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Butler-Laporte, Guillaume, Povysil, Gundula, Kosmicki, Jack, Cirulli, Elizabeth, Drivas, Theodore, Furini, Simone, Saad, Chadi, Schmidt, Axel, Olszewski, Pawel, Korotko, Urszula, Quinodoz, Mathieu, Çelik, Elifnaz, Kundu, Kousik, Walter, Klaudia, Jung, Junghyung, Stockwell, Amy, Sloofman, Laura, Charney, Alexander, Jordan, Daniel, Beckmann, Noam, Przychodzen, Bartlomiej, Chang, Timothy, Pottinger, Tess, Shang, Ning, Brand, Fabian, Fava, Francesca, Mari, Francesca, Chwialkowska, Karolina, Niemira, Magdalena, Pula, Szymon, Baillie, Kenneth, Stuckey, Alex, Ganna, Andrea, Karczewski, Konrad, Veerapen, Kumar, Bourgey, Mathieu, Bourque, Guillaume, Eveleigh, Robert J. M.; Forgetta, Vincenzo, Morrison, David, Langlais, David, Lathrop, Mark, Mooser, Vincent, Nakanishi, Tomoko, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklos, Marincevic-Zuniga, Yanara, Nordlund, Jessica, Schiabor Barrett, Kelly, Lee, William, Bolze, Alexandre, White, Simon, Riffle, Stephen, Tanudjaja, Francisco, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Casadei, Nicolas, Motameny, Susanne, Alaamery, Manal, Massadeh, Salam, Aljawini, Nora, Almutairi, Mansour, Arabi, Yaseen, Alqahtan, Saleh, Al Harthi, Fawz, Almutairi, Amal, Alqubaishi, Fatima, Alotaibi, Sarah, Binowayn, Albandari, Alsolm, Ebtehal, Bardisy, Hadeel El, Fawzy, Mohammad, Geschwind, Daniel, Arteaga, Stephanie, Stephens, Alexis, Butte, Manish, Boutros, Paul, Yamaguchi, Takafumi, Tao, Shu, Eng, Stefan, Sanders, Timothy, Tung, Paul, Broudy, Michael, Pan, Yu, Gonzalez, Alfredo, Chavan, Nikhil, Johnson, Ruth, Pasaniuc, Bogdan, Yaspan, Brian, Smieszek, Sandra, Rivolta, Carlo, Bibert, Stephanie, Bochud, Pierre-Yves, Dabrowski, Maciej, Zawadzki, Pawel, Sypniewski, Mateusz, Kaja, Elżbieta, Chariyavilaskul, Pajaree, Nilaratanakul, Voraphoj, Hirankarn, Nattiya, Shotelersuk, Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Kawai, Yosuke, Hasegawa, Takanori, Naito, Tatsuhiko, Namkoong, Ho, Edahiro, Ryuya, Kimura, Akinori, Ogawa, Seishi, Kanai, Takanori, Fukunaga, Koichi, Okada, Yukinori, Imoto, Seiya, Miyano, Satoru, Mangul, Serghei, Abedalthagafi, Malak, Zeberg, Hugo, Grzymski, Joseph, Washington, Nicole, Ossowski, Stephan, Ludwig, Kerstin, Schulte, Eva, Riess, Olaf, Moniuszko, Marcin, Kwasniewski, Miroslaw, Mbarek, Hamdi, Ismail, Said, Verma, Anurag, Goldstein, David, Kiryluk, Krzysztof, Renieri, Alessandra, Ferreira, Manuel, Richards, Brent, Initiative, Covid- Host Genetics, De, C. O. I. Host Genetics Group, Study, Gen-Covid Multicenter, Gen, Omicc Consortium, Japan, Covid-Task Force, Regeneron Genetics, Center.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332108

ABSTRACT

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,048 severe disease cases and 571,009 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p=5.41×10 -7 ). These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.

