key: cord-0884567-p7djk342
authors: Anwar, Sumadi Lukman; Cahyono, Roby; Hardiyanto, Herjuna; Suwardjo, Suwardjo; Darwito, Darwito; Harahap, Wirsma Arif
title: The prioritation and gap of preoperative COVID-19 vaccination in cancer surgery of the breast, head and neck, and skin: A cohort study of 367 patients in an Indonesian hospital
date: 2021-11-18
journal: Ann Med Surg (Lond)
DOI: 10.1016/j.amsu.2021.103089
sha: ac8a5a2174398879a5bfb6cc9acb6ff9d52b0230
doc_id: 884567
cord_uid: p7djk342

BACKGROUND: Postoperative infection of Coronavirus Disease 2019 (COVID-19) has been associated with higher risks of mortality and pulmonary complication. Preoperative vaccination could significantly prevent postoperative-related mortality and morbidity particularly for cancer patients. METHODS: Cancer patients who were scheduled for elective major surgery were questioned for status and their willingness to receive COVID-19 vaccination and were prospectively monitored for the presence of postoperative COVID-19 infection and major complications. RESULTS: During the period of April–July 2021, 367 patients with median age of 49 years were scheduled for cancer surgery. Procedures for breast cancer were the most frequently performed (N = 166, 45.2%). Surgery procedures with potential aerosol generating procedures (AGPs) were performed in total of 104 patients (28.3%). Only 6 of 367 patients (1.6%) were fully vaccinated in the day of surgery and 351 patients (95.6%) were willing to receive COVID-19 vaccination. Fully vaccinated patients were significantly higher among those who were living in urban areas (OR = 22.897, 95%CI:4.022–130.357, P = 0.0001). Willingness to get the COVID-19 vaccination was significantly higher among female patients (OR = 4.661, 95%CI:1.685–12.896, P = 0.003). Postoperative COVID-19 infection was confirmed in 17 patients (4.6%) and major surgical complications were observed in 12 patients (3.3%). None of preoperatively vaccinated patients experienced postoperative COVID-19 infection or the related major complications. CONCLUSION: Although prioritizing COVID-19 vaccination in preoperative cancer patients has been recommended to prevent postoperative fatalities, only a small proportion of our patients have been vaccinated. Preoperatively vaccinated patients show advantages in the prevention of postoperative COVID-19 infection and major surgery complications. The slow rollout and disparity in the vaccination progress for patients requiring a major cancer surgery need to be specifically addressed.

The prolonged COVID-19 pandemic has disrupted elective cancer surgery with 3 frequent cancellation of non-essential procedures [1] [2] [3] . Technical assistance and 4 recommendation for triage and prioritization of cancer surgery has been developed by several 5 professional organizations to redirect hospital resources for COVID-19 management [3] [4] [5] . 6 However, specific considerations related to deferring cancer surgery in developing countries 7 need to compromise between prevention of ongoing COVID-19 transmission and preservation 8 of patient's long-term prognosis [1] . Cancers in developing countries are often diagnosed in 9 late stages [6-9] and postponing surgery might have significant impact to the treatment 10 outcomes and patients' quality of life. However, maintaining elective cancer surgery service 11 during the pandemic will face several challenges. In the area with high levels of community 12 transmission and elective surgery has been performed in COVID-19-free pathway, surgical 13 patients are still at a high risk of COVID-19 infection [10] conferring them with significant 14 higher rates of mortality and pulmonary complications after surgery [11, 12] . 15

The World Health Organization (WHO) has currently listed 12 vaccines for emergency 16 use globally [13] . Implementation of preoperative vaccination has been associated with a 17 reduced risk of postoperative pulmonary complications and mortality due to infection [11] . Relatively higher effectivity to save lives has been projected if the vaccination 19 is prioritized to older cancer patients [11] . Because of the shortage in the availability of 20 vaccines globally, low-and middle-income countries including Indonesia have to prioritize the 21 populations at greater risk to receive the vaccine [11, 14] . It is predicted that far-reaching 22 coverage of the COVID-19 vaccination in developing countries will be achieved only until late 23 2022 [15] . 24

