ABSTRACT
ObjectivesIn severe COVID-19 pneumonia, the appropriate timing and dosing of corticosteroids(CS) is not known. Patient subgroups for which CS could be more beneficial also need appraisal. The aim of this study was to assess the effect of early CS in COVID-19 pneumonia patients admitted to the ICU on the occurrence of 60-day mortality, ICU-acquired-bloodstream infections(ICU-BSI), and hospital-acquired pneumonia and ventilator-associated pneumonia(HAP-VAP).MethodsWe included patients with COVID-19 pneumonia admitted to 11 ICUs belonging to the French OutcomeReaTM network from January to May 2020. We used survival models with ponderation with inverse probability of treatment weighting (IPTW). Inflammation was defined as Ferritin >1000 µg/l or D-Dimers >1000 µg/l or C-Reactive Protein >100 mg/dL.ResultsThe study population comprised 302 patients having a median age of 61.6(53-70) years of whom 78.8% were male and 58.6% had at least one comorbidity. The median SAPS II was 33(25-44). Invasive mechanical ventilation was required in 34.8% of the patients. Sixty-six (21.8%) patients were in the Early-CS-subgroup. Most of them (n=55, 83.3%) received high doses of steroids. Overall, 60-day mortality was 29.4%. The risks of 60-day mortality (IPTWHR =0.88;95% CI 0.55 to 1.39, p=0.58), ICU-BSI and HAP-VAP were similar in the two groups. Importantly, early CS treatment was associated with a lower mortality rate in patients aged 60 years or more (IPTWHR, 0.51;95% CI, 0.29 – 0.91; p=0.02). But, CS was associated with an increased risk of death for the patients younger than 60 years without inflammation on admission (IPTWHR =8.17;95% CI, 1.76, 37.85; p=0.01).ConclusionFor patients with COVID-19 pneumonia, early CS treatment was not associated with patient survival. Interestingly, inflammation and age can significantly influence the effect of CS.
Subject(s)
Pneumonia , Critical Illness , COVID-19 , InflammationABSTRACT
Little is known about the time-dependent immune responses in severe COVID-19. Data of 15 consecutive patients were sequentially recorded from intensive care unit admission. Lymphocyte subsets and total monocyte and subsets counts were monitored as well as the expression of HLA-DR. For 5 patients, SARS-CoV-2-specific T-cell polyfunctionality was assessed against Spike and Nucleoprotein SARS-CoV-2 peptides. Non-specific inflammation markers were increased in all patients. Median monocyte HLA-DR expression was below the 8,000 AB/C threshold defining acquired immunodepression. A "V" trend curve for lymphopenia, monocyte numbers, and HLA-DR expression was observed with a nadir between days 11-14 after symptoms onset. Intermediate CD14++CD16+ monocytes increased early with a reduction in classic CD14++CD16- monocytes. Polyfunctional SARS-Cov-2-specific CD4 T-cells were present and functional, whereas virus-specific CD8 T-cells were less frequent and not efficient. We report a temporal variation of both innate and adaptive immunity in severe COVID-19 patients, helpful in guiding therapeutic decisions (e.g. anti-inflammatory vs. immunostimulatory ones). We describe a defect in virus-specific CD8 T-cells, a potential biomarker of clinical severity. These combined data also provide helpful knowledge for vaccine design. Trial registration numberNCT04386395