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Abstract Background Patients with end stage renal disease (ESRD) undergoing hemodialysis are at increased risk for infection and impaired vaccination responses. We analyzed overlap and influencing factors of vaccination responses against severe acute respiratory syndrome corona virus disease 2 (SARS-CoV-2) and Hepatitis B virus (HBV). Methods SARS-CoV-2 and HBV vaccination response was assessed in a cohort of German ESRD hemodialysis patients. Anti-HBs- and SARS-CoV-2 anti-S-IgG were analyzed by ELISA. Demographic and clinical data were extracted from clinical files. Results Sixty-four patients with complete information on HBV and SARS-CoV-2 vaccination responses were included. More than one-third (35.4%) of non-responders upon HBV vaccination were identified. Unresponsiveness after HBV and poor response after SARS-CoV-2 vaccination showed strong overlap, and overall, 70.3% of patients were classified into concordant HBV/SARS vaccination response groups. HBV vaccination non-responsiveness, but not poor SARS-CoV-2 post-vaccination immunity was associated with obesity, while poor SARS-CoV-2 vaccination responses were associated increased age. Conclusion Our findings confirm previous reports on impaired vaccination response in hemodialysis patients and show that post-vaccination humoral responses against SARS-CoV-2 and HBV display strong overlap in this vulnerable patient group. These results may help to adapt vaccination strategies in this highly vulnerable population. Trial registration: German Clinical Trial Registry, DRKS00021152.

Abstract The recently detected Omicron BA.2.86 lineage contains more than 30 amino acid mutations relative to BA.2. BA.2.86 and its JN.1 derivative evade neutralization by serum antibodies of fully vaccinated individuals. In this study, we elucidate epitopes driving the immune escape of BA.2.86 and JN.1 via pseudovirus neutralization. Here we generate 33 BA.2.86 mutants, each reverting a single mutation back to BA.2. We use this library in an approach that we call reverse mutational scanning to define distinct neutralization titers against each epitope. Mutations within the receptor binding domain at K356T, V483Δ, and to a lesser extent N460K, A484K, and F486P enhance immune escape. Interestingly, 16insMPLF within the spike N-terminal domain and P621S within S1/S2 also significantly contribute to antibody escape of BA.2.86. Upon XBB.1.5 booster vaccination, neutralization titers against JN.1 and BA.2.86 improve considerably, and residual immune escape is driven by 16insMPLF, N460K, E554K, and to a lesser extent P621S, and A484K.

Background: Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022. Methods: Using different media, we recruited Ukrainian refugees at 13 sites between 9–12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration. Results: Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children.Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B. Conclusions: We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts.

Summary: In July/August 2023, the highly mutated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2.86 lineage emerged and its descendant JN.1 is on track to become the dominant SARS-CoV-2 lineage globally. Compared to the spike (S) protein of the parental BA.2.86 lineage, the JN.1 S protein contains one mutation, L455S, which may affect receptor binding and antibody evasion. Here, we performed a virological assessment of the JN.1 lineage employing pseudovirus particles bearing diverse SARS-CoV-2 S proteins. Using this strategy, it was found that S protein mutation L455S confers increased neutralization resistance but reduces ACE2 binding capacity and S protein-driven cell entry efficiency. Altogether, these data suggest that the benefit of increased antibody evasion outweighs the reduced ACE2 binding capacity and further enabled the JN.1 lineage to effectively spread in the human population.

New SARS-CoV-2 lineages continue to evolve and may exhibit new characteristics regarding host cell entry efficiency and potential for antibody evasion. Here, employing pseudotyped particles, we compared the host cell entry efficiency, ACE2 receptor usage, and sensitivity to antibody-mediated neutralization of four emerging SARS-CoV-2 lineages, KP.2, KP.2.3, KP.3, and LB.1. The XBB.1.5 and JN.1 lineages served as controls. Our findings reveal that KP.2, KP.2.3, KP.3, and LB.1 lineages enter host cells efficiently and in an ACE2-dependent manner, and that KP.3 is more adept at entering Calu-3 lung cells than JN.1. However, the variants differed in their capacity to employ ACE2 orthologues from animal species for entry, suggesting differences in ACE2 interactions. Moreover, we demonstrate that only two out of seven therapeutic monoclonal antibody (mAbs) in preclinical development retain robust neutralizing activity against the emerging JN.1 sublineages tested, while three mAbs displayed strongly reduced neutralizing activity and two mAbs lacked neutralizing activity against any of the lineages tested. Furthermore, our results show that KP.2, KP.2.3, KP.3, and LB.1 lineages evade neutralization by antibodies induced by infection or vaccination with greater efficiency than JN.1, particularly in individuals without hybrid immunity. This study indicates that KP.2, KP.2.3, KP.3, and LB.1 differ in ACE2 interactions and the efficiency of lung cell entry and suggest that evasion of neutralizing antibodies drove the emergence of these variants.

