COVID-19 in the Cancer Patient : Anesthesia & Analgesia (original) (raw)

The novel coronavirus disease 2019 (COVID-19) first emerged as an outbreak in the province of Hubei, China, in December 2019, with its causative virion formally known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a beta coronavirus, in the same genus as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS), which is thought to have originated from an animal host with eventual spread to humans.1 COVID-19 became a global pandemic in a matter of months, affecting over 100 countries and totaling 824,559 infections and 40,673 deaths worldwide as of March 31, 2020.2

Coronaviruses constitute a large family of viruses known to infect both humans and animals. Bats have been implicated as vectors in the largest variety of coronaviruses. The human coronaviruses can be subclassified into alpha and beta coronaviruses. Clinical manifestations of coronavirus infections are typically respiratory and enteric, although some present with neurologic manifestations.1

At the time of publication of this article, COVID-19 is thought to have an incubation period of approximately 2 weeks, with most infected individuals becoming symptomatic 5 days after exposure. Illness severity ranges from mild to critical and fatal. Approximately 80% of cases are asymptomatic or have mild symptoms, 15% have severe illness, and 5% have critical illness. Due to testing availability and limitations, the true case fatality rate (CFR) with COVID-19 is difficult to determine, but it is believed to range from 1% to 2%–3% based on existing data from different countries.1,2 Patients typically present with fever, cough, shortness of breath, gastrointestinal, musculoskeletal, and neurologic symptoms. When severe, these patients present with pneumonia and acute respiratory distress syndrome (ARDS), and 1%–3% progress to multiorgan failure and ultimately succumb to the viral syndrome.3 This review adheres to applicable Enhancing the Quality and Transparency of health Research (EQUATOR) guidelines.

IMMUNOCOMPROMISED STATE OF THE CANCER PATIENT

Underlying health conditions that increase susceptibility to severe COVID-19 include hypertension, chronic obstructive pulmonary disease, diabetes mellitus, and cardiovascular disease.4,5 An immunocompromised state, such as autoimmune disease, nonautoimmune inflammatory diseases; patients taking immunosuppressive agents with transplanted organs; and active cancer also increase susceptibility for severe COVID-19.

As the pandemic is evolving, incidence rates in cancer patients have suggested higher rates of severe and critical disease. One prospective cohort study of COVID-19 in cancer patients observed that patients with cancer had a higher risk of severe events compared with patients without cancer.6 Patients who recently underwent chemotherapy or surgery had a higher risk of clinically severe events compared with patients who did not.6 However, several limitations included a small sample size, different cancer types, variable disease courses, diverse treatment strategies, and contribution of age to the risk.7 The Chinese Center for Disease Control and Prevention (CDC) has published the largest case series to date of COVID-19 in mainland China and reported a CFR of 5.6% among patients with cancer.8 Insufficient data on the current COVID-19 in cancer patients require examining past studies for coronavirus disease in the immunocompromised population and extrapolating risk of susceptibility and/or development of severe COVID-19. Nevertheless, a nationwide analysis in China observed that patients with cancer had a higher risk of severe events compared with patients without cancer and that patients who underwent chemotherapy or surgery in the previous month had a higher risk of severe events.6 They noted that cancer patients had a higher risk of COVID-19 and that these patients had poorer outcomes than patients without cancer.6

Immunocompromised patients remain vulnerable to respiratory viral infections. Viral pneumonia has been associated with a mortality rate of 19% in immunocompromised patients.8 More specifically, conventional coronaviruses have been shown to be associated with higher rates of oxygen requirement and mortality in patients with hematologic malignancies and hematopoietic cell transplant.9 In one study, coronavirus pneumonia had a 24% mortality in cancer patients compared to 3% in noncancer patients.10 Furthermore, these patients tend to have frequent prolonged viral shedding.11

The immune system is altered in several ways in cancer patients, putting them at increased risk of infection. This can be the result of the specific cancer therapies, extent of disease, or location of primary disease origin. Lymphopenia has been observed in 20% of patients with advanced cancer disease and in 3% of patients with localized disease.12 Lymphopenia can be seen in a variety of cancer types from pancreatic, melanoma, sarcoma, hepatocellular, non-Hodgkin lymphoma, and colon cancer.12 In several studies of patients with hematologic malignancies with respiratory viral infections, lymphopenia independently predicted progression to pneumonia.13–15 Laboratory findings in patients with COVID-19 have included lymphopenia in most hospitalized patients, with nonsurvivors developing more severe lymphopenia over time.16–18 Platelets also play an important immune system role and have viricidal effects against some viruses.19 Cancers that invade and displace normal bone marrow, such as leukemia or lymphoma, can lead to thrombocytopenia and an associated immunocompromised state.

