Ferritin as a predictive biomarker of severity in Covid-19 / La ferritine comme biomarqueur prédictif des formes sévères de Covid-19

Background: To prevent the crisis-level shortage of beds in hospitals and for a more efficient support, it's necessary to early identify coronavirus disease-19 (Covid-19) patients at risk to develop a severe form of the disease. Objective: The goal of our study was to determine whether biological markers, including the serum ferritin, could predict the severity of the Covid-19. Methods: One hundred and seventy-one patients, who were admitted to Caen University Hospital, were included retrospectively with a positive diagnosis of Covid-19 by RT-PCR. A serum ferritin measurement was performed for all patients. They were further classified either into a non-severe or a severe group based on their hospitalization in intense care unit (ICU) for mechanical ventilation or death. Results: Univariate analysis revealed a significant association between increased serum ferritin and CRP levels, obesity, CT scan lesions, pathological respiratory rate, decreased PaO2/FiO2 ratio, the NEWS-2 score and the severe (n = 59) vs the non-severe (n = 112) outcome of Covid-19 patients. However, in a multivariate analysis, only CRP and obesity were associated with the severe form of Covid-19. Conclusion: While pathological level of serum ferritin at admission is associated with severe form of Covid-19, combination of increased CRP level and obesity would better predict the severity of the disease.

Pour une meilleure prise en charge, il est nécessaire de pouvoir identifier précocement les patients atteints de la Covid-19 susceptibles de développer une forme sévère. L'objectif de notre étude était de déterminer si des marqueurs biologiques, notamment la ferritinémie, peuvent prédire la sévérité de la Covid-19. Nous avons inclus de manière rétrospective 171 patients au CHU de Caen avec un diagnostic de Covid-19. Les patients devaient avoir un bilan biologique incluant la ferritinémie à l'admission et ont été classés en formes sévères (n = 59, hospitalisation et ventilation invasive en soins intensifs ou en réanimation, et/ou décès) et non-sévères (n = 112, tous les autres patients). L'analyse univariée a montré une association entre les formes sévères de Covid-19 avec les niveaux élevés de ferritine et de CRP, l'obésité, les lésions pulmonaires, la fréquence respiratoire élevée, la diminution du ratio PaO2/FiO2 et le score de NEWS-2. Cependant, en analyse multivariée seules la CRP et l'obésité montraient une association avec les formes sévères. En conclusion, alors que la ferritinémie élevée est associée à un risque accru de développer une forme sévère de la Covid-19, la CRP et la présence d'une obésité seraient de meilleurs marqueurs prédictifs.

PD-L1 Copy Number Variation Does Not Correlate With PD-L1 Expression or Response to Anti-PD-1 Immunotherapy In Patients With Advanced Melanomas.

Predicting the response to PD-1/PD-L1 immune checkpoint blockade in patients with metastatic melanoma remains challenging. In this study, we have investigated for the relationships between PD-L1 expression, PD-L1 copy number variations, and the response to anti-PD-1 therapies. We studied the formalin-fixed paraffin-embedded tumor samples of 36 patients with metastatic melanoma using PD-L1 immunohistochemistry (IHC) and PD-L1/chromosome 9 fluorescent in situ hybridization (FISH). PD-L1 IHC was positive in 3 patients (8.33%, with >5% stained tumor cells) and PD-L1 FISH test revealed 5 (13.8%) PD-L1 amplifications, 8 (22.2%) PD-L1 gains, and 2 (5.5%) PD-L1 losses. Among 14 responders and 13 nonresponders to anti-PD-1 immunotherapy, we concluded that there was no significant relationship between PD-L1 expression, PD-L1 copy number variations, and the response to anti-PD-1 therapies. In our study, the determination of PD-L1 expression using IHC and PD-L1 copy number using FISH was insufficient to predict the response to PD-1/PD-L1 immune checkpoint blockade in patients with advanced melanomas.