Clinical and immunological outcomes of SARS-CoV-2-infected vaccine responders, vaccine non-responders, and unvaccinated patients evaluated for neutralizing monoclonal antibody treatment at a single German tertiary care center: a retrospective cohort study with prospective follow-up.

PURPOSE: This study assessed the clinical and immunological outcomes of SARS-CoV-2-infected patients with risk factors for severe disease depending on their immunological status. METHODS: In this retrospective study with single follow-up visit, clinical outcome and humoral immunity was monitored in SARS-CoV-2 infected patients at risk. The results were compared based on the patients' initial immunological status: unvaccinated (UV), patients who did not develop neutralizing antibodies after vaccination (vaccine non-responders, VNR), and patients who expressed neutralizing antibodies after vaccination (vaccine responders, VR). Patients who lacked neutralizing antibodies (VNR and UV) were treated with nMABs. RESULTS: In total, 113 patients at risk of severe COVID-19 consented to participate in the study. VR and UV were not admitted to the hospital. During the observation period, UVs had the highest rate of SARS-CoV-2 re-infections. Three of 41 VNRs (7.3%) were hospitalized due to severe COVID-19, with two of them having undergone iatrogenic B-cell depletion. The humoral immune response after infection was significantly lower in the VNR group than in the VR group in terms of anti-N, anti-receptor-binding domain (RBD), anti-S antibody titers, and anti-S antibody avidity. In a sub-analysis of VNR, B cell-deficient non-responders had significantly lower levels of anti-N antibodies and anti-S avidity after infection than other VNRs. CONCLUSION: VNR, particularly B-cell-depleted VNR, remained at risk of hospitalization due to COVID-19. In the VR group, however, no clinical complications or severe disease were observed, despite not receiving nMAbs. Tailoring the administration of nMABs according to patient vaccination and immunological status may be advisable.

Rapid point-of-care detection of SARS-CoV-2 infection in exhaled breath using ion mobility spectrometry: a pilot study.

BACKGROUND: An effective testing strategy is essential for pandemic control of the novel Coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Breath gas analysis can expand the available toolbox for diagnostic tests by using a rapid, cost-beneficial, high-throughput point-of-care test. We conducted a bi-center clinical pilot study in Germany to evaluate breath gas analysis using multi-capillary column ion mobility spectrometry (MCC-IMS) to detect SARS-CoV-2 infection. METHODS: Between September 23, 2020, and June 11, 2021, breath gas measurements were performed on 380 patients (SARS-CoV-2 real-time polymerase chain reaction (PCR) positive: 186; PCR negative: 194) presenting to the emergency department (ED) with respiratory symptoms. RESULTS: Breath gas analysis using MCC-IMS identified 110 peaks; 54 showed statistically significant differences in peak intensity between the SARS-CoV-2 PCR-negative and PCR-positive groups. A decision tree analysis classification resulted in a sensitivity of 83% and specificity of 86%, but limited robustness to dataset changes. Modest values for the sensitivity (74%) and specificity (52%) were obtained using linear discriminant analysis. A systematic search for peaks led to a sensitivity of 77% and specificity of 67%; however, validation by transferability to other data is questionable. CONCLUSIONS: Despite identifying several peaks by MCC-IMS with significant differences in peak intensity between PCR-negative and PCR-positive samples, finding a classification system that allows reliable differentiation between the two groups proved to be difficult. However, with some modifications to the setup, breath gas analysis using MCC-IMS may be a useful diagnostic toolbox for SARS-CoV-2 infection. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on September 21, 2020 (NCT04556318; Study-ID: HC-N-H-2004).

A proof of concept study for the differentiation of SARS-CoV-2, hCoV-NL63, and IAV-H1N1 in vitro cultures using ion mobility spectrometry.

Rapid, high-throughput diagnostic tests are essential to decelerate the spread of the novel coronavirus disease 2019 (COVID-19) pandemic. While RT-PCR tests performed in centralized laboratories remain the gold standard, rapid point-of-care antigen tests might provide faster results. However, they are associated with markedly reduced sensitivity. Bedside breath gas analysis of volatile organic compounds detected by ion mobility spectrometry (IMS) may enable a quick and sensitive point-of-care testing alternative. In this proof-of-concept study, we investigated whether gas analysis by IMS can discriminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from other respiratory viruses in an experimental set-up. Repeated gas analyses of air samples collected from the headspace of virus-infected in vitro cultures were performed for 5 days. A three-step decision tree using the intensities of four spectrometry peaks correlating to unidentified volatile organic compounds allowed the correct classification of SARS-CoV-2, human coronavirus-NL63, and influenza A virus H1N1 without misassignment when the calculation was performed with data 3 days post infection. The forward selection assignment model allowed the identification of SARS-CoV-2 with high sensitivity and specificity, with only one of 231 measurements (0.43%) being misclassified. Thus, volatile organic compound analysis by IMS allows highly accurate differentiation of SARS-CoV-2 from other respiratory viruses in an experimental set-up, supporting further research and evaluation in clinical studies.