An effective immune response against viral infections depends on the activation of T cells that help clear the infection. In a recent study of COVID-19 patients, over 70% of nonintensive care unit cases had decreased total T cells, whereas 95% of intensive care unit (ICU) patients had decreases in total T cells.20,21

THERAPIES CONTRIBUTING TO IMMUNOCOMPROMISED STATE

Chemotherapy

Use of corticosteroids and immunosuppressive therapy are risk factors for severe respiratory viral infections.22 Chemotherapy damage to bone marrow cells can lead to thrombocytopenia and neutropenia, rendering patients more susceptible to infections. Patients are at greater risk during their nadir period when their neutrophil numbers are the lowest. This nadir occurs 7–12 days after completion of each dose of chemotherapy and can sometimes last up to 1 week.23 Most chemotherapeutic agents can depress the immune system, but cytotoxic agents that cause bone marrow suppression, such as temozolomide, cyclophosphamide, paclitaxel, methotrexate, and alemtuzumab, can increase infection risks for cancer patients. Of the chemotherapy drugs, cyclophosphamide, cisplatin, methotrexate, fludarabine, and taxanes are among the most potent agents that result in lymphopenia.12

Since limited data are available to estimate mortality risk in patients who undergo chemotherapy and become infected with SARS-CoV-2, 1 article used modeling to extrapolate this risk. They found that most cancer patients have a >5% mortality risk if infected with SARS-CoV-2 and that older patients with solid tumors have a greater risk, with harm likely to outweigh the benefit for most chemotherapy in most patients.24 Recommendations have been made to postpone adjuvant chemotherapy for stable cancer in active pandemic areas. Based on limited data, decisions about initiating or continuing cytotoxic chemotherapy will need to be considered individually and carefully.

Radiation Therapy

Radiation treatment can affect the immune system. High-dose body irradiation is a significant risk factor for progression to lower respiratory tract infection with respiratory syncytial virus (RSV) in hematopoietic cell transplant patients.25 Lymphocytes are affected by external beam radiation, resulting in radiation-induced lymphopenia. Because lymphocytes are exposed through the irradiated field, there is a direct toxic effect. This phenomenon has been reported to occur in 40%–70% of patients undergoing conventional external beam radiation therapy.12,26 This risk can be mitigated by using proton beam therapy, stereotactic body radiation, or a hypofractionated schedule.12 There are no clear guidelines on continuing or initiating radiation therapy during the COVID-19 pandemic, and each case should be reviewed on an individual level with a risk-benefit analysis.

Immunotherapy

Immunotherapy to treat certain cancer types include immune checkpoint inhibitors, T-cell transfer therapy, vaccines, and immune-modulating agents.27 There are no well-defined guidelines for continuing or initiating immunotherapy during the COVID-19 pandemic. However, some side effects of this therapy may serve as a guide in decision making. The basis of these side effects is due to hyperactivated T-cell response with reactivity directed against normal tissue.27 Immune checkpoint inhibitors have rare side effects of thrombocytopenia and pneumonitis. T-cell transfer therapy, consists of tumor-infiltrating lymphocytes (TIL) and chimeric antigen receptor (CAR) T-cell therapy. Side effects for TIL include prolonged lymphopenia, and CAR T-cell therapy can lead to cytokine release syndrome.27–29 Cancer vaccines are associated with minimal toxicity.27 Finally, certain immune-modulating agents can cause thrombocytopenia, anemia, leukopenia, and vascular permeability leading to pleural effusion or pulmonary edema.27 Interestingly, some immune-modulating agents that diminish inflammation during infection have shown therapeutic promise in mice models infected with various influenza strains.30

