There are only few data concerning persistence of neutralizing antibodies (NAbs) among SARS-CoV-2-infected healthcare workers (HCW). These individuals are particularly exposed to SARS-CoV-2 infection ...and at potential risk of reinfection. We followed 26 HCW with mild COVID-19 three weeks (D21), two months (M2) and three months (M3) after the onset of symptoms. All the HCW had anti-receptor binding domain (RBD) IgA at D21, decreasing to 38.5% at M3 (p < 0.0001). Concomitantly a significant decrease in NAb titers was observed between D21 and M2 (p = 0.03) and between D21 and M3 (p < 0.0001). Here, we report that SARS-CoV-2 can elicit a NAb response correlated with anti-RBD antibody levels. However, this neutralizing activity declines, and may even be lost, in association with a decrease in systemic IgA antibody levels, from two months after disease onset. This short-lasting humoral protection supports strong recommendations to maintain infection prevention and control measures in HCW, and suggests that periodic boosts of SARS-CoV-2 vaccination may be required.
Anecdotal evidence rapidly accumulated during March 2020 from sites around the world that sudden hyposmia and hypogeusia are significant symptoms associated with the SARS-CoV-2 pandemic. Our ...objective was to describe the prevalence of hyposmia and hypogeusia and compare it in hospitalized and non-hospitalized COVID-19 patients to evaluate an association of these symptoms with disease severity. We performed a cross-sectional survey during 5 consecutive days in March 2020, within a tertiary referral center, associated outpatient clinic, and two primary care outpatient facilities in Paris. All SARS-CoV-2-positive patients hospitalized during the study period and able to be interviewed (
n
= 198), hospital outpatients seen during the previous month (
n
= 129), and all COVID-19-highly suspect patients in two primary health centers (
n
= 63) were included. Hospitalized patients were significantly more often male (64 vs 40%) and older (66 vs 43 years old in median) and had significantly more comorbidities than outpatients. Hyposmia and hypogeusia were reported by 33% of patients and occurred significantly less frequently in hospitalized patients (12% and 13%, respectively) than in the health centers’ outpatients (33% and 43%, respectively) and in the hospital outpatients (65% and 60%, respectively). Hyposmia and hypogeusia appeared more frequently after other COVID-19 symptoms. Patients with hyposmia and/or hypogeusia were significantly younger and had significantly less respiratory severity criteria than patients without these symptoms. Olfactory and gustatory dysfunction occurs frequently in COVID-19, especially in young, non-severe patients. These symptoms might be a useful tool for initial diagnostic work-up in patients with suspected COVID-19.
Abstract
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.
Elderly patients with hip fracture have a 5 to 8 fold increased risk of death during the months following surgery. We tested the hypothesis that early geriatric management of these patients focused ...on co-morbidities and rehabilitation improved long term mortality.
In a cohort study over a 6 year period, we compared patients aged >70 years with hip fracture admitted to orthopedic versus geriatric departments in a time series analysis corresponding to the creation of a dedicated geriatric unit. Co-morbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Each cohort was compared to matched cohorts extracted from a national registry (n = 51,275) to validate the observed results. Main outcome measure was 6-month mortality. We included 131 patients in the orthopedic cohort and 203 in the geriatric cohort. Co-morbidities were more frequent in the geriatric cohort (median CIRS: 8 vs 5, P<0.001). In the geriatric cohort, the proportion of patients who never walked again decreased (6% versus 22%, P<0.001). At 6 months, re-admission (14% versus 29%, P = 0.007) and mortality (15% versus 24%, P = 0.04) were decreased. When co-morbidities were taken into account, the risk ratio of death at 6 months was reduced (0.43, 95%CI 0.25 to 0.73, P = 0.002). Using matched cohorts, the average treatment effects on the treated associated to early geriatric management indicated a reduction in hospital mortality (-63%; 95% CI: -92% to -6%, P = 0.006).
