ABSTRACT
Purpose: Influenza infections have a substantial impact on health care institutions. While vaccination is the most effective preventive measure against influenza infections, overall vaccination coverage in healthcare workers is low. The study was conducted to investigate the impact of an intensified influenza vaccination campaign in a maximum-care hospital on influenza vaccination coverage in healthcare workers during the COVID-19 pandemic in 2020/21. Methods: Vaccination coverage following an intensified influenza vaccination campaign comprising a mobile vaccination team providing on-site vaccination and vaccination at a recurring central vaccination site in addition to promotional measures was analysed. A survey querying vaccination motivation was performed. Additionally, campaign strategies and respective vaccination coverage of influenza seasons between 2017/18 and 2019/20 were analysed. Results: The intensified influenza vaccination campaign 2020/21 led to a significant 2.4-fold increase yielding an overall vaccination coverage of 40% among healthcare workers. A significant increase in vaccination coverage was observed across all professional fields, especially among nurses, a 2.7-fold increase, reaching a vaccination coverage of 48% was observed. The COVID-19 pandemic positively influenced vaccination decision in 72% of first-time ever or first-time in over ten years influenza vaccinees. Vaccination coverage during prior vaccination campaigns focusing on educational measures did not exceed 17%. Conclusion: A mobile vaccination team providing on-site vaccination and vaccinations at a central vaccination site in addition to intensified promotional measures can be implemented to increase influenza vaccination coverage in healthcare workers. Our concept can inform future influenza and other vaccination campaigns for healthcare workers.
Subject(s)
COVID-19ABSTRACT
Background: In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARS-CoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual’s medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over one year.Methods/Design: EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged ≥75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax®) vs. BNT162b2 (Comirnaty®) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T-cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T-cell response and neutralising capacity will be assessed.The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed.Discussion: The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax®) and BNT162b2 (Comirnaty®) as 4th SARS-CoV-2 vaccine dose in adults ≥75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population.
Subject(s)
COVID-19ABSTRACT
Vaccines are the most important means to overcome the SARS-CoV-2 pandemic. They induce specific antibody and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 5 months after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both. Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV-2 - including variants of concern such as Delta or Omicron - was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homologous ChAd immunization. T-cell responses showed less waning irrespective of the vaccination regimen. These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent approach to induce long-term humoral and cellular immune protection.
ABSTRACT
Due to the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), deepening the host genetic contribution to severe COVID-19 may further improve our understanding about underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany, as well as hypothesis-driven targeted analysis of the human leukocyte antigen (HLA) region and chromosome Y haplotypes. We include detailed stratified analyses based on age, sex and disease severity. In addition to already established risk loci, our data identify and replicate two genome-wide significant loci at 17q21.31 and 19q13.33 associated with severe COVID-19 with respiratory failure. These associations implicate a highly pleiotropic ~0.9-Mb 17q21.31 inversion polymorphism, which affects lung function and immune and blood cell counts, and the NAPSA gene, involved in lung surfactant protein production, in COVID-19 pathogenesis.
Subject(s)
COVID-19 , Respiratory InsufficiencyABSTRACT
Administration of a first dose of the COVID-19 vaccine ChAdOx1 nCoV-19 (Vaxzevria(R), AstraZeneca) is associated with a certain risk for vaccine-induced immune thrombotic thrombocytopenia. Therefore, several countries have recommended replacing the second dose of ChAdOx1 nCoV-19 with an mRNA-based vaccine as a precautionary measure, although data on safety and efficacy of such heterologous prime-boost regimen are sparse. Therefore, vaccinees, who had received a heterologous vaccination using ChAdOx1 nCoV-19 as prime and BNT162b2 (Comirnaty(R), BioNTech-Pfizer) mRNA as boost vaccination were offered SARS-CoV-2 antibody testing to quantify their vaccine-induced neutralizing antibody response. The results were compared to cohorts of healthcare workers or volunteers, who received homologous BNT162b2 or homologous ChAdOx1 nCoV-19 vaccination regimens, respectively. A striking increase of vaccine-induced SARS-CoV-2 neutralizing antibody activity was observed in 229 vaccinees that received a BNT162b2 boost 9 to 12 weeks after ChAdOx1 nCoV-19 prime. In our cohort comprising over 480 individuals, the heterologous vaccination scheme induced significantly higher neutralizing antibody titers than homologous ChAdOx1 nCoV-19 and even than homologous BNT162b2 vaccination. This proves that a single dose of a COVID-19 mRNA vaccine after ChAdOx1 nCoV-19 prime vaccination is sufficient to achieve high neutralizing antibody levels predicting immune protection from SARS-CoV-2 infection, and may even increase vaccine efficacy offering an alternative in a setting of vaccine shortage.