Bone Marrow Transplant

Severity of viral respiratory disease, with the highest morbidity and mortality, has been observed in patients with hematopoietic stem cell transplant (HSCT).15,31 This treatment essentially eliminates the host immune system and replaces it with a donor’s. These patients are most vulnerable for infection during the first 3 months after transplant, with recovery to baseline extending up to 1 year in some cases.32

CANCER PATIENTS AND INFECTIOUS RISK

Specific cancer patients are at particularly high risk for infections due to their cancer type and treatment. Patients with blood malignancies involving immune system cells, such as lymphomas, aplastic anemia, myelomas, and most leukemias, are vulnerable to infection by virtue of their cancer. Janus kinase inhibitors (JAKi) and Bruton tyrosine kinase inhibitors (BTKi) used in the treatment of certain cancers, including leukemias and lymphomas, can also cause immunosuppression by inhibiting cytokine and growth factor signaling pathways and inhibition of B-cell maturation, respectively.

Nosocomial infections are more common in cancer patients who are at increased risk for viral, bacterial, and fungal pathogens.33–35 While patients are hospitalized, they are susceptible to various respiratory infections such as human RSV, influenza A and B viruses, parainfluenza virus, and human metapneumovirus. Patients who have undergone HSCT and then acquired parainfluenza viruses with lower respiratory tract involvement had a 40% greater likelihood of respiratory failure and death.34 In addition, HSCT patients who have community-acquired pulmonary viral infections can have severe lower respiratory tract involvement, late airway outflow obstruction, and multiple fungal and bacterial coinfections.36

Postsurgical infection is a common and not but often severe complication in cancer patients. Depending on the type, location, tumor size, lymph node involvement, and organ involvement, subsequent infectious complications can range from minor to moderate or severe.37 Bevacizumab, an angiogenesis inhibitor that works by blocking vascular endothelial growth factor (VEGF), can cause significant delays in wound healing and obligates timed surgical resection for various cancers. Type of surgery and tumor location can also have significant effect on postoperative infection. Oral and maxillofacial tumor resection with complex reconstructions, radical neck dissections, prolonged length of surgery (>6 hours), and need for blood transfusion were associated with an infection rate of >12%.38

Younger cancer survivors often have more robust reconstituted immune systems compared to older survivors; however, survivors at any age have higher rates of infectious complications compared to their noncancer counterparts. Cancer survivors were more likely to be hospitalized for respiratory infections39 with increasing particulate matter pollution;40 were at least 2 times more likely to develop sepsis;41 and had increased infectious-related mortality rates.39

Cancer patients with SARS-CoV-2 infection may have increased morbidity and mortality from COVID-19 than noncancer patients with SARS-CoV-2 infection. Liang et al6 reported a Chinese nationwide analysis of cancer patients with SARS-CoV-2 infection. In their analysis of 1590 COVID-19 cases, they included 12 patients with cancer history, 2 patients with unknown cancer treatment, and 4 patients with recent cancer treatment. These cancer patients were older with history of smoking, dyspnea, and more advanced computed tomography (CT) scan findings than those without cancer. They reported that 7 of these 18 patients had higher risk of severe events (ICU admission, mechanical ventilation, death); 3 of 4 patients who had recent cancer treatment experienced severe events; and patients with cancer exhibited faster clinical deterioration (13 vs 43 days). The small study sample size, age bias (63 years in cancer group versus 48 years noncancer group),42 and higher rate of smoking in the cancer cohort7 limited the external validity (generalizability) of the findings.

In a recent study, Williams et al24 created models that estimated mortality risk of age-matched cancer patients with COVID-19 infection. The article was based on data from the Chinese CDC, Italian public health authorities, and the cohort on the Diamond Princess cruise ship. Williams et al24 demonstrated a strong effect of age on mortality (>15% for those >70 years) and increased CFR due to cancer and chemotherapy. They conclude that cancer patients have >5% mortality compared to cancer-free patients and that this increase in mortality is greater than any purported aggregate benefit of solid tumor chemotherapy.

