Corticosteroid Therapy in COVID-19 Associated With In-hospital Mortality in Geriatric Patients: A Propensity Matched Cohort Study.

BACKGROUND: Few data are available on the prognosis of older patients who received corticosteroids for COVID-19. We aimed to compare the in-hospital mortality of geriatric patients hospitalized for COVID-19 who received corticosteroids or not. METHODS: We conducted a multicentric retrospective cohort study in 15 acute COVID-19 geriatric wards in the Paris area from March to April 2020 and November 2020 to May 2021. We included all consecutive patients aged 70 years and older who were hospitalized with confirmed COVID-19 in these wards. Propensity score and multivariate analyses were used. RESULTS: Of the 1 579 patients included (535 received corticosteroids), the median age was 86 (interquartile range 81-91) years, 56% of patients were female, the median Charlson Comorbidity Index (CCI) was 2.6 (interquartile range 1-4), and 64% of patients were frail (Clinical Frailty Score 5-9). The propensity score analysis paired 984 patients (492 with and without corticosteroids). The in-hospital mortality was 32.3% in the matched cohort. On multivariate analysis, the probability of in-hospital mortality was increased with corticosteroid use (odds ratio [OR] = 2.61 [95% confidence interval (CI) 1.63-4.20]). Other factors associated with in-hospital mortality were age (OR = 1.04 [1.01-1.07], CCI (OR = 1.18 [1.07-1.29], activities of daily living (OR = 0.85 [0.75-0.95], oxygen saturation < 90% on room air (OR = 2.15 [1.45-3.17], C-reactive protein level (OR = 2.06 [1.69-2.51], and lowest lymphocyte count (OR = 0.49 [0.38-0.63]). Among the 535 patients who received corticosteroids, 68.3% had at least one corticosteroid side effect, including delirium (32.9%), secondary infections (32.7%), and decompensated diabetes (14.4%). CONCLUSIONS: In this multicentric matched-cohort study of geriatric patients hospitalized for COVID-19, the use of corticosteroids was significantly associated with in-hospital mortality.

Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8+ T Cells in Elderly Humans.

Aging is associated with functional deficits in the naive T cell compartment, which compromise the generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found that naive CD8+ T cells in elderly humans were prone to apoptosis and proliferated suboptimally in response to stimulation via the TCR. These abnormalities were associated with dysregulated lipid metabolism under homeostatic conditions and enhanced levels of basal activation. Importantly, reversal of the bioenergetic anomalies with lipid-altering drugs, such as rosiglitazone, almost completely restored the Ag responsiveness of naive CD8+ T cells. Interventions that favor lipid catabolism may therefore find utility as adjunctive therapies in the elderly to promote vaccine-induced immunity against targetable cancers and emerging pathogens, such as seasonal influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients.

Highlights: Innate immune activation during Covid-19 infection is associated with pernicious clinical outcome. Background: Coronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity. Methods: We measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death. Results: Severe and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity. Conclusion: We propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.

Clinical Characteristics and Outcomes of 821 Older Patients With SARS-Cov-2 Infection Admitted to Acute Care Geriatric Wards.

BACKGROUND: There is limited information describing the characteristics and outcomes of hospitalized older patients with confirmed coronavirus disease 2019 (COVID-19). METHOD: We conducted a multicentric retrospective cohort study in 13 acute COVID-19 geriatric wards, from March 13 to April 15, 2020, in Paris area. All consecutive patients aged 70 years and older, with confirmed COVID-19, were enrolled. RESULTS: Of the 821 patients included in the study, the mean (SD) age was 86 (7) years; 58% were female; 85% had ≥2 comorbidities; 29% lived in an institution; and the median [interquartile range] Activities of Daily Living scale (ADL) score was 4 [2-6]. The most common symptoms at COVID-19 onset were asthenia (63%), fever (55%), dyspnea (45%), dry cough (45%), and delirium (25%). The in-hospital mortality was 31% (95% confidence interval [CI] 27-33). On multivariate analysis, at COVID-19 onset, the probability of in-hospital mortality was increased with male gender (odds ratio [OR] 1.85; 95% CI 1.30-2.63), ADL score <4 (OR 1.84; 95% CI 1.25-2.70), asthenia (OR 1.59; 95% CI 1.08-2.32), quick Sequential Organ Failure Assessment score ≥2 (OR 2.63; 95% CI 1.64-4.22), and specific COVID-19 anomalies on chest computerized tomography (OR 2.60; 95% CI 1.07-6.46). CONCLUSIONS: This study provides new information about older patients with COVID-19 who are hospitalized. A quick bedside evaluation at admission of sex, functional status, systolic arterial pressure, consciousness, respiratory rate, and asthenia can identify older patients at risk of unfavorable outcomes.