key: cord-0732822-crr9vlq9
authors: Zuliani, Serena; Zampiva, Ilaria; Tregnago, Daniela; Casali, Miriam; Cavaliere, Alessandro; Fumagalli, Arianna; Merler, Sara; Riva, Silvia Teresa; Rossi, Alice; Zacchi, Francesca; Zaninotto, Elisa; Auriemma, Alessandra; Pavarana, Michele; Soldà, Caterina; Benini, Lavinia; Borghesani, Michele; Caldart, Alberto; Casalino, Simona; Gaule, Marina; Kadrija, Dzenete; Mongillo, Marta; Pesoni, Camilla; Biondani, Pamela; Cingarlini, Sara; Fiorio, Elena; Melisi, Davide; Parolin, Veronica; Tondulli, Luca; Belluomini, Lorenzo; Zecchetto, Camilla; Avesani, Barbara; Biasi, Assunta; Bovo, Chiara; Dazzani, Elena; Dodi, Alessandra; Gelmini, Sara; Leta, Luigi Carmine; Lo Cascio, Giuliana; Lombardo, Fiorella; Lucin, Eleonora; Martinelli, Ilaria Asja; Messineo, Luisa; Moscarda, Viola; Pafumi, Sarah; Reni, Anna; Sartori, Giulia; Scaglione, Ilaria Mariangela; Shoval, Yiftach; Sposito, Marco; Tacconelli, Evelina; Trestini, Ilaria; Zambonin, Valentina; Zanelli, Sara; Pilotto, Sara; Milella, Michele
title: Organizational challenges, volumes of oncological activity, and patients' perception during the SARS-CoV-2 epidemic
date: 2020-06-11
journal: Eur J Cancer
DOI: 10.1016/j.ejca.2020.05.029
sha: 0c8d723517a087a9cdc52a06e0351e252d4a37b4
doc_id: 732822
cord_uid: crr9vlq9

BACKGROUND: On February 23(rd), the 1(st) case of SARS-CoV-2 infection was diagnosed at the University Hospital Trust of Verona, Italy. On March 13(th), the Oncology Section was converted into a 22-inpatient beds COVID unit and we reshaped our organization to face SARS-CoV-2 epidemic, while maintaining oncological activities. METHODS: We tracked down: i) volumes of oncological activities (January 1(st) - March 31(st), 2020 versus the same period of 2019), ii) patients' and caregivers' perception, iii) SARS-CoV-2 infection rate in oncology health professionals and SARS-CoV-2 infection-related hospital admissions of "active" oncological patients. RESULTS: As compared with the same trimester in 2019, the overall reduction in total numbers of inpatient admissions, chemotherapy administrations, and specialty visits in January-March 2020 was 8%, 6%, and 3%, respectively; based on the weekly average of daily accesses, reduction in some of the oncological activities became statistically significant from week 11. The overall acceptance of adopted measures, as measured by targeted questionnaires administered to a sample of 241 outpatients, was high (>70%). Overall, 8/85 oncology health professionals tested positive for SARS-CoV-2 infection (all but one employed in the COVID unit, no hospital admissions and no treatment required); among 471 patients admitted for SARS-CoV-2 infection, 7 had an "active" oncological disease (2 died of infection-related complications). CONCLUSIONS: A slight, but statistically significant reduction in oncology activity was registered during the SARS-CoV-2 epidemic peak in Verona, Italy. Organizational and protective measures adopted appear to have contributed to keep infections in both oncological patients and health professionals to a minimum.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has caused more than 4,347,000 cases and 297,241 deaths worldwide[1], translating into previously unseen challenges for healthcare systems, hospital resource overload, and impairment of routine medical care [2] [3] [4] .

Cancer patients are felt to be particularly vulnerable, both in terms of risks of infection [5] [6] [7] and need to avoid undue delays in cancer treatment [3, 8, 9] . For cancer patients, the fear that measures adopted to limit the spread of infection and strained hospital resources might negatively affect their disease management and prognosis overwhelms fears related to the new pandemic, generating mistrust and lack of compliance towards protective measures. In that respect, the current lack of structured, real-life data on the impact of containment measures on volumes and quality of oncology activities, fuels patients' and caregivers' fears and disappointment. A recent survey conducted by the "Codice Viola" patients' association on 484 cancer patients depicts drastic and important reductions in cancer care-related activities in Italy, especially with regard to delays in cancer surgery [10] .

In order to address the actual changes in oncological activity volumes in relationship to the organizational changes implemented, we tracked down protective/organizational measures, oncological activity, patient perception of adopted measures, and confirmed SARS-CoV-2 cases among our healthcare professionals and cancer patients during the peak of SARS-CoV-2 epidemics at the Verona University Hospital Trust (Italy).