2.
Clin Infect Dis ; 74(4): 584-590, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1709326

ABSTRACT

BACKGROUND: With limited severe acute respiratory syndrome coronavirus (SARS-CoV-2) testing capacity in the United States at the start of the epidemic (January-March 2020), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic. METHODS: All of Us study participants in all 50 US states provided blood specimens during study visits from 2 January to 18 March 2020. Participants were considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies with the Abbott Architect SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. The sensitivity and specificity of these ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated, along with 95% confidence intervals (CIs). RESULTS: The estimated sensitivities of the Abbott and EUROIMMUN assays were 100% (107 of 107 [95% CI: 96.6%-100%]) and 90.7% (97 of 107 [83.5%-95.4%]), respectively, and the estimated specificities were 99.5% (995 of 1000 [98.8%-99.8%]) and 99.7% (997 of 1000 [99.1%-99.9%]), respectively. The net sensitivity and specificity of our sequential testing algorithm were 90.7% (97 of 107 [95% CI: 83.5%-95.4%]) and 100.0% (1000 of 1000 [99.6%-100%]), respectively. Of the 24 079 study participants with blood specimens from 2 January to 18 March 2020, 9 were seropositive, 7 before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. CONCLUSIONS: Our findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states.


Subject(s)
COVID-19 , Population Health , Antibodies, Viral , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G , SARS-CoV-2 , Sensitivity and Specificity
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323710

ABSTRACT

There is an urgent need to identify effective therapies for COVID-19. The SARS-CoV-2 host factor protease TMPRSS2 is required for viral entry and thus an attractive target for therapeutic intervention. In mouse, knockout of tmprss2 led to protection against SARS-CoV-1 with no deleterious phenotypes, and in human populations genetic loss of TMPRSS2 does not appear to be selected against. Here, we mined publicly available gene expression data to identify several compounds that down-regulate TMPRSS2. Recognizing the need for immediately available treatment options, we focused on FDA-approved drugs. We found 20 independent studies that implicate estrogenic and androgenic compounds as transcriptional modulators of TMPRSS2, suggesting these classes of drugs may be promising therapeutic candidates for clinical testing and observational studies of COVID-19. We also note that expression of TMPRSS2 is highly variable and skewed in humans, with a minority of individuals having extremely high expression. Combined with literature showing that inhibition of TMPRSS2 protease activity reduces SARS-CoV-2 viral entry in human cells, our results raise the hypothesis that modulation of TMPRSS2 expression is a promising therapeutic avenue for COVID-19.

4.
Journal of Clinical Investigation ; 131(15):1-1,1A, 2021.
Article in English | ProQuest Central | ID: covidwho-1338047

ABSTRACT

[...]the power computation shown in their Figure 1 is based on an incorrect hypothesis about the odds ratio, which would be expected to be lower when using general population controls (as they did) than when using paucisymptomatic and asymptomatic infected individuals (as we did). (iv) The ethnic origin of the patients differs between the 2 studies: 58% of our 659 patients (and 8 of our 9 pLOF carriers) were European, versus only 10% of their 713 patients with severe disease (and the pLOF carrier was East Asian). (v) Age is a key factor neglected in their comparison: our sample was much younger (mean age, 51.8 years) than theirs (mean, 65.9 years), and 7 of our 9 pLOF carriers were younger than 60 years. Because the rates of pLOFs vary considerably across populations, adjustment for only 3 principal components of ancestry in rare-variant association tests of multiethnic cohorts does not provide adequate control for population structure. [...]none of the associations showed even marginal significance. [...]consistent with our study, these findings do not support substantial contributions of inborn errors in type I IFN immunity to COVID-19 severity.

6.
Trials ; 22(1): 431, 2021 Jul 05.
Article in English | MEDLINE | ID: covidwho-1298059

ABSTRACT

BACKGROUND: Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity. METHODS: This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3-5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated. DISCUSSION: In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04397718. Registered on May 21, 2020.


