key: cord-0779659-6w80tw8i
authors: Fuentes‐Antrás, Jesús; Manzano, Aránzazu; Marquina, Gloria; Paz, Mateo; Aguado, Carlos; Granja, Mónica; Benítez, Javier; Ortega, Justo; Priego, Araceli; González, Carlos; Tejerina‐Peces, Julia; Flores, Paloma; de Sa, Alfonso López; Toledano, Carmen; Olalla, Jennifer; de Luna, Alicia; Bartolomé, Jorge; Pérez‐Segura, Pedro
title: A snapshot of COVID‐19 infection in patients with solid tumors
date: 2020-12-19
journal: Int J Cancer
DOI: 10.1002/ijc.33420
sha: b70c0d7cb84a80a6e78503fdb1964cb89a256ff7
doc_id: 779659
cord_uid: 6w80tw8i

Coronavirus disease 2019 (COVID‐19) pandemic is affecting a high percentage of the population at an unprecedented rate. Cancer patients comprise a subgroup especially vulnerable to this infection. Herein, we present a prospective analysis of epidemiological, clinical, radiological and laboratory data of consecutive adult cancer patients seen in the Clínico San Carlos University Hospital (Madrid, Spain), and admitted to hospital and tested for COVID‐19 between 21 February 2020 and 8 May 2020 due to clinical suspicion of infection. Data from 73 patients with confirmed COVID‐19 and active solid tumors or diagnosed within the previous 5 years were analyzed. The most frequent malignancy was lung cancer (19%) and 54 patients (74%) were on active cancer treatment. Most common findings on presentation included cough (55%), fever (52%) and dyspnea (45%), and 32 (44%) patients showed oxygen saturation levels below 95%. Radiologically, 54 (73%) patients presented an abnormal pattern, the most frequent being infiltrates (64%). 18 (24.7%) patients died in hospital and 55 (75.3%) were discharged with clinical resolution of the event. Multivariable logistic regression adjusted for age and tumor stage showed higher odds of in‐hospital death associated with a history of cardiovascular disease, hospitalization in the previous 30 days, and several features on admission including dyspnea, higher qSOFA score, higher C‐reactive protein levels and an abnormal neutrophil count. We present prospective, real‐world evidence that can help articulate cancer care protocols for patients infected with SARS‐CoV‐2, with special focus on features on admission that can stratify patients with a higher risk of death from COVID‐19.

outbreak of 2003, to which it is genetically related. 2, 3 In February 2020, the World Health Organization designated this disease as . Although transmission appeared to start from animals, with bat as the candidate reservoir for the virus, person-to-person transmission was reported in a Wuhan seafood and wild animal trade market. 4, 5 The clinical picture of COVID-19 encompasses different levels of severity, with most of those infected being asymptomatic or showing mild respiratory symptoms. However, the conjunction of a high transmissibility and a significant incidence of acute respiratory distress syndrome (ARDS) can ultimately lead to high hospitalization rates and nonnegligible mortality. [6] [7] [8] [9] There are scarce data about how the virus behaves in the cancer population, who usually harbor dysfunctional immune systems, and particularly in those exposed to active chemotherapy or biological agents. Epidemiological research conducted in the Chinese population has indicated a higher incidence of infection (1% vs 0.29%) as well as a higher mortality rate (39% vs 8%). 10 Similarly, Zhang et al reported a retrospective cohort of 28 cancer patients, in which 28.6% experienced a composite endpoint including Intensive Care Unit (ICU) referral, use of mechanical ventilation or death. 11 The largest available cohort to date, composed of 928 individuals from United States, Canada and Spain, showed a mortality rate of 13% at study cutoff. 9 However, it remains unclear if cancer treatments could increase the risk of COVID-19. 12 Here, we analyzed a prospective series of patients with solid tumors and infected with SARS-CoV-2 in a large urban area of Western Europe (Madrid, Spain). A specific area in our outpatient facility was enabled in order to evaluate suspicious cases for COVID-19. Patients were actively interrogated for signs and symptoms of COVID-19 infection and contact history with positive patients before their scheduled appointment at the Medical Oncology Department. Particularly, patients were assessed for the following: (a) fever (37.5 C), cough, difficulty breathing, headache, sore throat/trouble swallowing, runny nose, loss of taste or smell, nausea/vomiting/diarrhea in the last 14 days; (b) close contact with someone who is sick or has confirmed COVID-19 in the previous 14 days;

(c) travel to/from high-risk areas in the previous 14 days before symptom onset. Suspicious cases were referred to the Emergency Department for screening, and positive tested patients were admitted and/or treated according to the Internal Management Protocol for COVID-19 disease of our institution. Microbiological assessment of SARS-CoV-2 infection was performed using real-time PCR analysis of nasopharyngeal and/or pharyngeal swabs. The primary outcome was all-cause inhospital mortality for both descriptive and analytical purposes. Mechanical ventilation or ICU referral were not explored as endpoints given the low number of cases occurring. This could be considerably attributed to the shortage of health resources at that time of the outbreak and would confound results. Clinical information and laboratory and radiological findings were prospectively collected from electronic medical records.