Phototactic behaviour correlates with gustatory responsiveness in honey bees (Apis mellifera L.).

The response threshold hypothesis of division of labour in honey bees assumes that individuals differ in their responsiveness to different stimulus modalities. However, previous experiments have shown that responsiveness to gustatory stimuli correlates with responsiveness to odours, pollen and tactile stimuli. Evaluation of these stimuli involves sensory receptors on the antenna. We tested whether responsiveness to gustatory stimuli correlates with responsiveness to visual stimuli in a phototaxis experiment, which is independent of antennal input. Gustatory responsiveness was measured using the proboscis extension response to antennal stimulation with water and different sucrose concentrations. Phototaxis was quantified by measuring the walking times a bee needed to reach light sources of different intensities. Walking behaviour in the darkness was measured to test for differences in locomotor behaviour. The walking time towards a light stimulus, the path length, and the walking speed depended on the intensity of the light stimulus. Responsiveness to visual stimuli correlated significantly with gustatory responsiveness. Bees displaying a high gustatory responsiveness were also very sensitive to light. Locomotor activity did not correlate with gustatory responsiveness. This shows that gustatory responsiveness is a good indicator of sensitivity for visual stimuli, which are not perceived by the antenna.

FMRFamide-like immunoreactivity in the brain of the honeybee (Apis mellifera). A light-and electron microscopical study.

Peptide-FMRFamide-like immunoreactivity in the brain and suboesophageal ganglion of the honeybee Apis mellifera L. is demonstrated with the peroxidase-antiperoxidase technique. Immunoreactivity is found in about 120 perikarya of the brain and in about 30 of the suboesophageal ganglion. These cells are distributed in 13 paired clusters representing neurons of different types including neurosecretory neurons projecting to neurohemal organs. Immunoreactivity of different intensity is found in the non-glomerular neuropil around the mushroom bodies, in the lateral protocerebrum, the central body, the optic tubercles, the lobula and medulla of optic lobe, the ocellar neuropil, in multiglomerular elements of the antennal lobes and in the dorsal deuterocerebrum. In the mushroom bodies, immunoreactivity is located in layers of the lobes and stalks, corresponding to intrinsic fibre bundles of some Kenyon cell types. The somata of these intrinsic cells did not show FMRFamide-like immunoreactivity. Electron microscopy of immunostained somata and nerve fibres was performed employing a pre-embedding peroxidase-antiperoxidase technique. Fibres of optic lobes and the non-glomerular neuropil contain immunoreactive dense core vesicles (diameter 50-165 nm) accumulated in boutons besides small synaptic vesicles and synaptic membrane specializations. Immunoreactive layers of the mushroom body neuropil were analysed at the ultrastructural level. Axon profiles with dense-core vesicles of a small type (diameter 35-75 nm) show only faint immunoreactive products. Immunoreactivity of intrinsic mushroom body neurons does not appear to be specifically correlated with synaptic organelles. Our results indicate that FMRFamide or related peptides peptides may be neuroactive compounds in different classes of nerve cells in the bee brain.

Operant conditioning of antennal movements in the honey bee.

An operant learning protocol was developed for honeybees that are fixed in small tubes. The bees had to touch one or two small silver plates within the range of one antenna. The contacts of the antenna with the silver plates were registered electronically. Three conditioning protocols were analysed. In the first series the conditioned increase of the contact frequency was tested. The animals could touch one plate and received a reward (a small drop of sucrose) whenever the instantaneous frequency at this plate was more than one or two standard deviations above the spontaneous frequency. After conditioning the bees showed a significant increase of the contact frequency. No significant changes were found in a group of yoked controls. In the second series differential conditioning was tested. The animals could touch two silver plates. The spontaneous behaviour was measured and the animals received the reward upon touching the plate with the lower spontaneous frequency. The rewards were only applied whenever the instantaneous frequency exceeded a defined threshold. After ten conditioning trials the animals showed a significant increase in contact frequency for the conditioned plate compared to spontaneous behaviour. No significant changes were found in a group of yoked controls. In the third series reversal learning was tested. The animals were able to touch two silver plates. They were first conditioned to touch the plate which had the lower spontaneous contact frequency. After these conditioning trials they were tested for 10 min and subsequently conditioned to the alternative plate. The experiments demonstrated significant reversal learning compared to yoked controls. This new operant conditioning paradigm for the bee offers the possibility to analyse at the physiological level the mechanisms underlying different forms of learning in this insect.

