key: cord-0984377-okz3pn77
authors: Rogado, Jacobo; Gullón, Pedro; Obispo, Berta; Serrano, Gloria; Lara, Miguel Ángel
title: Prolonged SARS-CoV-2 viral shedding in patients with solid tumors and associated factors
date: 2021-02-23
journal: Eur J Cancer
DOI: 10.1016/j.ejca.2021.02.011
sha: 31f95fa7f0a0b74481ebbf737eba7d678b858f94
doc_id: 984377
cord_uid: okz3pn77

nan

To the editor: SARS-CoV-2 is a highly contagious virus and can cause potentially fatal complications in cancer patients [1] [2] [3] [4] . Until now, the most accurate and common methods to detect active viral infection are: (1) a positive RT-PCR, (2) a serological test (IgM+ and IgG-), (3) or a positive antigen test 5 . Previous studies have characterized time length of viral shedding in immunocompetent patients 6 ; however, there are scarce reports on immunosuppressed cancer patients. Aydillo et al. studied shedding of viable SARS-CoV-2 in transplanted hematological patients or those receiving CAR-T cell therapy 7 . In fact, the CDC's recommendations for this patient profile is still based on limited data 8 . Thus, we aim to study SARS-CoV-2 viral shedding in patients with solid tumors and its associated factors.

For this study, we recruited all patients in our center (Hospital Universitario Infanta Leonor, Madrid, Spain) diagnosed with solid tumors and COVID-19 from March 1, 2020, to November 30, 2020. COVID-19 diagnosis was based on positive nasopharyngeal RT-PCR. We prospectively followed the patients until SARS-CoV-2 shedding, defined as RT-PCR negativization or incidence of positive IgG antibodies by ELISA. We made a descriptive analysis of our sample, and then analysed time until viral shedding. After this, we used Kaplan-Meier visualization and cox regression models to study associated factors. The study was approved by the ethics committee of our center (Code: COVID-CANCER-HUIL 213/20).

Of the 149 patients with solid tumors diagnosed with COVID-19 in our center, 48 patients were finally selected and prospectively followed up (32.3%). Fifty-eight patients were excluded because they died during follow-up (38.9%). Another 43 patients were excluded because they were not able to be prospectively followed-up (28.8%).

In our study, 28 patients were male (58.3%) and median age was 69 years. Twenty-nine patients received chemotherapy (60.4%), 1 immunotherapy (2.1%) and 18 patients other treatments as targeted therapy or radiotherapy, among others (37.5%). The most predominant histology was lung cancer and breast cancer (n=14, 29.2%; n=10, 20.8%, respectively). Seven patients (14.6%) had localized disease, compared to 41 patients (85.4%) with locally advanced or metastatic disease. Only 3 patients received convalescent plasma transfusion (6.3%) and 24 specific treatment for COVID-19 (50.0%) (dexamethasone, hydroxychloroquine, lopinavir/ritonavir or remdesivir). Only one patient was admitted to the Intensive Care Unit (ICU) due to severity of COVID-19. Median time until viral shedding was 22 days. We detected reactivations in 7 patients (14.6%) with positive RT-PCR and compatible symptoms; four were receiving the first cycle of chemotherapy after recovery from COVID-19.

Patients diagnosed with metastatic or locally advanced tumors mostly present positive RT-PCR for 25 days or more, compared to those with localized tumors (22/41 -53.6%-vs 1/7 patients -14.2% -, p=0.05). No differences between age (71 years old in patients with PCR≥25 vs 68 years old in patients with PCR>25; p = 0.7), sex (p = 0.7), tumor localization (p = 0.7), cancer treatment class (p = 0.5), type of COVID-19 treatment (p = 0.4) or administration of COVID-19 hyperimmune plasma (p = 0.4) were detected (Table 1 ). Time to viral shedding was higher in those with advanced tumors (Figure 1) , although a trend towards statistical significance only was detected (28 days vs 15 days, p=0.10); patients with localized tumors were less likely to present longer duration of COVID-19 until viral shedding (HR 0.37, CI 95% 0.11-1.24, p=0.10). We found no further associations in terms of the types of tumor or COVID-19 treatments received, neither in terms of sex or age.

Regarding reactivations of COVID-19, we observed that lung cancer patients have a higher percentage of reactivations compared to breast cancer patients (4/14 -28.4% -vs 1/10 -10% -, p=0.05). This is, to our knowledge, the first published cohort of patients with solid tumors studying viral shedding and its associated risk factors, although we are aware of the small sample size and that we developed a single-center study. In our study, we observed that patients with advanced cancer at COVID-19 diagnosis have a greater risk of continuing to present positive RT-PCR with prolonged COVID-19 symptoms, similar to that observed in hematological patients undergoing transplant or CAR-T cell therapy 7 . In addition, we observed that these patients with advanced disease have the worst prognosis 1-2 , like lung cancer patients and hematologic cancer patients 2, 8 . The advanced state of immunosuppression induced by their cancer and by the specifical oncological treatments received, it could may justify our findings.

For this reason, as is suggested in two studies 7, 10 , we consider a priority to review the current management recommendations in oncological patients to define when it is safe to finish isolation as well as to restart treatment. Also, there is a need for further research in reactivations, especially in advanced cancer patients, hematologic and lung cancer patients, as they have had the worst prognosis in published series 1, 2, 9 . 

Medical Oncology Department. Hospital Universitario Infanta Leonor. Gran vía del este, 80, 28031

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Dutch Oncology COVID-19 consortium: Outcome of COVID-19 in patients with cancer in a nationwide cohort study

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High mortality among hospital-acquired COVID-19 infection in patients with cancer: A multicentre observational cohort study

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