Subject(s)
COVID-19 , Veterans , Clinical Trials, Phase II as Topic , Hospitalization , Humans , Male , Multicenter Studies as Topic , Oligopeptides , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
7.
Clin Infect Dis ; 74(4): 584-590, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1269569

ABSTRACT

BACKGROUND: With limited severe acute respiratory syndrome coronavirus (SARS-CoV-2) testing capacity in the United States at the start of the epidemic (January-March 2020), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic. METHODS: All of Us study participants in all 50 US states provided blood specimens during study visits from 2 January to 18 March 2020. Participants were considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies with the Abbott Architect SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. The sensitivity and specificity of these ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated, along with 95% confidence intervals (CIs). RESULTS: The estimated sensitivities of the Abbott and EUROIMMUN assays were 100% (107 of 107 [95% CI: 96.6%-100%]) and 90.7% (97 of 107 [83.5%-95.4%]), respectively, and the estimated specificities were 99.5% (995 of 1000 [98.8%-99.8%]) and 99.7% (997 of 1000 [99.1%-99.9%]), respectively. The net sensitivity and specificity of our sequential testing algorithm were 90.7% (97 of 107 [95% CI: 83.5%-95.4%]) and 100.0% (1000 of 1000 [99.6%-100%]), respectively. Of the 24 079 study participants with blood specimens from 2 January to 18 March 2020, 9 were seropositive, 7 before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. CONCLUSIONS: Our findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states.


Subject(s)
COVID-19 , Population Health , Antibodies, Viral , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G , SARS-CoV-2 , Sensitivity and Specificity
8.
Otolaryngol Head Neck Surg ; 164(2): 297-299, 2021 02.
Article in English | MEDLINE | ID: covidwho-1125701

ABSTRACT

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 has upended surgical practice. In an effort to preserve resources, mitigate risk, and maintain health system capacity, nonurgent surgeries have been deferred in many jurisdictions, with urgent procedures facing increasing wait times and unpredictability given potential future surges. Shared decision making, a process that integrates patient values and preferences with the scientific expertise of clinicians, may be of particular benefit during these unprecedented times. Aligning patient choices with their values, reducing unnecessary health care use, and promoting consistency between providers are now more critical than ever before. We review important aspects of shared decision making and provide guidance for its perioperative application during the coronavirus disease 2019 pandemic.


Subject(s)
COVID-19/prevention & control , Decision Making, Shared , Infection Control , Perioperative Care , COVID-19/epidemiology , COVID-19/transmission , Humans , Patient Selection
10.
Cancers (Basel) ; 13(3)2021 Jan 20.
Article in English | MEDLINE | ID: covidwho-1038627

ABSTRACT

We describe our experience conducting a prospective observational cohort study on the management of small, low risk papillary thyroid cancer during the COVID-19 pandemic. Our study participants are given the choice of active surveillance (AS) or surgery, and those in the AS arm are followed at the study center, whereas surgical patients undergo usual care. During the pandemic we have transitioned from in-person research patient visits to largely virtual care of patients under AS. As of 30 October 2020, we had enrolled 181 patients enrolled in our study (including 25 during the pandemic), of which 92.3% (167/181) consented to telephone communication and 79.0% (143/181) consented to secure videoconferencing communication. Prior to the pandemic, 74.5% (117/157) of our patients chose AS over surgery, whereas during the pandemic, 96.0% (24/25) chose AS. Of the 133 study patients who were under AS within the timeframe from 12 March 2020, to 30 October 2020, the percentage of patients who missed appointments was 8.3% (11/133, for neck ultrasound and physician visits, respectively) and delayed appointments was 23.3% (31/133). This preliminary data suggests that prospective observational research on AS of thyroid cancer can safely continue during the pandemic.

