1518/2020 Coronavirus disease 2019 (COVID-19): Risks for patients with cancer, lsical presentation, and approach to SARS-CoV? testing - UpTOD. UpToDate” Reimpresién oficial de UpToDate ® www.uptodate.com © 2020 UpToDate, Inc. y / 0 sus filiales. Todos los derechos reservados. @.Wolters Kluwer El contenido del sitio web de UpToDate no esta destinado ni recomendado como sustituto del asesoramiento, diagnéstico o tratamiento médico. Siempre busque el consejo de su propio médico u otro profesional de la salud calificado con respecto a cualquier pregunta o condicién médica. El uso del contenido de UpToDate se rige por los Términos de uso de UpToDate . © 2020 UpToDate, Inc, Todos los derechos reservados. Enfermedad por coronavirus 2019 (COVID-19): riesgos para pacientes con cancer, presentacion clinica y enfoque para las pruebas de SARS-CoV-2 Autores: Robert G Uzzo, MD, MBA, FACS, Alexander Kutikov, MD, FACS, Daniel M Geynisman, MD Editores de seccién: Dr. Michael B Atkins, Larissa Nekhlyudov, MD, MPH, Richard A. Larson, MD, David I Soybel, MD Editores adjuntos: Diane MF Savarese, MD, Sadhna R Vora, MD Todos los temas se actualizan a medida que se dispone de nueva evidencia y se completa nuestro proceso de revision Rocparos Revisién de la literatura vigente hasta: julio de 2020. | Este tema se actualizé por ultima vez: 15 de julio de 2020. INTRODUCCION Los coronavirus son importantes patégenos humanos y animales. A finales de 2019, se identificé un nuevo coronavirus como la causa de un grupo de casos de neumonia en Wuhan, una ciudad en la provincia china de Hubei. Se propagé rapidamente, dando como resultado una epidemia en toda China, seguida de un numero creciente de casos en otros paises del mundo. En febrero de 2020, la Organizacién Mundial de la Salud (OMS) designé la enfermedad COVID-19, que significa enfermedad por coronavirus 2019 [ 4]. El virus que causa COVID-19 se denomina coronavirus 2 del sindrome respiratorio agudo severo (SARS-CoV-2); anteriormente, se denominaba 2019-nCoV. El 30 de enero de 2020, la OMS declaré que el brote de COVID-19 era una emergencia de salud publica de preocupacién internacional y, en marzo de 2020, comenzé a caracterizarlo como una pandemia, para enfatizar la gravedad de la situacién e instar a todos los paises a tomar accién para detectar infecciones y prevenir la propagacién tps www uptodate. comiontenslcoronavirus-isease-2019.covit-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-cov... 1281182020 Coronauiusesease 2019 (COVID-19) Risks for patients wih cancer, cial presentation an approach to SARS-CoV? testing - UpTD. La rapida expansién de la pandemia respiratoria aguda COVID-19 ha impactado todas las areas de la vida diaria, incluida la atencién médica, La intervencién primaria para disminuir la propagacién de la enfermedad ha sido el distanciamiento fisico, la higiene de las manos y las vias respiratorias, y quedarse en casa tanto como sea posible. (Ver "Enfermedad por coronavirus 2019 (COVID-19): Epidemiologia, virologia y prevencién", seccién sobre ‘Medidas preventivas personales’ ). Brindar atencién a los pacientes con cancer durante esta crisis es un desafio dados los riesgos de muerte por cancer versus muerte 0 complicaciones graves del SARS-CoV-2, y la probable mayor letalidad de COVID-19 en huéspedes inmunodeprimidos [ 2,3 ]. Los médicos deben equilibrar los riesgos de retrasar los tratamientos contra el cancer frente a los riesgos de exposicién al SARS-CoV- 2 la posible mayor vulnerabilidad a los resultados adversos del COVID-19, mientras navegan por la interrupcién en la atencién asociada con el distanciamiento fisico y los recursos limitados de atencién médica. Este tema discutird los riesgos de COVID-19 entre pacientes con cancer, la presentacién clinica de COVID-19 en pacientes con cancer, la influencia de la terapia activa contra el céncer en la gravedad de la enfermedad y un enfoque para las pruebas de SARS-CoV-2 en esta poblacién, Cuestiones relacionadas con el equilibrio del riesgo de retrasar el diagnéstico de cancer, la estadificacién y el tratamiento versus el dario de COVID-19; formas de minimizar el compromiso de distanciamiento fisico durante la prestacién de atencién; cémo los recursos limitados de atencién médica pueden asignarse de manera adecuada y justa; asi como también se proporcionan revisiones de las recomendaciones para la atencién del cancer durante la epidemia COVID-19 de grupos de expertos en otros lugares. Los problemas relacionados con el coronavirus en la poblacién general y los problemas relacionados con poblaciones particulares de pacientes no cancerosos también se presentan en otra parte. * (Ver “Enfermedad por coronavirus 2019 (COVID-19): caracteristicas clinicas" y “Enfermedad por coronavirus 2019 (COVID-19): diag ). + (Consulte "Enfermedad por coronavirus 2019 (COVID-19): cuidados criticos y problemas de manejo de las vias respiratorias" .) sobre ‘Mujeres embarazadas y lactante tps www uptodate. comiontenslcoronavirus-isease-2019.covit-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-cov... 2281518/2020 Coronavirus disease 209 (COVID-19): Risks for patients with cancer, linia presentation, and approach to SARS-CoV? testing - UpTOD. EPIDEMIOLOGIA Incidencia de COVID-19 en pacientes con cancer : aunque la informacién sobre la incidencia de COVID-19 entre pacientes con céncer es variable, los datos disponibles sugieren una mayor incidencia de COVID-19 en pacientes con cancer en relacién con la poblacién general. Como ejemplos: * Ina study from Wuhan, China, of the 1524 patients with cancer admitted to an oncology department over a six-week period from December 2019 to February 2020, 0.79 percent (12 patients) had infection with SARS-CoV-2 [2]. Although this infection rate was higher than the cumulative incidence in the community served by the hospital (0.37 percent), these patients were all sick enough to be