We retrospectively analysed the activity of our Section of Oncology at the University Hospital Trust of Verona (Italy) from January 1 st to March 31 st 

To assess patients' perception of risks and their acceptance of protective/organizational measures, anonymous questionnaires (see Supplementary Methods), developed by our Psycho-Oncology service, were administered at triage to all patients accessing our outpatient facilities, over a 21-day period; questionnaires were returned on a voluntary basis.

For oncological activity volumes, total numbers and daily average numbers ± SD were reported for the January-March trimester of 2019 and 2020; variations in daily average activity volumes (calculated on a monthly or weekly bases, as indicated) between the two periods were compared using a two-tailed Student's t-test for unpaired samples with unequal variance. Percentage of relevant answers to relevant questionnaire items are reported with 95% confidence intervals (95% CI).

On February 23 rd , 2020, the first confirmed case of SARS-CoV-2 infection was diagnosed at the Verona University Hospital Trust. Daily and cumulative hospital admissions for SARS-CoV-2 infection are shown in Fig. 1A ; a peak of 33 daily admissions was reached on March 20 th , 16 days after the national lockdown on March 4 th , and a plateau at 360 hospital admissions was reached as of March 30 th .

During the epidemiological peak, inpatient and ICU beds were increased to a total of 199 SARS-CoV-2dedicated beds.

Our Oncology Section adopted progressive restrictions to hospital access to visitors/caregivers and organizational measures, according to the timelines shown in On March 13 th , the Oncology ward was converted into a 22-bed COVID unit, initially staffed by Oncology personnel on a voluntary basis and oncological inpatients were transferred to a surgical ward, where they were followed by Oncology physicians. Segregated personnel teams were created, one dedicated to the COVID unit and a "clean" one dedicated to oncological patients (see Supplementary Methods). Such organization resulted in an overall 40% and 43% reduction in oncology-dedicated medical and nursing/auxiliary staff, respectively; over subsequent weeks, Oncology personnel was gradually substituted for by other specialists, returning to a full Oncology staffing by the end of April (Fig. 1C) .

We tracked down volumes of Oncology activities from January 1 st to March 31 st , 2020, in comparison to the same period in 2019. Priority was given to avoiding ongoing systemic treatment interruptions; activation of new systemic treatments was subjected to a structured waiting list, designed to allow for the initiation of treatment within a maximum of 14 days, according to priorities described in the Supplementary results. Total hospital admissions for oncological procedures during the first trimester 2020 showed an overall 8% reduction as compared to 2019; average weekly admissions, calculated on a monthly basis, showed a 40% reduction in March (p=0•08, Fig. 2A) . Changes in total and daily average chemotherapy administrations (calculated on a weekly basis) are shown in Fig. 2B : a 6% reduction in total chemotherapy administrations was observed; an average 14% reduction in daily average chemotherapy administrations over weeks 11-13 was also observed, reaching statistical significance on weeks 11 and 13 (p=0.03 and p=0.04, respectively). Total specialty visits were reduced by 3%; changes in daily average specialty visits (calculated on a weekly basis) showed a more pronounced decline in weeks 11-13, with an average 35% reduction, which was statistically significant (p<0.03) for weeks 11, 12, and 13 ( Fig. 2C) . Variations in disease-specific specialty, chemotherapy, and follow-up visits are shown in Supplementary Fig. 1 . Follow up evaluations were conducted remotely (phone calls, e-mails, and transmission of diagnostic tests and exams), except for those patients who needed an urgent evaluation in presence.

We surveyed our population of oncological outpatients, in order to understand their perception of risks and their acceptance of the adopted organizational measures. Among 241 respondents (demographics described in Supplementary Fig. 2A) , fear of accessing hospital facilities and fear that chemotherapy treatment could increase the risk of contracting SARS-CoV-2 infection was reported as quite high or high in 34% (95% CI: 29-41%) and 27% (95% CI: 21-33%), respectively ( Fig. 3 top) .

Awareness of disease-related risks of infection and strategies to reduce such risks were reported as "very" or "quite clear" by the vast majority [83% (95% CI: 78-88%) and 93% (95% CI: 90-96%), respectively] of respondents ( Fig. 3 bottom) . Interestingly, almost all patients felt that the organizational measures adopted to minimize the risk of SARS-CoV-2 infection were clearly expressed (98%, 95% CI: 96-100%) and mostly derived by information received at the triage point (73%, 95% CI: 67-79%; Supplementary Fig. 2B ). Overall acceptance of organizational and social distancing measures was very high (Supplementary Fig. 2C ); the only notable exception was acceptance of phone-based follow-up and restaging visits, which were perceived as "not very adequate" or "not adequate at all" by 17% (95% CI: 12-22%) and 18% (95% CI: 13-23%) of respondents, respectively.

Among a total of 85 Oncology healthcare professionals (Fig. 4) , 40 were at least temporarily employed in the newly created COVID unit.