11.
Radiother Oncol ; 154: 70-75, 2021 01.
Article in English | MEDLINE | ID: covidwho-733649

ABSTRACT

PURPOSE: To determine the outcomes of oral cavity squamous cell cancer (OSCC) patients treated with non-surgical approach i.e. definitive intensity-modulated radiation therapy (IMRT). METHODS: All OSCC patients treated radically with IMRT (without primary surgery) between 2005-2014 were reviewed in a prospectively collected database. OSCC patients treated with definitive RT received concurrent chemotherapy except for early stage patients or those who declined or were unfit for chemotherapy. The 5-year local, and regional, distant control rates, disease-free, overall, and cancer-specific survival, and late toxicity were analyzed. RESULTS: Among 1316 OSCC patients treated with curative-intent; 108 patients (8%) received non-operative management due to: medical inoperability (n = 14, 13%), surgical unresectability (n = 8, 7%), patient declined surgery (n = 15, 14%), attempted preservation of oral structure/function in view of required extensive surgery (n = 53, 49%) or extensive oropharyngeal involvement (n = 18, 17%). Sixty-eight (63%) were cT3-4, 38 (35%) were cN2-3, and 38 (35%) received concurrent chemotherapy. With a median follow-up of 52 months, the 5-year local, regional, distant control rate, disease-free, overall, and cancer-specific survival were 78%, 92%, 90%, 42%, 50%, and 76% respectively. Patients with cN2-3 had higher rate of 5-year distant metastasis (24% vs 3%, p = 0.001), with detrimental impact on DFS (p = 0.03) and OS (p < 0.02) on multivariable analysis. Grade ≥ 3 late toxicity was reported in 9% of patients (most common: grade 3 osteoradionecrosis in 6%). CONCLUSIONS: Non-operative management of OSCC resulted in a meaningful rate of locoregional control, and could be an alternative curative approach when primary surgery would be declined, unsuitable or unacceptably delayed.


Subject(s)
Head and Neck Neoplasms , Mouth Neoplasms , Radiotherapy, Intensity-Modulated , Combined Modality Therapy , Humans , Mouth Neoplasms/therapy , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies
12.
Clin Auton Res ; 30(4): 299-315, 2020 08.
Article in English | MEDLINE | ID: covidwho-705370

ABSTRACT

The pandemic viral illness COVID-19 is especially life-threatening in the elderly and in those with any of a variety of chronic medical conditions. This essay explores the possibility that the heightened risk may involve activation of the "extended autonomic system" (EAS). Traditionally, the autonomic nervous system has been viewed as consisting of the sympathetic nervous system, the parasympathetic nervous system, and the enteric nervous system. Over the past century, however, neuroendocrine and neuroimmune systems have come to the fore, justifying expansion of the meaning of "autonomic." Additional facets include the sympathetic adrenergic system, for which adrenaline is the key effector; the hypothalamic-pituitary-adrenocortical axis; arginine vasopressin (synonymous with anti-diuretic hormone); the renin-angiotensin-aldosterone system, with angiotensin II and aldosterone the main effectors; and cholinergic anti-inflammatory and sympathetic inflammasomal pathways. A hierarchical brain network-the "central autonomic network"-regulates these systems; embedded within it are components of the Chrousos/Gold "stress system." Acute, coordinated alterations in homeostatic settings (allostasis) can be crucial for surviving stressors such as traumatic hemorrhage, asphyxiation, and sepsis, which throughout human evolution have threatened homeostasis; however, intense or long-term EAS activation may cause harm. While required for appropriate responses in emergencies, EAS activation in the setting of chronically decreased homeostatic efficiencies (dyshomeostasis) may reduce thresholds for induction of destabilizing, lethal vicious cycles. Testable hypotheses derived from these concepts are that biomarkers of EAS activation correlate with clinical and pathophysiologic data and predict outcome in COVID-19 and that treatments targeting specific abnormalities identified in individual patients may be beneficial.


Subject(s)
Autonomic Nervous System/physiology , Betacoronavirus , Coronavirus Infections/physiopathology , Homeostasis/physiology , Pneumonia, Viral/physiopathology , Stress, Physiological/physiology , COVID-19 , Coronavirus Infections/diagnosis , Humans , Pandemics , Pneumonia, Viral/diagnosis , SARS-CoV-2
13.
J Otolaryngol Head Neck Surg ; 49(1): 59, 2020 Aug 10.
Article in English | MEDLINE | ID: covidwho-705369

ABSTRACT

With the COVID-19 pandemic, there has been significant changes and challenges in the management of oncology patients. One of the major strategies to reduce transmission of the virus between patients and healthcare workers is deferral of follow-up visits. However, deferral may not be possible in total laryngectomy patients. Urgent procedures may be necessary to prevent complications related to ill-fitting tracheoesophageal puncture (TEP) voice prostheses, such as aspiration or loss of voicing. In this paper, we describe the Princess Margaret Cancer Center's approach to managing this unique patient population.