admitted, and this report does not address the incidence of COVID-19 among community-dwelling outpatients with cancer. Other Chinese reports also suggest an incidence of approximately 1 percent in cancer patients, compared with 0.29 percent in the general population [4] * Higher rates were reported in a study of 1069 patients with cancer admitted to a hospital in Madrid, Spain over a two-month period in 2019 [5]. The cumulative incidence of COVID-19 (diagnosed by the World Health Organization criteria and/or confirmed by reverse-transcriptase polymerase chain reaction of nasopharyngeal specimens) among cancer patients was 4.2 percent (45 of 1069), as compared with a cumulative incidence rate of 0.63 percent for the entire city population, Prevalence of cancer in those with COVID-19 — The prevalence of cancer in those with COVID-19 has also varied across reports. Studies from Wuhan, China suggest that among those with COVID- 19, approximately 1 to 2 percent have cancer [6-9]. On the other hand, a higher prevalence of cancer in those with COVID-19 has been reported from the New York City area (in one report of 5700 hospitalized patients with COVID-19, 6 percent had cancer [10}). In Lombardy, Italy, 8 percent of the patients admitted to the intensive care unit for COVID-19 had either active or prior history of malignancy [14]. In another report, 20 percent of the deaths from COVID-19 in all of Italy were in patients with active cancer [12]. As the infection becomes more widespread, the population concurrently challenged by cancer and COVID-19 will undoubtedly expand asymmetrically across different geographies and risk cohorts. case fatality rates’ and “Coronavirus disease 2019 (COVID-19). Clinical features”, section on ‘Impact of age’.) tps: www uptodate. comicontenslcoronavirus-isease-2019.covit-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-cov... 1281518/2020 Coronavirus disease 208 (COVID-19): Risks fr patients with cancer, lsical presentation, and approach to SARS-CoV? testing - UpTOD. CLINICAL PRESENTATION AND OUTCOMES As in noncancer populations, the clinical characteristics of COVID-19 in patients with cancer usually include fever, dry cough, dyspnea, chills, muscle pain, headache, sore throat, rigors, and a loss of taste or smell (‘able 1). Reddish-purple nodules on the distal digits similar in appearance to pernio (chilblains) have also been described, mainly in children and young adults with documented or suspected COVID-19 ("COVID-toes"). (See "Coronavirus disease 2019 (COVID-19): Clinical features", section on ‘Clinical manifestations’) Although COVID-19 is typically more severe and lethal among older people, people of any age with underlying medical conditions are at increased risk if they contract the virus. These conditions include active or past history of cancer, particularly if they recently received or are continuing to receive treatment, However, data are extremely limited and more studies are needed. However, increasing age is the single most significant risk factor. (See “Coronavirus disease 2019 (COVID-19): Clinical features", section on ‘Impact of age'.) Is illness more severe in patients with malignancy? — Accumulating data suggest that the likelihood of a severe illness and death from COVID-19 is higher among adult patients with cancer, particularly those with hematologic malignancies, lung cancer, metastatic disease, and those who are older and with other comorbidities (7,13-26]. The particularly high mortality rate among lung cancer patients is discussed in more detail separately. (See "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during the pandemic", section on ‘Patients with lung cancer’) Examples of available data are as follows: * A higher case-fatality ratio (CFR) for patients with COVID-19 and a cancer diagnosis relative to those without cancer was seen in a report from a New York City hospital system [14]. Over a three-week period, 218 COVID-19-positive patients with a diagnosis of malignancy were identified, and 61 died, with a CFR of 37 percent for hematologic malignancies, and 25 percent for solid tumors, which included 6 deaths in 11 patients with lung cancer (CFR 55 percent). When compared with an age- and sex-matched cohort of 1090 patients with SARS-CoV-2 infection but without cancer from the same hospital system and same time period, the CFR for cancer patients was double that of noncancer patients (28 versus 14 percent). In multivariate analysis, the higher mortality rate in cancer patients was associated with older age; multiple comorbidities (heart and chronic lung disease, but not diabetes or chronic kidney disease); need for intensive care unit (ICU) support; and elevated levels of D-dimers, lactate dehydrogenase, and lactate. tps www uptodate.comicontenslcoronavirus-isease-2019.covit-19.isksfo-patonts-wth-cancer-cliical-presentation-and-approact-to-sars-cov... 4251182020 Coronauiusesease 2019 (COVID-19) Risks for patients wih cancer, cial presentation an approach to SARS-CoV? testing - UpTD. + A meta-analysis addressing the effect of cancer on clinical outcomes of patients with COVID-19 included 32 international studies totaling 46,499 patients (1776 with cancer) with COVID-19 from Asia, Europe, and the United States [17]. The following conclusions were reached: + All-cause mortality was higher in patients with versus those without cancer (8 studies, 37,807 patients; pooled risk ratio [RR] 1.66, 95% Cl 1.33-2.07). + The need for ICU admission was also more likely in patients with cancer (26 studies, 15,375 patients; RR 1.56, 95% Cl 1.31-1.87). + In prespecified subgroup analysis of patients over age 65 years, all-cause mortality was comparable in those with and without cancer (8 studies, 5438 patients; RR 1.06, 95% Cl 0.79-1.14). + The impact of specific malignancy type and recent active cancer treatment was not addressed. Assecond, smaller