Behavioural pharmacology of dopamine, serotonin and putative aminergic ligands in the mushroom bodies of the honeybee (Apis mellifera).

The proboscis extension response (PER) which can be elicited in bees by stimulating one antenna with water vapour, was used to quantify the effects of dopamine, serotonin (5-HT) and putative receptor ligands in the mushroom body of the bee. The drugs were microinjected into the alpha-lobe of the mushroom body in one brain hemisphere. Injection of dopamine reduces the water vapour-elicited PER significantly. The effects of dopamine are limited to the treated side. Injection of 5-HT has similar effects to dopamine. The effects of 5-HT are apparent on the treated and partly also on the contralateral side. Significant effects for dopamine on the treated side were found when the concentration in the injected drop was 10(-7) M. For 5-HT significant effects on the treated side were apparent for concentrations of 10(-8) M. Putative dopamine and 5-HT receptor ligands were injected alone and coinjected with the amines. Two ligands with dopamine-antagonistic effects were found: buspirone > spiperone, while lisuride, sulpiride, chlorpromazine, SCH 23390, butaclamol and haloperidol had no dopamine-antagonistic effects. All tested putative 5-HT receptor ligands had significant 5-HT-antagonistic effects: butaclamol > methysergide > lisuride > cyproheptadine > SCH 23390. Good correlations between the behavioural data and in vitro radioligand binding studies were found for 5-HT receptor ligands, while there exist only partial correlations for dopamine receptor ligands.

Responsiveness to sucrose affects tactile and olfactory learning in preforaging honey bees of two genetic strains.

Using sucrose solution as reward, we conditioned preforaging honey bees of two genetic strains to tactile stimuli or to odours. Acquisition, extinction of conditioned responses and discrimination between the conditioned stimuli and alternative tactile or olfactory stimuli were measured. Bees of the two genetic strains were selected for their foraging behaviour. In addition, they differ in their responsiveness to sucrose. To analyse the effects of sucrose perception on learning parameters independent of foraging behaviour, we conditioned preforaging bees of the two strains and compared their performance in tactile and olfactory learning paradigms. In both strains, acquisition in tactile and olfactory conditioning is determined by responsiveness to sucrose. There is no genetic effect on the relationship between responsiveness to sucrose and acquisition. Bees responding to low sucrose concentrations perform better than ones that only respond to higher concentrations. Extinction of conditioned responses correlates with acquisition. Responses to alternative stimuli are independent of responsiveness to sucrose.

Quantitative autoradiographic localization of [125I]alpha-bungarotoxin binding sites in the honeybee brain.

Binding sites for the nicotinic acetylcholine receptor antagonist, [125I]alpha-bungarotoxin, were localized in the honeybee brain by in vitro autoradiography. Highest binding site densities were localized in the suboesophageal ganglion, the optic tubercles, optic lobes medulla and lobula, antennal lobes, dorsal lobes and the alpha-lobes of the mushroom bodies. The distribution pattern of these putative nicotinic acetylcholine receptors suggests that acetylcholine is involved in several sensory pathways and in central information processing in the honeybee brain.

Forgetting in the workplace: attributions and recommendations for young and older employees.

Preceivers assumed the role of manager in a hypothetical company that had either high or low bottom-line pressure. Then perceivers made attributions for a young or old, male or female, subordinate target employee's memory-related performance problems, predictions about future problems, and recommendations about urgency of action and type of action necessary. Target age, target gender, and bottom-line pressure had no effect on attributions. However, when under high bottom-line pressure, perceivers had greater expectation that performance problems would continue, felt greater urgency for immediate action, and were less likely to recommend training when target employees were old than when they were young.

Everyday memory failure: age differences in appraisal and attribution.

A person perception paradigm was used to test 86 young and 84 older Ss for evidence of a double standard in appraising everyday memory failures of young and older targets. Vignettes were judged on separate Likert scales for possible attributions for the failure (ability, effort, task difficulty, chance, and 2 measures of attention), signs of mental difficulty, need for memory training, and indications of need for professional evaluation. Results confirmed a double standard used by young and old: The failures of older targets were judged as signifying greater mental difficulty and greater need for memory training than were the identical failures of young targets. Older Ss were more lenient overall than young Ss in their appraisals. Young Ss judged target persons' memory failures as signifying more mental difficulty, and they more readily recommend professional evaluation.

