[Influence of the contact restrictions against SARS-CoV-2 on physical activity among public sector employees.] / Einfluss der Kontaktbeschränkungen gegen SARS-CoV-2 auf die körperliche Aktivität von Beschäftigten des öffentlichen Dienstes.

Objective: Preliminary results from activity surveys conducted in spring 2020 suggest that athletic activity may have decreased within the contact restrictions against the spread of coronavirus. The coronavirus pandemic poses many challenges to the workforce in the healthcare system. Therefore, this study investigated whether the measures to limit the pandemic have an influence on the activity behavior of employees in the public sector. Method: A retrospective cross-sectional survey was conducted to collate the activity behavior among employees of three institutions in the public sector before and during the measures against the coronavirus in April 2020. An online version of the Freiburg Activity Questionnaire was used. Using Wilcoxon tests on connected samples with a significance level of p < 0.05, the activity behavior was examined for differences before compared to during the contact restrictions in min/week and MET-min./week. Results: A total of 1797 public sector employees in Freiburg (36.0% male, 63.9% female, and 0.1% diverse) participated in the survey. For sports activity, a relevant difference (p < 0.05) was measured in the medians (Mdn) of activities per week before (Mdn = 180 min) and during (Mdn = 120 min) the relevant contact restrictions. Similarly, for energy expenditure through exercise, the median value within the contact restrictions decreased from Mdn = 1022 MET-min/week to Mdn = 750 MET-min./week. Conclusion: Measures to limit the spread of the coronavirus have led to a reduction in activity levels among public sector employees. In particular, fewer employees engaged in sports. This could be related to the closure of fitness studios as these activities were particularly reduced. Decreased physical activity can lead to unfavorable individual risk profiles, which must be compensated for in the future.

[Subjective well-being and ability to work after SARS-CoV-2 immunization with the vector vaccine ChAdOx1-S (AstraZeneca COVID-19 vaccine)]. / Subjektives Befinden und Arbeitsfähigkeit nach SARS-CoV-2-Immunisierung mit dem Vektor-Impfstoff ChAdOx1-S (AstraZeneca COVID-19­Vakzin): Ergebnisse einer anonymen Umfrage.

Background: The SARS coronavirus 19 vaccine ChAdOx1­S (Vaxzevria, AstraZeneca) has been licensed since January 2021 by the Paul Ehrlich Institute for Germany. In several campaigns, healthcare workers and medical students were offered this vaccine on a voluntary basis. Aim: The primary endpoint of the study was to assess the rate and duration of the incapacity to work as a result of initial immunization with ChAdOx1­S. Secondary endpoints were type and severity of adverse events and self-perceived tolerability. Material and methods: Anonymized online questionnaire to be completed once by all vaccinated individuals after receiving the first dose of ChAdOx1­S. The severity of side effects was queried using an ordinal numerical rating scale with values ranging from 0 to 10. Other key data points were age, sex, and occupational group. Ability to work in the days following the injection was also assessed by self-reporting. Results: Data from 1988 respondents were analyzed. The mean age was 37.13 years (standard deviation 13.7 years). Of the respondents 69.8% were female, 48.1% belonged to therapeutic and technical professions with patient contact, 38% were students, 10.6% were nursing personnel and 4% were physicians. Only 14.4% of respondents reported having tolerated the vaccination without side effects. The most common side effect was fatigue, followed by pain at the injection site. This was followed in descending frequency by headache, aching limbs, and chills. After vaccination 18% of respondents felt able to return to work immediately, 51% of all respondents had to report themselves unfit for work for at least 1 day after vaccination. Side effects were more prevalent in male and younger respondents. Conclusion: Vaccination with ChAdOx1­S frequently resulted in side effects. These resulted in 37% of respondents reporting sick. Nevertheless, 89.6% of all respondents would choose coronavirus vaccination with ChAdOx1­S again.

[Development of specific guidance for the safe opening and operation of recreational destinations under pandemic conditions]. / Entwicklung konkreter Handlungsoptionen für die sichere Öffnung und den Betrieb von Freizeitdestinationen unter Pandemiebedingungen.