Abstract Background Many people experience long-term symptoms such as fatigue, cognitive problems, or shortness of breath after an acute infection with COVID-19. This emerging syndrome, known as long COVID, is new and complex in many aspects. This study aims to collect the experiences of people with long COVID with ambulatory healthcare structures. Methods Four focus groups were conducted with a total of 23 adults with long COVID in June and July 2022. These discussions were audio-recorded, subsequently transcribed, and analyzed using the qualitative content analysis of Mayring and Kuckartz. Results Fourteen out of 19 participants who had a primary care encounter regarding their long COVID symptoms did not perceive it as helpful. Many respondents reported that their general practitioners did not take their long COVID symptoms seriously and did not refer them to specialists or made therapeutic recommendations. However, some participants reported that they were prescribed non-pharmaceutical therapies (e.g., group meetings supported by psychotherapists, occupational therapy, etc.) that improved their condition. 14 of 23 respondents perceived care barriers such as providers’ lack of awareness of long COVID, poor access to specialists, a lack of specialized care (e.g., long COVID clinics), or high bureaucratic hurdles for specific healthcare services. To improve medical care, participants suggested campaigns to raise awareness of long COVID among healthcare providers and the general population, increase research and government investments regarding the development of treatment structures for long COVID, expanding existing therapeutic services, and establishing one-stop shops for integrated specialist healthcare for people with long COVID. Conclusions Several implications for healthcare professionals and policymakers can be derived from this study: (1) general practitioners should take the symptoms of long COVID seriously, assume a care coordinating role, make referrals, and establish contact with long COVID clinics; (2) care planners should focus on developing interprofessional evidence-based care and treatment approaches for long COVID; (3) existing care structures such as long COVID outpatient clinics should be expanded. The overarching goal must be to develop consistent guidelines for long COVID diagnosis, care, and treatment. Trial registration The study is registered in the German register for clinical trials (DRKS00026007, first registration on 09/09/2021).

BackgroundPost–COVID-19 syndrome (PCS; also known as “long COVID”) is a relatively novel disease comprising physical, psychological, and cognitive complaints persisting several weeks to months after acute infection with SARS-CoV-2. Approximately 10% of patients with COVID-19 are affected by long-term symptoms. However, effective treatment strategies are lacking. The ErgoLoCo (Occupational Therapy [Ergotherapie] for Long COVID) study was designed to develop and evaluate a novel occupational therapy (OT) concept of online delivery of therapy for long COVID. ObjectiveThe primary study objective is to assess the feasibility of the online OT intervention in PCS. Secondary aims include the evaluation of online OT concerning cognitive problems, occupational performance, and social participation. MethodsThis randomized controlled interventional pilot study involves parallel mixed methods process analyses and a realist evaluation approach. A total of 80 clients with PCS aged at least 16 years will be recruited into two interventional groups. The control cohort (watch and wait) comprises 80 clients with long COVID. Treatment is provided through teletherapy (n=40) or delivery of prerecorded videos (n=40) using the same standardized OT concept twice weekly over 12 weeks. Analyses of quantitative questionnaires and qualitative interviews based on the theoretical framework of acceptability will be performed to assess feasibility. Focus group meetings will be used to assess how acceptable and helpful the intervention was to the participating occupational therapists. Standardized tests will be used to assess the initial efficacy of the intervention on neurocognitive performance; limitations in mobility, self-care, and everyday activities; pain; disabilities; quality of life (QoL); social participation; and anxiety and depression in PCS, and the possible effects of online OT on these complaints. ResultsThe German Ministry of Education and Research provided funding for this research in March 2022. Data collection took place from October 2022 to August 31, 2023. Data analysis will be completed by the end of April 2024. We anticipate publishing the results in the fall of 2024. ConclusionsDespite the enormous clinical need, effective and scalable treatment options for OT clients who have PCS remain scarce. The ErgoLoCo study will assess whether online-delivered OT is a feasible treatment approach in PCS. Furthermore, this study will assess the effect of the intervention on cognitive symptoms, QoL, and occupational performance and participation in everyday life. Particular emphasis will be placed on the experiences of clients and occupational therapists with digitally delivered OT. This study will pave the way for novel and effective treatment strategies in PCS. Trial RegistrationGerman Clinical Trial Registry DRKS00029990; https://drks.de/search/de/trial/DRKS00029990 International Registered Report Identifier (IRRID)PRR1-10.2196/50230