Subject(s)
COVID-19 , Purpura, Thrombotic ThrombocytopenicABSTRACT
Recently, an increasing number of cases with delayed large cutaneous reaction after immunisation with mRNA-based vaccines have been reported. This adverse reaction – which is considered a delayed-type or T-cell mediated hypersensitivity reaction – has been described primarily for the Moderna (mRNA-1273) vaccine and to a lesser extent for Comirnaty (Pfizer/BioNTech, BNT162b2).We describe a delayed large cutaneous reaction in a patient who received the viral vector vaccine Vaxzevria (ChAdOx1-S). The time course and clinical symptoms of delayed major skin reaction after vaccination with Moderna or Pfizer/BioNTech have a similar pattern that we recognized in our patient after Vaxzevria vaccination. In contrast to the Moderna vaccine trials, this phenomenon has not been described in the Vaxzevria clinical trials and is to the best of our knowledge the first report of this adverse reaction to a vector-based vaccine against SARS-CoV-2.With this, we hope to raise awareness about delayed injection site reactions that also occur after viral vector vaccines and to encourage additional reporting and patient education regarding the cutaneous reactions after COVID-19 vaccination.
Subject(s)
COVID-19ABSTRACT
BackgroundDuring the SARS-CoV-2 pandemic a mass casualty incident of ambulatory patients occurred at the COVID-19 rapid response infrastructure (CRRI) facility at the University Hospital of Cologne (UHC). We report the development of a patient-centred mobile-device solution to support efficient management of the facility, triage of patients and rapid delivery of test results.MethodsThe UHC-Corona Web Tool (CWT) was developed as a web-based application useable on each patient's smartphone. It provides, among others, a self-reported medical history including type and duration of symptoms and potential risk contacts and links all retrieved information to the digital patient chart via a QR code. It provides scheduling of outpatient appointments and automated transmission of SARS-CoV-2 test results.ResultsThe UHC-CWT was launched on April 9th, 2020. It was used by 28652 patients until August 31st,2020. Of those, 15245 (53,2%) consulted the CRRI, representing 43,1% of all CRRI patients during the observed period.There were 8304 (29,0%) specifications concerning travel history and 17145 (59,8%) indications of ≥1 symptom of SARS-CoV-2 infection. The most frequently indicated symptoms were sore throat (60,0%), headache (50,7%), common cold (45,1%) and cough (42,6%) while 11057 (40,2%) patients did not report any symptoms. After implementation of the UHC-CWT, the number of patient contacts per physician rose from 38 to 98,7 per day. The personnel for communication of test results was reduced from four on seven days to one on five days.ConclusionThe UHC-CWT is an effective digital solution for management of large numbers of outpatients for SARS-CoV-2 testing.
Subject(s)
COVID-19 , HeadacheABSTRACT
Immunoassays are a standard diagnostic tool assessing immunity in severe acute respiratory syndrome coronavirus type 2 (SARS‑CoV‑2) infection. However, immunoassays do not provide information about contaminating antigens or cross‑reactions and might exhibit inaccurately high sensitivity and low specificity. We aimed to gain insight into the serological immune response of SARS‑CoV‑2 patients by immunoblot analysis.We analyzed serum immunoglobulins IgM, ‑A, and ‑G directed against SARS‑CoV‑2 proteins by immunoblot analysis from 12 infected patients. We determined IgG isotype antibodies by commercially available ELISA and assessed the clinical parameters of inflammation status and kidney and liver injury.We found evidence for antibody cross‑reactivity, which calls into question a reliable assessment of serum samples tested negative for anti‑SARS‑CoV‑2 antibodies by immunoassays. Nevertheless, for the detection of IgG anti‑SARS‑CoV‑2 antibodies, our data suggest that the use of the spike glycoprotein in immunoassays should be sufficient to identify positive patients. Using a combination of the spike glycoprotein and the open reading frame 8 protein could prove to be the best for the detection of patients positive for anti‑SARS‑CoV‑2 IgM antibodies. We found that the antibody response alone is not decisive for the course of the disease, but inflammation parameters are promising indicators.