Subject(s)
Coronavirus Infections/prevention & control , Infection Control/organization & administration , Laryngeal Neoplasms/surgery , Laryngectomy/statistics & numerical data , Outcome Assessment, Health Care , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , COVID-19 , Coronavirus Infections/epidemiology , Cross Infection/prevention & control , Elective Surgical Procedures/methods , Elective Surgical Procedures/statistics & numerical data , Female , Humans , Laryngeal Neoplasms/diagnosis , Laryngectomy/methods , Larynx, Artificial , Male , Ontario , Pandemics/statistics & numerical data , Pneumonia, Viral/epidemiology , Prosthesis Implantation/methods , Prosthesis Implantation/statistics & numerical data , Risk Assessment
14.
Cancer ; 126(22): 4895-4904, 2020 11 15.
Article in English | MEDLINE | ID: covidwho-704955

ABSTRACT

BACKGROUND: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, access to surgical care for patients with head and neck cancer (HNC) is limited and unpredictable. Determining which patients should be prioritized is inherently subjective and difficult to assess. The authors have proposed an algorithm to fairly and consistently triage patients and mitigate the risk of adverse outcomes. METHODS: Two separate expert panels, a consensus panel (11 participants) and a validation panel (15 participants), were constructed among international HNC surgeons. Using a modified Delphi process and RAND Corporation/University of California at Los Angeles methodology with 4 consensus rounds and 2 meetings, groupings of high-priority, intermediate-priority, and low-priority indications for surgery were established and subdivided. A point-based scoring algorithm was developed, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN-HN). Agreement was measured during consensus and for algorithm scoring using the Krippendorff alpha. Rankings from the algorithm were compared with expert rankings of 12 case vignettes using the Spearman rank correlation coefficient. RESULTS: A total of 62 indications for surgical priority were rated. Weights for each indication ranged from -4 to +4 (scale range; -17 to 20). The response rate for the validation exercise was 100%. The SPARTAN-HN demonstrated excellent agreement and correlation with expert rankings (Krippendorff alpha, .91 [95% CI, 0.88-0.93]; and rho, 0.81 [95% CI, 0.45-0.95]). CONCLUSIONS: The SPARTAN-HN surgical prioritization algorithm consistently stratifies patients requiring HNC surgical care in the COVID-19 era. Formal evaluation and implementation are required. LAY SUMMARY: Many countries have enacted strict rules regarding the use of hospital resources during the coronavirus disease 2019 (COVID-19) pandemic. Facing delays in surgery, patients may experience worse functional outcomes, stage migration, and eventual inoperability. Treatment prioritization tools have shown benefit in helping to triage patients equitably with minimal provider cognitive burden. The current study sought to develop what to the authors' knowledge is the first cancer-specific surgical prioritization tool for use in the COVID-19 era, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN-HN). This algorithm consistently stratifies patients requiring head and neck cancer surgery in the COVID-19 era and provides evidence for the initial uptake of the SPARTAN-HN.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Head and Neck Neoplasms/surgery , Health Resources , Pneumonia, Viral/epidemiology , Triage/methods , Algorithms , COVID-19 , Clinical Decision-Making , Consensus , Coronavirus Infections/virology , Humans , International Cooperation , Pandemics , Pneumonia, Viral/virology , Reproducibility of Results , Research Design , SARS-CoV-2 , Surgeons
15.
J Otolaryngol Head Neck Surg ; 49(1): 53, 2020 Jul 29.
Article in English | MEDLINE | ID: covidwho-684545