Although the benefits of preoperative COVID-19 vaccination have been studied, the 25 prioritization and rolling out for surgery patients are not yet manifested in some countries. In 26 Indonesia, a national program for vaccination was initiated in January 2021 with prioritization 27 for health care workers, the elderly, and public service workers [16] . After India experienced 28 the second wave of COVID-19 pandemic with surging cases and mortality in March -June 29 2021[17], Indonesia has also been affected by the second pandemic wave in the following 30 months (June -July 2021) with daily cases over 50,000 including during the period of this 31 study [18] . In the presence of high levels of community transmission, infection control and 32 associated medical complications during postoperative care need to be well managed [11] . To 33 maintain and re-establish elective cancer surgery services during and after the pandemic, preoperative vaccination is a very important step to support safe surgical care [11, 19] . This 1 study surveyed and estimated the status and gap in the preoperative COVID-19 vaccination of 2 cancer patients within a hospital setting in a developing country. 3 4 5 2. Materials and Methods 6 2.1 Study design 7 8 The study was performed by direct survey to preoperative cancer patients in an 9 oncology clinic 1-7 days before the scheduled surgery. The planned procedures were 10 performed in COVID-19-free surgical pathway in a referral hospital in Indonesia All patients were followed-up for a 30-day period after surgery for the presence of 1 COVID-19 infection (using hospital checklist of COVID-19 screening, history taking, physical 2 examination, and testing following the local procedure of COVID-19 assessment and testing 3 pathway). We used Clavien-Dindo grade III-V as a measure of postoperative major 4 complications. The secondary outcome measures were post-operative major complications 5 including mortality, pulmonary complication, prolonged intensive care, unexpected 6 ventilation, re-admission, and pneumonia during the 30-day period after surgery. We were able to recruit 367 cancer patients scheduled for surgery during the period of 20 1 April 2021 to 31 July 2021. The majority of patients were female (N=297, 80.9%) and surgery 21 procedures in the breast were the most frequently performed (N=166, 45.3%, Table 1 ). Surgery 22 in the thyroid, lymph nodes, soft tissue sarcoma, head and neck, skin, and salivary glands were 23 performed in 18.3%, 9.5%, 8.7%, 7.1%, 6.5%, 6.5%, and 4.6%, respectively. Wide excision 24 with / or without skin flap or skin graft was the most common surgery procedures during the 25 study (N=115, N=31.4%). Mastectomy and thyroidectomy accounted for almost half of the 26 surgical procedures in this study (28.1% and 17.2%, respectively). Aerosol generating 27 procedures (AGPs) during the process of general anesthesia and surgery were potentially found 28 in the procedures of thyroidectomy, neck dissection, parotidectomy, hemimandibulectomy, 29 hemoglossectomy, and hemimaxilectomy (in a total of 104 patients, 28.3%). 30

Safety and efficacy of COVID-19 vaccination vary among populations with complex 31 medical comorbidities. Among preoperative cancer patients in this study (N=367), 22.1% 32 (N=81) had hypertension (Grade 1-3), 13.4% (N=49) had type-2 diabetes, 2.2% (N=8) had 33 chronic infection (human immunodeficiency virus infection, hepatitis-B infection, and erythematosus), 0.8% (N=3) had chronic renal diseases (hydronephrosis), 0.8% (N=3) had 1 cardiovascular diseases (stroke, congestive heart failure), 2.7% (N=10) had dyslipidemia, and 2 29.4% (N=108) patients were overweight or obese. In total, 122 (33.2%) patients had at least 3 one medical comorbidity and 29 (7.9%) patients had multiple comorbidities (Table 1) vaccines were first deployed. All preoperative fully vaccinated patients (N=6) received Sinovac 10 vaccines. We found no significant different between male and female patients in the status of 11 preoperative vaccination (P=0.880, Table 2 ). Patients who lived in urban areas were 12 significantly associated with higher chance to be fully vaccinated before cancer surgery 13 compared to those who lived in rural areas (OR=22.897, 95%CI:4.022-130.357, P=0.0001). 14 Of all patients, 95.6% (N=351) expressed that they were willing to take COVID-19 vaccine. 15

Acceptance to COVID-19 vaccination was significantly higher among female patients 16 (OR=4.661, 95%CI=1.685-12.896, P=0.003, Table 2 ). Vaccination acceptance was not 17 associated with patients' residence in rural and urban areas. One in a thousand of the COVID-19-related mortalities could be prevented with 21 preoperative vaccination [11] . The number of lives that could be saved with preoperative 22 vaccination could be even higher in older cancer patients [11] . This study surveyed status and 23 willingness of getting the COVID-19 vaccination among preoperative cancer patients and 24

prospectively observed the presence of COVID-19 infection and major surgery complications 25 within period of 30-day after surgery. In our study, half patients were at age of 35-55 years 26 (Table 1 ) and 4.6% (N=17) were older than 70 years that were most benefited from vaccination 27 to prevent COVID-19 related mortality [11] . Surgery procedures with potential AGPs were 28 performed in 28.2% patients causing higher risks of COVID-19 transmission to healthcare 29 workers and other surgery patients in the ward. Although elective surgery was performed in 30 COVID-19-free pathway, there was still a risk of cross-infection from patients in the incubation 31 period who had tested negative at admission [21] and the risk was even higher in procedures 32 involving AGPs. 33 J o u r n a l P r e -p r o o f Cancer has been considered as a comorbidity for COVID-19 patients with three times 1 higher risk of death [1, 10] . Pre-existing comorbidities in cancer patients have been associated 2 with high risks of transmission and poorer outcome after contracting COVID-19 [21] . 3