meta-analysis came to similar conclusions [21]. + A multivariate analysis of 20,133 United Kingdom (UK) patients in the hospital with COVID-19 (1743 with malignancy) found that age >50 years was the strongest variable associated with in- hospital mortality after adjusting for major comorbidity; the hazard ratio (HR) for death for those with versus without malignancy was 1.13 (95% Cl 1.02-1.24) [19] * Another analysis from the UK included records of over 17 million individuals included in a national primary care electronic database, which were linked to over 10,000 deaths from COVID- 19 [27]. In multivariate analysis adjusted for age and sex, individuals with a nonhematologic malignancy diagnosed within one year prior to diagnosis had a 1.83-fold higher risk of death (95% Cl 1.51-2.21); for those with a hematologic malignancy, the risk was fourfold elevated (HR for death 4.03, 95% Cl 2.76-5.88). The risks were lower for patients diagnosed 1 to 4.9 years prior to diagnosis of COVID-19, but still elevated for both nonhematologic and hematologic malignancies; beyond five years, risks for death remained elevated for those with hematologic but not nonhematologic malignancies. (See "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during the pandemic", section on ‘Cancer survivors'.) What is the effect of recent cancer treatment on COVID-19 severity? — The available data linking recent active oncologic therapy to poor outcomes from COVID-19 are mixed: * A meta-analysis of data from four retrospective studies, all from Wuhan, China, concluded that having received active cancer therapy within two to four weeks of developing COVID-19 was associated with a nearly fourfold higher rate of in-hospital death compared with not having tps www uptodate. comicontenslcoronavirus-isease-2019.covit-19.isksfor-patonts-wth-cancer-cliical-presentation-and-approact-to-sars-cov... 1251182020 Coronauiusesease 2019 (COVID-19) Risks for patients wih cancer, cial presentation an approach to SARS-CoV? testing - UpTD. received such treatment (odds ratio [OR] 3.99, 95% Cl 2.08-7.64) [28]. However, the largest of the studies included in this analysis (n = 205) [29] was criticized for incomplete documentation, the fact that patients were enrolled from inpatient hospitals designated for COVID-19 treatment, and the lack of information on treatment strategies and thrombophilic complications. The three smaller studies only contained a total of 48 patients [2,4,30]. * On the other hand, more recent data collected internationally suggest that recent active oncologic therapy does not increase the risk of mortality from COVID-19: + The international COVID-19 and Cancer Consortium registry collected data on 928 patients from the United States, Canada, and Spain with active or previous malignancy who had confirmed SARS-CoV-2 infection over a one-month period [34]. The most prevalent malignancies were breast (21 percent) and prostate cancer (16 percent); 43 percent had active cancer (ie, measurable disease), and 39 percent had received chemotherapy treatment within four weeks of virus diagnosis. The use of any form of anticancer therapy (cytotoxic or noneytotoxic) within four weeks of infection was not associated with higher 30- day mortality rates. However, in multivariate analysis, independent factors associated with greater 30-day mortality included older age, male sex, former smoker, two or more comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or worse (\able 2), active cancer (versus those in remission; OR 5.2, 95% Cl 2.77-9.77), and receipt of azithromycin and hydroxychloroquine, although the limited number of events precluded a full analysis. (See ‘What is the impact of COVID-19 treatments in patients with cancer with SARS-CoV-2 infection?’ below.) + Similarly, a lack of detrimental impact of recent chemotherapy was also noted in an analysis of 800 patients with a diagnosis of active cancer and symptomatic COVID-19 derived from the UK Coronavirus Cancer Monitoring Project registry [32]. The mortality rate was 28 percent. However, after adjusting for age, gender, and comorbidity, patients who had cytotoxic chemotherapy within the preceding four weeks did not have greater mortality compared with those not on anticancer treatment (adjusted OR for death 1.18, 95% C1 0.81- 1.72). However, the urgency with which data were obtained meant short follow-up times and high proportions of missing data in these studies [33] * The type of cancer treatment may influence the risk. In a retrospective study, among 423 cancer patients with symptomatic COVID-19, those treated with immune checkpoint inhibitors had a nearly threefold risk of hospitalization (HR 2.84, 95% Cl 1.24-6.72) and severe respiratory illness (HR 2.74, 95% Cl 1.37-5.46) [20]. Recent chemotherapy did not show a significant association tps www uptodate.com/ontenslcoronavirus-isease-2019.covit-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-cov... 612511/2020 Coronauiusdaease 2019 (COVID-19) Risks for patients wih cancer, cial presentation an approach to SARS-CoV? testing - UpTD. with either hospitalization or severe respiratory illness. However, this study is subject to the limitations of retrospective data, For example, immunotherapy is more likely to be administered to patients with lung cancer, who have worsened outcomes from COVID-19, irrespective of prior immunotherapy use. Other data in lung cancer patients specifically have not suggested worsened COVID-19 among those with recent immunotherapy treatment, These data are discussed separately. (See "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during the pandemic" section on ‘Patients with lung cancer’ and "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during ) ‘stemic anticancer treatment the pandemi Despite these data, it remains uncertain if cancer patients other than those with hematologic malignancies or