Objectives: This study aims to investigate the impact of gender and parental tasks on social participation, health-related quality of life (hrQoL), and mental health in persons with long COVID. Methods: A mixed-methods approach was followed including a cross-sectional web-based survey and semi-structured interviews. Multivariable linear regressions were used to quantify the effect of gender and parenting tasks on social participation, hrQoL, and mental health. Qualitative data from interviews with participants experiencing long COVID symptoms was analyzed using content analysis. Results: Data from 920 participants in the quantitative study and 25 participants in the qualitative study was analyzed. Parenting tasks were associated with increased impairments in family and domestic responsibilities in persons with long COVID compared to lower impairments in persons without long COVID ( P = .02). The qualitative data indicate that coping with long COVID and pursuing parenting tasks limit participants’ ability to perform leisure activities and attend social gatherings. In long COVID, men had higher anxiety symptoms than women, and in those without long COVID, the opposite was observed ( P

ABSTRACTObjective The COVID-19 pandemic has affected how people go about their daily lives, often in various and substantial ways. This study aims to prospectively evaluate the changes in social participation during the COVID-19 pandemic in persons with a high risk for a severe COVID-19 course in Germany.Methods A paper-pencil-based survey was conducted starting at March 2021. Participants filled out questionnaires at four time points based on their COVID-19 vaccination status: before COVID-19 vaccination, one month, six months and twelve months after COVID-19 vaccination. Social participation measures included the Pandemic Social Participation Questionnaire (PSP-Q) and the Index for measuring participation restrictions (IMET). Repeated measures ANOVA and paired t-test were used to test for changes between time-points. Repeated measures correlation was used to assess the relationship between social participation and local COVID-19 incidences.Results Data from 245 participants was analyzed before and one month after COVID-19 vaccination. In addition, data from 156 participants was analyzed at time points one, six and twelve months after COVID-19. PSP-Q and IMET scores changed significantly after participants received a COVID-19 vaccination. Between one month and twelve months after vaccination, social participation improved significantly measured by PSP-Q. Social participation was negatively correlated with regional COVID-19 incidences before and after COVID-19 vaccination. Social participation was positively correlated with COVID-19 incidences between one month and twelve months after COVID-19 vaccination.Conclusions Social participation improved in persons with a high risk for a severe COVID-19 course during the pandemic. The local COVID-19 incidence showed a negative association with social participation only until the fall of 2021 when it was used as the sole metric to regulate COVID-19 protective measures. Although our data describes the trends in social participation, further studies are needed to identify the influencing factors for the observed increase in social participation.

Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.1 are unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for efficient spread in the population.

IntroductionMigrant healthcare workers played an important role during the COVID-19 pandemic, but data are lacking especially for high-resourced European healthcare systems. This study aims to research migrant healthcare workers through an intersectional health system-related approach, using Germany as a case study.MethodsAn intersectional research framework was created and a rapid scoping study performed. Secondary analysis of selected items taken from two COVID-19 surveys was undertaken to compare perceptions of national and foreign-born healthcare workers, using descriptive statistics.ResultsAvailable research is focused on worst-case pandemic scenarios of Brazil and the United Kingdom, highlighting racialised discrimination and higher risks of migrant healthcare workers. The German data did not reveal significant differences between national-born and foreign-born healthcare workers for items related to health status including SARS-CoV-2 infection and vaccination, and perception of infection risk, protective workplace measures, and government measures, but items related to social participation and work conditions with higher infection risk indicate a higher burden of migrant healthcare workers.ConclusionsCOVID-19 pandemic policy must include migrant healthcare workers, but simply adding the migration status is not enough. We introduce an intersectional health systems-related approach to understand how pandemic policies create social inequalities and how the protection of migrant healthcare workers may be improved.