ABSTRACT

INTRODUCTION: The SARS-CoV-2 virus (COVID19) pandemic has placed extreme pressures on the Canadian Healthcare system. Many health care regions in Canada have cancelled or limited surgical and non-surgical interventions on patients to preserve healthcare resources for a predicted increase in COVID19 related hospital admissions. Also reduced health interventions may limit the risk of possible transmission of COVID19 to other patients and health care workers during this pandemic. The majority of institutions in Canada have developed their own operational mandates regarding access to surgical resources for patients suffering from Head and Neck Cancers during this pandemic. There is a large degree of individual practitioner judgement in deciding access to care as well as resource allocation during these challenging times. The Canadian Association of Head and Neck Surgical Oncology (CAHNSO) convened a task force to develop a set of guidelines based on the best current available evidence to help Head and Neck Surgical Oncologists and all practitioners involved in the care of these patients to help guide individual practice decisions. MAIN BODY: The majority of head and neck surgical oncology from initial diagnosis and work up to surgical treatment and then follow-up involves aerosol generating medical procedures (AGMPs) which inherently put head and neck surgeons and practitioners at high risk for transmission of COVID19. The aggressive nature of the majority of head and neck cancer negates the ability for deferring surgical treatment for a prolonged period of time. The included guidelines provide recommendations for resource allocation for patients, use of personal protective equipment for practitioners as well as recommendations for modification of practice during the current pandemic. CONCLUSION: 1. Enhanced triaging should be used to identify patients with aggressive malignancies. These patients should be prioritized to reduce risk of significant disease progression in the reduced resource environment of COVID19 era. 2. Enhanced triaging including aggressive pre-treatment COVID19 testing should be used to identify patients with high risk of COVID19 transmission. 3. Enhanced personal protective equipment (PPE) including N95 masks and full eye protection should be used for any AGMPs performed even in asymptomatic patients. 4. Enhanced PPE including full eye protection, N95 masks and/or powered air purifying respirators (PAPRs) should be used for any AGMPs in symptomatic or presumptive positive COVID 19 patients.


Subject(s)
Coronavirus Infections/epidemiology , Head and Neck Neoplasms/surgery , Pneumonia, Viral/epidemiology , Betacoronavirus , COVID-19 , Canada/epidemiology , Decision Making , Humans , Infection Control/standards , Pandemics , Patient Selection , Personal Protective Equipment/standards , Resource Allocation/standards , SARS-CoV-2 , Societies, Medical , Triage
17.
Cancer ; 126(15): 3426-3437, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-457377

ABSTRACT

BACKGROUND: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT-hypo) during the COVID-19 pandemic. METHODS: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT-hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT-acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005-2017 were included. Locoregional control (LRC) and distant control (DC) after RT-hypo, RT-acc, and CCRT were compared for various subgroups. RESULTS: The study identified 994 human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT-hypo, RT-acc, and CCRT, respectively) and 1045 HPV- HNSCC cases (with 263, 451, and 331 receiving RT-hypo, RT-acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy-alone patients were older. The median follow-up was 4.6 years. RT-hypo, RT-acc, and CCRT produced comparable 3-year LRC and DC for HPV+ T1-2N0-N2a disease (seventh edition of the TNM system [TNM-7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1-T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1-2N2c/T3N0-N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT-hypo or RT-acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV- HNSCC, 3-year LRC and DC were similar with RT-hypo, RT-acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT-hypo and RT-acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT-acc (62%) but not RT-hypo (80%) or CCRT (92%; RT-hypo vs CCRT: P = .270; RT-acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT-hypo or RT-acc in stage IV (73%, 65%, and 66%; P = .336). CONCLUSIONS: It is proposed that RT-hypo be considered in place of CCRT for HPV+ T1-T3N0-N2c (TNM-7) HNSCCs, HPV- T1-T2N0 HNSCCs, and select stage III HNSCCs during the COVID-19 outbreak.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Radiation Dose Hypofractionation , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Adult , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/epidemiology , Female , Follow-Up Studies , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/virology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Oropharyngeal Neoplasms/drug therapy , Oropharyngeal Neoplasms/radiotherapy , Oropharyngeal Neoplasms/virology , Pandemics , Papillomavirus Infections/complications , Pneumonia, Viral/epidemiology , Radiotherapy, Intensity-Modulated , Risk Factors , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/virology , Treatment Outcome
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