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BackgroundThe Co-HCW study is a prospective, longitudinal single center observational study on the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital (JUH) in Jena, Germany.Material and MethodsThis follow-up study covers the observation period from 19th May 2020 to 22nd June 2021. At each out of three voluntary study visits, participants filled out a questionnaire on individual SARS-CoV-2 exposure. In addition, serum samples to assess specific SARS-CoV-2 antibodies were collected. Participants with antibodies against nucleocapsid and/or spike protein without previous vaccination and/or a reported positive SARS-CoV-2 PCR test were regarded as participants with detected SARS-CoV-2 infection. Multivariable logistic regression modeling was applied to identify potential risk factors for infected compared to non-infected participants.ResultsOut of 660 participants that were included during the first study visit, 406 participants (61.5%) were eligible for final analysis as they did not change the COVID-19 risk area (high-risk n=76; intermediate-risk n=198; low-risk n=132) during the study. Forty-four participants (10.8%, 95% confidence interval (95%CI) 8.0%-14.3%) had evidence of a current or past SARS-CoV-2 infection detected by serology (n=40) and/or PCR (n=28). No association of any SARS-CoV-2 infection with the COVID-19 risk group according to working place could be detected. But exposure to a SARS-CoV-2 positive household member (adjusted OR (AOR) 4.46, 95%CI 2.06-9.65) or colleague (AOR 2.30, 95%CI 1.10-4.79) significantly increased the risk of a SARS-CoV-2 infection.ConclusionOur results demonstrate that non-patient-related SARS-CoV-2 exposure imposed the highest infection risk in hospital staff members of JUH.

BackgroundHealthcare workers (HCWs) are at particular risk to acquire SARS-CoV-2 infections.AimThe objectives of this study were to compare SARS-CoV-2 IgG seroprevalence and compliance to wear personal protective equipment (PPE) between HCWs working within (high-risk) or outside (intermediate-risk) units treating suspected or confirmed COVID-19 patients. In addition, administration staff (low-risk) was included.MaterialsCo-HCW is a prospective cohort study among employees at the Jena University Hospital, Germany. Since 16th March 2020, 50 SARS-CoV-2 inpatients and 73 outpatients were treated in our hospital. Mandatory masking was implemented on 20th March 2020. We here evaluated seroprevalence using two IgG detecting immunoassays, assessed COVID-19 exposure, clinical symptoms and compliance to wear PPE.FindingsBetween 19th May and 19th June 2020 we analysed 660 employees [out of 3,228; 20.4%]. Eighteen participants (2.7%) had SARS-CoV-2 antibodies in at least one immunoassay. Among them, 13 (72.2%) were not aware of direct COVID-19 exposure and 9 (50.0%) did not report any clinical symptoms. We observed no evidence for an association between seroprevalence and risk area (high-risk: 2 of 137 HCWs (1.5%), intermediate-risk: 10 of 343 HCWs (2.9%), low-risk: 6 of 180 administration employees (3.3%); p=0.574). Reported compliance to wear PPE differed (pConclusionNo evidence for higher seroprevalence against SARS-CoV-2 in HCWs working in high-risk COVID-19 areas could be observed, probably due to high compliance to wear PPE. Compared to administration employees, we observed no additional risk to acquire SARS-CoV-2 infections by patient care.

Universal masking the health care setting and in the community to contain the spread of SARS-CoV-2 has been recently recommended by the WHO, but supporting data are rare. The City of Jena was the first community in Germany to issue an order on mandatory public masking. Here, we report the development of the number of novel infections in our hospital and in the city of Jena after implementation of universal masking in our hospital and the city.

BackgroundDue to the substantial proportion of asymptomatic and mild courses many SARS-CoV-2 infections remain unreported. Therefore, assessment of seroprevalence may detect the real burden of disease. We aimed at determining and characterizing the rate of SARS-CoV-2 infections and the resulting immunity in a defined population.MethodsCoNAN is a population-based cohort study in the previously quarantined community Neustadt-am-Rennsteig, Germany six weeks after a SARS-CoV-2 outbreak with 49 cases identified by PCR screening of all 883 inhabitants. The primary objective of the study was to assess SARS-CoV-2 antibody seroconversion rate using six different IgG detecting immunoassays. Secondary objectives of the study were: i.) to determine the rate of seroconversion in children; ii.) to determine potential risk factors for symptomatic vs. asymptomatic Covid19 courses; iii.) to investigate the rate of virus persistence.FindingsWe enrolled 626 participants (71% of the community population). All actual SARS-CoV-2 PCR tests were negative; while a total of 8·4% (52 of 620 tested) had antibodies against SARS-CoV-2 in at least two independent tests. Twenty of the antibody positive participants had previously a positive SARS-CoV-2 PCR. On the contrary, of those 38 participants with SARS-CoV-2 infection, only 20 (52·6%) were antibody positive.InterpretationSeveral antibody tests conducted six weeks after an outbreak of SARS-CoV-2 did not detect all previously PCR-positive tested individuals. Cautious evaluation of antibody testing strategies to assess immunity against the infection is warranted.FundingCoNAN was funded by the Thuringian Ministry for Economic Affairs, Science and Digital Society (TMWWDG).