Vaccines against SARS-CoV-2 have changed the course of the COVID-19 pandemics, but waning immunity necessitates repeated immunization. Authors here show that immunity declines faster following two doses of vector-based vaccine compared to a first dose of vector-based vaccine followed by boosting with an mRNA vaccine, but application of an mRNA vaccine as a third dose minimises the difference between the two groups.

Persistence of vaccination-induced cellular and humoral immune responses is crucial to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or at least provide protection against severe coronavirus disease (COVID-19) [...]

Abstract Background Immunocompromised people (ICP) and elderly individuals (older than 80 years) are at increased risk for severe coronavirus infections. To protect against serious infection with SARS-CoV-2, ICP are taking precautions that may include a reduction of social contacts and participation in activities which they normally enjoy. Furthermore, for these people, there is an uncertainty regarding the effectiveness of the vaccination. The COVID-19 Contact (CoCo) Immune study strives to characterize the immune response to COVID-19 vaccination in immunocompromised, elderly people, and patients with hematological or oncological diseases. The study uses blood-based screenings to monitor the humoral and cellular immune response in these groups after vaccination. Questionnaires and qualitative interviews are used to describe the level of social participation. Methods The CoCo Immune Study is a mixed methods prospective, longitudinal, observational study at two large university hospitals in Northern Germany. Starting in March 2021, it monitors anti-SARS-CoV-2 immune responses and collects information on social participation in more than 600 participants, at least 18 years old. Inclusion criteria and subcohorts: Participants with (1) regularly intake of immunosuppressive medication (ICP-cohort) or (2) age ≥ 80 years (80 + -cohort). Additionally, patients with current or former (3) myeloid, (4) lymphatic disease or (5) solid tumor under checkpoint inhibition (3–5: HO-cohort). Exclusion criteria: (1) refusal to give informed consent, (2) contraindication to blood testing, (3) inability to declare consent. Participants complete a questionnaire at four different time points: prior to full vaccination, and 1, 6 and 12 months after completed vaccination. In addition, participants draw blood samples themselves or through a local health care provider and send them with their questionnaires per post at the respective time points after vaccination. Patients of the HO cohort dispense additional blood samples at week 3 to 12 and at month 6 to 9 after 2nd vaccination to gain additional knowledge in B and T cell responses. Selected participants are invited to qualitative interviews about social participation. Discussion This observational study is designed to gain insight into the immune response of people with weakened immune systems and to find out how social participation is affected after COVID-19 vaccination. Trial registration: This study was registered with German Clinical Trial Registry (registration number: DRKS00023972) on 30th December 2020.

IntroductionViolence against healthcare workers is a global health problem threatening healthcare workforce retention and health system resilience in a fragile post-COVID ‘normalisation’ period. In this perspective article, we argue that violence against healthcare workers must be made a greater priority. Our novel contribution to the debate is a comparative health system and policy approach.MethodsWe have chosen a most different systems comparative approach concerning the epidemiological, political, and geographic contexts. Brazil (under the Bolsonaro government) and the United Kingdom (under the Johnson government) serve as examples of countries that were strongly hit by the pandemic in epidemiological terms while also displaying policy failures. New Zealand and Germany represent the opposite. A rapid assessment was undertaken based on secondary sources and country expertise.ResultsWe found similar problems across countries. A global crisis makes healthcare workers vulnerable to violence. Furthermore, insufficient data and monitoring hamper effective prevention, and lack of attention may threaten women, the nursing profession, and migrant/minority groups the most. There were also relevant differences. No clear health system pattern can be identified. At the same time, professional associations and partly the media are strong policy actors against violence.ConclusionIn all countries, muchmore involvement from political leadership is needed. In addition, attention to the political dimension and all forms of violence are essential.

