Longitudinal data on humoral response and neutralizing antibodies against SARS-CoV-2 Omicron BA.1 and subvariants BA.4/5 and BQ.1.1 after COVID-19 vaccination in cancer patients.

PURPOSE: The SARS-CoV-2 Omicron variant of concern (VOC) and subvariants like BQ.1.1 demonstrate immune evasive potential. Little is known about the efficacy of booster vaccinations regarding this VOC and subvariants in cancer patients. This study is among the first to provide data on neutralizing antibodies (nAb) against BQ.1.1. METHODS: Cancer patients at our center were prospectively enrolled between 01/2021 and 02/2022. Medical data and blood samples were collected at enrollment and before and after every SARS-CoV-2 vaccination, at 3 and 6 months. RESULTS: We analyzed 408 samples from 148 patients (41% female), mainly with solid tumors (85%) on active therapy (92%; 80% chemotherapy). SARS-CoV-2 IgG and nAb titers decreased over time, however, significantly increased following third vaccination (p < 0.0001). NAb (ND50) against Omicron BA.1 was minimal prior and increased significantly after the third vaccination (p < 0.0001). ND50 titers against BQ.1.1 after the third vaccination were significantly lower than against BA.1 and BA.4/5 (p < 0.0001) and undetectable in half of the patients (48%). Factors associated with impaired immune response were hematologic malignancies, B cell depleting therapy and higher age. Choice of vaccine, sex and treatment with chemo-/immunotherapy did not influence antibody response. Patients with breakthrough infections had significantly lower nAb titers after both 6 months (p < 0.001) and the third vaccination (p = 0.018). CONCLUSION: We present the first data on nAb against BQ.1.1 following the third vaccination in cancer patients. Our results highlight the threat that new emerging SARS-CoV-2 variants pose to cancer patients and support efforts to apply repeated vaccines. Since a considerable number of patients did not display an adequate immune response, continuing to exhibit caution remains reasonable.

Risk assessment of banknotes as a fomite of SARS-CoV-2 in cash payment transactions.

The COVID 19 pandemic has triggered concerns and assumptions globally about transmission of the SARS-CoV-2 virus via cash transactions. This paper assesses the risk of contracting COVID-19 through exposure to SARS-CoV-2 via cash acting as a fomite in payment transactions. A quantitative microbial risk assessment was conducted for a scenario assuming an infectious person at the onset of symptoms, when virion concentrations in coughed droplets are at their highest. This person then contaminates a banknote by coughing on it and immediately hands it over to another person, who might then be infected by transferring the virions with a finger from the contaminated banknote to a facial mucous membrane. The scenario considered transfer efficiency of virions on the banknote to fingertips when droplets were still wet and after having dried up and subsequently being touched by finger printing or rubbing the object. Accounting for the likelihood of the scenario to occur by considering (1) a local prevalence of 100 COVID-19 cases/100,000 persons, (2) a maximum of about one-fifth of infected persons transmit high virus loads, and (3) the numbers of cash transactions/person/day, the risk of contracting COVID-19 via person-to-person cash transactions was estimated to be much lower than once per 39,000 days (107 years) for a single person. In the general populace, there will be a maximum of 2.6 expected cases/100,000 persons/day. The risk for a cashier at an average point of sale was estimated to be much less than once per 430 working days (21 months). The depicted scenario is a rare event, therefore, for a single person, the risk of contracting COVID-19 via person-to-person cash transactions is very low. At a point of sale, the risk to the cashier proportionally increases but it is still low.

Efficient Inactivation of Monkeypox Virus by World Health Organization‒Recommended Hand Rub Formulations and Alcohols.

Increasing nonzoonotic human monkeypox virus (MPXV) infections urge reevaluation of inactivation strategies. We demonstrate efficient inactivation of MPXV by 2 World Health Organization‒recommended alcohol-based hand rub solutions. When compared with other (re)emerging enveloped viruses, MPXV displayed the greatest stability. Our results support rigorous adherence to use of alcohol-based disinfectants.

In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant.

