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Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2–3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigen-naive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus.

Background: Immunogenicity of SARS-CoV-2 vaccines is modestly impaired in cancer patients due to a generally weakened immune system. Immune checkpoint inhibitors (ICI) are expected to enhance immune response. This has already been described to be the case in influenza vaccines, and first data about COVID-19 vaccines show a trend in this direction. Aim: We aimed to investigate the immune response of patients with melanoma under ICI therapy after COVID-19 vaccination. Patients and Methods: In the Skin Cancer Center Hanover (Germany), we recruited 60 patients with advanced melanoma who either received ICI therapy during or before the vaccination period. Serological blood analysis was performed using quantitative ELISA for Anti-SARS-CoV-2 spike protein 1 IgG antibodies. Results: We did not observe an enhanced humoral immune response in patients under active or past ICI therapy after COVID-19 vaccination. Nevertheless, there is a tendency of higher antibody levels when ICI therapy was received within the last 6 months before vaccination. Subgroup analysis revealed that patients in our study population under ongoing targeted therapy during vaccination period had significantly higher median antibody levels than patients without any active antitumor treatment. Conclusion: Melanoma patients under ICI therapy show comparable antibody response after SARS-CoV-2 vaccination to healthy health care professionals. This finding is independent of the timing of ICI therapy.

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.

Objectives People living with HIV (PLWH) with low CD4 T‐cell counts may be at a higher risk for severe coronavirus disease 2019 (COVID‐19) outcomes and in need of efficient vaccination. The World Health Organization (WHO) now recommends prioritizing PLHIV for COVID‐19 vaccination. Data on immune responses after messenger RNA (mRNA) vaccination in PLHIV in relation to CD4 counts are scarce. We aimed at assessing the humoral immune response in PLHIV after mRNA vaccination against COVID‐19. Methods We examined a cohort of PLHIV after prime (n = 88) and boost (n = 52) vaccination with BNT162b2. We assessed levels of anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike (S) protein‐specific immunoglobulin G (IgG)/IgA and circulating neutralizing antibodies in plasma and correlated results to the cellular immune status. BNT162b2‐vaccinated health care workers served as controls. Results All PLWH had a viral load of ≤ 200 HIV‐1 RNA copies/mL and 96.5% had a viral load of

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitates viral entry into host cells and is the key target for neutralizing antibodies. The SARS-CoV-2 lineage B.1.620 carries fifteen mutations in the S protein and is spread in Africa, the US and Europe, while lineage R.1 harbors four mutations in S and infections were observed in several countries, particularly Japan and the US. However, the impact of the mutations in B.1.620 and R.1 S proteins on antibody-mediated neutralization and host cell entry are largely unknown. Here, we report that these mutations are compatible with robust ACE2 binding and entry into cell lines, and they markedly reduce neutralization by vaccine-induced antibodies. Our results reveal evasion of neutralizing antibodies by B.1.620 and R.1, which might have contributed to the spread of these lineages.

