key: cord-0894239-wbdbavxg
authors: Roberto, Michela; Basta, Fabio; Mazzuca, Federica; Curgliano, Giuseppe; Marchetti, Paolo
title: Risk of COVID-19 in patients treated for cancer: an immune response-based hypothesis
date: 2020-05-18
journal: Eur J Cancer
DOI: 10.1016/j.ejca.2020.05.003
sha: ed071978a63083a40ae3ee7bc755395f0c3064d8
doc_id: 894239
cord_uid: wbdbavxg

nan

cancer patients a risk of infection and a mortality rate of about 2% and 4% respectively. [1] [2] [3] (Table 1) Mildly different was the Italian report on a subsample of 2,351 patients with COVID-19 who died in hospital with preexisting conditions, where 383 (16.3%) patients had had active cancer in the past 5 year. [4] Although the mortality of cancer patients was higher than that reported in the Chinese studies, a direct comparison is not allowed for the lack of detailed information about anti-cancer treatment adopted and type of cancer. Moreover, as reported by Onder et al, a plausible explanation for the higher Italian case-fatality rate is based on defining COVID-19-related deaths independently from preexisting diseases that may have caused the death. [5] Therefore, whether this finding is secondary to cancer or a preexisting comorbidity is unknown.

We appreciated the study of Trapani D et al. [6] published in European Journal of Cancer, which, to the best of our knowledge, was the first Italian report of cancer patients experiencing COVID-19. The authors reported data of 9 cancer patients referred to the European Institute of Oncology in Lombardy Region, epicenter of the outbreak in Italy. According to previously published studies focused on cancer patients [1] [2] [3] , the majority of patients were male (78%), with a median age higher than 65 years (range 42-79) and a median of one comorbidity per patient (range: 0-2). In this report, 8 patients were under active treatment, mostly chemotherapy (50%), followed by experimental immune checkpoint inhibitors (25%) and small molecules (25%). (Table 1 ) However, none of those patients died or accessed the intensive therapy unit and out of two patients with severe pneumonia which required hospitalization, all the other patients had a mild COVID-19 syndrome and were referred to home-based management.

Although the overall limited sample size, patients with cancer are thought to be more susceptible to the infection due to their immunocompromised status caused by both the malignancy and anticancer treatments. As a matter of fact, COVID-19 is a highly contagious infection to which everyone may be vulnerable. [7] However, not all people exposed to SARS-CoV-2 became infected and not all infected patients develop severe respiratory illness. Furthermore, not all cancer patients correspond to advanced cancer patients, who are supposed to be immunosuppressed.

To thicken the plot, an effectual host immune response, including innate and adaptive immunity, seems crucial to control and resolve the SARS-CoV-2 infection. During the first period of incubation an effective specific adaptive immune response is required to eliminate the virus and to preclude disease progression to severe stages. Therefore, a nonimmunocompromised status as well as an appropriate genetic background (e.g. HLA) are both important. At this initial stage, strategies to boost immune responses, such as checkpoint inhibitors immunotherapy, could even be more useful than harmful in cancer patients.

Otherwise, when the adaptive immune response is impaired or dysregulated, virus can propagate and lead to massive destruction of the affected tissues, especially lungs or organs displaying ACE2 hyperexpression. [8] At this advanced stage, the excessive production of proinflammatory cytokines eventually followed by the so called "cytokine storm" is supposed to play an important role in the development of life-threatening acute respiratory distress syndrome (ARDS). [9] Paradoxically, at this later stage a good general health may be disadvantageous for cancer patients and contrariwise a strong immunosuppression could lead to better outcomes. Beyond "cytokine storm" we should also consider the role of a multifactorial process to justify the rapid evolution of lung and multiorgan injury. We endorse the idea of a microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS) as a new name for severe pulmonary coronavirus disease 2019 (COVID-19) . In predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis. [10] This progressive endothelial thromboinflammatory syndrome may also involve the microvascular bed of the brain and other vital organs, leading to multiple organ failure and death. Future steps in the understanding of the disease and in the identification of treatments may benefit from this definition and hypothesized sequence of events.

In this context, immunotherapy, chemotherapy, as well as antiangiogenic targeted agents, could represent bivalent options for cancer patients, with opposite role according to the different viral infection stages.

A separate analysis is necessary for lung radiotherapy, which in addition to a systemic immunosuppressive effect might result in lung locoregional tissue damage.

Lastly, it should be reminded that cancer patients are often older and frequently affected with comorbidities, such as diabetes and hypertension that, even taken individually, are those most related to COVID-19 infection damage and deaths. [7] Thus, we did not consider all the patients as the same, but by consider patients by patients, including sex, age, comorbidities, tumor characteristics and the ongoing anticancer treatment. According to the current evidence, the limited sample size of cancer patients, especially for those actively receiving anticancer treatment, and the heterogeneous characteristics of patients included in published studies (up to May 4th, 2020), we think that data on cancer patients are still inconclusive. We agree with Trapani D. and colleagues that our goal, as oncologist, is to ensure the best possible support to our patients by taking further more detailed analyses to better understand the role of each anticancer drugs in the fight against COVID-19, and which kind of behavior we should adopt towards our patients rather than believing everything as evidence. 

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

SARS-CoV-2 transmission in patients with cancer at a tertiary care hospital in Wuhan, China

et al Clinical characteristics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan

-Characteristics of SARS-CoV-2 patients dying in Italy Report based on available data on

Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

The experience on COVID-19 and cancer from an oncology hub institution in Milan, Lombardy Region

Clinical Characteristics of Coronavirus Disease 2019 in China. The New England journal of medicine

COVID-19 infection: the perspectives on immune responses

Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory medicine

Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis

Lung cancer Declaration of interests: all authors have nothing to disclose in relation to this manuscript