Estimated protection against COVID-19 based on predicted neutralisation titres from multiple antibody measurements in a longitudinal cohort, France, April 2020 to November 2021.

BackgroundThe risk of SARS-CoV-2 (re-)infection remains present given waning of vaccine-induced and infection-acquired immunity, and ongoing circulation of new variants.AimTo develop a method that predicts virus neutralisation and disease protection based on variant-specific antibody measurements to SARS-CoV-2 antigens.MethodsTo correlate antibody and neutralisation titres, we collected 304 serum samples from individuals with either vaccine-induced or infection-acquired SARS-CoV-2 immunity. Using the association between antibody and neutralisation titres, we developed a prediction model for SARS-CoV-2-specific neutralisation titres. From predicted neutralising titres, we inferred protection estimates to symptomatic and severe COVID-19 using previously described relationships between neutralisation titres and protection estimates. We estimated population immunity in a French longitudinal cohort of 905 individuals followed from April 2020 to November 2021.ResultsWe demonstrated a strong correlation between anti-SARS-CoV-2 antibodies measured using a low cost high-throughput assay and antibody response capacity to neutralise live virus. Participants with a single vaccination or immunity caused by infection were especially vulnerable to symptomatic or severe COVID-19. While the median reduced risk of COVID-19 from Delta variant infection in participants with three vaccinations was 96% (IQR: 94-98), median reduced risk among participants with infection-acquired immunity was only 42% (IQR: 22-66).ConclusionOur results are consistent with data from vaccine effectiveness studies, indicating the robustness of our approach. Our multiplex serological assay can be readily adapted to study new variants and provides a framework for development of an assay that would include protection estimates.

Neutralising antibody responses to SARS-CoV-2 omicron among elderly nursing home residents following a booster dose of BNT162b2 vaccine: A community-based, prospective, longitudinal cohort study.

Background: The protective immunity against omicron following a BNT162b2 Pfizer booster dose among elderly individuals (ie, those aged >65 years) is not well characterised. Methods: In a community-based, prospective, longitudinal cohort study taking place in France in which 75 residents from three nursing homes were enrolled, we selected 38 residents who had received a two-dose regimen of mRNA vaccine and a booster dose of Pfizer BNT162b2 vaccine. We excluded individuals that did not receive three vaccine doses or did not have available sera samples. We measured anti-S IgG antibodies and neutralisation capacity in sera taken 56 (28-68) and 55 (48-64) days (median (range)) after the 2nd and 3rd vaccine doses, respectively. Antibodies targeting the SARS-CoV-2 Spike protein were measured with the S-Flow assay as binding antibody units per milliliter (BAU/mL). Neutralising activities in sera were measured as effective dilution 50% (ED50) with the S-Fuse assay using authentic isolates of delta and omicron BA.1. Findings: Among the 38 elderly individuals recruited to the cohort study between November 23rd, 2020 and April 29th, 2021, with median age of 88 (range 72-101) years, 30 (78.95%) had been previously infected with SARS-CoV-2. After three vaccine doses, serum neutralising activity was lower against omicron BA.1 (median ED50 of 774.5, range 15.0-34660.0) than the delta variant (median ED50 of 4972.0, range 213.7-66340.0), and higher among previously infected (ie, convalescent; median ED50 against omicron: 1088.0, range 32.6-34660.0) compared with infection-naive residents (median ED50 against omicron: 188.4, range 15.0-8918.0). During the French omicron wave in December 2021-January 2022, 75% (6/8) of naive residents were infected, compared to 25% (7/30) of convalescent residents (P=0.0114). Anti-Spike antibody levels and neutralising activity against omicron BA.1 after a third BNT162b2 booster dose were lower in those with breakthrough BA.1 infection (n=13) compared with those without (n=25), with a median of 1429.9 (range 670.9-3818.3) BAU/mL vs 2528.3 (range 695.4-8832.0) BAU/mL (P=0.029) and a median ED50 of 281.1 (range 15.0-2136.0) vs 1376.0 (range 32.6-34660.0) (P=0.0013), respectively. Interpretation: This study shows that elderly individuals who received three vaccine doses elicit neutralising antibodies against the omicron BA.1 variant of SARS-CoV-2. Elderly individuals who had also been previously infected showed higher neutralising activity compared with naive individuals. Yet, breakthrough infections with omicron occurred. Individuals with breakthrough infections had significantly lower neutralising titers compared to individuals without breakthrough infection. Thus, a fourth dose of vaccine may be useful in the elderly population to increase the level of neutralising antibodies and compensate for waning immunity. Funding: Institut Pasteur, Fondation pour la Recherche Médicale (FRM), European Health Emergency Preparedness and Response Authority (HERA), Agence nationale de recherches sur le sida et les hépatites virales - Maladies Infectieuses Emergentes (ANRS-MIE), Agence nationale de la recherche (ANR), Assistance Publique des Hôpitaux de Paris (AP-HP) and Fondation de France.