BackgroundHaemodialysis patients are at-risk for severe COVID-19 and were among the first to receive a fourth COVID-19 vaccination.MethodsWe analysed humoral responses by multiplex-based IgG measurements against the receptor-binding domain (RBD) and ACE2-binding inhibition towards variants of concern including Omicron in haemodialysis patients and controls after triple BNT162b2 vaccination and in dialysis patients after a fourth full-dose of mRNA-1273. T-cell responses were assessed by interferon γ release assay.FindingsAfter 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 38% 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.ConclusionsA fourth full-dose mRNA-1273 after triple BNT162b2 vaccination in haemodialysis patients leads to efficient humoral responses against Omicron. Our data support current national recommendation and suggest that other immune-impaired individuals may benefit from this mixed mRNA vaccination regimen.FundingInitiative and Networking Fund of the Helmholtz Association of German Research Centres, EU Horizon 2020 research and innovation program, State Ministry of Baden-Württemberg for Economic Affairs, Labour and Tourism, European Regional Development FundResearch in the contextEvidence before this studyInformation on how to best maintain immune protection after SARS-CoV-2 vaccination in at-risk individuals for severe COVID-19 such as haemodialysis patients is limited. We searched PubMed and medRxiv for keywords such as “haemodialysis”, “SARS-CoV-2”, “vaccine”, “decay”, “antibody kinetics”, “cellular immunity”, “longitudinal vaccination response”, “immunisation scheme”. To date, no peer-reviewed studies comprehensively assessed impact of both cellular and humoral immunogenicity after a triple BNT162b2 vaccination in combination with a fourth full-dose of mRNA-1273 and addressed the impact of currently dominating SARS-CoV-2 variants of concern on vaccine-induced immunity in this at-risk population.Added value of the studyWe provide to the best of our knowledge for the first time longitudinal vaccination response data over the course of the pandemic in dialysis patients. We studied not only systemic T- and B-cell but also mucosal responses in this at-risk group and determined levels of neutralizing antibodies towards Omicron BA.1 and Delta variants after a mixed mRNA vaccine schedule.Implications of all the available evidencePatients on haemodialysis show inferior response rates and thus a more rapid decline in humoral immune response after triple vaccination with BNT162b2. Our data strongly support the concept of administering a fourth full-dose of mRNA-1273 as part of a heterologous vaccination scheme to boost immunity and to prevent severe COVID-19 within this at-risk population. Strategic application of modified vaccine regimens may be an immediate response against SARS-CoV-2 variants with increased immune evasion potential.

Zusammenfassung Hintergrund In der ambulanten Versorgung wurde Telemedizin im Lockdown von März bis Mai 2020 eingesetzt. Ziel der Studie war es, Patienten aus einer Praxis und der Hochschulambulanz bezüglich Patientenzufriedenheit mit Telemedizin, COVID-19-Sorgen und Impfverhalten auszuwerten sowie die Gesprächsführung durch eine rheumatologische Fachassistenz (RFA) mit einem Arzt zu vergleichen. Methoden Patienten mit rheumatoider Arthritis, Psoriasisarthritis oder Spondyloarthritis ohne Therapieänderung seit der letzten Vorstellung wurde ein telemedizinischer Ersatztermin im Rahmen dieser Studie bei Terminabsage durch die versorgenden Zentren angeboten. Randomisiert wurden sie von einem Arzt oder einer RFA (RFA nur Universität) telemedizinisch versorgt. Die Anamnese erfolgte telefonisch standardisiert mittels Fragebogen. Die Krankheitsaktivität wurde mittels modifizierten Clinical Disease Activity Score (CDAI) und BASDAI festgestellt. Im Anschluss erhielten die Patienten einen pseudonymisierten Evaluationsbogen. Ergebnisse Von 112/116 (96 %) eingeschlossenen Patienten schickten 88/112 (79 %) den Fragebogen zurück. RFAs führten 19/112 (17 %) Telefonate. Die Therapie wurde in 19/112 (17 %) geändert. Die meisten Sorgen bezüglich COVID-19 hatten Patienten mit der höchsten Krankheitsaktivität (p = 0,031), den meisten schmerzhaften Gelenken (p = 0,001) sowie den meisten Schmerzen (VAS Score ≥7) (p = 0,009). Diese Patienten hätten auch selbst ihren Termin abgesagt (p = 0,015). Die Patientenzufriedenheit mit der Gesprächsführung war gut (Mittelwert 4,3/5,0 modifizierter FAPI), unabhängig von der Institution, der Gesprächsdauer oder dem Gesprächspartner. Patienten mit hoher Schmerzintensität waren am unzufriedensten (p = 0,036); 42/100 (38,2 %) Patienten waren gegen Pneumokokken und 59/100 (53,6 %) gegen Influenza geimpft. Zusammenfassung Für ausgewählte Patienten ist die telemedizinische Versorgung im Rahmen eines Telefongespräches gut geeignet. Hinsichtlich der Patientenzufriedenheit ist die Delegation einer telefonischen Visite an eine RFA möglich. Bezüglich des Impfverhaltens besteht Verbesserungsbedarf.