All data were checked by at least two researchers, and a third researcher (AM) decided on conflicting information. This study was approved by the Ethics Committee of the Clínico San Carlos University Hospital.

Written informed consent was not required given the emergency of the current pandemic.

Fever was defined as the presence of a temperature equal to or greater than 37.5 C. Cut-off values in laboratory data for analytic purposes were based in those defined by the internal protocol of our institution and international clinical standards. Cardiovascular disease indicates a composite of ischemic heart disease, arrhythmia, cerebrovascular disease and thromboembolism. CURB65 is a widely used mortality prediction score in patients with community-acquired pneumonia. 13 Quick Sepsis-related Organ Failure Assessment (qSOFA) is the recommended score to assess high-risk patients for in-hospital mortality with suspected infection outside ICU units. 14 High-dose steroids were defined as a dose of more than 1.5 mg per kg of methylprednisolone daily or equivalent steroid dose.

Clinical data and results from complementary tests were stored and managed using a Research Electronic Data Capture (REDCap)

This report provides prospective data about cancer patients with COVID-19 in a situation of maximum pressure on the healthcare system of a large urban area in Western Europe.

Despite a milder clinical profile on presentation, in-hospital mortality of COVID-19 was higher in cancer patients than in the general population. The mortality risk was associated with a history of cardiovascular disease and several variables on admission, but seemed not to be influenced by tumor type or anti-tumor therapy. The evidence could help articulate cancer care protocols for patients infected with SARS-CoV-2 and identify patients with a higher risk of in-hospital death.

T A B L E 1 Demographic, baseline and oncological characteristics of cancer patients admitted with COVID-19 

The main clinical, laboratory and radiological findings at hospital admission are collected in (Table S1 ). Only one patient was admitted in the ICU and could be successfully extubated and eventually discharged.

A multivariate logistic regression analysis was performed adjusting for age and tumor stage ( 

This study shows the clinical characteristics and prognosis of 73 prospectively collected, confirmed COVID-19 patients with solid tumors, admitted during a short time frame in a tertiary university hospital and experienced a definite outcome. In sum, our observations depict a milder profile on presentation and yet a higher in-hospital mortality of COVID-19 compared to the general population. The risk of mortality was associated through logistic regression to a history of cardiovascular disease and to variables on admission including an abnormal neutrophil count, lower oxygen saturation levels, higher CRP levels and anemia, but seemed not to be influenced by any specific tumor type or antitumor therapy, nor by the time from its administration to the infection onset.

Clinical presentation typically consisted of fever, cough, dyspnea and/or asthenia, accompanied by oxygen saturation levels below 95%, and evidence of bilateral infiltrates in chest X-ray. However, cancer patients appeared less symptomatic on presentation than the general population (eg, fever 52% vs 83%-98.6%; cough 55% vs 59.4%-82%;

pneumonia 73% vs 75%-100%), while showing similar laboratory findings with the exception of increased D-dimer levels. [6] [7] [8] Remarkably, most patients scored low (0-1) on both qSOFA and CURB65 scales on admission, suggesting that they were assessed at an early phase of the disease. This idea is reinforced by a median time from symptom onset to hospital admission of only 3.5 days (IQR 1.3-7.0).

We report an overall mortality rate of 24.7%, and COVID-19-related mortality of 19.2%, which clearly exceeds that of the general population (2%-3%), but is consistent with previous communications. 9, 11, 17 Although cancer patients are slightly older than the general population, the increased severity of the disease may rather rely on an impaired immune system. 10 during the first days of outbreak, and high-dose steroids were included in treatment protocols in the last weeks of our observation period ( Figure S1 ).

To the best of our knowledge, we report herein one of the largest prospective series of patients with solid tumors diagnosed with COVID-19 in Western Europe. We described the main clinical features on presentation and found that a history of cardiovascular disease, higher CRP levels and an altered neutrophil count on admission are associated with a higher risk of in-hospital death. No specific tumor type or oncological therapy had a significant effect on mortality. Our finding of a high proportion of suspected nosocomial cases may encourage the development of care protocols that ensure patient safety without compromising the quality of cancer treatment. A joint effort is required to establish evidence-based strategies for the management of COVID-19-positive cancer patients.

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SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section at the end of this article. How to cite this article

We want to thank the effort made by all the professionals involved in the management of COVID-19-positive cancer patients in collaborating in the design, writing and analysis of this work, despite the great care burden that exists.No founding sources. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

The authors declare no conflict of interest.

The data supporting the findings of this study are available within the article and/or its supplementary materials. Raw data compliant with the institutional and home country confidentiality policies can be available upon request from the corresponding author.

Carlos University Hospital and performed in accordance with the Declaration of Helsinki. Written informed consent was waived given the emergency of the current pandemic.

Jesús Fuentes-Antrás https://orcid.org/0000-0001-5805-2362