With the emergence of novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs), vaccination studies that elucidate the efficiency and effectiveness of a vaccination campaign are critical to assess the durability and the protective immunity provided by vaccines. SARS-CoV-2 vaccines have been found to induce robust humoral and cell-mediated immunity in individuals vaccinated with homologous vaccination regimens. Recent studies also suggest improved immune response against SARS-CoV-2 when heterologous vaccination strategies are employed. Yet, few data exist on the extent to which heterologous prime-boost-boost vaccinations with two different vaccine platforms have an impact on the T cell-mediated immune responses with a special emphasis on the currently dominantly circulating Omicron strain. In this study, we collected serum and peripheral blood mononuclear cells (PBMCs) from 57 study participants of median 35-year old's working in the health care field, who have received different vaccination regimens. Neutralization assays revealed robust but decreased neutralization of Omicron VOC, including BA.1 and BA.4/5, compared to WT SARS-CoV-2 in all vaccine groups and increased WT SARS-CoV-2 binding and neutralizing antibodies titers in homologous mRNA prime-boost-boost study participants. By investigating cytokine production, we found that homologous and heterologous prime-boost-boost-vaccination induces a robust cytokine response of CD4+ and CD8+ T cells. Collectively, our results indicate robust humoral and T cell mediated immunity against Omicron in homologous and heterologous prime-boost-boost vaccinated study participants, which might serve as a guide for policy decisions.

Recommendation of the German Society of Hospital Hygiene (DGKH): Prevention of COVID-19 by virucidal gargling and virucidal nasal spray - updated version April 2022.

The German Society of Hospital Hygiene develops guidelines, recommendations and standard operation procedures on a voluntary basis, published on the DGKH-website (https://www.krankenhaushygiene.de/). The original German version of this recommendation was published in April 2022 and has now been made available to the international professional public in English. Evaluating the current data on the efficacy of virucidal gargle/mouthwash solutions and nasal sprays against SARS-CoV-2 in vitro and in clinical trials, conducted with preventive or therapeutic objectives, recommendations are given for the prevention of COVID-19. The following areas are considered: Protection of the community when regional clusters or high incidences of infection become knownProtection of the community at low risk of infectionPre-exposure prophylaxis for the protection of healthcare workersPost-exposure prophylaxis.

Recommendation of the German Society of Hospital Hygiene (DGKH): Prevention of COVID-19 by virucidal gargling and virucidal nasal spray – updated version April 2022 Empfehlung der Deutschen Gesellschaft für Krankenhaushygiene (DGKH): Prävention von COVID-19 durch viruzides Gurgeln und viruzides Nasenspray – aktualisierte Fassung April 2022

The German Society of Hospital Hygiene develops guidelines, recommendations and standard operation procedures on a voluntary basis, published on the DGKH-website (https://www.krankenhaushygiene.de/). The original German version of this recommendation was published in April 2022 and has now been made available to the international professional public in English. Evaluating the current data on the efficacy of virucidal gargle/mouthwash solutions and nasal sprays against SARS-CoV-2 in vitro and in clinical trials, conducted with preventive or therapeutic objectives, recommendations are given for the prevention of COVID-19. The following areas are considered: Protection of the community when regional clusters or high incidences of infection become known Protection of the community at low risk of infection Pre-exposure prophylaxis for the protection of healthcare workers Post-exposure prophylaxis

[Interdisciplinary Perspectives on the Role of Aerosol Transmission in SARS-CoV-2 Infections]. / Interdisziplinäre Perspektiven zur Bedeutung der Aerosolübertragung für das Infektionsgeschehen von SARS-CoV-2.

The relevance of aerosols for the transmission of the Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is still debated. However, over time, in addition to distancing and hygiene rules, aerosol physics-based measures such as wearing face masks and ventilating indoor spaces were found to be efficient in reducing infections. In an interdisciplinary workshop "Aerosol & SARS-CoV-2" of the Association for Aerosol Research (GAeF) in cooperation with the German Society for Pneumology and Respiratory Medicine (DGP), the Professional Association of General Air Technology of the VDMA, the German Society for Virology (GfV), the Health Technology Society (GG) and the International Society for Aerosols in Medicine (ISAM) under the auspices of the Robert Koch Institute (RKI) in March 2021, the need for research and coordination on this topic was addressed. Fundamental findings from the various disciplines as well as interdisciplinary perspectives on aerosol transmission of SARS-CoV-2 and infection mitigation measures are summarized here. Finally, open research questions and needs are presented.