The malignancies with the most severe immune deficits are likely at greatest risk and include lymphomas, leukemias, and multiple myelomas. Severity of viral respiratory disease with the highest morbidity and mortality was found in patients with myelosuppression and hematopoietic cell transplant.15,31 Risk factors for lower respiratory tract disease included age >50 years, graft versus host disease, corticosteroid use, neutropenia, lymphopenia, and hypoalbuminemia.43,44 An effective immune response against viral infections depends on the activation of T cells that assist in clearing the infection.

Approximately 3.3 million cases of tobacco-associated cancer were reported in the United States during 2010–2014, with lung cancer accounting for about one-third of these cases. The majority are also diagnosed with chronic obstructive pulmonary disease.45 One prospective cohort study determined the most frequent type of cancer among COVID-19 patients was lung cancer (28% of COVID-19 cases).6

Recent data demonstrated a significantly higher angiotensin-converting enzyme 2 (ACE2) gene expression in former smoker’s lung compared to nonsmoker’s lung.46 SARS-CoV-2 binds to the host cell receptor, ACE2, which is a critical step for viral cell entry.5,47 The ACE2 enzyme is an important regulator of the immune response, particularly in acute lung injury.48 Murine studies have observed that overexpression of ACE2 leads to a protective effect against acute lung injury.48,49 Possible mechanisms include a proliferation of receptors for virus binding, leading to greater risk, or perhaps that increased gene expression confers a protective immunologic mechanism. Further investigation is needed to determine whether smokers are at greater risk of acute lung injury after viral infection.

PERIOPERATIVE MANAGEMENT OF THE CANCER PATIENT WITH COVID-19

Perioperative management of the patient with suspected or confirmed COVID-19 focuses on several aspects, including regional and institution-specific factors; patient, community, and employee safety; and conservation of resources such as staff, hospital beds, equipment, and supplies.

As of March 2020, organizations such as the American College of Surgeons and the Ambulatory Surgery Center Association have provided guidance for the management of nonemergent surgical procedures in the setting of COVID-19. If a procedure can be safely postponed without significant risk to the patient, it should be delayed until after the pandemic.50,51

Cancer patients pose unique management dilemmas during viral pandemics like COVID-19 because cancer is a life-threatening disease process. While cancers vary in natural history, prognosis, and mortality rates, all patients regardless of cancer type struggle with feelings of anxiety and fear that can only be alleviated with the relief and hope that come from medical and surgical treatment. Hence, according to tools like the Elective Surgery Acuity Scale (ESAS) used for the triage of nonemergent operations, most cancer surgeries are considered of high acuity and should proceed as planned assuming resource availability.50,51

Certain procedures and surgeries (eg, otolaryngology, dental, pulmonary, and gastroenterology) are high risk for aerosolizing virus regardless of cancer status. Many professional societies have released statements on delaying, restricting, rescheduling nonurgent procedures.52–55 Considerations should always be made to avoid high-risk aerosolizing procedures. If such cases must proceed due to life-threatening circumstances, all providers involved in care should be attired with appropriate personal protective equipment (PPE) such as N95 masks, eye protection, water-resistant gowns, and gloves, and furthermore, such procedures should be performed in negative pressure rooms when available.

Preoperative Phase

Care must be taken preoperatively to closely screen patients for influenza-like symptoms before their arrival to the hospital. This may be done with a telephone call before hospital arrival, in addition to screening on hospital admission. The number of caregivers having direct contact with each patient should be limited to only those necessary throughout the perioperative period.

Intraoperative Phase

A patient with suspected or confirmed COVID-19 requiring emergency surgery should avoid a preoperative holding area and instead be transported directly to a designated operating room (OR), preferably in a mobile isolation unit. Signs should be posted on all OR entry points, and all attempts should be made to minimize health care staff exposure by ensuring that only required staff remain in the OR.56

PPE is essential for health care providers throughout the perioperative period to ensure airborne/droplet/contact isolation precautions can be achieved. Full PPE for airway manipulation includes a fit-tested, disposable N95 respirator or a powered air-purifying respirator (PAPR), goggles, face shield, water-resistant gowns, double gloves, and protective footwear. Protocols for donning and doffing of PPE must be strictly adhered to.

