key: cord-0704098-mtjp0m5i
authors: Fong, Dominic; Mair, Maximilian J.; Lanthaler, Florian; Alber, Monika; Mitterer, Manfred
title: Mobility as a driver of severe acute respiratory syndrome coronavirus 2 in cancer patients during the second coronavirus disease 2019 pandemic wave
date: 2021-10-15
journal: Int J Cancer
DOI: 10.1002/ijc.33838
sha: 3aeecad4208f6735fdb4553f4f7ff8b4b42994cc
doc_id: 704098
cord_uid: mtjp0m5i

We retrospectively analyzed the epidemiological characteristics of cancer patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and their correlations with publicly available mobility data. Between 19 October 2020 and 28 February 2021, 4754 patient visits were carried out, and 1454 treatments have been applied at the Haemato‐Oncology Day Hospital Merano. Additional measures to prevent local SARS‐CoV‐2 transmission included a specific questionnaire for coronavirus disease 2019 (COVID‐19) symptoms as well as a SARS‐CoV‐2 real‐time polymerase‐chain reaction (RT‐PCR) 2 days prior to any intravenous or subcutaneous therapy. Community mobility was assessed through publicly available mobile phone tracking data from Google; 106/719 (14.7%) cancer patients have been tested positive for SARS‐CoV‐2 by PCR during the second wave compared to 5/640 (0.8%) within the first wave (P < .001); 66/106 (62%) had solid tumors, and 40/106 (38%) had hematological malignancies; 90/106 (85%) patients received ongoing antitumor therapies. Mortality rate of COVID‐19 positive cancer patients (7/106; 6.6%) was higher compared to the overall population (731/46 421; 1.6%; P < .001). Strict control measures at our department led to a significantly lower test positivity rate compared to the general population, resulting in a reduction of 58.5% of new SARS‐CoV‐2 cases. Over time, infection rates and community mobility correlated in the first and second wave after initiating and lifting restrictions. Our findings underscore the importance of strict preventive control measures including testing and contact tracing in vulnerable subpopulations such as cancer patients, particularly if social restriction policies are being lifted. Smartphone‐based mobility data may help to guide policy makers to prevent a vulnerable population like cancer patients from virus transmission.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus, characterized by human-to-human transmission that causes the coronavirus disease 2019 (COVID-19). 1 The COVID-19 outbreak, declared a pandemic on 11 March 2020 by the World Health Organization (WHO), has resulted in more than 129 million confirmed cases and over 2.8 million deaths all over the world by 31 March 2021. 2 Northern Italy, one of the epicenters during the first COVID-19 wave, was affected early and severely before spreading SARS-CoV-2 across surrounding regions. As a consequence, the Italian government implemented a nationwide strict lockdown in March 2020 to contain the spread of the epidemic. 3 Restrictions on mobility, closure of school, university and nonessential workplaces and a national stay-at-home order in conjunction with proactive testing and contact tracing have emerged drastically, leading to a reduction of the growth rate of confirmed cases and deaths.

In early May, as the incidence of cases declined after more than 2 months of nationwide lockdown measures, Italy lifted restrictions cautiously in phases followed by the complete re-opening implemented on 3 June 2020. 4 Despite the acute situation in spring 2020, the COVID-19 epidemic was largely mitigated during the summer. 5 However, as other countries, Italy experienced a resurgence of COVID-19 in autumn with a rise in daily infections. As a consequence, the Italian government has enacted again decrees that gradually introduced containment measures to reduce the pandemic.

During the second wave of the pandemic, several countries resorted to targeted measures, in an attempt to protect the health care system from being overwhelmed while preserving the economy as much as possible. The Italian government enforced a zone system on 3 November 2020, entailing different levels of restriction based on the severity of the epidemic in each region. 6 South Tyrol is a province (autonomous province of Bolzano) in northern Italy with a total population of more than 530 000 inhabitants as of 2019. As of 28 February 2021, a total of 53 804 SARS-CoV-2 cases and 1031 COVID-19-associated deaths were reported in South Tyrol. 2 Based on South Tyrol's autonomy, the province may exercise varying degrees of self-government. Therefore, the local authorities decided for less stringent restrictions than those recommended at national level during the second COVID-19 pandemic wave.