Background: The SARS-CoV­2 pandemic led to the closure of leisure and recreation facilities worldwide. As part of a model study funded by the Baden-Wuerttemberg Ministry of Social Affairs, Health and Integration, it was possible to demonstrate how a hygiene and safety concept can be successfully implemented in practice using the example of the opening and operation of an amusement park in Baden-Wuerttemberg (Germany) under scientific supervision. Objective: The aim of the model project was, besides the verification of a possible infection event through a visit to the amusement park, to develop and review a recommended course of action for the safe opening and operation of leisure facilities under pandemic conditions, which can be transferred to other destinations. Methods: A variety of data sources were used for this project: Recurrent expert rounds of multidisciplinary teams (business administration, healthcare research, sociology and medicine), aerosol measurement data, observation protocols, official infection statistics and interview data from visitor surveys. Results: The action plan developed in this project provides guidance and recommendations for operators of recreation and leisure facilities to implement measures that enhance staff and guest safety, allowing facilities to operate under pandemic conditions. Conclusion: This study sets a precedent using the example of a recreational park in Baden-Wuerttemberg (Germany) to serve as a guide for other facilities; however, operations in the leisure and tourism sector are unique and measures are accordingly difficult to transfer directly. The recommended action plan is further intended to support policy makers in future pandemic situations regarding measures to close, open and operate such facilities.

Photodegradation Pathways of Protein Disulfides: Human Growth Hormone.

PURPOSE: Comprehensive product characterization was performed for the photodegradation of protein disulfides, representatively of human growth hormone (somatotropin; hGH), in order to provide a product database, which will be useful for the general analysis of protein stability. METHODS: HGH was photo-irradiated at λ = 254 and λ > 295 nm and tryptic digests were analyzed by HPLC-MS to investigate light-induced disulfide degradation pathways. RESULTS: A total of 60 products were detected, and structures/tentative structures were assigned to the products by MS2 and MS3 analysis. The main products were reduced Cys residues, dithiohemiacetal, thioether and disulfide scrambling products. In addition, we detected Cys degradation products such as Cys thioaldehyde, dehydroalanine (Dha), Ala, Ser semialdehyde, Ser, S-sulfocysteine, and Gly. Frequently, the tryptic fragments contained more than one modification, i.e. a Cys degradation product in close proximity to a dehydrated amino acid. Several novel cross-links were detected between Cys and Tyr, Cys, Ser and Phe, Cys and Trp, and Trp and Tyr. Photo-induced protein fragmentation was detected specifically at or in close proximity to the disulfide bond between T6 and T16. An in-house packed 75 cm nano-column enabled us to resolve various isomers/diastereomers of the photo-degradation products. CONCLUSION: A comprehensive analysis of photodegradation products revealed a variety of novel photo-products, including cross-links, originating from disulfide degradation. The mechanisms of product formation are discussed.

The pressure drop across the endotracheal tube in mechanically ventilated pediatric patients.

BACKGROUND: During mechanical ventilation, the airway pressure (Paw) is usually monitored. However, Paw comprises the endotracheal tube (ETT)-related pressure drop (∆PETT ) and thus does not reflect the pressure in the patients' lungs. Therefore, monitoring of mechanical ventilation should be based on the tracheal pressure (Ptrach ). We systematically investigated potential factors influencing ∆PETT in pediatric ETTs. METHODS: In this study, the flow-dependent pressure drop across pediatric ETTs from four manufacturers [2.0-4.5 mm inner diameter (ID)] was estimated in a physical model of the upper airways. Additionally, ∆PETT was examined with the ETTs shortened to 75% of their original length and at different curvatures. In nine healthy mechanically ventilated children (aged between 9 days and 29 months), Ptrach was compared to Paw . RESULTS: ∆PETT was nonlinearly flow dependent. Low IDs corresponded to high ∆PETT . Differences between ETTs from different manufacturers were identified. Shortening of the ETTs' length by 25% reduced ∆PETT on average by 14% of the value at original length. Ventilation frequency and tube curvature did not influence ∆PETT to a relevant extent. In the pediatric patients, the root mean square deviation between Paw and Ptrach was 2.3 cm H2O. CONCLUSION: Paw and Ptrach differ considerably (by ∆PETT ) during mechanical ventilation of pediatric patients. The ETTs' ID, tube length, and manufacturer type are significant factors for ∆PETT and should be taken into account when Paw is valuated. For this purpose, Ptrach can be continuously calculated with good precision by means of the Rohrer approximation.