Nanoscale copper and silver thin film systems display differences in antiviral and antibacterial properties.

The current Coronavirus Disease 19 (COVID-19) pandemic has exemplified the need for simple and efficient prevention strategies that can be rapidly implemented to mitigate infection risks. Various surfaces have a long history of antimicrobial properties and are well described for the prevention of bacterial infections. However, their effect on many viruses has not been studied in depth. In the context of COVID-19, several surfaces, including copper (Cu) and silver (Ag) coatings have been described as efficient antiviral measures that can easily be implemented to slow viral transmission. In this study, we detected antiviral properties against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) on surfaces, which were coated with Cu by magnetron sputtering as thin Cu films or as Cu/Ag ultrathin bimetallic nanopatches. However, no effect of Ag on viral titers was observed, in clear contrast to its well-known antibacterial properties. Further enhancement of Ag ion release kinetics based on an electrochemical sacrificial anode mechanism did not increase antiviral activity. These results clearly demonstrate that Cu and Ag thin film systems display significant differences in antiviral and antibacterial properties which need to be considered upon implementation.

Low Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission by Fomites: A Clinical Observational Study in Highly Infectious Coronavirus Disease 2019 Patients.

BACKGROUND: The contribution of droplet-contaminated surfaces for virus transmission has been discussed controversially in the context of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. More importantly, the risk of fomite-based transmission has not been systematically addressed. Therefore, the aim of this study was to evaluate whether confirmed hospitalized coronavirus disease 2019 (COVID-19) patients can contaminate stainless steel carriers by coughing or intensive moistening with saliva and to assess the risk of SARS-CoV-2 transmission upon detection of viral loads and infectious virus in cell culture. METHODS: We initiated a single-center observational study including 15 COVID-19 patients with a high baseline viral load (cycle threshold value ≤25). We documented clinical and laboratory parameters and used patient samples to perform virus culture, quantitative polymerase chain reaction, and virus sequencing. RESULTS: Nasopharyngeal and oropharyngeal swabs of all patients were positive for viral ribonucleic acid on the day of the study. Infectious SARS-CoV-2 could be isolated from 6 patient swabs (46.2%). After coughing, no infectious virus could be recovered, however, intensive moistening with saliva resulted in successful viral recovery from steel carriers of 5 patients (38.5%). CONCLUSIONS: Transmission of infectious SARS-CoV-2 via fomites is possible upon extensive moistening, but it is unlikely to occur in real-life scenarios and from droplet-contaminated fomites.

Mouthrinses against SARS-CoV-2 - High antiviral effectivity by membrane disruption in vitro translates to mild effects in a randomized placebo-controlled clinical trial.

The emergence of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an unprecedented threat for the human population, necessitating rapid and effective intervention measures. Given the main infection route by airborne transmission, significant attention has been bestowed upon the use of antiseptic mouthrinses as a way to possibly reduce infectious viral titers. However, clinical evaluations are still sparse. Thus, we evaluated a wide variety of antiseptic agents that can be used as mouthrinses for their antiviral effects in vitro and their respective mode of action. One of the most promising antiseptic agents (benzalkoniumchloride, BAC) was used in a randomized placebo-controlled clinical trial with subsequent analysis of viral loads by RT-qPCR and virus rescue in cell culture. Mechanistic analysis revealed that treatment with BAC and other antiseptic agents efficiently inactivated SARS-CoV-2 in vitro by primarily disrupting the viral envelope, without affecting viral RNA integrity. However, the clinical application only resulted in a mild reduction of viral loads in the oral cavity. These results indicate that gargling with mouthrinses comprising single antiseptic agents may play a minor role towards a potential reduction of transmission rates and thus, these findings are of utmost importance when considering alternative COVID-19 prevention strategies.