Age, gender, and individual differences in memory failure appraisal.

Young adults (22 men and 24 women) and older adults (24 men and 24 women) rated 12 gender-neutral vignettes describing short-term, long-term, and very-long-term memory failures. Vignette target persons were young (21-32) or older (65-75) men or women. Subjects of both age and gender groups used a double standard: Failures of older targets of both genders were rated as signifying greater mental difficulty than failures of young targets; failures of young targets were attributed to lack of effort and attention. Young subjects judged very-long-term failures more harshly than did older subjects. Subjects' objective memory performance, self-rated memory failure frequency, memory failure discomfort, and depression made little difference in their target person ratings.

Age and forgetfulness: managing perceivers' impressions of targets' capability.

Two experiments investigated the effect of positive endorsement on perceivers' impressions of young and old female targets. In Experiment 1, 160 young adult perceivers listened to a tape of a young or old forgetful target being interviewed for a volunteer job. They read a nonelaborative or elaborative reference letter for the target either before or after listening to the tape. Perceivers who read the elaborative letter after listening to the tape rated themselves as more likely to assign tasks to both young and old targets and had a higher general capability opinion of old targets. In Experiment 2, 84 older adult perceivers read an elaborative letter and listened to one of the same taped interviews. Reading the letter after the tape resulted in higher task ratings than reading it before the tape, but letter order had no effect on general capability ratings. Results are discussed in terms of impression management.

Age and forgetfulness: perceivers' impressions of targets' capability.

In a person perception paradigm, 72 young and 72 old adult Ss listened to tape recordings of a nonforgetful, moderately forgetful, or highly forgetful female target person being interviewed for a volunteer job. Ss then rated their opinion of the target's memory and how likely they would be to assign the target to easy and difficult tasks. Overall, Ss gave higher memory opinion ratings to old than to young targets. As expected, they were more likely to assign tasks to nonforgetful than to forgetful targets. However, they were more egalitarian than was hypothesized in their task assignment ratings for forgetful young versus forgetful old targets.

Ain't misbehavin': the effects of age and intentionality on judgments about misconduct.

In 2 person perception experiments, young and older perceivers read a scenario about a young or old female target who leaves a store without paying for a hat. In Experiment 1, the target claims she forgot she was wearing the hat when questioned by the manager. Perceivers thought the manager would have greater sympathy, less anger, and would recommend less punishment when the target was old. In Experiment 2, the target clearly forgot to pay for the hat, clearly stole it, or had ambiguous intentions. In the ambiguous condition, perceivers attributed the young target's behavior more to stealing and the old target's behavior more to forgetting. In the forget condition, young perceivers had equal sympathy for the young and old targets and held them similarly responsible, but older perceivers had greater sympathy for the forgetful old target and held her less responsible than they did the forgetful young target.

Age and forgetfulness: confidence in ability and attribution for memory failures.

Perceivers read a script of a forgetful young, middle-aged, or older male or female target being interviewed for a volunteer position. Afterward perceivers rated their opinion of the target's memory, confidence in the target's capability of performing tasks, and attributions for the target's memory failures. Perceivers were more confident and attributed failures more to lack of effort and attention when targets experienced episodic than semantic memory failures. Perceivers' memory opinion was less negative for older than for young and middle-aged targets, but their confidence ratings were equivalent across target age groups. Perceivers used an age-based double standard in their attribution ratings. However, double-standard evidence was not as strong as in prior studies using less evaluative contexts.

Forgetful but forgiven: how age and life style affect perceptions of memory failure.

Young and older perceivers read a narrative in which a forgetful young or old target was described as having either a young or old life style. Perceivers attributed memory failures more to mental difficulty for old targets but to lack of effort for young targets, regardless of life style. Life style did make a difference in perceivers' memory opinion and sympathy for the old but not for the young targets. Perceivers had a less negative memory opinion when the old target had an old rather than a young life style. Also, the old target with the old life style elicited a greater degree of sympathy in young perceivers, but a lesser degree of sympathy in older perceivers.

Age differences in self-reported anxiety and psychomotor performance.

10 young and 10 older adults completed a self-report questionnaire on Debilitative and Facilitative Anxiety both prior to and following 10 psychomotor coding trials. Older adults were higher on Facilitative Anxiety at both times. These scores were negatively correlated with coding task performance for the total group but not for the individual age groups. There was no age effect for Debilitative Anxiety, although it was lower at Time 2, particularly for older adults. Debilitative Anxiety was not correlated with psychomotor performance. These results do not support the hypothesis that the psychomotor performance of older adults is differentially negatively affected by anxiety.