Kimberley L Kiong MBBS 1 , Theresa Guo MD 1 , Christopher MKL Yao MD 1 , Neil D Gross MD 1 , Matthew M Hanasono MD 2 , Renata Ferrarotto, MD 3 , David I Rosenthal MD 4 , Jeffrey N Myers MD 1 , Ehab Y Hanna MD1, Stephen Y Lai MD 1 1 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States 2 Department of Plastics and Reconstructive Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States 3Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. 4Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States Corresponding author: Stephen Y Lai, MD PhD Professor Patient Safety Quality Officer The University of Texas MD Anderson Cancer Center Department of Head and Neck Surgery Division of Surgery 1515 Holcombe Blvd, Unit 1445 Houston, TX 77030  [email protected]  This work did not receive any grant support and has not been presented at any meeting Running title: Changing Head & Neck surgical practice during COVID-19 Keywords : Otolaryngology, Oncology, SARS-CoV2 Abstract: Background: The COVID-19 pandemic has changed healthcare, challenged by resource constraints and fears of transmission. We report the surgical practice pattern changes in a Head and Neck Surgery department of a tertiary cancer care center and discuss the issues surrounding multidisciplinary care during the pandemic. Methods: We report data regarding outpatient visits, multidisciplinary treatment planning conference, surgical caseload, and modifications of oncologic therapy during this pandemic and compared this data to the same interval last year. Results: We found a 46.7% decrease in outpatient visits and a 46.8% decrease in surgical caseload, compared to 2019. We discuss the factors involved in the decision-making process and perioperative considerations. Conclusions: Surgical practice patterns in head and neck oncologic surgery will continue to change with the evolving pandemic. Despite constraints, we strive to prioritize and balance the oncologic and safety needs of patients with head and neck cancer in the face of COVID-19. IntroductionThe rapid spread of the novel coronavirus 2019 (COVID-19) has disrupted healthcare systems globally. Some of the biggest challenges include shortage of hospital beds, healthcare workers and personal protective equipment (PPE). Given these constraints, there has been a simultaneous push for a reduction in elective clinical practice, to further reduce transmission and conserve resources 1.Cancer care is generally not considered elective and decision making about when to initiate or delay treatment during the pandemic has raised complex ethical and resource utilization issues. Yet amidst the pandemic, patients continue to develop and seek treatment for cancer. Head and neck cancers (HNC) can challenge essential functions such as eating, speaking and breathing. Tumor doubling time ranges between 15 to 99 days 2,3 and delaying treatment decreases survival and contributes to adverse outcomes 4,5. As such, there are recommendations for prompt initiation of treatment of HNC after diagnosis and to reduce the total treatment package time6,7. In an effort to limit the potential adverse effects of delaying cancer treatment during this pandemic, an increasing number of oncology guidelines have been developed, both general and specific to HNC 8,9.At the University of Texas MD Anderson Cancer Center (MDACC), our Head and Neck surgical practice has gradually changed as a result of evolving internal and external guidelines (Table 1). Harris County, Texas reported its first COVID-19 case on March 5th, 2020. Since then, the number of cases has been steadily rising with the current incidence at 35 per 100,000 residents in Texas 10. At the institutional level, MDACC has taken many pre-emptive actions and policy changes in response to the growing pandemic (Table 1).The institutional policies described have served to limit hospital attendances in anticipation of a surge in COVID-19 cases in the region. The number of new patients visits to the institution have decreased from 782/week in the first week of March to 207/week in the last week of March (-73.5%) while systemic treatment appointments, indicative of patients already in the process of treatment, have remained fairly stable (3864 to 3288 visits, -14.9%). As a downstream effect, the number of diagnostic imaging visits has decreased from 9616 to 3971 (first and last weeks of March respectively, -58.7%). Surgeries within the institution have shown a more drastic decrease, from 463 to 149 cases per week (-67.8%). Current institutional census at the time of writing (April 7th, 2020) shows 55% general bed occupancy and 35% ICU occupancy. The numbers will continue to change in response to the development of COVID-19 within the region, as we have not yet reached the peak of infection. Predictive models have suggested that the peak in COVID-19 cases will occur at the end of April11 and there are institutional plans on standby to repurpose physical facilities and the workforce to shift focus from oncology care to COVID-19 treatment if needed.In the context of the developing pandemic and tightening institutional guidelines, we seek to understand the early impact of the COVID-19 pandemic on head & neck oncologic surgery practices. We performed a review of outpatient clinic and surgical caseload within the MDACC Head and Neck Surgery department during the pandemic and compared this to the same time period in the preceding year, along with the deviations in management of patients due to COVID-19.