A touch transfer assay to determine surface transmission of highly pathogenic viruses.

Transmission via fomites poses a major dissemination route for many human pathogens, particularly because of transfer via fingertips. Here, we present a protocol to investigate direct transfer of infectious agents from fomites to humans via naked fingertips. The protocol is suitable for pathogens requiring highest biosafety levels (e.g., SARS-CoV-2). We used an artificial skin to touch a defined volume of virus suspension and subsequent quantification of infectious entities allows quantitative measurement of transfer efficiency and risk assessment. For complete information on the generation and use of this manuscript, please refer to Todt et al. (2021).

Risk Stratification of SARS-CoV-2 Breakthrough Infections Based on an Outbreak at a Student Festive Event.

In early 2022, the Coronavirus disease 2019 (COVID-19) remains a global challenge. COVID-19 is caused by an increasing number of variants of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here, we report an outbreak of SARS-CoV-2 breakthrough infections related to a student festive event with 100 mostly vaccinated guests, which took place in Northern Bavaria, Germany, in October 2021. The data were obtained by retrospective guest interviews. In total, 95 students participated in the study, with 94 being fully vaccinated and 24 reporting infection by the delta variant. Correlation analyses among 15 examined variables revealed that time spent at the event, conversation with the supposed index person, and a homologous viral vector vaccination regime were significant risk factors for infection. Non-significant observations related to higher rates of infection included time since last vaccination, shared use of drinking vessels, and number of individual person-to-person contacts at the event. Our data suggest that a high rate of breakthrough infections with the delta variant occurs if no preventive measures are practiced. To limit infection risk, high-quality testing of participants should be considered a mandatory measure at gatherings, irrespective of the participants' vaccination status.

Differential interferon-α subtype induced immune signatures are associated with suppression of SARS-CoV-2 infection.

Type I interferons (IFN-I) exert pleiotropic biological effects during viral infections, balancing virus control versus immune-mediated pathologies, and have been successfully employed for the treatment of viral diseases. Humans express 12 IFN-alpha (α) subtypes, which activate downstream signaling cascades and result in distinct patterns of immune responses and differential antiviral responses. Inborn errors in IFN-I immunity and the presence of anti-IFN autoantibodies account for very severe courses of COVID-19; therefore, early administration of IFN-I may be protective against life-threatening disease. Here we comprehensively analyzed the antiviral activity of all IFNα subtypes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to identify the underlying immune signatures and explore their therapeutic potential. Prophylaxis of primary human airway epithelial cells (hAEC) with different IFNα subtypes during SARS-CoV-2 infection uncovered distinct functional classes with high, intermediate, and low antiviral IFNs. In particular, IFNα5 showed superior antiviral activity against SARS-CoV-2 infection in vitro and in SARS-CoV-2-infected mice in vivo. Dose dependency studies further displayed additive effects upon coadministration with the broad antiviral drug remdesivir in cell culture. Transcriptomic analysis of IFN-treated hAEC revealed different transcriptional signatures, uncovering distinct, intersecting, and prototypical genes of individual IFNα subtypes. Global proteomic analyses systematically assessed the abundance of specific antiviral key effector molecules which are involved in IFN-I signaling pathways, negative regulation of viral processes, and immune effector processes for the potent antiviral IFNα5. Taken together, our data provide a systemic, multimodular definition of antiviral host responses mediated by defined IFN-I. This knowledge will support the development of novel therapeutic approaches against SARS-CoV-2.

Induction of Hepatitis E Virus Anti-ORF3 Antibodies from Systemic Administration of a Muscle-Specific Adeno-Associated Virus (AAV) Vector.