The most experienced anesthesia provider should perform the intubation, especially if the patient is severely ill. Video laryngoscopy should be considered and adequate paralysis ensured before intubation to avoid aerosol generation through bucking and coughing.56

Postoperative Phase

Patients with suspected or confirmed COVID-19 should not be transferred to a postanesthesia care unit (PACU). These patients should be recovered in the OR or transferred directly to an airborne isolation infection room. To minimize contamination, heat and moisture exchanging filter (HMEF), which can remove airborne particles of 0.3 μm or greater, should be applied to the endotracheal tube during transfer.56 After the patient has left the OR, as much time as possible should be allowed before subsequent patient care (for optimal decontamination of the OR).57

Visitor policy may be fluid, with restrictions ranging from limitations on number of visitors per patient to a strict no-visitor policy. These will be determined by federal and state mandates. Exceptions may be considered for special situations, such as end-of-life and pediatric care.

CURRENT TREATMENT OF THE CANCER PATIENT WITH COVID-19

To date, treatment of most patients with COVID-19 centers on supportive measures. Several treatment modalities are currently available for COVID-19 patients. While all existing therapies are still investigational, certain drugs have proven helpful.1

Overall, treatment is determined by infection severity and patient comorbidities. Patients with mild infections and self-limiting courses can recover uneventfully with home management. The focus for these patients should be isolation and prevention of spread to others.1 Patients with moderate symptoms and pneumonia may require hydroxychloroquine and azithromycin in addition to supportive care (Table 1).

Table 1. - Drug Therapies for Patients With COVID-19

Abbreviations: ALT, alanine aminotransferase; COVID-19, coronavirus disease 2019; CrCl, creatinine clearance; GI, gastrointestinal; LFTs, liver function tests.

While anecdotal, hydroxychloroquine and azithromycin have shown potential in both prophylaxis and treatment of patients with COVID-19. Of note, combination of drugs appears to reinforce the beneficial effect and significantly decreases viral load, thereby reducing the length of the infection.58,59 If bronchodilators are needed for moderate infections, a metered dose inhaler is recommended instead of nebulizer treatments so as to limit viral spread. Remdesivir and lopinavir/ritonavir are currently recommended for patients with severe symptoms, including ARDS, and requiring mechanical ventilation (Table 1).1,60 Patients with severe symptoms and cytokine release syndrome (ARDS with acute lung injury and high levels of inflammatory markers) should be started on tocilizumab.1 In the most refractory severe infections with worsening symptoms, interferon B-1a and convalescent plasma should be considered (Table 2).61–63

Table 2. - Additional Drug Therapies for Patients With COVID-19

Abbreviations: CBC, complete blood count; COVID-19, coronavirus disease 2019; IL-6, Interleukin 6.

As previously mentioned, the cancer patient with an immunocompromised state is more likely to present with more severe disease states like pneumonia and ARDS that may warrant intubation and mechanical ventilation with consideration of aforementioned drug therapies.1 Special caution must be taken in immunosuppressed cancer patients when prescribing tocilizumab and interferon B-1a, and recommendations should be made on an individual basis.1

The US CDC recommends avoiding steroids during COVID-19 treatment, and the American Heart Association (AHA) recommends continuing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) for all patients already prescribed these medications.1,64,65 Perioperatively, it is important to continue all prescribed treatment medications and understand associated considerations.

CONCLUSIONS

Our review on COVID-19 and the cancer patient is based on the latest information and knowledge available to the medical community at this time. As the COVID-19 pandemic continues to evolve and unfold, it is likely that the health care community will be faced with additional, yet unknown challenges.

It is imperative that we stay abreast of all developments with COVID-19 to protect ourselves as frontline health care providers and to provide our most vulnerable patients with the care needed for their best chance of survival and return to optimal health.

DISCLOSURES

Name: Cindy B. Yeoh, MD.

Contribution: This author helped with the study of this manuscript, including conception of the work, drafting, writing, editing, and revising for important intellectual content, as well as final approval.

Name: Kathleen J. Lee, MD.

Contribution: This author helped with the study of this manuscript, including writing, editing, and final approval.

Name: Elizabeth F. Rieth, MD.