lung cancer are at increased risk of severe outcome from COVID-19, when the analysis is controlled for age, the mortality/morbidity associated with their cancer, and other comorbidities [33-35]. The impact of whether the cancer is active and whether the patient is currently receiving treatment also remains unknown. In contrast to adults, limited data suggest that most pediatric cancer patients are not necessarily more vulnerable than other children to infection, or to severe morbidity resulting from SARS-CoV-2 [36,37]. Exceptions may include very young patients [38] and those undergoing treatment for acute leukemia with hematopoietic cell transplantation [39,40]. (See "Coronavirus disease 2019 ( manifestations and diagnosis in children", section on ‘Risk factors for severe disease’) WHICH CANCER PATIENTS SHOULD GET SARS-COV-2 TESTING? The diagnosis of COVID-19 is made primarily by direct detection of SARS-CoV-2 RNA by nucleic acid amplification tests (NAATs), most commonly reverse-transcriptase polymerase chain reaction (RT- PCR) from the upper respiratory tract (table 3). A general discussion of the various tests available for SARS-CoV-2 testing is available elsewhere. (See "Coronavirus disease 2019 (COVID-19): Diagnosis", section on ‘Specific diagnostic techniques'.) Patients with COVID-19 symptoms or a known COVID-19 exposure — Cancer can be an immunocompromised state, and many cancer treatments can further compromise the immune system. As such, cancer patients with fever or lower respiratory findings (eg, cough, dyspnea, hypoxia) are among the highest priority for SARS-CoV-2 testing. Subsequent approach, depending on the results of SARS-CoV-2 testing, is discussed below. (See ‘Approach to those who have had SARS-CoV-2 testing’ below.) These patients should also be evaluated for alternative causes of their symptoms other than COVID- 19, such as influenza, bacterial pneumonia, pulmonary progression of their underlying cancer (eg, tps www uptodate. comiontenslcoronavirus-isease-2019.covit-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-cov... 7/2811/2020 Coronauiusdaease 2019 (COVID-19) Risks for patients wih cancer, cial presentation an approach to SARS-CoV? testing - UpTD. lymphangitic spread), or treatment-related side effects such as postsurgical or systemic therapy- related pulmonary events (eg, atelectasis, pulmonary embolism, pneumonitis, pulmonary edema/fluid overload, immunotherapy-related pneumonitis, etc). Other symptoms (eg, chills, muscle pain, sore throat) also raise the suspicion for COVID-19 and may warrant testing. (See "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during the pandemic", section on ‘Differentiating lymphangitic spread, pneumonitis, and COVID-19' and “Toxicities associated with checkpoint inhibitor immunotherapy" and "Radiation-induced lung injury" and "Coronavirus disease We also recommend SARS-CoV-2 testing for cancer patients with an exposure to someone with confirmed COVID-19. Particular considerations for testing of lung cancer patients are discussed separately. (See "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during the pandemic’, section on ‘Patients with lung cancer.) These recommendations are all supported by American Society of Clinical Oncology (ASCO) guidelines for cancer care delivery during the COVID-19 pandemic [41] Patients admitted to the hospital or undergoing elective surgery — Some hospitals are testing all patients who are admitted to inpatient units, irrespective of whether they have a cancer diagnosis, or symptoms of COVID-19. While such a strategy is reasonable, and is supported by the National Comprehensive Cancer Network (NCCN) [42], local testing availability will dictate whether it is feasible, Elective surgeries, including many cancer surgeries, have not been performed during the COVID-19 pandemic, but, as the pandemic wanes, many institutions have begun scheduling “elective” cancer procedures. (See "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during the pandemic", section on ‘Cancer surgery’) ‘Some institutions are routinely performing SARS-CoV-2 testing for all patients regardless of symptoms before scheduling elective surgery, and some states have specific mandates or advisories for testing. A joint statement from the American Society of Anesthesiologists (ASA) and the Anesthe: APSF) recommends that in areas of high COVID-19 prevalence, testing for SARS-CoV-2 should be performed for all patients prior to nonemergency Patient Safety Foundation surgery, and that surgery should be delayed until the patient is no longer infectious and has recovered from COVID-19. (See "Coronavirus disease 2019 (COVID-19): Anesthetic concerns, including airway management and infection control’, section on ‘Patients who are not known to have had COVID-19'.) Should asymptomatic patients receiving immunosuppressive therapy be tested? — For patients with cancer without symptoms of COVID-19, guidance regarding SARS-CoV-2 testing is tps www uptodate. comicontenslcoronavirus-isease-2019.covit-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-cow... 81251182020 Coronauiusesease 2019 (COVID-19) Risks for patients wih cancer, cial presentation an approach to SARS-CoV? testing - UpTD. evolving, and the approach among UpToDate experts is variable, Some institutions are routinely testing all cancer patients 48 to 72 hours prior to immunosuppressive therapies and prior to medical procedures. This policy is supported by updated guidelines from the Infectious Disease Society of America, which now recommends SARS-CoV-2 RNA testing in asymptomatic individuals before immunosuppressive procedures, regardless of a known exposure to COVID-19 [43]. According to these guidelines, immunosuppressive procedures are defined as cytotoxic chemotherapy, solid organ or stem cell transplantation, long-acting biologic therapy, cellular immunotherapy, or