Mobile phone data can provide relevant information about how people move and how these patterns change or take effect after implementation of mobility restrictions in a state of emergency such as a pandemic. 7 Recent studies have investigated the impact of human mobility and control measures on the SARS-CoV-2 spread in different countries. [8] [9] [10] [11] [12] [13] [14] However, these effects may differ in particularly vulnerable population groups such as cancer patients. Due to disease and treatment-related immune deficiency, cancer patients who are infected by SARS-CoV-2 may experience more difficult outcomes than other nonvulnerable populations. 15 There is still no information available on the effects of large-scale social restrictions policy on COVID-19 epidemic in cancer patients, and the impact of less severe measures remains unclear. The aim of our study is to investigate the region-specific spread of COVID-19 in South Tyrol during the second epidemic wave after local restrictions were relaxed and its impact on cancer patients.

All patients treated at the outpatient department of the "Franz Tappeiner" Hospital Merano between 19 October 2020 and 28 February 2021 were included in our retrospective study. Specific infection prevention and control measures were maintained by the hospital as well as our outpatient clinic as described previously. 16, 17 In addition, the healthcare team was separated by Home Office to reduce the risk of infection, and medical care was provided by telemedicine on a case-by-case basis. Testing for SARS-CoV-2 RNA 2 days prior to any intravenous or subcutaneous (i.v./s.c.) treatment was performed using a real-time polymerase-chain reaction (RT-PCR) on respiratory samples obtained from nasopharyngeal swabs. Test results were required before patients entered our department, and treatment was deferred for all patients with positive tests until they had been tested negative. Our approach was to recognize symptomatic as well as asymptomatic SARS-CoV-2 infection in patients before entering our outpatient clinic, to protect both patients and healthcare workers. These additional local preventive measures facilitated our continued provision of oncological treatment throughout the pandemic. The reported, daily RT-PCR-confirmed SARS-CoV-2 cases, COVID-19-related mortalities as well as number of hospitalized patients during the observation period were acquired from the Italian Civil Protection Department. 2 

Since October 2020, the Italian Government has started to implement a series of travel restrictions and lockdown policies at the national level, which was then followed by a second Italian lockdown on 3 November 2020. 6 In particular, the Italian government tightened the coronavirus rules over the festive season including New Year and Epiphany. Travel between the regions was only allowed for work, health, and emergency reasons with the need to hold a completed self-certification. Year and Epiphany. 20 Furthermore, bars and restaurants reopened on 7 January 2021. 21 However, general rules on physical spacing, wearing of face masks, social distancing and hygiene were recommended throughout the observation period.

Considering the different lockdown policies of the Italian government and the autonomous province of Bolzano, we examined the relationship of temporal variation of SARS-CoV-2 rates, policy implementation and mobility levels in South Tyrol during the second wave (19 October 2020 to 28 February 2021) . We used open access cellphone mobility data for the autonomous province of Bolzano, since they show movement trends across different categories of places to a reference period before the implementation of any measures. 22 The data show how visits to places, such as residential, workplaces or groceries and pharmacy, change compared to a prepandemic baseline value for that day of the week. The baseline was defined as the median value, for the corresponding day of the week, during the 5-week period 3 January until 6 February 2020. Average mobility was taken as the average reduction in mobility across the five Google mobility categories (retail and recreation, grocery and pharmacy, parks, transit stations and workplace).

Independence of categorical variables was tested using the chi-square and Fisher's exact tests as appropriate. Means of continuous variables were compared using the Mann-Whitney U test. Correlations between mobility and infection/hospitalization rates as well as fatalities per week were evaluated using Spearman's rho, where a |r| > .7 was interpreted as strong correlation, .5 < |r| ≤ .7 as medium correlation and .3 < |r| ≤ .5 as weak correlation. Each Although a decrease in mobility could also be observed in the second wave, mobility measures declined to a much lesser extent as compared to the first wave. Figure 2 shows the week-specific mobility Figure 2B ).

More specifically, Figure 3 shows Figure 4A shows the positivity rates of SARS-CoV-2 PCR tests per

week from our outpatient department compared to the general population in South Tyrol, with significant differences in 7/19 weeks (P-values as given in Figure 4A , chi-square test). Our findings demonstrate that the test positivity rate in the general population as well as To the best of our knowledge, this is the first report to take into account the effect of changes in mobility and its impact on SARS- and treatment-related side effects. 38 As the pandemic increased the unhealthy behaviors in the population, maintenance and adherence to an active lifestyle are crucial. In order to optimize daily physical activity and reach as many patients, the use of personalized telehealth tools may be helpful. 39 In addition, COVID-19 amplifies the health risks of hot weather particularly in people with underlying medical conditions. 40 Therefore, authorities and communities should be prepared for hot weather and heat waves to reduce heat-related illness.