Why selenocysteine replaces cysteine in thioredoxin reductase: a radical hypothesis.

Thioredoxin reductases, important biological redox mediators for two-electron transfers, contain either 2 cysteines or a cysteine (Cys) and a selenocysteine (Sec) at the active site. The incorporation of Sec is metabolically costly, and therefore surprising. We provide here a rationale: in the case of an accidental one-electron transfer to a S-S or a S-Se bond during catalysis, a thiyl or a selanyl radical, respectively would be formed. The thiyl radical can abstract a hydrogen from the protein backbone, which subsequently leads to the inactivation of the protein. In contrast, a selanyl radical will not abstract a hydrogen. Therefore, formation of Sec radicals in a GlyCysSecGly active site will less likely result in the destruction of a protein compared to a GlyCysCysGly active site.

Photodegradation of human growth hormone: a novel backbone cleavage between Glu-88 and Pro-89.

The exposure of protein pharmaceuticals to light can cause loss of potency, oxidation, structural changes and aggregation. To elucidate the chemical pathways of photodegradation, we irradiated human growth hormone (hGH) at λ = 254 nm, λ ≈ 265-340 nm, and λ ≈ 295-340 nm (using the spectral cutoff of borosilicate glass) and analyzed the products by mass spectrometry. By means of LC-MS/MS analysis, we observed an unusual peptide backbone cleavage between Glu-88 and Pro-89. The crystal structure of hGH indicates that these residues are in proximity to Trp-86, which likely mediates this backbone cleavage. The two cleavage fragments observed by MS/MS analysis indicate the loss of CO from the amide bond and replacement of the Glu-C(═ O)Pro bond with a Glu-H bond, accompanied by double bond formation on proline. The reaction is oxygen-independent and likely involves hydrogen transfer to the Cα of Glu-88. To probe the influence of the protein fold, we irradiated hGH in its unfolded state, in 1:1 (v/v) acetonitrile/water, and also the isolated tryptic peptide Ile-78-Arg-90, which contains the Glu-88-Pro-89 sequence. In both cases, the cleavage between Glu-88 and Pro-89 was largely suppressed, while other cleavage pathways became dominant, notably between Gln-84 and Ser-85, as well as Ser-85 and Trp-86.

Role of surface exposed tryptophan as substrate generators for the antibody catalyzed water oxidation pathway.

The reaction of singlet oxygen with water to form hydrogen peroxide was catalyzed by antibodies and has been termed as the antibody catalyzed water oxidation pathway (ACWOP) (Nieva and Wentworth, Trends Biochem. Sci. 2004, 29, 274-278; Nieva et al. Immunol. Lett. 2006, 103, 33-38). While conserved and buried tryptophans in the antibody are thought to play a major role in this pathway, our studies with a monoclonal antibody, mAb-1 and its mutant W53A, clearly demonstrate the role of surface-exposed tryptophans in production of hydrogen peroxide, via the photo-oxidation pathway. Reactive oxygen species (ROS) such as singlet oxygen and superoxide were detected and site-specific tryptophan (Trp53) oxidation was observed under these conditions using RP-HPLC and mass spectrometry. The single mutant of the surface exposed Trp53 to Ala53 (W53A) results in a 50% reduction in hydrogen peroxide generated under these conditions, indicating that surface exposed tryptophans are highly efficient in transferring light energy to oxygen and contribute significantly to ROS generation. ACWOP potentially leads to the chemical instability of mAb-1 via the generation of ROS and is important to consider during clinical and pharmaceutical development of mAbs.

A Comparison of the Impact of COVID-19-Related Restrictions on Physical Activity Among Public Employees.

OBJECTIVES: This article compares the impact of COVID-19-related restrictions on the level of physical activity, performed by public servants, in April and November 2020. METHODS: The survey examined the amount (in minutes per week) and the energy expenditure (in metabolic equivalent of task in minutes per week [METmin/week]) of physical activity for both before and during contact restrictions in April and November 2020, respectively. RESULTS: Especially for sports activity difference was determined by the medians before (April/November: median [Mdn] = 180.0 min/wk) and during (April: Mdn = 130 minutes, November: Mdn = 60 min/wk) restrictions ( P < 0.05).Also for energy consumption (METmin/wk), the medians before and during the contact restrictions declined for both periods. CONCLUSIONS: Measures against the coronavirus have led to a reduction in activity levels among public employees, regardless of their work environment. The decrease in participation in sport activities seemed to be even more noticeable within the second restriction period.

