figure 10a,c show the projections of case counts over a 90-day period if a restriction
                                  was relaxed exclusively. Figure 10b,d show Scenario 2, which projects all changes from April 21, 2020 to July 19,
                                  2020, assuming that the restriction was relaxed on April 28, 2020. Because the two scenarios are exactly one week
                                  apart, it allows us to determine the impact of delaying the lifting of a restriction by 1 week. From the analysis, the
                                  lifting of contact restrictions, i.e., the rule limiting movement in public spaces, had the biggest impact on new
                                  case counts. Compared to keeping the restrictions in place, lifting contact restrictions is associated with a 150%
                                  (IQR: 144–156%) increase in daily case numbers in Scenario 1 and a 108% (IQR: 103.7–112.5%) increase in
                                  Scenario 2. However, lifting educational facilities closure is associated with an increase in daily case numbers by
                                  46.1% (IQR: 44.0–48.1%) in Scenario 1 and 34.4% (IQR: 32.7–36.2%) in Scenario 2. Opening of retail outlets is
                                  linked to a 33.9% (IQR: 33.0–34.8%) increase in daily case numbers in Scenario 1 and a 24.5% (IQR: 23.4–25.6%)
                                  increase in Scenario 2. Lifting restrictions on initial business closures is associated with an increase in daily case
                                  numbers by 18.6% (IQR: 17.8–19.5%) in Scenario 1 and 14.4% (IQR: 13.7–15.0%) in Scenario 2, and easing
                                  non-essential service closures is associated with an increase in daily case numbers by 3.6% (IQR: 3.1–4.1%) in
                                  Scenario 1 and 2.6% (IQR: 2.2–3.0%) in Scenario 2. These results show that NPIs have differential impacts on
                                  lowering disease spread and suggest a measured approach to lifting restrictions. For example, the opening of
                                  retail outlets could be balanced by maintaining the restrictions around limiting the number of individuals in a
                                  given place or store (e.g., controlling entry)—thereby allowing for the resumption of economic activity while
                                  limiting the risk of contagion.
                                       Figure 10e shows the increases in the expected number of cases if a restriction was lifted on April 21 versus
                                  on April 28. Delaying the lifting of certain restrictions by one week could also have a significant impact on the
                                  total case counts. This occurs not only due to the delay, but also because the number of infected individuals
                                  that a person could come in contact with decreases over the week. For example, delaying the lifting of contact
                                  restrictions by one week is associated with a reduction in the number of new cases over the 90-day forecast by
                                  an average of 20% (IQR: 14.6–25.7%). We also observe that lifting restrictions on educational facilities closure
                                  and retail outlets closure is linked to an average 8.9% (IQR: 5.1–12.2%) and 7.5% (IQR: 4.8–10.2%) increase in
                                  total case numbers over the 90-day forecast period.

                                  Discussion
                                  This study explores the role of NPIs in reducing the spread of COVID-19. We extend the spatio-temporal SEIR
                                  model ­in20 by incorporating daily social distancing numbers from transportation data and mobility patterns.
                                  While our analysis does not allow for causal identification, each policy’s association with the mitigation in disease
                                  spread provides meaningful insights. We do this by first relating the NPIs to social mobility changes across the
                                  16 states. Next, we link these changes in social mobility to the spread of COVID-19 by reconstructing patterns
                                  of disease spread across Germany’s 16 states. Using this link with social mobility changes, we investigate the
                                  marginal association of each of the various NPIs implemented by state governments in Germany with disease
                                  mitigation. The model suggests that without NPIs, COVID-19 cases may have shown a 24.6-fold increase across
                                  Germany as of May 7, 2020. Finally, we forecast the number of new cases when policies are relaxed one at a time,
                                  suggesting that certain policies have a larger impact on disease spread than others. Our model forecasts suggest
                                  that early relaxation of some NPIs could result in an increase in the number of cases, potentially leading to a
                                  future wave. This observation is confirmed by an estimated increase in the effective reproduction number Re (in


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                                            Figure 9.  SEIR Model Predictions. Panel (a) shows the predictions of new case counts in Germany with and
                                            without any distancing measures, against actual cases for the same time period. Panel (b) presents the expected
                                            increase of cumulative cases (in multiples) when there is no social distancing as compared to the actual cases
                                            numbers. Panel (c) plots the predictions of new case counts with and without any distancing measures, against
                                            actual case numbers for all states. The box and whiskers provide the median, interquartile range, and up to a
                                            maximum of 1.5*IQR from the box hinges derived from 4000 simulations using the inferred model parameters.
                                            Our predictive accuracy is higher for states with high case numbers such as Baden-Württemberg (BW) and
                                            Bavaria (BY) than for the small city-states Berlin (BE), Bremen (HB), and Hamburg (HB). We note that the last
                                            17 days of Panels (a,c) correspond to out-of-sample forecasts from the SEIR model.




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                                  Figure 10.  Lifting of Policy Restrictions. Panels (a,b) show the predictions of new case counts across all states of
                                  Germany due to lifting of policy restrictions from April 21, 2020 to July 19, 2020. In Panel (a) policy restrictions
                                  are relaxed, one-at-a-time on April 21, 2020, in Panel (b) policy restrictions are relaxed, one-at-a-time on April
                                  28, 2020. Panels (c,d) illustrate the same for all of Germany. Panel (e) charts the predicted increase in cases due
                                  to policy easing a week earlier.




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                                            Figure 10.  (continued)


                                            the Supplementary Material). We also compare case counts for policies relaxed with a one-week delay; keeping
                                            some NPIs in place for an extra week is associated with a reduction in COVID-19 cases by up to 20% (as of July
                                            19, 2020). The results confirm that policy restrictions are not all equal in their ability to affect disease spread. The
                                            policy of restricting mass gatherings (Contact Restriction) is estimated to be the most effective NPI to contain
                                            COVID-19, followed by closures of various businesses and stay at home orders. Due to this variation in effect,
                                            it is advisable to lift restrictions with minimal effects first, gradually easing restrictions that potentially lead to
                                            higher case numbers. This study presents a comprehensive quantitative analysis that includes individual effects
                                            of NPIs on the transmission of COVID-19. To the best of our knowledge this is the first study that uses variations


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                                  in policy interventions by governments to discover their differential impacts at reducing mobility, which in turn
                                  reduces disease spread. Prolonged lockdowns and restrictive policies can have devastating social and economic
                                  consequences; however, opening too soon could result in rapid disease spread. Therefore, governments need to
                                  develop cautious approaches to lifting restrictions to return to ­normalcy36. The approach presented in this paper
                                  allows for a deeper understanding of the policy effects on mitigating the spread of COVID-19. The forecasts
                                  of disease spread when NPIs are partially loosened guide policymakers towards the appropriate strategy when
                                  reversing restrictions.

                                  Data availability
                                  All code and data are available in the supplementary materials and posted online in a public repository https​://
                                  githu​b.com/ehgh/COVID​-19-case-estim​ation​-and-polic​y-effec​ts.

                                  Received: 1 July 2020; Accepted: 26 October 2020


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                                            Acknowledgements
                                            Jörn Boehnke gratefully acknowledges the support of the Center of Mathematical Sciences and Applications at
                                            Harvard University during the course of this work.

                                            Author contributions
                                            All authors contributed equally to the manuscript.

                                            Competing interests
                                            The authors declare no competing interests.

                                            Additional information
                                            Supplementary information is available for this paper at https​://doi.org/10.1038/s4159​8-020-76244​-6.
                                            Correspondence and requests for materials should be addressed to A.A.
                                            Reprints and permissions information is available at www.nature.com/reprints.
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