Abstract
Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
Highlights
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel beta-coronavirus that has caused a worldwide pandemic of the human respiratory illness COVID-19, resulting in a severe threat to public health and safety worldwide
Prolonged viral shedding and higher viral loads in cancer patients compared with cancer-free COVID-19+ patients swabs, respectively (Fig. S2)
To explore the clinical significance of viral and/or immunological CoV-2 RNA detection in 35 cancer patients (Cancer_FR1_TR) and 45 parameters in cancer patients, we gathered the data from healthcare workers (HCW) using 168 and 118 samples, respectively
Summary
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel beta-coronavirus that has caused a worldwide pandemic of the human respiratory illness COVID-19, resulting in a severe threat to public health and safety worldwide. Gender, cancer-associated risk factors, metabolic syndrome, and side effects induced by their specific therapies (such as cardiomyopathy, systemic immunosuppression, and cellular senescence), cancer patients appear more vulnerable to severe infection than individuals without cancer [1]. A high hospitalization and mortality rates of SARS-CoV-2 infection were heralded in patients with malignancy in several studies across distinct geographical sites [2,3,4,5]. Performance status, and stage are additional risk factors for severe COVID-19 in this patient population. Patients diagnosed with metastatic cancers are more vulnerable to severe forms of COVID-19 than individuals with localized malignancies [9].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