Early admission to a dedicated geriatric unit improved 6-month mortality and morbidity in elderly patients with hip fracture.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Immune checkpoints and their ligands are important actors of lymphocytes and monocytes activation's regulation. Their expression level within T cells changes with aging. Despite the major impact of ...aging on monocytes, there is no data about the expression of ICs on monocytes from old patients. The objective of our study is to describe the expression of ICs and their ligands on monocytes from young individuals compared to old patients.
We included 18 old control (>75 years old), 10 young control (<55 years old) and 45 old patients with hip fracture (HF). Phenotypical and functional analyses were performed on cryopreserved PBMCs.
There is a differential expression of immune checkpoints and their ligands within monocyte subtypes regardless of age at baseline. After stimulation, a differential expression of immune checkpoints in young subjects but not in old subjects was observed which would be in favor of a regulation defect in old subjects. We hypothesize that this lack of regulation could partially explain the excess production of pro-inflammatory cytokines by the stimulated monocytes in old subjects. In HF, we also observe a differential expression of immune checkpoints, especially in old patients with a poor prognosis.
Our results suggest that the immune regulation which should take place post-acute stress may be affected in old individuals.
Background
There is currently no international recommendation for the admission or treatment of the critically ill older patients over 80 years of age in the intensive care unit (ICU), and there is ...no valid prognostic severity score that includes specific geriatric assessments.
Main body
In this review, we report recent literature focusing on older critically ill patients in order to help physicians in the multiple-step decision-making process. It is unclear under what conditions older patients may benefit from ICU admission. Consequently, there is a wide variation in triage practices, treatment intensity levels, end-of-life practices, discharge practices and frequency of geriatrician’s involvement among institutions and clinicians. In this review, we discuss important steps in caring for critically ill older patients, from the triage to long-term outcome, with a focus on specific conditions in the very old patients.
Conclusion
According to previous considerations, we provide an algorithm presented as a guide to aid in the decision-making process for the caring of the critically ill older patients.
Abstract
Background
Few data are available regarding post-operative atrial fibrillation (POAF) in non-cardiothoracic surgery, particularly orthopedic surgery. Hence, given the frequent incidence of ...POAF after surgery and its marked impact, we need to identify modifiable factors associated with POAF after hip fracture surgery in older patients.
Methods
We conducted a nested case–control study in the unit for perioperative geriatric care of an academic hospital in Paris from July 1, 2009 to December 31, 2019, enrolling all consecutive patients aged ≥ 70 years with hip fracture surgery and no history of permanent AF before admission (retrospective analysis of prospectively collected data). Patients with and without POAF were matched 1:5 on 5 baseline characteristics (age, hypertension, diabetes, coronary artery disease, cardiac failure).
Results
Of the 757 patients included, 384 were matched, and 64 had POAF. The incidence of POAF was 8.5%. The mean age was 86 ± 6 years, 298 (78%) patients were female, and the median Charlson Comorbidity Index was 6 (interquartile range 4–8). The median time from surgery to the occurrence of POAF was 2 days (1–4). On multivariable conditional logistic regression analysis (matched cohort), the modifiable factors present at admission associated with POAF were time to surgery > 48 h (odds ratio OR = 1.66, 95% confidence interval 1.01–2.81) and > 2 units of packed red blood cells (OR = 3.94, 1.50–10.03).
Conclusions
This study provides new information about POAF in older patients with hip fracture surgery, a surgical emergency whose complexity requires multidisciplinary care.
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response ...factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown. Using drug screening in C. elegans nematodes with neuronal expression of human exon-1 huntingtin (128Q), we found that 3ß-Methoxy-Pregnenolone (MAP4343), 17ß-oestradiol (17ßE2) and 12 flavonoids including isoquercitrin promote neuronal function in 128Q nematodes. MAP4343, 17ßE2 and isoquercitrin also promote stress resistance in mutant Htt striatal cells derived from knock-in HD mice. Interestingly, daf-16/FOXO is required for MAP4343, 17ßE2 and isoquercitrin to sustain neuronal function in 128Q nematodes. This similarly applies to the GSK3 inhibitor lithium chloride (LiCl) and, as previously described, to resveratrol and the AMPK activator metformin. Daf-16/FOXO and the targets engaged by these compounds define a sub-network enriched for stress-response and neuronally-active pathways. Collectively, these data highlights the dependence on a daf-16/FOXO-interaction network as a common feature of several compound families for prolonging neuronal function in HD.