high-dose corticosteroids. Other institutions follow a selective approach to testing, based upon the individual clinician's judgment as to the immunosuppressive potential of the specific regimen. As examples: * Testing would be preferred prior to highly myelosuppressive treatments such as oxaliplatin plus irinotecan and short-term infusional fluorouracil (FU) and leucovorin (FOLFIRINOX) for advanced colorectal cancer, but not necessarily for less myelosuppressive regimens such as oxaliplatin plus FU and leucovorin without irinotecan (FOLFOX). (See "Systemic chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations", section on ‘Three- versus two-drug combinations'.) * Testing might also be recommended for patients with a B-cell hematologic malignancy who are receiving anti-CD20 monoclonal antibodies, which are associated with severe lymphopenia, a risk factor for adverse outcomes from COVID-19. (See "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during the pandemic", section on ‘Anti-CD20 monoclonal antibodies',) Specific considerations for patients with lung cancer are discussed separately. (See "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during the pandemic”, section on ‘Patients with lung cancer'.) However, test availability is still limited in many jurisdictions. ASCO guidelines on this subject state that operational testing policies are dependent on available testing resources and laboratory capacity, Asymptomatic individuals prior to receipt of immunosuppressive therapy are priority 3 for testing, behind symptomatic patients, who are priority 1 and 2 groups [41]. As testing becomes more widely available, it may be reasonable to test all asymptomatic patients who will be receiving immunosuppressive anticancer therapy or who are believed to otherwise be at risk for serious complications from COVID-19, Results of such testing can inform decisions about delaying cancer therapy and increase the protection of health care providers and other patients. The approach depending on SARS-CoV-2 test results is discussed below. (See ‘Approach to those who have had SARS-CoV-2 testing’ below.) tps www uptodate.comicontenslcoronavirus-lisease-2019.covit-19.isksfr-patonts-with-cancer-clincal-presentation-and-approact-to-sars-cov... 8281518/2020 Coronavirus disease 2079 (COVID-19): Risks fr patients with cancer, clinical presentation, and approach to SARS-CoV? testing - UpTOD. APPROACH TO THOSE WHO HAVE HAD SARS-COV-2 TESTING Positive test for SARS-CoV-2 infection Holding immunosuppressives and COVID-19 management considerations — In the event of a positive result, the patient's oncologist, in consultation with the patient, should determine next steps [44]. * In general, immunosuppressive cancer therapy should be withheld in patients who test positive for SARS-CoV-2 infection. + However, although data are very limited, one small study and at least two case reports have suggested that the use of Bruton tyrosine kinase (BTK) inhibitors for patients with a chronic hematologic malignancy may be associated with less severe infection [44-46], and continuation of this class of drugs should be considered on a case-by-case basis [47]. The rationale for possible benefit from a BTK inhibitor is that patients with severe SARS-CoV-2 infection have a hyper-inflammatory immune response suggestive of macrophage activation, and BTK inhibitors regulate macrophage signaling and activation [48]. Ultimately, randomized studies will be needed to prove benefit from continued use of BTK inhibitors in adults”, section on ‘Others'.) + Glucocorticoids may be beneficial for patients who are hospitalized with severe SARS-CoV-2 infection. (See "Coronavirus di 2019 (COVID-19): Management in hospitalized adults", section on ‘Dexamethasone’,) In other situations, for patients who are receiving glucocorticoids for management of their cancer or treatment-associated toxicities, the decision as to whether to continue or discontinue in a patient diagnosed with COVID-19 must be individualized, and depends in part on the dose and indication for the glucocorticoid. As an example, decision-making for high-dose glucocorticoids in a patient with brain metastases or epidural spinal cord compression, or a serious immunotherapy-related adverse event, is more difficult, and must be addressed on a case-by-case basis. (See "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during the pandemic", section on ‘Glucocorticoids'.) * Additionally, some oral nonimmunosuppressive therapies such as hormonal therapies, including androgen deprivation therapy [50] or drugs targeting activating mutations (eg, epidermal growth factor receptor inhibitors or BRAF/MEK inhibitors) may be continued on a case-by-case basis. tps www uptodate. comicontenslcoronavirus-isease-2019.covit-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-co.. 101261182020 Coronauiusdsease 2019 (COVID-19) Risks for patients wih cancer, cial presentation an approach to SARS-CoV. testing - UpTD. Given the interaction between transmembrane protease serine 2, encoded for by the TMPRSS2 fusion gene, and penetration of the SARS-CoV-2 virus, preclinical data raise the possibility of a favorable interaction between therapies that target the androgen receptor and infectivity of SARS-CoV-2 [51-55]. However, clinical trials are needed to test whether antagonists of androgen receptor signaling might mitigate the SARS-CoV-2 infection. Issues related to COVID-19 management — Many mild cases (eg, fever, cough, and/or myalgias without dyspnea or hypoxia) and asymptomatic infections can be managed conservatively at home, if individuals can be adequately isolated. However, patients with more severe disease may warrant a likely hospital admissior What is the impact of COVID-19 treatments in patients with cancer with SARS-CoV-2 infection? — As with noncancer cases, the use of investigational agents