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.

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.

Background With 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. Objective In 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. Methods With 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. Results Recruitment started in September 2021. Up until July 2022, we recruited approximately 4500 participants via our web-based database. Conclusions This 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 Registration German Clinical Trial Registry DRKS00026007; https://tinyurl.com/yh282fkt International Registered Report Identifier (IRRID) DERR1-10.2196/38718

The Omicron variant of SARS-CoV-2 evades antibody-mediated neutralization with unprecedented efficiency. At least three Omicron sublineages have been identified-BA.1, BA.2, and BA.3-and BA.2 exhibits increased transmissibility. However, it is currently unknown whether BA.2 differs from the other sublineages regarding cell entry and antibody-mediated inhibition. Here, we show that BA.1, BA.2, and BA.3 enter and fuse target cells with similar efficiency and in an ACE2-dependent manner. However, BA.2 was not efficiently neutralized by seven of eight antibodies used for COVID-19 therapy, including Sotrovimab, which robustly neutralized BA.1. In contrast, BA.2 and BA.3 (but not BA.1) were appreciably neutralized by Cilgavimab, which could constitute a treatment option. Finally, all sublineages were comparably and efficiently neutralized by antibodies induced by BNT162b2 booster vaccination after previous two-dose homologous or heterologous vaccination. Collectively, the Omicron sublineages show comparable cell entry and neutralization by vaccine-induced antibodies but differ in susceptibility to therapeutic antibodies.

Evaluating long-term protection against SARS-CoV-2 variants of concern in convalescing individuals is of high clinical relevance. In this prospective study of a cohort of 46 SARS-CoV-2 patients infected with the Wuhan strain of SARS-CoV-2 we longitudinally analyzed changes in humoral and cellular immunity upon early and late convalescence. Antibody neutralization capacity was measured by surrogate virus neutralization test and cellular responses were investigated with 31-colour spectral flow cytometry. Spike-specific, isotype-switched B cells developed already during the disease phase, showed a memory phenotype and did not decrease in numbers even during late convalescence. Otherwise, no long-lasting perturbations of the immune compartment following COVID-19 clearance were observed. During convalescence anti-Spike (S1) IgG antibodies strongly decreased in all patients. We detected neutralizing antibodies against the Wuhan strain as well as the Alpha and Delta but not against the Beta, Gamma or Omicron variants for up to 7 months post COVID-19. Furthermore, correlation analysis revealed a strong association between sera anti-S1 IgG titers and their neutralization capacity against the Wuhan strain as well as Alpha and Delta. Overall, our data suggest that even 7 month after the clearance of COVID-19 many patients possess a protective layer of immunity, indicated by the persistence of Spike-specific memory B cells and by the presence of neutralizing antibodies against the Alpha and Delta variants. However, lack of neutralizing antibodies against the Beta, Gamma and Omicron variants even during the peak response is of major concern as this indicates viral evasion of the humoral immune response.

Background Serology testing is explored for epidemiological research and to inform individuals after suspected infection. During the coronavirus disease 2019 (COVID-19) pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist. Methods In a large German university hospital, we performed weekly questionnaire assessments and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements with various commercial tests, a novel surrogate virus neutralisation test, and a neutralisation assay using live SARS-CoV-2. Results From baseline to week 6, 1080 screening measurements for anti-SARS CoV-2 (S1) IgG from 217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12.4% in week 6, p

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.