Important limitations of our study include the retrospective study design within a single institution as well as not considering here the potential impact to infection rates due to population-based interventions including social distancing and personal protective equipment that may also lead to a reduction of the transmissibility. In addition, mobile phone data may not be generalizable and applicable to the overall population, as some demographic groups like children or elderly may be under-represented. 31 Furthermore, as noticed in other countries, emergence of novel SARS-CoV-2 variants, which is a natural event due to mutations in the 

A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster

Italian Civil Protection Department. Coronavirus Emergency: The National response n

Ulteriori disposizioni attuative del decreto-legge 23 febbraio 2020, n. 6, recante misure urgenti in materia di contenimento e gestione dell'emergenza epidemiologica da COVID-19, applicabili sull'intero n

Disposizioni attuative del decreto-legge 25 marzo 2020, n. 19, recante misure urgenti per fronteggiare l'emergenza epidemiologica da COVID-19, e del decreto-legge 16 maggio 2020, n. 33, recante ulteriori n

The evolution of Covid-19 in Italy after the spring of 2020: an unpredicted summer respite followed by a second wave

Ulteriori disposizioni attuative del decreto-legge 25 marzo 2020, n. 19, convertito, con modificazioni, dalla legge 25 maggio 2020, n. 35, recante «Misure urgenti per fronteggiare l'emergenza epidemiologica da COVID-19», e del decreto-legge 16 maggio 2020, n. 33, convertito, con modificazioni, dalla legge 14 luglio 2020, n. 74, recante «Ulteriori misure urgenti per fronteggiare l'emergenza epidemiologica da COVID-19

Measuring mobility to monitor travel and physical distancing interventions: a common framework for mobile phone data analysis

Reduction in mobility and COVID-19 transmission

Mining Google and Apple mobility data: temporal anatomy for COVID-19 social distancing

Effects of social distancing on the spreading of COVID-19 inferred from mobile phone data

Mobility and the effective reproduction rate of COVID-19

Enacting national social distancing policies corresponds with dramatic reduction in COVID19 infection rates

The effect of human mobility and control measures on the COVID-19 epidemic in China

Association of mobile phone location data indications of travel and stay-at-home mandates with COVID-19 infection rates in the US

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Infection rate and clinical management of cancer patients during the COVID-19 pandemic: experience from a tertiary care hospital in northern Italy

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Adjusting for multiple testing -when and how?

Rapid antigen tests for large-scale diagnostic campaigns: a case study from North-Eastern Italy

A systematic review and meta-analysis of cancer patients affected by a novel coronavirus

Mortality in patients with cancer and coronavirus disease 2019: a systematic review and pooled analysis of 52 studies

SARS-CoV-2 testing in patients with cancer treated at a tertiary care hospital during the COVID-19 pandemic

Countrywide population movement monitoring using mobile devices generated (big) data during the COVID-19 crisis

COVID-19 outbreak response, a dataset to assess mobility changes in Italy following national lockdown

Human mobility and poverty as key drivers of COVID-19 transmission and control

The use of mobile phone data to inform analysis of COVID-19 pandemic epidemiology

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Retrospective analysis of the Italian exit strategy from COVID-19 lockdown

Lockdown timing and efficacy in controlling COVID-19 using mobile phone tracking

Association between mobility patterns and COVID-19 transmission in the USA: a mathematical modelling study

Lessons learnt from easing COVID-19 restrictions: an analysis of countries and regions in Asia Pacific and Europe

Medical liability in cancer care during COVID-19 pandemic: heroes or guilty? Front Public Health

Special attention to physical activity in breast cancer patients during the first wave of COVID-19 pandemic in Italy: the DianaWeb cohort

mHealth: mobile technologies to virtually bring the patient into an oncology practice

COVID-19 and heat waves: new challenges for healthcare systems

Public health actions to control new SARS-CoV-2 variants

Mobility as a driver of severe acute respiratory syndrome coronavirus 2 in cancer patients during the second coronavirus disease 2019 pandemic wave

The authors thank all the staffs of the Outpatient Clinic for their efforts and dedication to the study and acknowledge all the participants whose contributions made our study possible. This work has been supported by the budget of the Südtiroler Sanitätsbetrieb.

The authors declare no conflicts of interest.

The datasets used and analyzed during our study are available from the corresponding author on reasonable request.

The study was approved by the local ethics committee of the