such as hydroxychloroquine is discouraged outside of a clinical research trial. At least some data (from the international COVID-19 and Cancer Consortium registry [CCC19}) suggest that treatment with the combination of hydroxychloroquine plus azithromycin to treat COVID-19 in cancer patients was associated with a significantly higher 30-day mortality than treatment with neither drug. (See "Coronavirus disease 2019 (COVID-19): Management in hospitalized adults", section on ‘COVID-19-specific therapy’) There are few data exploring the benefit of any COVID-19 treatment in patients with cancer and SARS-CoV-2 infection, The benefits of specific COVID-19 treatments in cancer patients were addressed in an observational cohort study from CCC19 that included 2186 adults with invasive cancer who were diagnosed with laboratory-confirmed SARS-CoV-2 infection over a three-month period [56]. Disease severity was mild, moderate, or severe in 47, 40, and 12 percent, respectively. Most patients had solid tumors (81 percent), of which breast cancer was the most common. Approximately one-half were in remission from cancer (51 percent), of whom 13 percent were receiving active antineoplastic treatment; 28 percent had present cancer that was stable or responding to treatment, and 11 percent had actively progressing cancer. Some form of anti-COVID- 19 therapy was administered to 865 patients (40 percent of the total); the therapies used were unproven and investigational, and most were administered outside of the context of a clinical trial, except for remdesivir. The most common treatment utilized was hydroxychloroquine plus azithromycin (HC plus AZ; n= 203, 23 percent), followed by HC alone (n = 179, 21 percent), AZ alone (n = 160, 18 percent), remdesivir alone (n = 57, 7 percent), HC plus AZ plus high-dose glucocorticoids (n = 24, 3 percent), high-dose glucocorticoids alone (n = 18, 2 percent), HC plus tocilizumab (n = 18, 2 percent), and HC plus AZ plus tocilizumab (n = 18, 2 percent). Baseline disease severity had the strongest association with anti COVID-19 treatment. tps www uptodate. comicontenslcoronavirus-isease-2019.covit-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-co.. 1172811/2020 Coronauiusdsease 2019 (COVID-19) Risks for patients wih cancer, cial presentation and approach to SARS-CoV? testing - UpTD. The 30-day mortality rate was 15 percent. In an adjusted analysis that used propensity-score matching to improve covariate balance and comparability between the comparator groups, remdesivir alone was associated with significantly decreased 30-day all-cause mortality in comparison with other treatments (adjusted odds ratio [aOR] 0.41, 95% Cl 0.17-0.99), but not when compared with those who received no anti-COVID-19 treatment (aOR 0.76, 95% Cl 0.31-1.85). High-dose glucocorticoids increased 30-day mortality compared with no COVID-19 treatment, but the difference was not significant (aOR 2.8, 95% Cl 0.77-10.15). Similarly, receiving HC plus any other therapy significantly increased mortality both when compared with other forms of treatment or not treatment, but HC alone did not increase mortality. The authors concluded that the use of treatments purported to improve COVID-19 outcomes was frequent and highly variable, but, that with the possible exception of remdesivir compared with other treatments, that there was little evidence to suggest benefit from any strategy. Furthermore, the receipt of hydroxychloroquine with any other medications (most commonly azithromycin) worsened outcomes. Management of COVID-19 in outpatients and in hospitalized adults and children is discussed in adults" and "Coronavirus disease 2019 (COVID-19): Management in children" Advance care planning for patients with severe disease — Importantly if a cancer patient with late-stage disease or with significant comorbid health conditions affecting the heart or lungs acquires severe COVID-19 and requires mechanical ventilation, the prognosis is likely to be dismal [57]. tis therefore imperative for clinicians to have proactive discussions with patients about goals of care and advance care planning, especially for those with advanced cancer [58]. Depending on state regulations, patients should be offered the option of completing a Physician Order for Life-Sustaining Treatment (POLST) form and/or other type of out-of-hospital do not resuscitate (DNR) order, especially if they would not want to receive cardiopulmonary resuscitation (CPR) or mechanical ventilation. In the absence of an advance directive, a patient with underlying severe chronic illness and acute respiratory failure from COVID-19 who is getting worse despite maximal therapy may be appropriate for a unilateral DNR order to reduce the risk of medically futile CPR to patients, families, and health care workers. This may occur through informed consent with the patient or his/her surrogate, or, occasionally, informed assent [58]. (See "Coronavirus disease 2019 (COVID-19): Screening, diagnosis, and treatment of cancer during the pandemic", section on ‘Advance care planning’.) Consultation with a palliative care specialist may be beneficial, although access to essential palliative care services may be limited in the face of high demand in all countries during the pandemic [59,60]. Helpful communication guides for clinicians on a wide range of pertinent topics related to COVID-19 are available from VitalTalk. In addition, a helpful guide to navigating difficult conversations remotely tps www uptodate. comiontenslcoronavirus-isease-2019.covit-19.isksfor-patonts-wth-cancer-cliical-presentation-and-approact-to-sars-co.. 12281182020 Coronauiusesease 2019 (COVID-19) Risks for patients wih cancer, cial presentation an approach to SARS-CoV? testing - UpTD. during the pandemic using the Setting, Perception, Invitation, Knowledge, Empathy/Emotion, and Strategy/Summarize (SPIKES) protocol is