Elderly head and neck cancer patients are at increased risk of adverse outcomes during and after treatment of head and neck cancer. COVID-19 severity and mortality can be expected to be significantly greater in elderly head and neck cancer patients, given that increased age, comorbidities, and presence of malignancy are known risk factors for disease severity and mortality in COVID-19 patients. Therefore, their management requires multidisciplinary consensus and patient input. A thorough geriatric assessment, which has been shown to be beneficial prior to the COVID-19 pandemic, could be particularly helpful in this patient population with the added dimension of COVID-19 risk. In many cases, prudent treatment plan modification may allow for overall best outcomes. Furthermore, recruitment of social services and, when appropriate, palliative care, may allow for optimal management of these patients.

Flora Yan, BA1; Shaun A. Nguyen, MD11: Department of Otolaryngology – Head and Neck Surgery, Medical University of South Carolina.Word Count: 1,260Conflicts of Interest: None to DiscloseCorresponding Author:Flora YanDepartment of Otolaryngology – Head and Neck Surgery135 Rutledge Avenue, MSC 550, Charleston, SC [email protected] first identified in December of 2019, COVID-19 has disseminated from Wuhan, China rapidly across the globe. 5-8% of these COVID-19 patients are estimated to become critically ill and will require ICU admission. Predictors of severe/critical ill COVID-19 disease may include increasing age, smoking status, immunosuppression and chronic conditions such as cardiovascular disease, diabetes, hypertension and also cancer. In this brief correspondence, we first describe the outcomes of critically ill patients with and without cancer and extrapolate these findings to the head and neck cancer population.Dear Dr. Hanna,Since first identified in December of 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has disseminated from Wuhan, China rapidly across the globe. On March 11th, 2020 the World Health Organization deemed Coronavirus Disease 2019 (COVID-19) a worldwide pandemic, with the global community in a state of emergency.1 As of April 10th, 2020, 1.6 million COVID-19 cases have been reported worldwide.2 Case-fatality rate have ranged from 2% to 7%.3 Clinically, COVID-19 is initially characterized by a constellation of non-specific symptoms such as cough, fever, and dyspnea. However, this can escalate quickly, with the median time from symptom onset to severe hypoxemia necessitating ICU admission seen to be from 7 to 12 days.4-6 It is clear certain populations such as patients with coexisting conditions, older age, an immunocompromised state and a smoking history are at a high risk for severe disease as well as poor outcomes.7 Head and neck cancer patients are placed in a vulnerable state and may equally be of high-risk to the consequences of COVID-19, given their immunosuppressed state from cancer and corresponding treatment as well as high prevalence of the aforementioned risk factors. In this correspondence, we aim to discuss sequelae of severe COVID-19 disease, in addition to describing head and neck cancer patients as a high-risk population.The majority of COVID-19 cases are of mild severity, however 5-8%5,8 of COVID-19 patients may become critically ill, experiencing respiratory failure, septic shock and/or multi-organ failure. This necessitates admission into the intensive care unit (ICU). Two-thirds of these critically ill patients have met criteria for acute respiratory distress syndrome (ARDS) and require advanced respiratory support. The acute severity and rapid progression of COVID-19 is illustrated with over 63% requiring invasive mechanical ventilation in the first 24 hours of admission.9 Mortality of COVID-19 patients in the ICU has been estimated to be 50%7,10. Of these, patients of older age > 70 years old and with severe comorbidities were seen to have mortality rates of 68 and 59%, respectively.9 As defined by the Center for Disease Control’s weekly morbidity and mortality report regarding COVID-19, these comorbidities may include diabetes mellitus, chronic lung disease, cardiovascular disease, chronic renal