Subject(s)
Infections , Severe Acute Respiratory Syndrome , Chemical and Drug Induced Liver Injury , InflammationABSTRACT
Although the global response to COVID-19 has not been entirely unified, the opportunity arises to assess the impact of regional public health interventions and to classify strategies according to their outcome. Analysis of genetic sequence data gathered over the course of the pandemic allows us to link the dynamics associated with networks of connected individuals with specific interventions. In this study, clusters of transmission were inferred from a phylogenetic tree representing the relationships of patient sequences sampled from December 30, 2019 to April 17, 2020. Metadata comprising sampling time and location were used to define the global behavior of transmission over this earlier sampling period, but also the involvement of individual regions in transmission cluster dynamics. Results demonstrate a positive impact of international travel restrictions and nationwide lockdowns on global cluster dynamics. However, residual, localized clusters displayed a wide range of estimated initial secondary infection rates, for which uniform public health interventions are unlikely to have sustainable effects. Our findings highlight the presence of so-called "super-spreaders", with the propensity to infect a larger-than-average number of people, in countries, such as the USA, for which additional mitigation efforts targeting events surrounding this type of spread are urgently needed to curb further dissemination of SARS-CoV-2.
Subject(s)
COVID-19ABSTRACT
The ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) first described from Wuhan, China. A subset of COVID-19 patients has been reported to have acquired secondary infections by microbial pathogens, such as fungal opportunistic pathogens from the genus Aspergillus. To gain insight into COVID-19 associated pulmonary aspergillosis (CAPA), we analyzed the genomes and characterized the phenotypic profiles of four CAPA isolates of Aspergillus fumigatus obtained from patients treated in the area of North Rhine-Westphalia, Germany. By examining the mutational spectrum of single nucleotide polymorphisms, insertion-deletion polymorphisms, and copy number variants among 206 genes known to modulate A. fumigatus virulence, we found that CAPA isolate genomes do not exhibit major differences from the genome of the Af293 reference strain. By examining virulence in an invertebrate moth model, growth in the presence of osmotic, cell wall, and oxidative stressors, and the minimum inhibitory concentration of antifungal drugs, we found that CAPA isolates were generally, but not always, similar to A. fumigatus reference strains Af293 and CEA17. Notably, CAPA isolate D had more putative loss of function mutations in genes known to increase virulence when deleted (e.g., in the FLEA gene, which encodes a lectin recognized by macrophages). Moreover, CAPA isolate D was significantly more virulent than the other three CAPA isolates and the A. fumigatus reference strains tested. These findings expand our understanding of the genomic and phenotypic characteristics of isolates that cause CAPA.
Subject(s)
COVID-19ABSTRACT
Coronavirus disease 2019 (COVID-19) displays high clinical variability but the parameters that determine disease severity are still unclear. Pre-existing T cell memory has been hypothesized as a protective mechanism but conclusive evidence is lacking. Here we demonstrate that all unexposed individuals harbor SARS-CoV-2-specific memory T cells with marginal cross-reactivity to common cold corona and other unrelated viruses. They display low functional avidity and broad protein target specificities and their frequencies correlate with the overall size of the CD4+ memory compartment reflecting the immunological age of an individual. COVID-19 patients have strongly increased SARS-CoV-2-specific inflammatory T cell responses that are correlated with severity. Strikingly however, patients with severe COVID-19 displayed lower TCR functional avidity and less clonal expansion. Our data suggest that a low avidity pre-existing T cell memory negatively impacts on the T cell response quality against neoantigens such as SARS-CoV-2, which may predispose to develop inappropriate immune reactions especially in the elderly. We propose the immunological age as an independent risk factor to develop severe COVID-19.