available [61]. (See "Discussing serious news", section on When can cancer treatment be safely restarted? — There are no universally accepted guidelines as to when cancer therapies can be safely restarted after COVID-19 diagnosis. Given that reinfection rates and their consequences are unknown, the effects of further suppressing or augmenting a patient's immune system quickly after COVID-19 must be weighed heavily against the risks of their unique tumors biology. We would only reinitiate therapy if at least 24 hours have passed since resolution of fever without the use of antipyretics, and there is improvement in symptoms (eg, cough, shortness of breath). For most patients, we prefer to obtain at least one negative SARS-CoV-2 test before reinitiating anticancer therapy. However, a nontest-based strategy such as that recommended by the United States Centers for Disease Control and Prevention (CDC) for discontinuation of transmission-based precautions for immunocompromised individuals (at least 20 days since symptoms first appeared, or, for asymptomatic individuals, 20 days after the initial positive SARS-CoV-2 test) is also reasonable. Guidance from expert groups on this issue is somewhat variable: + American Society of Clinical Oncology (ASCO) guidelines state that if the decision was made to. interrupt treatment, it should not be resumed until symptoms of COVID-19 have resolved and there is some certainty the virus is no longer present (eg, at least one negative SARS-CoV-2 test), unless the cancer is rapidly progressing and the risk-benefit assessment favors proceeding with cancer treatment, However, in the absence of cancer-specific information, the CDC has issued recommendations on discontinuing transmission-based precautions for patients with COVID-19; initiating/resuming anticancer therapy once transmission-based precautions are no longer necessary would be reasonable. Earlier guidelines had recommended at least two negative SARS-CoV-2 tests, at least 24 hours apart. * This position is also generally concordant with the World Health Organization (WHO) guidelines for discontinuing home isolation. The United Kingdom National Institute for Health and Care Excellence (NICE) has also published rapid guidance on the delivery of cancer therapy that suggests treatment may be initiated or resumed after only one negative SARS-CoV-2 test [62] * Updated guidance from the CDC for discontinuing transmission-based precautions, as well as criteria to return to work for health care personnel with SARS-CoV-2 infection, no longer recommends a test-based strategy, except for rare circumstances. In both situations, for patients (or health care providers) with severe or critical illness or who are severely immunocompromised, they suggest discontinuation of transmission-based precautions no sooner than 20 days after tps www uptodate. comicontenslcoronavirus-isease-2019-covid-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-co.. 131281182020 Coronauiuseaease 2019 (COVID-19) Risks for patients wih cancer, cial presentation and approach to SARS-CoV. testing - UpTD. symptom onset (or, for asymptomatic, severely inmunocompromised individuals, 20 days after the initial positive SARS-CoV-2 test), as long as patients are fever-free for at least 24 hours (without the use of antipyretics), and symptoms such as cough or dyspnea have resolved. (See "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on ‘Discontinuation of precautions'.) There is no consensus on this issue. However, we still favor at least one negative SARS-CoV-2 test before reinitiating anticancer therapy. One reason is that infection control policies at local institutions and clinics generally require repeat testing and clearing of viral RNA (ie, at least one negative test for SARS-CoV-2) before patients are allowed to resume care alongside noninfected individuals. However, following guidelines for discontinuation of transmission-based precautions (ie, 20 days after symptom onset) is also reasonable. Regardless, when treatment delay is being considered because of COVID-19, clinical judgment and individualized decision-making are needed, particularly in settings in which curative therapies are being withheld. As an example, in advanced testicular cancer, delaying chemotherapy for any extended period of time is usually not appropriate, and the risk-benefit ratio would favor continuing treatment even if the patients had persistent viral shedding but felt clinically well. Serologic assays to identify SARS-CoV-2 antibodies are being developed and are discussed below. Once validated and widely available, such assays can be used to identify patients with previous exposure and possible immunity, Examples of other strategies for managing anticancer therapy in patients who have had COVID-19 endorsed by expert groups and at other institutions are as follows: * ASCO guidelines also suggest that specific areas and dedicated staff be designated for treatment of COVID-19-positive patients [41] + At some institutions, even COVID-19-positive patients who have been cleared of SARS-CoV-2 are recommended to resume treatment at an isolated infusion center, away from the main infusion center. This position stems from concerns as to the limitations of test strategies, and that ‘some proportion of recovered patients who initially test negative might in fact be persistent virus shedders [63]. Regardless of the timing of reinitiation of treatment, physical distancing rules and contact limitation remain essential components of cancer treatments amid the pandemic to protect the patient, the health care workers, and other non-COVID-19 patients being treated in the same center. (See on ‘Preventing infection in the community’.) tps www uptodate. comicontenslcoronavirus-isease-2019-covit-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-co.. 1412811/2020 Coronauiusdsease 2019 (COVID-19) Risks for patients wih cancer, cial presentation an approach to SARS-CoV? testing - UpTD. Management of persistent viral shedding — Some patients have persistently positive nucleic acid amplification tests (NAATs) for weeks after resolution of symptoms. This poses a challenge in the health care setting, since concerns that the patient could stil be infectious may result in continued infection control precautions and delay in treatments, procedures, or tests. At least some data suggest poor outcomes among patients with hematologic malignancies who are persistently positive for SARS-CoV-2 by NAAT [64] Although there is no standardized approach when this occurs, itis important that essential treatments and procedures not be delayed. Available data suggest that prolonged viral RNA shedding after symptom resolution is not clearly associated with prolonged infectiousness, as isolation of infectious virus from upper respiratory specimens more than nine days after illness onset has not yet been documented. (See "Coronavirus disease 2019 (COVID-19): Diagnosis”, section o1 recurrent positive NAAT.) ‘ersistent or As noted above, the most recent guidance from the CDC on discontinuation of transmission-based precautions and disposition of patients with COVID-19 in health care settings states that except for rare situations, a test-based strategy is no longer recommended to determine when to discontinue transmission-based precautions. (See ‘When can cancer treatment be safely restarted?’ above.) However, infection control policies at local institutions and clinics may require repeat testing and clearing of viral RNA (ie, at least one negative test for SARS-CoV-2) before patients are allowed to resume care alongside noninfected individuals. Treatment decisions must be individualized in these cases, carefully weighing the risks and benefits of withholding versus restarting treatment, particularly if the withheld treatments are potentially curative. In the interest of caution, cancer patients who have persistently positive NAATs despite ‘symptom resolution should avoid treatment in the same infusion room with other uninfected cancer patients receiving chemotherapy until they convert to a negative test. Persistent viral shedding and discontinuation of precautions for the general population are discussed in detail elsewhere. (See "Coronavirus disease 2019 (COVID-19): Epidemiology, virology, and prevention", section on ‘Viral shedding and period of infectiousness' and "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on ‘Discontinuation of precautions’.) Negative test for SARS-CoV-2 infection — For individuals who test negative for SARS-CoV-2, the approach depends on whether the patient is symptomatic, and, if so, the cause for the respiratory symptoms and the cancer in question. For those with only mild respiratory symptoms, following an approach that is similar to those without respiratory symptoms may be appropriate. tps www uptodate. comicontenslcoronavirus-isease-2019-covit-19.isksfor-patonts-wth-cancer-clincal-presentation-and-approact-to-sars-co.. 181261182020 Coronauiusesease 2019 (COVID-19) Risks for patients wih cancer, cial presentation an approach to SARS-CoV? testing - UpTD. However, travel history, recent contacts, and prevailing local public health conditions should be considered given the imperfect negative predictive value of current SARS-CoV-2 testing, which is discussed in detail elsewhere. Retesting may be needed if the index of suspicion is high. (See "Coronavirus disease 2019 (COVID-19): Diagnosis", section on Test interpretation and additional testing!.) For those with more severe symptoms, management will depend on the underlying etiology and goals of care. Careful consideration for non-COVID-19 and potentially cancer and/or treatment-related etiologies causing similar constellations of symptoms must always be considered. Role of serologic testing — Serologic tests detect antibodies to SARS-CoV-2 in the blood. Those that have been adequately validated may help identify patients who have had COVID-19 or exposure to SARS-CoV-2. However, there are many unknown factors, including sensitivity, specificity, and positive and negative predictive value [65,66]; how much immunity is conferred by a prior infection, and for how long; and the level and types of antibodies that indicate immunity. Furthermore, at least some limited data from France suggest that rates of seroconversion 15 days or later after documented SARS-CoV-2 by reverse-transcriptase polymerase chain reaction testing are significantly lower in cancer patients than in others, such as health care workers (30 versus 71 percent) [67]. Additionally, while serologic tests may be able to identify some patients with current infection (particularly those who present late in the course of illness), it is less likely that antibodies will be reactive in the first several days to weeks of infection, and therefore, serologic tests offer little utility for diagnosis in the acute setting. This subject is discussed elsewhere. (See "Coronavirus disease 2019 (COVID-19): Diagnosis", section on 'Serology to identify prior/late infection'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored disease-specific guidelines (including those for hematology and oncology patients) from selected countries and regions around the world are provided separately. (See "Society guideline links: Coronavirus disease 2019 (COVID-19) ~ International public health and government guidelines" and "Society guideline links: Coronavirus disease 2019 (COVID-19) — Resources for patients" | INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics” and "Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5" to 6'" grade reading level, and tps: www uptodate. comiontenslcoronavirus-isease-2019-covit-19.isksfor-patonts-wth-cancer-clncal-presentation-and-approact-to-sars-co.. 16128