Why do proteins use selenocysteine instead of cysteine?

Selenocysteine is present in a variety of proteins and catalyzes the oxidation of thiols to disulfides and the reduction of disulfides to thiols. Here, we compare the kinetic and thermodynamic properties of cysteine with its selenium-containing analogon, selenocysteine. Reactions of simple selenols at pH 7 are up to four orders of magnitude faster than their sulfur analogs, depending on reaction type. In redox-related proteins, the use of selenium instead of sulfur can be used to tune electrode, or redox, potentials. Selenocysteine could also have a protective effect in proteins because its one-electron oxidized product, the selanyl radical, is not oxidizing enough to modify or destroy proteins, whereas the cysteine-thiyl radical can do this very rapidly.

Oxidation of human growth hormone by oxygen-centered radicals: formation of Leu-101 hydroperoxide and Tyr-103 oxidation products.

Human growth hormone (hGH) was exposed to oxygen-centered radicals generated through the thermolysis of AAPH in the presence of dioxygen. Such conditions mimic oxidative processes which protein pharmaceuticals can encounter during formulation in the presence of polysorbates. We detected the oxidation of Met to Met sulfoxide, the formation of protein carbonyls, the oxidation of Tyr to dityrosine and several additional Tyr oxidation products, the conformation-dependent oxidation of Trp, and the site-specific formation of protein hydroperoxides. The sensitivity of Met oxidation correlates with their solvent accessible surface, i.e. the yields of MetSO decreased in the order Met-14 > Met-125 > Met-170. Trp oxidation in native hGH was negligible, but was enhanced through denaturation. Dityrosine formed predominantly intramolecularly but did not contribute significantly to protein cross-linking. Hydroperoxides formed selectively on Leu-101 and were generated specifically by alkoxyl radicals, generated through the decomposition of peroxyl radicals. Tyr-103 was converted into a series of oxidation products characterized by mass shifts of Tyr + 14 Da and Tyr + 16 Da.

Prospective model-based comparison of different laryngoscopes for difficult intubation in infants.

BACKGROUND: Difficult intubation in infants is uncommon but may be a challenge for the anesthesiologist. Many optical-assisted techniques are available to ease endotracheal placement of tube but have not been systemically evaluated for pediatric practice. AIM: The study was performed to compare conventional pediatric Macintosh - with different optical laryngoscopes in difficult endotracheal intubation in infants. We hypothesized that inexperienced anesthetists would perform more successful with optical devices and that differences between the devices would be found. METHODS/MATERIALS: In this randomized controlled study, 30 anesthesia residents performed endotracheal intubation in an infant model of difficult airway presenting with airway obstruction and neck immobilization. Primary endpoints were intubation success rate and intubation time. Beyond that glottis view, dental trauma and difficulty of technique were evaluated and measured by a study observer. Macintosh, Airtraq(®), Storz DCI(®) -, and Gyrus Infant Bullard(®) laryngoscopes were used in random order. After standardized briefing every resident had three attempts of at most 120 s with every device to place a 3-mm tube into the trachea. Glottis view and difficulty of technique were rated by the residents using classification of Cormack/Lehane and Visual Analogue Scale (VAS; 0 = easy to 10 = very difficult). RESULTS: Success rate was 41% with conventional Macintosh, 43% with Airtraq(®), 62% with Storz DCI(®), and 100% with Bullard(®) laryngoscopes. Median time from passing the lips to first ventilation was 67 s (Storz DCI(®) laryngoscope), 54 s (Macintosh laryngoscope), 45 s (Airtraq(®) laryngoscope), and 21 s (Bullard(®) laryngoscope), respectively. Dental trauma did not occur with Bullard(®) laryngoscope and was frequent with Storz DCI(®) laryngoscope (39%) and Macintosh laryngoscope (42%). Glottis view was best with Bullard(®) laryngoscope (Grade 1 in 100%) and worst with Macintosh laryngoscope (Grade 1 in 2%). Difficulty of technique was rated with a VAS score of 2 (Bullard(®) laryngoscope), 4.5 (Storz DCI(®) laryngoscope) and 6 (Airtraq(®) - and Macintosh laryngoscopes). CONCLUSIONS: Inexperienced anesthetists have higher success rates and shorter intubation times with optical-assisted laryngoscopes compared with conventional Macintosh laryngoscope. Gyrus Infant Bullard(®) laryngoscope significantly undertakes best success rate and shortest intubation time with mildest impact to maxillary dents and easiest technique. Our findings support the hypothesis that optical laryngoscopes can be used successfully by inexperienced anesthetists in simulated difficult pediatric airway conditions.