Background/aims The COVID-19 pandemic situation poses new challenges for research. Ethical issues might arise if especially vulnerable individuals for severe COVID-19 course expose themselves because of participation in studies to a higher risk of infection for study purposes. How is the feasibility and acceptance of self-organized blood sample collections to measure anti-SARS-CoV-2 Spike IgG antibodies in persons with a high risk for a severe COVID-19 disease progression? Methods Persons with a high risk for a severe COVID-19 disease progression (immunocompromised, oncology patients or over 80 years old) were recruited between January and September 2021 to send in blood samples (at least 500 μl) 1 month and 6 months after second COVID-19 vaccination. Participants were given the choice of drawing capillary or venous blood themselves or having blood drawn by health professionals belonging to either the study’s own research team or the personnel found in local practices or clinics. Participants were surveyed via a telephone interview in December 2021 and January 2022 about their choice of blood sampling methods and influence of blood collection choice upon study participation. Results Data from 360 participants was collected via telephone follow-up. First blood samples were collected by the participants themselves (35.8%), local practices or clinics (31.9%) and the research team (22.5%). Second blood samples were mostly collected in local practices or clinics (35.6%) followed by participants themselves (25.9%) and the research team (11.5%). Blood samples were not collected in 2.5% and 19.1% of persons during first and second blood draw, respectively. Only 2% of blood samples did not reach the laboratory or were not analyzable. About one-fourth (26%) of participants stated that they would not have participated in the study if it would have been required to travel to the university hospital to give their blood sample. Conclusions Participants were able to self-organize blood collection, making use of several different blood sample methods. Nearly all blood samples were analyzable when self-collected and sent in by post. One-fourth of the participants would not have participated in the study if required to give their blood sample in the study location. Trial registration German Clinical Trial Registry, DRKS00021152.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic impacted how people perform their daily lives in manifold and sometimes massive ways. Particularly, individuals who are at high risk for a severe disease progression, like immunocompromised people, may have experienced drastic changes in social participation during the pandemic. A COVID-19 basic vaccination may have changed the safety behavior of immunocompromised individuals in terms of infection risk and thereby influence social participation and mental wellbeing.MethodsThis study aims to investigate self-perceived social participation at baseline before and at follow-up 1 and 6 months after basic vaccination. Beginning in March 2021, 274 immunocompromised persons 18 years or older were enrolled in the COVID-19 Contact Immune study (CoCo study) in Lower Saxony, Germany. Measurements were performed at three time points regarding social participation [Index for the Assessment of Health Impairments (IMET)], mental health [Patient Health Questionnaire-4 (PHQ-4)], subjective health status (five-point Likert-scale) and quality of life (five-point Likert-scale).ResultsIn total, 126 participants were included in the final analysis. About 60% of the participants showed increasing social participation over time. The greatest increase in social participation was observed within the first month after basic vaccination (p < 0.001). During the following 5 months, social participation remained stable. The domains “social activities,” “recreation and leisure” and “close personal relationships” were responsible for the overall change in social participation. No association was found between social participation and mental health, sociodemographic or medical factors (except hypertension).DiscussionIt is unclear why social participation increased after basic vaccination. Perceived vaccine efficacy and a feeling of being protected by the vaccine may have caused relaxed social distancing behaviors. Reducing safety behaviors may, however, increase the risk of a COVID-19 infection for immunocompromised individuals. Further investigations are needed to explore the health-related consequences of more social participation among immunocompromised persons.

Author(s): Joana Barros-Martins [sup.1] , Swantje I. Hammerschmidt [sup.1] , Anne Cossmann [sup.2] , Ivan Odak [sup.1] , Metodi V. Stankov [sup.2] , Gema Morillas Ramos [sup.2] , Alexandra Dopfer-Jablonka [...], Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca&apos;s ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of already ChAd-primed individuals with the decision to receive either a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School&apos;s COVID-19 Contact Study cohort of healthcare professionals to monitor ChAd-primed immune responses before and 3 weeks after booster with ChAd (n = 32) or BioNTech/Pfizer&apos;s BNT162b2 (n = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4.sup.+ and CD8.sup.+ T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants of concern of severe acute respiratory syndrome coronavirus 2. In a study of healthcare professionals previously vaccinated with ChAdOx-1 nCoV-19, booster vaccination with BNT162b2 elicited more neutralizing antibodies with greater breadth, as well as higher frequencies of virus-specific T cells, than ChAdOx-1 nCoV-19.

