COVID-19 in cancer patients: clinical characteristics and outcome—an analysis of the LEOSS registry

Introduction Since the early SARS-CoV-2 pandemic, cancer patients have been assumed to be at higher risk for severe COVID-19. Here, we present an analysis of cancer patients from the LEOSS (Lean European Open Survey on SARS-CoV-2 Infected Patients) registry to determine whether cancer patients are at higher risk. Patients and methods We retrospectively analyzed a cohort of 435 cancer patients and 2636 non-cancer patients with confirmed SARS-CoV-2 infection, enrolled between March 16 and August 31, 2020. Data on socio-demographics, comorbidities, cancer-related features and infection course were collected. Age-, sex- and comorbidity-adjusted analysis was performed. Primary endpoint was COVID-19-related mortality. Results In total, 435 cancer patients were included in our analysis. Commonest age category was 76–85 years (36.5%), and 40.5% were female. Solid tumors were seen in 59% and lymphoma and leukemia in 17.5% and 11% of patients. Of these, 54% had an active malignancy, and 22% had recently received anti-cancer treatments. At detection of SARS-CoV-2, the majority (62.5%) presented with mild symptoms. Progression to severe COVID-19 was seen in 55% and ICU admission in 27.5%. COVID-19-related mortality rate was 22.5%. Male sex, advanced age, and active malignancy were associated with higher death rates. Comparing cancer and non-cancer patients, age distribution and comorbidity differed significantly, as did mortality (14% vs 22.5%, p value < 0.001). After adjustments for other risk factors, mortality was comparable. Conclusion Comparing cancer and non-cancer patients, outcome of COVID-19 was comparable after adjusting for age, sex, and comorbidity. However, our results emphasize that cancer patients as a group are at higher risk due to advanced age and pre-existing conditions

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Urinary T cells in active lupus nephritis show an effector memory phenotype

Background Systemic lupus erythematosus (SLE) is accompanied by alterations in T cell homeostasis including an increased effector response. Migrated effector memory T cells (CD45RO(+) CCR7(-); T-EM) appear to be involved in tissue injury. The objective of this study was to investigate the distribution and phenotype of effector memory T cells in the peripheral blood (PB), and their presence in renal biopsies and urine of patients with SLE. The hypothesis that these T EM cells migrate to the kidney during active disease was tested. Methods A total of 43 patients with SLE and 20 healthy controls were enrolled. CD4(+)T(EM) cells and CD8(+)T(EM) cells were analysed in PB and urine using flow cytometric analysis. In 10 patients with active lupus nephritis a parallel analysis was performed on the presence of T EM cells in kidney biopsies. Results The percentage of circulating CD8(+)T(EM) cells in patients with SLE was significantly decreased versus healthy controls (33.9 +/- 18.3% vs 42.9 +/- 11.0%, p=0.008). In patients with active renal involvement (n=12) this percentage was further decreased to 30.4 +/- 15.9%, p=0.01. Analysis of the urinary sediment in active renal disease showed increased numbers of CD4(+)T cells (134 +/- 71 cells/ml) and CD8(+)T cells (287 +/- 220 cells/ml), respectively, while in healthy controls and patients without active renal disease almost no T cells were present. In all, 73.6 +/- 8.3% of urinary CD4(+)T cells and 69.3 +/- 26.0% of urinary CD8(+)T cells expressed the T EM phenotype. CD8(+) cells were also found in renal biopsies. Conclusions The data presented are compatible with the hypothesis that CD8(+) effector memory cells migrate from the PB to the kidney and appear in the urine during active renal disease in patients with SLE. These cells could serve as an additional marker of renal activity in patients with SLE

Urinary CD8(+) T-cell counts discriminate between active and inactive lupus nephritis

<p>Introduction: Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Early detection of initial renal manifestations and relapses during follow-up is pivotal to prevent loss of renal function. Apart from renal biopsies, current urinary and serological diagnostic tests fail to accurately demonstrate the presence of active LN. Previously, we demonstrated that effector memory T-cells (CD45RO(+)CCR7(-);T-EM) migrate into the urine during active LN. The objective of this study was to assess the diagnostic value of urinary T-cells in comparison with traditional markers of active LN.</p><p>Methods: T-cells in the urine during active LN and remission were investigated. Twenty-two, in most cases biopsy-proven, active LN patients and 24 SLE patients without active LN were enrolled and serial measurements were performed in 16 patients.</p><p>Results: Analysis of the urinary sediment in active renal disease showed an increased number of CD8(+) T-cells and absence of these cells during remission. Enumerating T-cell counts in LN patients with a history of renal involvement was a superior marker of active LN in comparison to traditional markers, such as proteinuria and s-creatinine.</p><p>Conclusions: In conclusion, urinary T-cells, in particular CD8(+) T cells, are a promising marker to assess renal activity in LN patients, in particular in those with prior renal involvement.</p>

COVID-19 in cancer patients: clinical characteristics and outcome-an analysis of the LEOSS registry

Introduction Since the early SARS-CoV-2 pandemic, cancer patients have been assumed to be at higher risk for severe COVID-19. Here, we present an analysis of cancer patients from the LEOSS (Lean European Open Survey on SARS-CoV-2 Infected Patients) registry to determine whether cancer patients are at higher risk. Patients and methods We retrospectively analyzed a cohort of 435 cancer patients and 2636 non-cancer patients with confirmed SARS-CoV-2 infection, enrolled between March 16 and August 31, 2020. Data on socio-demographics, comorbidities, cancer-related features and infection course were collected. Age-, sex- and comorbidity-adjusted analysis was performed. Primary endpoint was COVID-19-related mortality. Results In total, 435 cancer patients were included in our analysis. Commonest age category was 76-85 years (36.5%), and 40.5% were female. Solid tumors were seen in 59% and lymphoma and leukemia in 17.5% and 11% of patients. Of these, 54% had an active malignancy, and 22% had recently received anti-cancer treatments. At detection of SARS-CoV-2, the majority (62.5%) presented with mild symptoms. Progression to severe COVID-19 was seen in 55% and ICU admission in 27.5%. COVID-19-related mortality rate was 22.5%. Male sex, advanced age, and active malignancy were associated with higher death rates. Comparing cancer and non-cancer patients, age distribution and comorbidity differed significantly, as did mortality (14% vs 22.5%, p value < 0.001). After adjustments for other risk factors, mortality was comparable. Conclusion Comparing cancer and non-cancer patients, outcome of COVID-19 was comparable after adjusting for age, sex, and comorbidity. However, our results emphasize that cancer patients as a group are at higher risk due to advanced age and pre-existing conditions