Patients undergoing chronic hemodialysis were among the first to receive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations because of their increased risk for severe coronavirus disease and high case-fatality rates. By using a previously reported cohort from Germany of at-risk hemodialysis patients and healthy donors, where antibody responses were examined 3 weeks after the second vaccination, we assessed systemic cellular and humoral immune responses in serum and saliva 4 months after vaccination with the Pfizer-BioNTech BNT162b2 vaccine using an interferon-γ release assay and multiplex-based IgG measurements. We further compared neutralization capacity of vaccination-induced IgG against 4 SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) by angiotensin-converting enzyme 2 receptor-binding domain competition assay. Sixteen weeks after second vaccination, compared with 3 weeks after, cellular and humoral responses against the original SARS-CoV-2 isolate and variants of concern were substantially reduced. Some dialysis patients even had no detectable B- or T-cell responses.

Reports suggest that COVID-19 vaccine effectiveness is decreasing, either due to waning immune protection, emergence of new variants of concern, or both. Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) appeared to be superior in inducing protective immunity, and large scale second booster vaccination is ongoing. However, data comparing declining immunity after homologous and heterologous vaccination as well as effects of a third vaccine application after heterologous ChAd/BNT vaccination are lacking. We longitudinally monitored immunity in ChAd/ChAd (n=41) and ChAd/BNT (n=88) vaccinated individuals and assessed the impact of a second booster with BNT in both groups. The second booster greatly augmented waning anti-spike IgG but only moderately increased spike-specific CD4+ and CD8+ T cells in both groups to cell frequencies already present after the boost. More importantly, the second booster efficiently restored neutralizing antibody responses against Alpha, Beta, Gamma, and Delta, but neutralizing activity against B.1.1.529 (Omicron) stayed severely impaired. Our data suggest that inferior SARS-CoV-2 specific immune responses after homologous ChAd/ChAd vaccination can be cured by a heterologous BNT vaccination. However, prior heterologous ChAd/BNT vaccination provides no additional benefit for spike-specific T cell immunity or neutralizing Omicron after the second boost.

Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) has been reported to be superior in inducing protective immunity compared to repeated application of the same vaccine. However, data comparing immunity decline after homologous and heterologous vaccination as well as effects of a third vaccine application after heterologous ChAd/BNT vaccination are lacking. Here we show longitudinal monitoring of ChAd/ChAd (n = 41) and ChAd/BNT (n = 88) vaccinated individuals and the impact of a third vaccination with BNT. The third vaccination greatly augments waning anti-spike IgG but results in only moderate increase in spike-specific CD4 + and CD8 + T cell numbers in both groups, compared to cell frequencies already present after the second vaccination in the ChAd/BNT group. More importantly, the third vaccination efficiently restores neutralizing antibody responses against the Alpha, Beta, Gamma, and Delta variants of the virus, but neutralizing activity against the B.1.1.529 (Omicron) variant remains severely impaired. In summary, inferior SARS-CoV-2 specific immune responses following homologous ChAd/ChAd vaccination can be compensated by heterologous BNT vaccination, which might influence the choice of vaccine type for subsequent vaccination boosts.

Since its declaration as a pandemic in March 2020, SARS-CoV-2 has infected more than 217 million people worldwide and despite mild disease in the majority of the cases, more than 4.5 million cases of COVID-19-associated death have been reported as of September 2021. The question whether recovery from COVID-19 results in prevention of reinfection can be answered with a “no” since cases of reinfections have been reported. The more important question is whether during SARS-CoV-2 infection, a protective immunity is built and maintained afterwards in a way which protects from possibly severe courses of disease in case of a reinfection. A similar question arises with respect to vaccination: as of September 2021, globally, more than 5.2 billion doses of vaccines have been administered. Therefore, it is of utmost importance to study the cellular and humoral immunity toward SARS-CoV-2 in a longitudinal manner. In this study, reconvalescent COVID-19 patients have been followed up for more than 1 year after SARS-CoV-2 infection to characterize in detail the long-term humoral as well as cellular immunity. Both SARS-CoV-2-specific T cells and antibodies could be detected for a period of more than 1 year after infection, indicating that the immune protection established during initial infection is maintained and might possibly protect from severe disease in case of reinfection or infection with novel emerging variants. Moreover, these data demonstrate the opportunity for immunotherapy of hospitalized COVID-19 patients via adoptive transfer of functional antiviral T cells isolated from reconvalescent individuals.