Up to April 12th, 8 Oncology healthcare professionals (9%) tested positive for SARS-COV-2 infection ( Fig. 4) . Although 7/8 positive cases were observed among personnel who had been employed in the COVID unit, none of these cases could be tracked down to inappropriate PPE use or intra-hospital contagion.

In all but one asymptomatic infected oncology healthcare professionals, SARS-CoV-2 infection presented with phenotype 1 (mild symptoms, see Supplementary Methods) [12] and did not require hospitalization or specific treatment; infection resolved after a median of 25.5 days (Fig. 4) .

Among 471 patients admitted to the hospital's COVID units as of April 14 th , 2020, a total of 75 patients had a history of cancer diagnosis; of these 15 were classified as "active" according to the definition given in the Supplementary methods. Among a total of 525 patients who had accessed our Section of Oncology in the period February 1 st -April 14 th , 2020, 7 "active" oncological patients were admitted for SARS-CoV-2 infection (1.3%); the remaining 8 active oncological patients retrieved in the database were followed for their oncological disease at other Institutions. Characteristics of the underlying oncological disease of the 7 patients analysed are reported in Supplementary Table 1 . The most common symptom at onset was fever (5/7), followed by dyspnoea (4/7); the most common COVID phenotype at onset was phenotype 2 and two patients progressed to a worse phenotype during hospitalization (Supplementary Table 2 ). Five patients received oxygen therapy (1 requiring NIV, and 1 requiring mechanical ventilation); all but one patient received hydroxychloroquine and 5/7 received lopinavir/ritonavir (Supplementary Table 2 ). Two patients died of SARS-CoV-2-related complications, 5/7 were discharged (all but one after at least one negative NPS), and 3 have resumed their oncological treatment.

Even though approximately half of our Oncology Section was temporarily involved in SARS-CoV-2 patient care, careful organizational measures allowed for a minimal reduction in the volumes of oncological activities (3-8%). Implementation of telephone and in presence triage, access reduction, social distancing policies, and remote consultation activities were largely accepted by patients and Cancer-specific protective measures endorsed by scientific societies (including restrictions to hospital access and telephone or web-based consultations, see Table 1 ) [13, 14] were adopted early during the course of the epidemic; oncological treatment prioritization was established based on a structured waiting list (Supplementary Results) and we maintained virtual multidisciplinary meetings on a weekly basis, as per our standard clinical practice [15, 16] . Considering the lack of clear data supporting the notion that oncological treatment-related adverse events may imply a higher risk of SARS-CoV-2 infection or predict a worse disease course, systemic treatments were not de-escalated and/or postponed [8, 17] .

Reduction in the overall volumes of oncological activity in the first trimester of 2020, as compared to the same period in 2019, was limited. These data are difficult to compare with the few other reported experiences, which have estimated a cumulative reduction in the overall number of cancer patients admitted to hospitals ranging from 20 to 30% [17, 18] ; such reductions are, however, similar to the statistically significant differences observed in some of our activities during the most acute epidemic phase (weeks 11-13). Discrepancy maybe due, in part, to the fact that we have included in the analysis specialty visits (~40%) and follow-up consultations (90%) which were carried out by telephone. A more prominent reduction was observed in the gap between chemotherapy visits and actual chemotherapy infusions (Supplementary Fig. 1) , likely due to previous-day telephone triage, which prevented patients with symptoms and/or laboratory abnormalities from unnecessarily accessing the hospital.

Reporting of real-world data should be encouraged to paint a clear picture of how the SARS-CoV-2 pandemic is impacting on cancer care in Italy and worldwide. Uncertainty may cause patients to feel abandoned, aggravate disease-related distress, and lead patients to abandon life-saving treatments, as recently reported in 15-20% of cases [19] . Moreover, fear that restrictive measures may negatively affect cancer management and prognosis may fuel patients' anger and mistrust, leading to low compliance to such measures: in a moment of extreme vulnerability, patient mind activates coping mechanisms that focus on their primary objective, cancer treatment, confining the fear of the infection in the background [20] . Adequate and timely information, an effective doctor-patient relationship, and prompt psychological support are critical to transcend the new physical barriers represented by masks and remote assistance [21] [22] [23] . This conclusion is supported by our data on patients' reported perception of restrictive measures: even though approximately 30% of patients still feared the risk of contracting SARS-CoV-2, the vast majority felt well informed and acceptance of the adopted measures was very high (>80%).