Hedonic deficits in Parkinson's disease: is consummatory anhedonia specific?

BACKGROUND: Anhedonia, the lowered ability to experience pleasure, is one of the non-motor symptoms of Parkinson's disease (PD) that is underdiagnosed and consequently undertreated. Few studies have investigated anhedonia in PD by taking into account the influence of socio-demographic variables and versus a control group composed of patients with a pure motor neurologic disease other than PD. The aim of this study was to investigate hedonic deficits in patients with PD compared to a control group of patients with non-Parkinson motor neurologic disease (OND), matched for age, gender, level of education, and inpatient/outpatient status. Distinctions between anticipatory and consummatory anhedonia and between endogenomorphic and non-endogenomorphic depression were taken into account. METHODS: The study population comprised 49 PD patients and 40 subjects with OND. Anhedonia was rated by using the anticipatory [Temporal Experience Pleasure Scale (TEPS)-ANT] and consummatory (TEPS-CONS) subscales of the TEPS and two subscales extracted from the revised Physical Anhedonia Scale (PAS), measuring physical anticipatory (PAS-ANT) and physical consummatory (PAS-CONS) anhedonias. The Snaith-Hamilton Pleasure Scale (SHAPS) and the Beck Depression Inventory-II (BDI-II) were also used together with a subscale extracted from the BDI-II (ENDO-BDI-II) for the diagnosis of endogenomorphic depression. Statistical analyses were performed on the whole group and on the PD group. RESULTS: As hypothesized, several anhedonia scores varied with age and gender in the whole population or in the PD group. On univariate or multivariate analyses, only PAS-CONS was specific for PD and only SHAPS scores differed between depression subtypes in the whole population or the PD group. CONCLUSION: This study suggests that physical consummatory anhedonia could be specific to PD subjects.

Association between caffeine intake and age at onset in Huntington's disease.

Habitual consumption of caffeine, a non-selective adenosine receptor (AR) antagonist, has been suggested to be beneficial in Parkinson's and Alzheimer's diseases. Experimental evidence support that ARs play a role in Huntington's disease (HD) raising the hypothesis that caffeine may be a life-style modifier in HD. To determine a possible relationship between caffeine consumption and age at onset (AAO) in HD, we retrospectively assessed caffeine consumption in 80 HD patients using a dietary survey and determined relationship with AAO. Following adjustment for gender, smoking status and CAG repeat length, caffeine consumption greater than 190mg/day was significantly associated with an earlier AAO. These data support an association between habitual caffeine intake and AAO in HD patients, but further studies are warranted to understand the link between these variables.

Emotional and cognitive social processes are impaired in Parkinson's disease and are related to behavioral disorders.

OBJECTIVE: Parkinson's disease (PD) is associated with behavioral disorders that can affect social functioning but are poorly understood. Since emotional and cognitive social processes are known to be crucial in social relationships, impairment of these processes may account for the emergence of behavioral disorders. METHOD: We used a systematic battery of tests to assess emotional processes and social cognition in PD patients and relate our findings to conventional neuropsychological data (especially behavioral disorders). Twenty-three PD patients and 46 controls (matched for age and educational level) were included in the study and underwent neuropsychological testing, including an assessment of the behavioral and cognitive components of executive function. Emotional and cognitive social processes were assessed with the Interpersonal Reactivity Index caregiver-administered questionnaire (as a measure of empathy), a facial emotion recognition task and two theory of mind (ToM) tasks. RESULTS: When compared with controls, PD patients showed low levels of empathy (p = .006), impaired facial emotion recognition (which persisted after correction for perceptual abilities) (p = .001), poor performance in a second-order ToM task (p = .008) that assessed both cognitive (p = .004) and affective (p = .03) inferences and, lastly, frequent dysexecutive behavioral disorders (in over 40% of the patients). Overall, impaired emotional and cognitive social functioning was observed in 17% of patients and was related to certain cognitive dysexecutive disorders. In terms of behavioral dysexecutive disorders, social behavior disorders were related to impaired emotional and cognitive social functioning (p = .04) but were independent of cognitive impairments. CONCLUSIONS: Emotional and cognitive social processes were found to be impaired in Parkinson's disease. This impairment may account for the emergence of social behavioral disorders.