Comparison of Bullard and Airtraq laryngoscopes with conventional laryngoscopy in a manikin study of simulated difficult intubation.

BACKGROUND: When airway management is difficult, various measures can be taken to facilitate tracheal intubation. The Bullard and Airtraq laryngoscopes were developed for this purpose. We hypothesised that the Bullard and Airtraq laryngoscopes would perform better than a conventional laryngoscope in the management of a simulated difficult airway. We also hypothesised that the indirect laryngoscopes would perform comparably. METHODS: In a randomised controlled study, 60 anaesthetists (30 with no or little experience and 30 with broader experience in the use of the Bullard laryngoscope, referred to as beginners and experts, respectively) performed three successive intubation attempts using conventional, Bullard and Airtraq laryngoscopes in two simulated difficult airway scenarios: neck immobilisation (scenario A) and neck immobilisation with additional tongue oedema (scenario B). The primary endpoint was overall intubation success rate. Secondary endpoints were time required for successful intubation, the amount of dental stress exerted during laryngoscopy and satisfaction with each airway device. RESULTS: In scenario A, intubation success rates were 97-100% with all devices. In scenario B, all participants failed to intubate the trachea using the conventional laryngoscope. When using the Bullard laryngoscope, intubation success rates of 87-97% did not differ significantly (P > 0.05) from those during scenario A and between groups (beginners vs. experts). In contrast, when using the Airtraq laryngoscope, the overall intubation success rate was significantly lower (P < 0.05) compared with scenario A and compared with use of the Bullard laryngoscope, and differed between beginners and experts (20 and 50%, respectively). In cases of successful intubation, intubation times were comparable between devices and groups. Intubation times were longer during scenario B. Dental stress was always lower (P < 0.05) during use of the Bullard and Airtraq laryngoscopes compared with the conventional laryngoscope, lowest (P < 0.05) during use of the Bullard laryngoscope and (with the exception of use of the conventional laryngoscope by the experts) higher during scenario B than during scenario A. In scenario A, participants preferred both video laryngoscopes to the conventional laryngoscope. CONCLUSION: In a moderately difficult airway scenario, all laryngoscopes performed equally well. However, in a more difficult airway scenario, the Bullard and Airtraq laryngoscopes performed better than the conventional laryngoscope, with the Bullard device performing better than the Airtraq. This may be in part related to differing prior experiences of operators with the respective airway devices.

Accuracy and real life performance of a novel interferon-γ release assay for the detection of SARS-CoV2 specific T cell response.

BACKGROUND: The reliable detection of T cell response to COVID-19 or COVID-19 vaccination is important for individual patient care and for monitoring the immune response e.g. in COVID-19 vaccine trials in a standardized fashion. OBJECTIVES AND STUDY DESIGN: We used blood samples from health care workers (HCW) with or without history of COVID-19 to define test accuracy of a novel interferon-γ release assay (IGRA). For a real-life performance evaluation, we analysed interferon-γ response to complete COVID-19 vaccination in HCW receiving homologous or heterologous vaccination regimens and in patients receiving immunosuppressive or immune modulating therapies. RESULTS: The assay had a specificity of 100%. Sensitivity of the IGRA to detect past infection was 72.2% after infection more than 5 months ago and 93.8% after COVID-19 up to 5 months ago. Quantitative results showed significant differences between first and second vaccine dose, but no difference between homologous and heterologous vaccination regimen. Immunocompromised patients often had no immune response or isolated T cell or antibody response to complete vaccination. CONCLUSIONS: The novel IGRA proved to be a highly specific tool to detect SARS-CoV-2 specific T cell response to COVID-19 as well as COVID-19 vaccination, with sensitivity getting lower over time. In perspective, it may serve as a standardized tool in COVID-19 vaccine trials and in clinical care of immunosuppressed patients.