Data reported on SARS-CoV-2 infections in Oncology healthcare professionals and oncological patients are meant to be purely descriptive and have no epidemiological value. The Wuhan Union hospital reported a 1.7% infection rate among healthcare workers [24] and in Italy, more than 21.800 healthcare workers were confirmed as infected [25] . However, epidemiological conclusions cannot be presently drawn, as testing strategies vary widely across different hospitals and within the same hospital; in addition, close contacts of positive oncology healthcare professionals were aggressively tracked down and none tested positive. Importantly, only 1 of the positive health professionals was actually in contact with oncological patients and colleagues in charge of "clean" oncological activity, supporting the effectiveness of a segregated-team model in containing infection risks [18] . With regard to cases of infection in our cancer patient population, we elected to collect and analyse only cases requiring hospital admission, for whom we had a reliable source of information and a precise reference population. A recent epidemiological study conducted in the Veneto region indicates a 0.3% prevalence of SARS-CoV-2 infection among male cancer patients, with a slightly but significantly higher odds ratio, as compared to the general population [OR: 1.79 (1.62-1.98) , P<0.0001] [26] ; however, these data should be interpreted with caution, since neither all cancer patients nor the general population have been systematically tested and NPS may not detect a resolved past infection, thus potentially underestimating the actual prevalence of SARS-CoV-2 exposure. Whether incidence and clinical severity of SARS-CoV-2 infection in oncological patients is different from those in the general population remains to be answered. Currently available series are limited and convey conflicting results [5] [6] [7] [27] [28] [29] ; larger, well-designed, epidemiological studies will need to be conducted, perhaps using serological approaches [30] , to definitively address these questions.

Nevertheless, the number of severe cases requiring hospital admission appears to be low in our experience, with a 1.3% (7/525) rate of severe infection in the population of patients who accessed Oncology facilities during the epidemics peak (February 1 st -April 14 th ).

Potential long-term impact of infection containment measures on Oncology care should be considered. Suspension of screening programs, diagnostic procedures, follow-up visits and the inadequate timing of supportive care, is predicted to lead to a 5-10% decrease in survival in highincome countries [31, 32] ; such figures could be even worse, if we also consider the possible slow down of oncology clinical trials and cancer research, education and collaboration [33] . However, the experience we report herein suggests that timely and thoughtful adoption of organizational and protective measures, coordinated efforts of all the figures involved in modern cancer care (physicians, psychologists, nurses, auxiliary and support personnel), and effective communication strategies to frankly share risks and needed sacrifices with patients/caregivers [22] can lead to effective protection of healthcare workers and cancer patients alike, while minimally disrupting adequate cancer care. All authors participated in drafting, reviewing, and approval of the final manuscript.

M.M. reports personal fees from Pfizer, EUSA Pharma and Astra Zeneca, outside the submitted manuscript. S.P. received honoraria or speakers' fee from Astra-Zeneca, Eli-Lilly, BMS, Boehringer Ingelheim, MSD and Roche, outside the submitted manuscript. All remaining authors have declared no conflicts of interest.

All the patients, families, caregivers, for their patience, understanding and constant support to our work.

The Division of General and Pancreatic Surgery, which has hosted and taken care of our Oncology inpatients when our ward, in a mere 3-hour time, was turned into a COVID unit.

All the colleagues, co-workers, collaborators across the entire Verona University Hospital Trust, as well as the Strategic Hospital Direction, for the constant help, support, and sharing of clinical and organizational decisions.

Without any of these components, such a huge and coordinated team effort and the results presented herein would not have been possible. 

To postpone, where possible and in accordance with the specialists, follow-up, to limit the time spent in health facilities (both to limit the risk of exposure to SARS-CoV-2, and to reduce the amount of work of structures already partially overloaded).

Delay physical examination of patient unless urgent clinical reasons. Where possible: telematical contact to allow examination of lab/imaging exams.

Routine blood tests may be carried out at local healthcare centers rather than in hospital. Essential imaging assessments to check on the progress of cancer will still go ahead, but these may be reduced in frequency, especially if you are in remission or have stable or slowly-progressing cancer.

Non-urgent FU visit suspended in presence. E-mail and phone contact with patient to allow examination of lab and imaging exams. 

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The authors would like to thank the amazing nursing team of the Oncology Section and all the auxiliary and atypical personnel, for their hard work, dedication, and self-sacrifice, always with a smile and a positive attitude towards patients, their families, colleagues and co-workers.

Organizational challenges, volumes of oncological activity, and patients' perception during the SARS-CoV-2 epidemic.

Timely adoption of protective measures can protect healthcare workers and patients Careful organization allowed to minimally reduce oncological activities volumes Information and psychological support are crucial to accept measures-related change Long-term impact of containment measures on cancer care should be further explored

M.M. reports personal fees from Pfizer, EUSA Pharma and Astra Zeneca, outside the submitted manuscript. S.P. received honoraria or speakers' fee from Astra-Zeneca, Eli-Lilly, BMS, Boehringer Ingelheim, MSD and Roche, outside the submitted manuscript. All remaining authors have declared no conflicts of interest.