Haemodialysis patients respond poorly to vaccination and continue to be at-risk for severe COVID-19. Therefore, dialysis patients were among the first for which a fourth COVID-19 vaccination was recommended. However, targeted information on how to best maintain immune protection after SARS-CoV-2 vaccinations in at-risk groups for severe COVID-19 remains limited. We provide, to the best of our knowledge, for the first time longitudinal vaccination response data in dialysis patients and controls after a triple BNT162b2 vaccination and in the latter after a subsequent fourth full-dose of mRNA-1273. We analysed systemic and mucosal humoral IgG responses against the receptor-binding domain (RBD) and ACE2-binding inhibition towards variants of concern including Omicron and Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell responses by interferon γ release assay. After triple BNT162b2 vaccination, anti-RBD B.1 IgG and ACE2 binding inhibition reached peak levels in dialysis patients, but remained inferior compared to controls. Whilst we detected B.1-specific ACE2 binding inhibition in 84% of dialysis patients after three BNT162b2 doses, binding inhibition towards the Omicron variant was only detectable in 38% of samples and declining to 16% before the fourth vaccination. By using mRNA-1273 as fourth dose, humoral immunity against all SARS-CoV-2 variants tested was strongly augmented with 80% of dialysis patients having Omicron-specific ACE2 binding inhibition. Modest declines in T-cell responses in dialysis patients and controls after the second vaccination were restored by the third BNT162b2 dose and significantly increased by the fourth vaccination. Our data support current advice for a four-dose COVID-19 immunisation scheme for at-risk individuals such as haemodialysis patients. We conclude that administration of a fourth full-dose of mRNA-1273 as part of a mixed mRNA vaccination scheme to boost immunity and to prevent severe COVID-19 could also be beneficial in other immune impaired individuals. Additionally, strategic application of such mixed vaccine regimens may be an immediate response against SARS-CoV-2 variants with increased immune evasion potential.

BackgroundWith population-wide vaccination availability, the global COVID-19 pandemic entered a new phase. Despite vaccination status, some people who were infected with SARS-CoV-2 experience long-term symptoms. ObjectiveIn this study, we aim to characterize the long-term effects of SARS-CoV-2 infection and the pandemic. We also aim to build symptom clusters and determine risk factors for developing long COVID symptoms. Furthermore, we assess social participation and health-related quality of life in patients with long COVID and in the general population during a global pandemic. MethodsWith a mixed-methods, web-based approach, we aim to recruit 2000 people in Germany who are older than 18 years and can provide informed consent. In the quantitative arm of the study, we identify symptoms of and predictive factors for long COVID manifestations with cluster analysis and assess social participation during the pandemic with standardized questionnaires. The qualitative arm of the study uses individual interviews and focus group discussions to better understand the illness experience of persons who experience long COVID. ResultsRecruitment started in September 2021. Up until July 2022, we recruited approximately 4500 participants via our web-based database. ConclusionsThis study aims to build an innovative, patient-centered, web-based research platform appropriate for the pandemic by minimizing physical contact between study personnel and participants. All study activities are designed to better understand the long COVID syndrome, social participation during the pandemic, and the illness experiences of persons affected by long COVID. Trial RegistrationGerman Clinical Trial Registry DRKS00026007; https://tinyurl.com/yh282fkt International Registered Report Identifier (IRRID)DERR1-10.2196/38718

New SARS-CoV-2 lineages continue to evolve and may exhibit new characteristics regarding host cell entry efficiency and potential for antibody evasion. Here, employing pseudotyped particles, we compared the host cell entry efficiency, ACE2 receptor usage, and sensitivity to antibody-mediated neutralization of four emerging SARS-CoV-2 lineages, KP.2, KP.2.3, KP.3, and LB.1. The XBB.1.5 and JN.1 lineages served as controls. Our findings reveal that KP.2, KP.2.3, KP.3, and LB.1 lineages enter host cells efficiently and in an ACE2-dependent manner, and that KP.3 is more adept at entering Calu-3 lung cells than JN.1. However, the variants differed in their capacity to employ ACE2 orthologues from animal species for entry, suggesting differences in ACE2 interactions. Moreover, we demonstrate that only two out of seven therapeutic monoclonal antibody (mAbs) in preclinical development retain robust neutralizing activity against the emerging JN.1 sublineages tested, while three mAbs displayed strongly reduced neutralizing activity and two mAbs lacked neutralizing activity against any of the lineages tested. Furthermore, our results show that KP.2, KP.2.3, KP.3, and LB.1 lineages evade neutralization by antibodies induced by infection or vaccination with greater efficiency than JN.1, particularly in individuals without hybrid immunity. This study indicates that KP.2, KP.2.3, KP.3, and LB.1 differ in ACE2 interactions and the efficiency of lung cell entry and suggest that evasion of neutralizing antibodies drove the emergence of these variants. [ABSTRACT FROM AUTHOR]

