Background

There is uncertainty as to the contribution of cancer patients’ features on severity and mortality from Covid-19 and little guidance as to the role of anti-cancer and anti-Covid-19 therapy in this population.

Methods

OnCovid is a retrospective observational study conducted across 19 European centers that recruited cancer patients aged >18 and diagnosed with Covid-19 between 26/02 and 01/04/2020. Uni- and multivariable regression models were used to evaluate predictors of Covid-19 severity and mortality.

Results

We identified 890 patients from UK (n=218, 24%), Italy (n=343, 37%), Spain (n=323, 36%) and Germany (n=6, 1%). Most patients were male (n=503, 56%) had a diagnosis of solid malignancy (n=753, 84%) and 556 (62%) had active disease. Mean (±SD) patient age was 68±13 years, and 670 (75%) had >1 co-morbidity, most commonly hypertension (n=386, 43%). Commonest presenting symptoms were fever (n=569, 63%) and cough (n=448, 50%), beginning 6.3 (±9.5 SD) days before diagnosis. Most patients (n=565, 63%) had >1 complication from Covid-19, including respiratory failure (n=527, 59%) and acute respiratory distress syndrome (n=127, 22%). In total, 110 patients (14%) were escalated to high-dependency or intensive care. At time of analysis, 299 patients had died (33%). Multi-variate logistic regression identified male gender, age>65 (p<0.0001) presence of >2 comorbidities (p=0.001) active malignancy (p=0.07) as predictors of complicated Covid-19. Mortality was associated with active malignancy (p<0.0001), age>65 and co-morbid burden (p=0.002). Provision of chemotherapy, targeted therapy or immunotherapy was not associated with higher mortality. Exposure to anti-malarials alone (chloroquine/hydroxychloroquine, n=182, p<0.001) or in combination with anti-virals (n=195, p<0.001) or tocilizumab (n=51, p=0.004) was associated with improved mortality compared to patients who did not receive any of these therapies (n=446) independent of patients’ gender, age, tumour stage and severity of Covid-19.

Conclusions

This study highlights the clinical utility of demographic factors for individualized risk-stratification of patients and supports further research into emerging anti Covid-19 therapeutics in SARS-Cov-2 infected cancer patients.

Clinical trial identification

NCT04393974.

Legal entity responsible for the study

Imperial College London.

Funding

Has not received any funding.

Disclosure

D.J. Pinato: Speaker Bureau/Expert testimony: ViiV Healthcare; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy: MiNa Therapeutics; Advisory/Consultancy: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): MSD. All other authors have declared no conflicts of interest.

Background

Systemic inflammation is a unifying mechanism common to cancer progression and SARS-CoV-2 infection. Mortality from Covid-19 strongly relates to systemic inflammatory reaction to SARS-CoV-2. We sought to determine whether inflammatory biomarkers can identify poor outcome in cancer patients with Covid-19.

Methods

Between 27/02 and 23/06/2020, OnCovid retrospectively accrued 1,318 consecutive Covid-19-infected cancer patients aged >18 from 25 academic centers in the U.K., Spain, Italy, Germany and Belgium. Patients with leukemia, myeloma or insufficient data were excluded. We tested neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and prognostic index (PI) as prognostic biomarkers. NLR, PLR and PNI were dichotomized around their medians.

Results

1,071 eligible patients were sorted into a training set (TS, n=529) and validation set (VS, n=542). TS and VS were matched by age (67.9±13.3 TS, 68.5±13.5 VS), active malignancy at Covid-19 diagnosis (66.7% TS, 61.6% VS), presence of >1 comorbidity (52.1% TS, 49.8% VS) and prevalence of complications including respiratory failure (58.0% TS, 59.0% VS) and ARDS (11.5% TS, 12.9% VS). In the TS, higher mortality rates were associated with NLR>6 (44.6% vs 28%, p<0.0001), PNI<40 (46.6% vs 20.9%, p<0.0001), mGPS (50.6% for mGPS2 vs 30.4% and 11.4% for mGPS1 and 0, p<0.0001), and PI (50% for PI2 vs 40% for PI1 and 9.1% for PI0, p<0.0001). Patients in poor risk categories had shorter median overall survival [OS], (NLR>6 30 days 95%CI 1-63, PNI<40 23 days 95%CI 10-35, mGPS2 20 days 95%CI 8-32, PI2 23 days 95%CI 1-56) compared to patients in good risk categories, for whom median OS was not reached (p<0.0001 for all comparisons). The PLR was not associated with survival. Analyses of survival in the VS confirmed NLR, PNI, PI and mGPS as predictors of survival (p<0.0001).

Conclusions

Systemic inflammation is a key driver of mortality from SARS-CoV-2 in cancer patients. The NLR, PNI, mGPS, and PI are externally validated biomarkers to quantify systemic inflammation in patients with cancer and can be used as bedside tests to stratify patients at risk of poorer outcome from Covid-19.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Imperial College London.

Funding

Wellcome Trust Strategic Fund (PS3416).

Disclosure

All authors have declared no conflicts of interest.