The hepatitis E virus (HEV) is a major global health problem, leading to large outbreaks in the developing world and chronic infections in the developed world. HEV is a non-enveloped virus, which circulates in the blood in a quasi-enveloped form. The quasi-envelope protects HEV particles from neutralising anti-capsid antibodies in the serum; however, most vaccine approaches are designed to induce an immune response against the HEV capsid. In this study, we explored systemic in vivo administration of a novel synthetic and myotropic Adeno-associated virus vector (AAVMYO3) to express the small HEV phosphoprotein ORF3 (found on quasi-enveloped HEV) in the musculature of mice, resulting in the robust and dose-dependent formation of anti-ORF3 antibodies. Neutralisation assays using the serum of ORF3 AAV-transduced mice showed a modest inhibitory effect on the infection of quasi-enveloped HEV in vivo, comparable to previously characterised anti-ORF3 antibodies used as a control. The novel AAVMYO3 capsid used in this study can serve as a versatile platform for the continued development of vector-based vaccines against HEV and other infectious agents, which could complement traditional vaccines akin to the current positive experience with SARS-CoV-2.

A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets.

Over the past 20 years, 3 highly pathogenic human coronaviruses (HCoVs) have emerged-Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and, most recently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-demonstrating that coronaviruses (CoVs) pose a serious threat to human health and highlighting the importance of developing effective therapies against them. Similar to other viruses, CoVs are dependent on host factors for their survival and replication. We hypothesized that evolutionarily distinct CoVs may exploit similar host factors and pathways to support their replication cycles. Herein, we conducted 2 independent genome-wide CRISPR/Cas-9 knockout (KO) screens to identify MERS-CoV and HCoV-229E host dependency factors (HDFs) required for HCoV replication in the human Huh7 cell line. Top scoring genes were further validated and assessed in the context of MERS-CoV and HCoV-229E infection as well as SARS-CoV and SARS-CoV-2 infection. Strikingly, we found that several autophagy-related genes, including TMEM41B, MINAR1, and the immunophilin FKBP8, were common host factors required for pan-CoV replication. Importantly, inhibition of the immunophilin protein family with the compounds cyclosporine A, and the nonimmunosuppressive derivative alisporivir, resulted in dose-dependent inhibition of CoV replication in primary human nasal epithelial cell cultures, which recapitulate the natural site of virus replication. Overall, we identified host factors that are crucial for CoV replication and demonstrated that these factors constitute potential targets for therapeutic intervention by clinically approved drugs.

[Disinfectants during the COVID-19 pandemic: a challenge]. / Desinfektionsmittel in der COVID-19-Pandemie: eine Herausforderung.

Disinfection measures have become more important as a result of the COVID-19 pandemic in Germany. The increased need for disinfectants at the beginning of the pandemic required temporary legal regulations in order to provide a sufficient quantity of products for the necessary disinfection in the medical sector on the one hand and for the additional demand in the population on the other. For this purpose, the Federal Institute for Drugs and Medical Devices (BfArM) and the Federal Institute for Occupational Safety and Health (BAuA) issued a general ruling, which is explained in more detail in this article. The focus was on measures for hygienic hand disinfection. However, other applications such as surface disinfection in relation to pandemic respiratory diseases are also addressed. The experience gained in ensuring the supply of disinfectants that are effective and safe to use should be used to prepare for further pandemics.

Desinfektionsmittel in der COVID-19-Pandemie: eine Herausforderung Disinfectants during the COVID-19 pandemic: a challenge

Durch die COVID-19-Pandemie haben Desinfektionsmaßnahmen auch in Deutschland an Bedeutung gewonnen. Der erhöhte Bedarf an Desinfektionsmitteln zu Beginn der Pandemie erforderte es, vorübergehende rechtliche Regelungen zu treffen, um einerseits ausreichend Mittel für die notwendige Desinfektion im medizinischen Bereich und andererseits für den zusätzlichen Bedarf in der Bevölkerung zur Verfügung zu haben. Dazu wurden vom Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) und der Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (BAuA) Allgemeinverfügungen erlassen, die in diesem Beitrag näher erläutert werden. Im Vordergrund stehen dabei die Maßnahmen für die hygienische Händedesinfektion. Aber auch weitere Anwendungen wie die Flächendesinfektion im Zusammenhang mit pandemischen Atemwegserkrankungen werden erörtert. Die Erfahrungen bei der Sicherstellung der Versorgung mit wirksamen und in der Anwendung sicheren Desinfektionsmitteln sollten für die Vorbereitung weiterer Pandemien genutzt werden.