Contribution: This author helped with the study of this manuscript, including writing and final approval.

Name: Renee Mapes, DO.

Contribution: This author helped with the study of this manuscript, including writing and final approval.

Name: Anna V. Tchoudovskaia, DNAP.

Contribution: This author helped with the study of this manuscript, including writing and final approval.

Name: Gregory W. Fischer, MD.

Contribution: This author helped with the study of this manuscript, including editing and final approval.

Name: Luis E. Tollinche, MD.

Contribution: This author helped with the study of this manuscript, including editing and revising for important intellectual content, as well as final approval.

This manuscript was handled by: Thomas R. Vetter, MD, MPH.

FOOTNOTES

GLOSSARY

ACE2 =

angiotensin-converting enzyme 2

ACEI =

angiotensin-converting enzyme inhibitors

AHA =

American Heart Association

ALT =

alanine aminotransferase

ARB =

angiotensin receptor blockers

ARDS =

acute respiratory distress syndrome

BTKi =

Bruton tyrosine kinase inhibitors

CAR =

chimeric antigen receptor

CBC =

complete blood count

CDC =

Centers for Disease Control and Prevention

CFR =

case fatality rate

COVID-19 =

coronavirus disease 2019

CrCl =

creatinine clearance

CT =

computed tomography

EQUATOR =

Enhancing the Quality and Transparency of health Research

ESAS =

Elective Surgery Acuity Scale

GI =

gastrointestinal

HMEF =

heat and moisture exchanging filter

HSCT =

hematopoietic stem cell transplant

ICU =

intensive care unit

IL-6 =

Interleukin 6

JAKi =

Janus kinase inhibitors

LFTs =

liver function tests

MERS-CoV =

Middle East respiratory syndrome coronavirus

OR =

operating room

PACU =

postanesthesia care unit

PAPR =

powered air-purifying respirator

PPE =

personal protective equipment

RSV =

human respiratory syncytial virus

SARS =

severe acute respiratory syndrome

SARS-CoV-2 =

severe acute respiratory syndrome coronavirus 2

TIL =

tumor-infiltrating lymphocytes

VEGF =

vascular endothelial growth factor

REFERENCES

2. World Health Organization. Coronavirus disease 2019 (COVID-19) situation report 48. 2020. Available at: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200308-sitrep-48-covid-19.pdf?sfvrsn=16f7ccef_4. Accessed March 31, 2020.

3. Wu YC, Chen CS, Chan YJ. The outbreak of COVID-19: an overview. J Chin Med Assoc. 2020;83:217–220.

4. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062.

5. Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 2020;7:11.

6. Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 2020;21:335–337.

7. Xia Y, Jin R, Zhao J, Li W, Shen H. Risk of COVID-19 for cancer patients. Lancet Oncol. 2020;21:e180.

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 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323:1239–1242.

9. Ogimi C, Waghmare AA, Kuypers JM, et al. Clinical significance of human coronavirus in bronchoalveolar lavage samples from hematopoietic cell transplant recipients and patients with hematologic malignancies. Clin Infect Dis. 2017;64:1532–1539.

10. Kim YJ, Lee ES, Lee YS. High mortality from viral pneumonia in patients with cancer. Infect Dis (Lond). 2019;51:502–509.

11. Milano F, Campbell AP, Guthrie KA, et al. Human rhinovirus and coronavirus detection among allogeneic hematopoietic stem cell transplantation recipients. Blood. 2010;115:2088–2094.

12. Ménétrier-Caux C, Ray-Coquard I, Blay JY, Caux C. Lymphopenia in cancer patients and its effects on response to immunotherapy: an opportunity for combination with Cytokines? J Immunother Cancer. 2019;7:85.

13. Chemaly RF, Ghosh S, Bodey GP, et al. Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center. Medicine (Baltimore). 2006;85:278–287.

14. Nichols WG, Guthrie KA, Corey L, Boeckh M. Influenza infections after hematopoietic stem cell transplantation: risk factors, mortality, and the effect of antiviral therapy. Clin Infect Dis. 2004;39:1300–1306.

15. Hakim H, Dallas R, Zhou Y, et al. Acute respiratory infections in children and adolescents with acute lymphoblastic leukemia. Cancer. 2016;122:798–805.

16. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 [Epub ahead of print].

17. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 [Epub ahead of print].

18. Qu R, Ling Y, Zhang YH, et al. Platelet-to-lymphocyte ratio is associated with prognosis in patients with Corona Virus Disease-19. J Med Virol. 2020 [Epub ahead of print].

19. Speth C, Löffler J, Krappmann S, Lass-Flörl C, Rambach G. Platelets as immune cells in infectious diseases. Future Microbiol. 2013;8:1431–1451.

20. Diao B, Wang C, Tan Y, et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). 2020 [Epub ahead of print].

21. Zheng M, Gao Y, Wang G, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 [Epub ahead of print].

22. Hijano DR, Maron G, Hayden RT. Respiratory viral infections in patients with cancer or undergoing hematopoietic cell transplant. Front Microbiol. 2018;9:3097.

23. 3 Steps Toward Preventing Infections During Cancer Treatment. Health tip sheet: neutropenia and nadir. Available at: www.preventcancerinfections.org/health-tip-sheet/neutropenia-and-nadir. Accessed March 31, 2020.

24. Williams M, Kerlann LC, Mi E, Chen J, Dadhania S, Pakzad-Shahabi L. Estimating the risks from COVID-19 infection in adult chemotherapy patients. 2020 [Epub ahead of print].

25. Kim YJ, Guthrie KA, Waghmare A, et al. Respiratory syncytial virus in hematopoietic cell transplant recipients: factors determining progression to lower respiratory tract disease. J Infect Dis. 2014;209:1195–1204.

26. Ellsworth SG. Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors. Adv Radiat Oncol. 2018;3:512–519.

27. Weber JS, Yang JC, Atkins MB, Disis ML. Toxicities of immunotherapy for the practitioner. J Clin Oncol. 2015;33:2092–2099.

28. Lewis AL, Chaft J, Girotra M, Fischer GW. Immune checkpoint inhibitors: a narrative review of considerations for the anaesthesiologist. Br J Anaesth. 2020;124:251–260.

29. Echeverry G, Fischer GW, Mead E. Next generation of cancer treatments: chimeric antigen receptor t-cell therapy and its related toxicities: a review for perioperative physicians. Anesth Analg. 2019;129:434–441.

30. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76:16–32.

31. Fisher BT, Danziger-Isakov L, Sweet LR, et al. A multicenter consortium to define the epidemiology and outcomes of inpatient respiratory viral infections in pediatric hematopoietic stem cell transplant recipients. J Pediatric Infect Dis Soc. 2018;7:275–282.

32. Ogonek J, Kralj Juric M, Ghimire S, et al. Immune reconstitution after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016;7:507.

33. Carlisle PS, Gucalp R, Wiernik PH. Nosocomial infections in neutropenic cancer patients. Infect Control Hosp Epidemiol. 1993;14:320–324.

34. Kamboj M, Sepkowitz KA. Nosocomial infections in patients with cancer. Lancet Oncol. 2009;10:589–597.

35. El-Sharif A, Elkhatib WF, Ashour HM. Nosocomial infections in leukemic and solid-tumor cancer patients: distribution, outcome and microbial spectrum of anaerobes. Future Microbiol. 2012;7:1423–1429.

36. Chen GC, Chen PY, Su YC, et al. Vascular, cognitive, and psychomental survey on elderly recycling volunteers in Northern Taiwan. Front Neurol. 2018;9:1176.

37. Pavlidis ET, Pavlidis TE. Role of bevacizumab in colorectal cancer growth and its adverse effects: a review. World J Gastroenterol. 2013;19:5051–5060.

38. Guo Z, Zhang J, Gong Z, Jing S. Correlation of factors associated with postoperative infection in patients with malignant oral and maxillofacial tumours: a logistic regression analysis. Br J Oral Maxillofac Surg. 2019;57:460–465.

39. Perkins JL, Chen Y, Harris A, et al.; Childhood Cancer Survivor Study. Infections among long-term survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study. Cancer. 2014;120:2514–2521.