A genetic variation in the ADORA2A gene modifies age at onset in Huntington's disease.

Based on the pathophysiological role of adenosine A(2A) receptors in HD, we have evaluated the association of the 1976C/T single-nucleotide polymorphism in the ADORA2A gene (rs5751876) with residual age at onset (AAO) in HD. The study population consisted of 791 unrelated patients belonging to the Huntington French Speaking Network. The variability in AAO attributable to the CAG repeats number was calculated by linear regression using the log (AAO) as the dependent variable, and the respective rs5751876 genotypes as independent variables. We show that the rs5751876 variant significantly influences the variability in AAO. The R(2) statistic rose slightly but significantly (p=0.019) when rs5751876 T/T genotype was added to the regression model. Patients harbouring T/T genotype have an earlier AAO of 3.8 years as compared to C/C genotype (p=0.02). Our data thus strengthens the pathophysiological role of A(2A) receptors in Huntington's disease.

Decrease in blood pressure after intravenous administration of urapidil during recombinant tissue plasminogen activator thrombolysis for acute ischemic stroke.

BACKGROUND: In patients who are candidates for IV recombinant tissue plasminogen activator (rtPA) thrombolysis for the treatment of acute ischemic stroke, blood pressure (BP)-lowering therapy is sometimes needed for systolic BP >185 mm Hg or diastolic BP >110 mm Hg. However, there is vast uncertainty regarding the appropriate choice of an antihypertensive agent. CASE SUMMARY: A 68-year-old Algerian woman (height, 161 cm; weight, 68 kg; body mass index, 26 kg/m2) was admitted to the Cardiology Unit of Amiens University Hospital, Amiens, France, for the assessment of nonvalvular atrial fibrillation. She was prescribed furosemide 40 mg/d to treat a slight left cardiac insufficiency. On day 10 of admission, the patient developed left-sided weakness. Neurologic examination revealed left hemiparesis. A computed tomography scan of the head showed no abnormality. Approximately 90 minutes after onset of the neurologic deficit, the patient had a BP of 180/100 mm Hg in both arms, an irregular pulse >75 bpm, and normal heart sounds. The patient was transferred to the Neurovascular Unit. There were no cervical or femoral bruits in this patient. During neurologic examination, the patient was alert and showed no signs of major cognitive deficit. The neurologic examination did reveal, however, minor hemisphere syndrome with left spatial neglect. There was a left lower-facial paresis. Motor examination revealed normal bulk with diminished tone in the patient's left arm and leg. Although there were no physical signs of dehydration, laboratory results revealed moderate signs of dehydration (total protein, 91 g/L [indicating proteinemia]; sodium, 147 mmol [indicating hypernatremia]; and elevated hematocrit, 42.0%). Considering the diagnosis of ischemic stroke and the duration of the symptoms (<3 hours), IV rtPA was administered. Approximately 10 minutes after intravenous rtPA administration, the patient's BP was 210/110 mm Hg, and an IV bolus of urapidil (20 mg) was administered. Approximately 2 minutes following urapidil administration, the patient developed neurologic worsening indicated by left-sided hemiplegia. Her BP was 105/60 mm Hg. The IV rtPA was immediately discontinued and volume replacement was started for 20 minutes. IV rtPA was restarted after the patient remained hemodynamically stable (15 minutes after rtPA was restarted). Following intensive physiotherapy, the patient was discharged on anticoagulation with a favorable outcome. At her 6-month follow-up, the patient had fully recovered. CONCLUSION: We report a probable case of hypotension associated with IV bolus of urapidil administration during rtPA thrombolysis for acute ischemic stroke in an elderly patient also treated with diuretics.