Hypertension and diabetes were the most common additional comorbidities in this study 4 (22.1% and 13.4%, respectively). Additional pre-existing comorbidities in cancer patients will 5 predispose them to higher medical complications after surgery in association with COVID-19 6 infection [10, 21, 22] . In addition to the elevated COVID-19 transmission [21, 22] , metabolic 7 comorbidities per se have adverse association with long-term prognosis of cancer patients [23]. 8

Surgery itself is also associated with higher risk of virus exposure due to proinflammatory 9 cytokines and mechanical ventilation [22] . In patients with advanced cancer stages at diagnosis 10 as commonly found in developing countries, systemic proinflammatory markers are usually 11 also higher [24] that might increase risks of complication after surgery. Preexisting 12 comorbidities have been associated with higher hesitancy to receive COVID-19 vaccination 13 due to safety concerns [11, 14] . In the beginning of the COVID-19 rollout, ageism emerged as 14 an important issue in Indonesia since elderly were often positioned at the back of queue [25] . 15

With high incidence of additional comorbidities (33.2%, N=122, Table 1) among cancer  16 patients, the queue and willingness to receive the COVID-19 vaccine might cause wider 17 vaccination gap. 18

We identified a significant vaccination gap between preoperative cancer patients living 19

in the rural and urban areas (OR 22.9, Table 2 ). Although a similar disparity has also been 20 reported in high income countries [26], policy priority and equitable vaccine distribution need 21 to be continuously improved in Indonesia. We also identified significantly lower acceptance of 22 COVID-19 vaccine among males and cancer patients older than 60 years (Table 2) Although frequency of medical comorbidity among preoperative cancer patients was completeness (Table 3 ). The proportion of fully vaccinated preoperative patients was very low 1 in this study that might be caused both those with and without comorbidities who were not yet 2 vaccinated. Comorbidity increases risks of infection, severely illness, and death, thus in the 3 scenario of limited vaccine availability, populations with comorbidities should be prioritized 4 [30] . Cancer itself is a comorbid condition that has 7 times increased risk to be infected [31] 5 and usually with worse COVID-19-related outcomes. Therefore, cancer patients should be 6 considered to be put in the first queue for COVID-19 vaccination [10, 11] . Preexisting medical 7 comorbidities in cancer patients including elderly, diabetes, overweight, and hypertension 8 should also warrant the prioritization [11, 30] . However, we identified lower willingness to get 9 the COVID-19 vaccination in cancer patients with additional comorbidities of hypertension, 10 chronic renal diseases, and cardiovascular diseases ( We observed that preoperative fully vaccinated patients did not experience COVID-19 20 infection and major surgery complications. It has been reported that 0.6-1.6% patients are 21 infected with COVID-19 virus after undergoing elective surgery thus predisposing them with 22 up to 8 times increased risk of mortality in the 30 days after surgery [11, 22] . In this study, we 23 confirmed 4.6% postoperative COVID-19 infection almost triple than previously reported [11] . hospital admission and community. This study had some limitations since only 6 patients 10 (1.4%) patients were fully vaccinated before the surgery that prevented some statistical tests. 11

In addition, we surveyed patients directly to assess acceptance or hesitancy to get the COVID-12 19 vaccination and did not provide further follow-up. A multicenter study with additional 13 exploration in the intended acceptance or hesitance to vaccination will provide more accurate 14 delineation of the advantages as well as challenges of preoperative vaccination to support 15 reinitiating safe elective surgery procedures in the resilience period after COVID-19 pandemic. J o u r n a l P r e -p r o o f 

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2021 14 update of the AGIHO guideline on evidence-based management of COVID-19 in patients 15 with cancer regarding diagnostics, viral shedding, vaccination and therapy

Risk factors of distant 18 metastasis after surgery among different breast cancer subtypes a hospital-based study in 19

Regional 21 lymph node infiltration and thick lesions are associated with poor prognosis in high-risk 22

SARS-CoV-2 vaccination modelling for safe 1 surgery to save lives: data from an international prospective cohort study

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Using 12 syndromic measures of mortality to capture the dynamics of COVID-19 in Java, Indonesia, in 13 the context of vaccination rollout

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India: barriers to effective governmental response

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A 14 modelling study investigating short and medium-term challenges for COVID-19 vaccination: 15 From prioritisation to the relaxation of measures

Analyses of risk, racial disparity, and outcomes among US 17 patients with cancer and COVID-19 infection

COVID-19 vaccination in cancer patients in Hong Kong: approaches to improve the 20 vaccination rate

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