40. Ou JY, Hanson HA, Ramsay JM, et al. Fine particulate matter and respiratory healthcare encounters among survivors of childhood cancers. Int J Environ Res Public Health. 2019;16:E1081.

41. Moore JX, Akinyemiju T, Bartolucci A, Wang HE, Waterbor J, Griffin R. A prospective study of community mediators on the risk of sepsis after cancer. J Intensive Care Med. 2020 [Epub ahead of print].

42. Wang H, Zhang L. Risk of COVID-19 for patients with cancer. Lancet Oncol. 2020;21:e181.

43. Eichenberger EM, Soave R, Zappetti D, et al. Incidence, significance, and persistence of human coronavirus infection in hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2019;54:1058–1066.

44. Hirsch HH, Martino R, Ward KN, Boeckh M, Einsele H, Ljungman P. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clin Infect Dis. 2013;56:258–266.

45. Gallaway MS, Henley SJ, Steele CB, et al. Surveillance for cancers associated with tobacco use - United States, 2010-2014. MMWR Surveill Summ. 2018;67:1–42.

46. Cai G. Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov. 2020 [Epub ahead of print].

47. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565–574.

48. Imai Y, Kuba K, Ohto-Nakanishi T, Penninger JM. Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis. Circ J. 2010;74:405–410.

49. Ye R, Liu Z. ACE2 exhibits protective effects against LPS-induced acute lung injury in mice by inhibiting the LPS-TLR4 pathway. Exp Mol Pathol. 2020;113:104350.

50. Ambulatory Surgery Center Association (ASCA) Foundation. COVID-19: guidance for ASCs on necessary surgeries. March 19, 2020. Available at: https://www.ascassociation.org/asca/resourcecenter/latestnewsresourcecenter/covid-19/covid-19-guidance. Accessed March 31, 2020.

51. American College of Surgeons. COVID-19: Guidance for Triage of Non-Emergent Surgical Procedures. 2020. Available at: www.facs.org/covid-19/clinical-guidance/triage. Accessed March 31, 2020.

52. American Academy of Otolaryngology-Head and Neck Surgery. Coronavirus Disease 2019: Resources. 2020. Available at: https://www.entnet.org/content/coronavirus-disease-2019-resources. Accessed March 31, 2020.

53. American Dental Association. ADA calls upon dentists to postpone elective procedures. March 16, 2020. Available at:https://www.ada.org/en/press-room/news-releases/2020-archives/march/ada-calls-upon-dentists-to-postpone-elective-procedures. Accessed March 31, 2020.

55. Gastroenterology Association. Joint GI society message: COVID-19 clinical insights for our community of gastroenterologists and gastroenterology care providers. 2020. Available at: www.gastro.org/press-release/joint-gi-society-message-covid-19-clinical-insights-for-our-community-of-gastroenterologists-and-gastroenterology-care-providers. Accessed March 31, 2020.

56. American Patient Safety Foundation. Perioperative considerations for the 2019 novel coronavirus (COVID-19). 2020. Available at: https://www.apsf.org/news-updates/perioperative-considerations-for-the-2019-novel-coronavirus-covid-19/. Accessed March 31, 2020.

57. American Society of Anesthesiologists: COVID-19 Resources for Anesthesiologists. 2020. Available at: www.asahq.org/about-asa/governance-and-committees/asa-committees/committee-on-occupational-health/coronavirus. Accessed March 31, 2020.

58. Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14:72–73.

59. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 [Epub ahead of print].

60. National Institutes of Health. NIH clinical trial of remdesivir to treat COVID-19 begins. February 25, 2020. Available at: https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins. Accessed March 31, 2020.

61. Hensley LE, Fritz LE, Jahrling PB, Karp CL, Huggins JW, Geisbert TW. Interferon-beta 1a and SARS coronavirus replication. Emerg Infect Dis. 2004;10:317–319.

62. Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020;20:398–400.

63. Soo YO, Cheng Y, Wong R, et al. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect. 2004;10:676–678.

64. Centers for Disease Control and Prevention. Coronavirus disease 2019 (COVID-19). 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/index.html. Accessed March 31, 2020.

65. American Heart Association. Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician. 2020. Available at:https://newsroom.heart.org/news/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician. Accessed March 31, 2020.

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