Circulating multimeric immune complexes contribute to immunopathology in COVID-19.

A dysregulated immune response with high levels of SARS-CoV-2 specific IgG antibodies characterizes patients with severe or critical COVID-19. Although a robust IgG response is considered to be protective, excessive triggering of activating Fc-gamma-receptors (FcγRs) could be detrimental and cause immunopathology. Here, we document excessive FcγRIIIA/CD16A activation in patients developing severe or critical COVID-19 but not in those with mild disease. We identify two independent ligands mediating extreme FcγRIIIA/CD16A activation. Soluble circulating IgG immune complexes (sICs) are detected in about 80% of patients with severe and critical COVID-19 at levels comparable to active systemic lupus erythematosus (SLE) disease. FcγRIIIA/CD16A activation is further enhanced by afucosylation of SARS-CoV-2 specific IgG. Utilizing cell-based reporter systems we provide evidence that sICs can be formed prior to a specific humoral response against SARS-CoV-2. Our data suggest a cycle of immunopathology driven by an early formation of sICs in predisposed patients. These findings suggest a reason for the seemingly paradoxical findings of high antiviral IgG responses and systemic immune dysregulation in severe COVID-19. The involvement of circulating sICs in the promotion of immunopathology in predisposed patients opens new possibilities for intervention strategies to mitigate critical COVID-19 progression.

COVID-19 mRNA booster vaccine induces transient CD8+ T effector cell responses while conserving the memory pool for subsequent reactivation.

Immunization with two mRNA vaccine doses elicits robust spike-specific CD8+ T cell responses, but reports of waning immunity after COVID-19 vaccination prompt the introduction of booster vaccination campaigns. However, the effect of mRNA booster vaccination on the spike-specific CD8+ T cell response remains unclear. Here we show that spike-specific CD8+ T cells are activated and expanded in all analyzed individuals receiving the 3rd and 4th mRNA vaccine shots. This CD8+ T cell boost response is followed by a contraction phase and lasts only for about 30-60 days. The spike-specific CD8+ T memory stem cell pool is not affected by the 3rd vaccination. Both 4th vaccination and breakthrough infections with Delta and Omicron rapidly reactivate CD8+ T memory cells. In contrast, neutralizing antibody responses display little boost effect towards Omicron. Thus, COVID-19 mRNA booster vaccination elicits a transient T effector cell response while long-term spike-specific CD8+ T cell immunity is conserved to mount robust memory recall targeting emerging variants of concern.

[Subjective well-being and ability to work of hospital staff after SARS-CoV2 immunization with the mRNA vaccine BNT162b2]. / Subjektives Wohlbefinden und Arbeitsfähigkeit von Krankenhauspersonal nach SARS-CoV-2-Immunisierung mit dem mRNS-Impfstoff BNT162b2 ­ Ergebnisse einer anonymen Umfrage.

BACKGROUND: Since December 27, 2020, employees of the health system in Germany have been vaccinated against the SARS coronavirus-2 with the vaccine BNT162B2. Initial observations show that especially among younger vaccinated people side effects are common. In this study, using the example of clinic employees, the self-perceived well-being after the first and second dose of the vaccine was examined. METHODS: Anonymized online questionnaire to be filled out once by all employees after the second dose of BNT162B2 was offered. The severity of side effects was queried using an ordinal numerical rating scale with values between 0 and 10. Other key data points were age, gender, and occupational group. The ability to work in the days following the injections was recorded by self-reporting. RESULTS: Data from 555 respondents were evaluated. The mean age was 40.25 years (standard deviation 12.35). 56 % of the respondents were female, 44.3 % belonged to the medical service, 42.9 % to the nursing service and 12.8 % were assigned to other professional groups with COVID-19 patient contact. Around 2 % of all employees did not experience any side effects at all. The most common side effect was pain at the injection site. Fatigue, headaches and myalgia followed with decreasing frequency. After the first dose, ¾ of the respondents said they had tolerated the vaccination well overall, after the second dose it was only half. After the first dose, over 90 % of the respondents felt that they were able to work again on the following day, after the second dose one third stated that they were only able to work again on the second day. 2.2 % of all employees had to report that they were unable to work for at least one day after the first dose and 19.5 % after the second dose. CONCLUSIONS: Vaccination with BNT162B2 frequently leads to side effects, especially after the second dose. Perception of side effects resulted in 19 % of those questioned being sick after the second dose. Nevertheless, 95 % of all respondents would choose a coronavirus vaccination again.

IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals.

Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We perform an observational study to investigate seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5-79 years). Seropositivity for SARS-CoV-2 Spike glycoprotein aligns with PCR results that confirm the previous infection. Anti-Spike IgG/IgM titers remain high 60 days post-infection and do not strongly associate with symptoms, except for fever. We analyze PBMCs from a subset of seropositive and seronegative adults. TLR7 agonist-activation reveals an increased population of IL-6+TNF-IL-1ß+ monocytes, while SARS-CoV-2 peptide stimulation elicits IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlates with CD4+ T cell activation in PBMCs from convalescent subjects and is likely due to T cell-mediated effects on IL-33-producing cells. IL-33 is associated with pulmonary infection and chronic diseases like asthma and COPD, but its role in COVID-19 is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid (BALF) from patients with mild to severe COVID-19 reveals a population of IL-33-producing cells that increases with the disease. Together these findings show that IL-33 production is linked to SARS-CoV-2 infection and warrant further investigation of IL-33 in COVID-19 pathogenesis and immunity.

Reduction of protein radicals by GSH and ascorbate: potential biological significance.

The oxidation of proteins and other macromolecules by radical species under conditions of oxidative stress can be modulated by antioxidant compounds. Decreased levels of the antioxidants glutathione and ascorbate have been documented in oxidative stress-related diseases. A radical generated on the surface of a protein can: (1) be immediately and fully repaired by direct reaction with an antioxidant; (2) react with dioxygen to form the corresponding peroxyl radical; or (3) undergo intramolecular long range electron transfer to relocate the free electron to another amino acid residue. In pulse radiolysis studies, in vitro production of the initial radical on a protein is conveniently made at a tryptophan residue, and electron transfer often leads ultimately to residence of the unpaired electron on a tyrosine residue. We review here the kinetics data for reactions of the antioxidants glutathione, selenocysteine, and ascorbate with tryptophanyl and tyrosyl radicals as free amino acids in model compounds and proteins. Glutathione repairs a tryptophanyl radical in lysozyme with a rate constant of (1.05±0.05)×10(5) M(-1) s(-1), while ascorbate repairs tryptophanyl and tyrosyl radicals ca. 3 orders of magnitude faster. The in vitro reaction of glutathione with these radicals is too slow to prevent formation of peroxyl radicals, which become reduced by glutathione to hydroperoxides; the resulting glutathione thiyl radical is capable of further radical generation by hydrogen abstraction. Although physiologically not significant, selenoglutathione reduces tyrosyl radicals as fast as ascorbate. The reaction of protein radicals formed on insulin, ß-lactoglobulin, pepsin, chymotrypsin and bovine serum albumin with ascorbate is relatively rapid, competes with the reaction with dioxygen, and the relatively innocuous ascorbyl radical is formed. On the basis of these kinetics data, we suggest that reductive repair of protein radicals may contribute to the well-documented depletion of ascorbate in living organisms subjected to oxidative stress.

Selenium and sulfur in exchange reactions: a comparative study.

Cysteamine reduces selenocystamine to form hemiselenocystamine and then cystamine. The rate constants are k(1) = 1.3 × 10(5) M(-1) s(-1); k(-1) = 2.6 × 10(7) M(-1) s(-1); k(2) = 11 M(-1) s(-1); and k(-2) = 1.4 × 10(3) M(-1) s(-1), respectively. Rate constants for reactions of cysteine/selenocystine are similar. Reaction rates of selenium as a nucleophile and as an electrophile are 2-3 and 4 orders of magnitude higher, respectively, than those of sulfur. Sulfides and selenides are comparable as leaving groups.