Abstract
Background
Mortality is high in older patients hospitalized with COVID-19. Previous studies observed lower mortality during the Omicron wave, yet no data is available on older patients. The ...objective was to compare in-hospital mortality between the Omicron and previous waves in older patients hospitalized with COVID-19.
Methods
This retrospective observational multicenter cohort study used the Greater Paris University Hospitals Group’s data warehouse (38 hospitals). Patients aged ≥ 75 years with a confirmed COVID-19 diagnosis and hospitalized from March 2020 to January 2022 were included. The study period was divided into five waves. The fifth wave (January 1st to 31st 2022) was considered as the Omicron wave as it was the predominant variant (≥ 50%), and was compared with waves 1 (March-July 2020), 2 (August-December 2020), 3 (January-June 2021) and 4 (July-December 2021). Primary outcome was in-hospital mortality. Secondary outcome was occurrence of ICU admission or in-hospital death. Multivariate logistic regression was performed, with a sensitivity analysis according to variant type.
Results
Of the 195,084 patients hospitalized with COVID-19, 19,909 patients aged ≥ 75 years were included (median age 85 IQR 79–90 years, 53% women). Overall in-hospital mortality was 4,337 (22%), reaching 345 (17%) during wave 5. Waves 1 and 3 were significantly associated with increased in-hospital mortality in comparison with wave 5 (adjusted Odds Ratios aOR 1.42 95%CI 1.21–1.66 and 1.56 95%CI 1.33–1.83 respectively). Waves 1 to 3 were associated with an increased risk of occurrence of ICU admission or in-hospital death in comparison with wave 5: aOR 1.29 95% CI 1.12 to 1.49 for wave 1, aOR 1.25 95% CI 1.08 to 1.45 for wave 2 and aOR 1.56 95% CI 1.36 to 1.79 for wave 3. Sensitivity analysis found that Omicron variant was associated with decreased mortality, in comparison with previous variants.
Conclusions
Mortality was lower during the 5th Omicron wave in the older population, but remained high, implying that this variant could be considered as “milder” but not “mild”. This persistently high mortality during the 5th Omicron wave highlights the importance of including older patients in clinical trials to confirm the benefit/risk balance of COVID-19 treatments in this fragile population.
Following acute stress such as trauma or sepsis, most of critically ill elderly patients become immunosuppressed and susceptible to secondary infections and enhanced mortality. We have developed a ...virus-based immunotherapy encoding human interleukin-7 (hIL-7) aiming at restoring both innate an adaptative immune homeostasis in these patients. We assessed the impact of this encoded hIL-7 on the ex vivo immune functions of T cells from PBMC of immunosenescent patients with or without hip fracture. T-cell ex vivo phenotyping was characterized in terms of senescence (CD57), IL-7 receptor (CD127) expression, and T cell differentiation profile. Then, post stimulation, activation status, and functionality (STAT5/STAT1 phosphorylation and T cell proliferation assays) were evaluated by flow cytometry. Our data show that T cells from both groups display immunosenescence features, express CD127 and are activated after stimulation by virotherapy-produced hIL-7-Fc. Interestingly, hip fracture patients exhibit a unique functional ability: An important T cell proliferation occurred compared to controls following stimulation with hIL-7-Fc. In addition, stimulation led to an increased naïve T cell as well as a decreased effector memory T cell proportions compared to controls. This preliminary study indicates that the produced hIL-7-Fc is well recognized by T cells and initiates IL-7 signaling through STAT5 and STAT1 phosphorylation. This signaling efficiently leads to T cell proliferation and activation and enables a T cell "rejuvenation." These results are in favor of the clinical development of the hIL-7-Fc expressing virotherapy to restore or induce immune T cell responses in immunosenescent hip fracture patients.
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