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Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816919


Cancer patients display immunomodulation related to malignancy and anti-cancer therapies, but how these factors impact COVID-19 remains unknown. To investigate immune responses in cancer patients with COVID-19, we undertook a prospective case-control study, enrolling hospitalized solid tumor patients with acute COVID-19, as well as age-, gender-, and comorbidity-matched COVID-19 patients without cancer as controls. Using biospecimens collected during hospitalization, we performed virologic measurements as well as in-depth immunophenotyping of cellular, antibody and cytokine responses. We enrolled 17 cancer patients (cases) admitted to Yale-New Haven Hospital between March 15 and June 30, 2020 with COVID-19, as well as 17 matched non-cancer patients (controls) admitted with COVID-19. No significant differences were observed between cases and controls based on patient characteristics (age, gender, race, co-morbidities, smoking history, days from symptom onset to COVID-19 diagnosis) or outcomes (COVID-19 severity, length of hospital stay, rate of intubation or mortality). The most common primary tumor sites were lung (4/17) and gastrointestinal (4/17);all cases had received cancer-directed therapy within 6 months of COVID-19 diagnosis, with 13/17 receiving treatment less than 1 month prior to hospitalization. Three of 17 cases had received immune checkpoint inhibitor therapies. Despite having similar SARS-CoV-2 viral RNA loads at the time of COVID-19 diagnosis when compared with controls, cancer cases had increased viral RNA abundance during hospitalization, suggesting slower clearance. Antibody responses against SARS-CoV-2 were preserved in cancer cases, with cases displaying similar levels of IgM and IgG antibodies directed against SARS-CoV-2 epitopes compared to controls. Cytokine profiling revealed higher plasma levels of CCL3, IL1A and CXCL12 in cancer cases compared to controls. Using flow cytometric immunophenotyping, we found that innate immune and non-T cell adaptive immune parameters were similar between cases and controls hospitalized with COVID-19. However, among cancer cases on conventional therapies, T cell lymphopenia was more profound, and these cases demonstrated higher levels of CD8+ exhausted (CD8+CD45RA-PD1+TIM3+ ), CD8+GranzymeB+ and CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ activated T cells when compared with controls;interestingly, these differences were not observed in patients who had received immune checkpoint inhibition. Thus, we found reduced viral RNA clearance and specific alterations in T cell and cytokine responses in cancer patients hospitalized with COVID-19 compared with matched controls with COVID-19. This dysregulated T cell response in cancer patients, which may reflect immune modulation due to chronic antigen stimulation as well as cancer therapies, may lead to altered virologic and clinical outcomes in this population.

Exercer-La Revue Francophone De Medecine Generale ; - (179):25-33, 2022.
Article in French | Web of Science | ID: covidwho-1755693


Background. The COVID-19 pandemic has resulted in rapid reorganization of health and social care services. Patients are already at significant risk of healthcare-associated harm and the wholesale disruption to service delivery during the pandemic stood to heighten those risks. Objective. We explored the type and nature of patient safety incidents in French primary care settings during the COVID-19 first wave to make tentative recommendations for improvement. Methods. A national patient safety incident reporting survey was distributed to General Practitioners (GPs) in France on April 28, 2020. Reports were coded using a classification system aligned to the WHO International Classification for Patient Safety (incident types, contributing factors, incident outcomes and severity of harm). Analysis involved data coding, processing, iterative generation of data summaries using descriptive statistical and thematic analysis. NCT04346121. Results. Of 132 incidents, 58 (44%) related to delayed diagnosis, assessments and referrals. Cancellations of appointments, hospitalizations or procedures was reported in 22 (17%) of these incidents. Home confinement-related incidents accounted for 15 (10%) reports, and inappropriate stopping of medications for five (4%). Patients delayed attending or did not consult their general practitioner or other healthcare providers due to their fear of contracting COVID-19 infection at an in-person visit in 26 (10%) incidents, or fear of burdening their GPs in eight (3%) incidents. Conclusion. Constraints arising from the first wave of the COVID-19 pandemic have contributed to patient safety incidents during non-COVID-19 care. Lessons from these incidents pinpoint where primary care services in France can focus resources to design safer systems for patients.