disease, and other chronic disease, of which a history of cancer falls under.11ARDS secondary to COVID-19 requires time on mechanical ventilation than is usually required. Bhatraju et al.7 reports a median of 10 days of time on mechanical ventilation before COVID-19 patients were extubated. This is in comparison to 3 to 8 days seen on average for non-COVID related indications for mechanical ventilation.12 Even then, most patients are unable to wean off mechanical ventilation, as seen by a tragically high mortality rate of COVID-19 patients on mechanical ventilation (Table 1) . The Intensive Care National Audit & Research Centre (ICNARC) demonstrated a 67.3% mortality rate of patients receiving advanced (i.e. non-invasive or invasive ventilation, tracheostomy or extracorporeal respiratory support) respiratory support.9 Studies from China examining critically ill COVID-19 patients placed on mechanical ventilation have reported mortality rates of 81% to 97%.4,5 A Seattle-based analysis of critically ill patients on mechanical ventilation saw a comparatively lower mortality rate of 50%, however at the time of this study 3 were still on mechanical ventilation without recovery from COVID-19.7 These extraordinary high mortality rates of patients on mechanical ventilation, ranging from 50% to 97%, may reveal that full intensive care support and life-sustaining therapies still cannot overcome the poor prognosis of certain high-risk populations afflicted by COVID-19. Deterioration despite mechanical ventilation may be confounded by multi-organ system failure. Those who fail mechanical ventilation may be placed on extracorporeal membrane oxygen (ECMO) therapy as end of the line care, however this is often accessible in most hospital systems. In fact, even with substantial cases of critically ill COVID-19 patients, ECMO therapy use has ranged from 6 to 12%.4,5As patients with cancer, especially those in active treatment or in the acute post-treatment phase, are in a particularly immunosuppressed conditions, elucidation of the course of COVID-19 in this patient population is paramount. Liang et al.13 describe a cohort of 18 cancer patients (1 [6%] of which with head and neck cancer) having a higher risk of mechanical ventilation or death (39% vs. 8%), compared to non-cancer patients. Cancer patients also more rapidly deteriorated, with a median time to a critical event taking 13 days as opposed to 43 days in non-cancer patients.Multiple other studies have described cancer patients with COVID-19. Desai et al.14 performed a meta-analysis of 11 studies describing clinical courses of COVID-19 cases and found a 2% prevalence of cancer in patients with COVID-19. Desai et al.14also discovered higher risk of severe events for patients recently treated with chemotherapy or surgery in the past 30 days, over non-cancer COVID-19 patients (75% vs. 43%).Zhang et al.15 revealed clinical characteristics of 28 COVID-19 infected cancer patients in Wuhan China, of which 3 (11%) had head and neck cancer. Of this cohort, 10 (36%) of patients required mechanical ventilation and 8 (29%) patients died. If assumed these 8 were on maximum respiratory therapy previous to death, a mortality rate of 80% can be extrapolated and is in line to mortality rates of critically ill non-cancer patients; this, however, is not explicitly validated in the study. Notably, stage IV disease was associated with higher rates of severe events (ICU admission, mechanical ventilation, or death) than stage I-III disease (70% vs 44%). Zhang et al.15 also revealed patients recently treated with chemotherapy, radiation therapy, and/or immunotherapy in the past 14 days had a 4-times increased odds of developing a severe event than those who received any treatment > 14 days.From this we can observe that 1) prevalence of cancer, active or in remission, in COVID-19 patients is higher than in the general population; 2) COVID-19 patients with cancer may deteriorate more rapidly than non-cancer patients 3) active treatment of cancer may be associated with increased risk of severe COVID-19 sequelae than in patients not undergoing treatment; and 4) critically ill COVID-19 patients who have cancer may more likely