Immunocompromised persons are at an increased risk for a severe SARS-CoV-2 infection and their safety behaviors may influence their social participation. Vaccinated persons have a lower incidence of infection and severe disease when infected compared to non-vaccinated persons. Therefore, their behavior may change and their social participation may increase after a complete vaccination. The aim of this study was to explore social participation of immunocompromised persons before and after complete COVID-19 vaccination. Between March and September 2021, 274 immunocompromised participants were recruited. Survey data were collected at baseline and follow-up from 194 participants including the Index for the Assessment of Health Impairments [IMET], Patient Health Questionnaire-4 [PHQ-4], subjective health status and quality of life. At baseline, participants were not yet completely vaccinated. Complete vaccination was achieved prior to the follow-up questionnaire. IMET scores decreased significantly at follow-up, indicating a higher social participation after complete vaccination. PHQ-4, subjective health status and quality of life did not differ between baseline and follow-up. There were no significant differences across sociodemographic factors. Significant PHQ-4 differences were observed regarding the population size of the participants' home community. Social participation of immunocompromised persons in our study increased after COVID-19 vaccination. Therefore, social participation should be explored further, especially with regards to the impact of vaccination on groups with a high health risk.

IntroductionThis study analyses how healthcare workers (HCWs) perceived risks, protection and preventive measures during the COVID-19 pandemic in relation to medically approved risks and organizational measures. The aim is to explore “blind spots” of pandemic protection and make mental health needs of HCWs visible.MethodsWe have chosen an “optimal-case” scenario of a high-income country with a well-resourced hospital sector and low HCW infection rate at the organizational level to explore governance gaps in HCW protection. A German multi-method hospital study at Hannover Medical School served as empirical case; document analysis, expert information and survey data (n = 1,163) were collected as part of a clinical study into SARS-CoV-2 serology testing during the second wave of the pandemic (November 2020-February 2021). Selected survey items included perceptions of risks, protection and preventive measures. Descriptive statistical analysis and regression were undertaken for gender, profession and COVID-19 patient care.ResultsThe results reveal a low risk of 1% medically approved infections among participants, but a much higher mean personal risk estimate of 15%. The majority (68.4%) expressed “some” to “very strong” fear of acquiring infection at the workplace. Individual protective behavior and compliance with protective workplace measures were estimated as very high. Yet only about half of the respondents felt strongly protected by the employer; 12% even perceived “no” or “little” protection. Gender and contact with COVID-19 patients had no significant effect on the estimations of infection risks and protective workplace behavior, but nursing was correlated with higher levels of personal risk estimations and fear of infection.ConclusionsA strong mismatch between low medically approved risk and personal risk perceptions of HCWs brings stressors and threats into view, that may be preventable through better information, training/education and risk communication and through investment in mental health and inclusion in pandemic preparedness plans.

Tinnitus, vertigo and dizziness are symptoms commonly reported among Long and Post COVID patients, however the severity of these symptoms has not been assessed in large trials. Therefore, in this study a large cohort of Long COVID patients was surveyed about the presence and severity of tinnitus and vertigo or dizziness symptoms. The online survey was completed by a German cohort of 1,082 adult Long COVID patients after a mean period of 43.2 weeks ± 23.4 weeks after infection. Eighty percent were not fully vaccinated (at least two vaccinations) at the time of their first COVID symptoms and 9.8% were hospitalized in the course of their acute SARS-CoV-2 infection. At the time of the survey, 60% of patients reported the presence of vertigo or dizziness with a mean severity of 4.6 ± 2.7 on a scale of 1 (least severe) to 10 (most severe) and 30% complained of tinnitus with a mean severity of 4.8 ± 3.0. Approximately one fifth of the participants with tinnitus and vertigo or dizziness, rated their symptoms to be severe. The data shown in this study confirms that tinnitus and vertigo or dizziness are common symptoms in Long COVID patients and demonstrates, that a compelling number of patients rate their symptoms as severe. The self-reported severity highlights the need for Long COVID clinics to address these symptoms effectively. We suggest a multidisciplinary diagnostic and therapeutic approach to prevent further morbidity and socioeconomic burden for Long COVID patients suffering from severe vertigo, dizziness or tinnitus.