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\title{Head and Neck Cancer: A High-Risk Population for COVID-19~~~~}



\author[1]{Flora Yan, BA}%
\affil[1]{Affiliation not available}%


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  \date{May 24, 2024}


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Flora Yan, BA\textsuperscript{1}; Shaun A. Nguyen, MD\textsuperscript{1}

1: Department of Otolaryngology -- Head and Neck Surgery, Medical
University of South Carolina.

Word Count: 1,260

Conflicts of Interest: None to Disclose

Corresponding Author:

Flora Yan

Department of Otolaryngology -- Head and Neck Surgery

135 Rutledge Avenue, MSC 550, Charleston, SC 29425

843-792-8299

yanf@musc.edu

\textbf{Abstract}

Since 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 11\textsuperscript{th}, 2020 the
World Health Organization deemed Coronavirus Disease 2019 (COVID-19) a
worldwide pandemic, with the global community in a state of
emergency.\textsuperscript{1} As of April 10\textsuperscript{th}, 2020,
1.6 million COVID-19 cases have been reported
worldwide.\textsuperscript{2} Case-fatality rate have ranged from 2\% to
7\%.\textsuperscript{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.\textsuperscript{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.\textsuperscript{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\%\textsuperscript{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.\textsuperscript{9} Mortality of
COVID-19 patients in the ICU has been estimated to be
50\%\textsuperscript{7,10}. Of these, patients of older age
\textgreater{} 70 years old and with severe comorbidities were seen to
have mortality rates of 68 and 59\%, respectively.\textsuperscript{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.\textsuperscript{11}

ARDS secondary to COVID-19 requires time on mechanical ventilation than
is usually required. Bhatraju et al.\textsuperscript{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.\textsuperscript{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 \textbf{(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.\textsuperscript{9} Studies from China examining critically ill
COVID-19 patients placed on mechanical ventilation have reported
mortality rates of 81\% to 97\%.\textsuperscript{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.\textsuperscript{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\%.\textsuperscript{4,5}

As 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.\textsuperscript{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.\textsuperscript{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.\textsuperscript{14}also 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.\textsuperscript{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.\textsuperscript{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 \textgreater{} 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 algorithms\textsuperscript{16}, 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 Cited

1. 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.\emph{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. \emph{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. \emph{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. \emph{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. \emph{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. \emph{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. \emph{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.\emph{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. \emph{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. \emph{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. \emph{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. \emph{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. \emph{Oral
Oncol.}2020:104684.

\par\null

\textbf{Hosted file}

\verb`HED-20-0517_COVID_Table_1.docx`  available at \url{https://authorea.com/users/312328/articles/443222-head-and-neck-cancer-a-high-risk-population-for-covid-19}

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