develop end-stage respiratory failure or death than non-cancer critically ill patients, barring presence of other chronic illnesses. It is difficult to ascertain how cancer patients in remission may far in comparison to the general population, however it is clear patients undergoing active treatment may present as a high-risk population for severe illness following COVID-19 infection. These observations are limited on data provided by retrospective studies of small sample sizes, and thus must be interpreted with caution.Cancer patients present as a high-risk population for COVID-19 development as well as poorer outcomes. Head and neck cancer patients in particularly may be susceptible to the deleterious effects of not only the viral pathogenesis of COVID-19 itself, but also the long-term psychosocial sequelae of intensive critical care, advanced respiratory treatment and other life-saving measures, all amidst a quarantined environment for a patient population characterized as having twice the suicide risk rate of other cancer patients. Given such high death rates of non-cancer patients on mechanical ventilation, the additive vulnerability from head and neck cancer may make severe or critical ill COVID-19 development quite fatal for our patients. Thus, more attention and perhaps additional testing for patients currently undergoing treatment may be warranted. As described in modified head and neck cancer treatment algorithms16, treatment only for advanced head and neck cancers should proceed with full precautions (i.e. COVID testing, PPE) and any possible methods to reduce nosocomial COVID-19 infection is warranted. We hope this correspondence provides insight in the high-risk of head and neck cancer patients for critical illness following COVID-19 infection.Works Cited1. World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19—11 March 2020. 2020; https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020.2. Worldometer. COVID-19 coronavirus pandemic. https://www.worldometers.info/coronavirus/. Accessed April 10th, 2020.3. Onder G, Rezza G, Brusaferro S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy.JAMA. 2020.4. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062.5. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020.6. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet.2020;395(10223):507-513.7. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. New England Journal of Medicine. 2020.8. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242.9. ICNARC COVID-19 Study Case Mix Programme Database. ICNARC report on COVID-19 in critica care. 2020; https://www.icnarc.org/About/Latest-News/2020/04/04/Report-On-2249-Patients-Critically-Ill-With-Covid-19.10. Guan W-j, Ni Z-y, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine. 2020.11. CDC COVID-19 Response Team. Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 — United States, February 12–March 28, 2020.Morbidity and Mortality Weekly Report. April 3, 2020.12. Seneff MG, Zimmerman JE, Knaus WA, Wagner DP, Draper EA. Predicting the duration of mechanical ventilation. The importance of disease and patient characteristics. Chest. 1996;110(2):469-479.13. Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol.2020;21(3):335-337.14. Desai A, Sachdeva S, Parekh T, Desai R. COVID-19 and Cancer: Lessons From a Pooled Meta-Analysis. JCO Global Oncology.2020(6):557-559.15. Zhang L, Zhu F, Xie L, et al. Clinical characteristics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan, China. Ann Oncol. 2020.16. Day AT, Sher DJ, Lee RC, et al. Head and neck oncology during the COVID-19 pandemic: Reconsidering traditional treatment paradigms in light of new surgical and other multilevel risks. Oral Oncol.2020:104684.

Authors: Arjun Gurmeet Singh MDS (Oral and Maxillofacial Surgery), MFDS (Glasgow) Department of Head and Neck Oncology  Tata Memorial Center and HBNI Mumbai, India (Email: [email protected]) Jayita Deodhar,  MD Department of Palliative Medicine Tata Memorial Center and HBNI Mumbai, India (Email: [email protected]) Pankaj Chaturvedi, MS, FACS, (Corresponding Author) Department of Head and Neck OncologyTata Memorial Center, Mumbai, India (Email: [email protected])