SUMMARYMost mammals express a functionalGGTA1gene encoding the N-acetyllactosaminide α-1,3-galactosyltransferase enzyme, which synthesizes Galα1-3Galβ1-4GlcNAc (αGal) and are thus tolerant to this self-expressed glycan epitope. Old World primates including humans, however, carryGGTA1loss-of-function mutations and lack αGal. Presumably, fixation of such mutations was propelled by natural selection, favoring the emergence of αGal-specific immunity, which conferred resistance to αGal-expressing pathogens. Here we show that loss ofGgta1function in mice enhances resistance to bacterial sepsis, irrespectively of αGal-specific immunity. Rather, the absence of αGal from IgG-associated glycans increases IgG effector function, via a mechanism associated with enhanced IgG-Fc gamma receptor (FcγR) binding. The ensuing survival advantage against sepsis comes alongside a cost of earlier onset of reproductive senescence. Mathematical modeling of this trade-off shows that under conditions of high exposure to virulent pathogens, selective pressure can fixGGTA1loss-of-function mutations, as likely occurred during the evolution of primates towards humans.

Trained immunity defines long-lasting adaptive responses of innate immunity, mediated by transcriptional and epigenetic modifications of myeloid cells. Here, we report that labile heme, an alarmin released extracellularily upon tissue damage and hemolysis, induces trained immunity in human and murine primary cells and in mice. Heme-trainning in monocytes is associated with epigenetic and transcriptional profiles that overlap to some extent with those seen in β-glucan-training, the prototype agonist of trained immunity. In sharp contrast to β-glucan training however, heme-training relied on activation of the Syk/JNK-pathway. Heme training in mice was associated with long-lasting expansion of myeloid-biased progenitor cells as well as with altered chromatin accessibility in hematopoietic stem and progenitor cells. Finally, heme-induced training was protective against bacterial sepsis in mice.In conclusion, we reveal that heme, a bona fide alarmin, induces innate immune memory regulating host response to infection.

SummarySynergy of resistance and disease tolerance mechanisms is necessary for an effective immune response leading to survival and return to homeostasis when an organism is challenged by infection. Antibiotics are used for their resistance enhancement capabilities by decreasing pathogen load, but several classes have long been known to have beneficial effects that cannot be explained strictly on the basis of their capacity to control the infectious agent. Here we report that tetracycline antibiotics, a class of ribosome-targeting drugs, robustly protects against sepsis by inducing disease tolerance, independently from their direct antibiotic properties. Mechanistically, we find that mitochondrial inhibition of protein synthesis perturbs the electron transfer chain and leads to improved damage repair in the lung and fatty acid oxidation and glucocorticoid sensitivity in the liver. Using a partial and acute deletion ofCRIF1in the liver, a critical mitoribosomal component for protein synthesis, we find that mice are protected against bacterial sepsis, an observation which is phenocopied by the transient inhibition of complex I of ETC by phenformin. Together, we demonstrate that ribosome-targeting antibiotics are beneficial beyond their antibacterial activity and that mitochondrial protein synthesis inhibition leading to ETC perturbation is a novel mechanism for the induction of disease tolerance.

BackgroundExosomes are involved in intracellular communication and contain proteins, mRNAs, miRNAs, and signaling molecules. Exosomes were shown to act as neuroinflammatory mediators involved in neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS). Brain aging has been associated to increased neuroinflammation. In addition, a decreased extracellular vesicle concentration was observed in aging tissues. The specific mechanisms how exosomes and aging are connected are not known yet.ResultsHere we have shown that peripheral injection had almost no effect on selected gene expression in the liver. However, exosome injection has led to changes in the specific markers of glial cell activation (CD68, Iba1, GFAP). Interestingly, only injection of exosomes isolated from aged mice induced significant activation of astrocyte cells, as shown by increased GFAP expression.ConclusionTranscription levels of genes GFAP, TGF-β, CD68, Iba1 known to be involved in glial cell function are significantly changing after introduction of peripheral extracellular vesicles. Exosomes were able to pass blood brain barrier and induce glial cell activation. GFAP known to be a specific astrocyte activation marker was significantly higher expressed after injection of old but not young exosomes, indicating a possible role of exosomes in the mechanisms of brain aging.