Recently, a recombinant SARS-CoV-2 lineage, XD, emerged that harbors a spike gene that is largely derived from the Omicron variant BA.1 in the genetic background of the Delta variant. This finding raised concerns that the recombinant virus might exhibit altered biological properties as compared to the parental viruses and might pose an elevated threat to human health. Here, using pseudotyped particles, we show that ACE2 binding and cell tropism of XD mimics that of BA.1. Further, XD and BA.1 displayed comparable sensitivity to neutralization by antibodies induced upon vaccination with BNT162b2/Comirnaty (BNT) or BNT vaccination followed by breakthrough infection. Our findings reveal important biological commonalities between XD and Omicron BA.1 host cell entry and its inhibition by antibodies.

Patients undergoing chronic hemodialysis were among the first to receive SARS-CoV-2 vaccinations due to their increased risk for severe COVID-19 disease and high case fatality rates. To date, there have been minimal longitudinal studies in hemodialysis patients to ascertain whether protection offered by vaccination is long-lasting. To assess how surrogates for protection changed over time, we examined both the humoral and cellular response in a previously reported cohort of at-risk hemodialysis patients and healthy donors, four months after their second dose of Pfizer BNT162b2. Compared to three weeks post-second vaccination, both cellular and humoral responses against the original SARS-CoV-2 isolate as well as variants of concern were significantly reduced, with some dialyzed individuals having no B- or T-cell response. Our data strongly support the need for a third booster in hemodialysis patients and potentially other at-risk individuals.

Cerebral venous thrombosis was reported as a rare but serious adverse event in young and middle-aged vaccinees following immunization with AstraZeneca’s ChAdOx1-nCov-19 vaccine. As a consequence, several European governments recommended using this vaccine only in individuals older than 60 years leaving millions of ChAd primed individuals with the decision to either receive 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’s COVID-19 Contact (CoCo) Study cohort of health care professionals (HCP) to monitor ChAd primed immune responses before and three weeks after booster with ChAd or BioNTech/Pfizer’s BNT162b2. Whilst both vaccines boosted prime-induced immunity, BNT induced significantly higher frequencies of Spike-specific CD4 and CD8 T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and the P.1 variants of concern of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).

Cerebral venous thrombosis was reported as a rare but serious adverse event in young and middle-aged vaccinees following immunization with AstraZeneca’s ChAdOx1-nCov-19 vaccine. As a consequence, several European governments recommended using this vaccine only in individuals older than 60 years leaving millions of ChAd primed individuals with the decision to either receive 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’s COVID-19 Contact (CoCo) Study cohort of health care professionals (HCP) to monitor ChAd primed immune responses before and three weeks after booster with ChAd or BioNTech/Pfizer’s BNT162b2. Whilst both vaccines boosted prime-induced immunity, BNT induced significantly higher frequencies of Spike-specific CD4 and CD8 T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and the P.1 variants of concern of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).

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’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’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’s BNT162b2 (n = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4+ and CD8+ 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.

BackgroundPatients with chronic renal insufficiency on intermittent hemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only few studies addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population.MethodsWe assessed immunogenicity of the mRNA vaccine BNT162b2 in at risk dialysis patients and characterized systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants of concern B.1.1.7, B.1.351, B.1.429 and Cluster 5 by ACE2-RBD competition assay.FindingsPatients on intermittent hemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to controls. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished.InterpretationQuantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on intermittent dialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in face of emerging variants of concern may favor this at risk population for re-vaccination using modified vaccines at the earliest opportunity.FundingInitiative and Networking Fund of the Helmholtz Association of German Research Centers, EU Horizon 2020 research and innovation program, State Ministry of Baden-Württemberg for Economic Affairs, Labor and Tourism.Research in the contextEvidence before this studyPatients on dialysis tend to have a reduced immune response to both infection and vaccination. We searched PubMed and MedRxiv for studies including search terms such as “COVID-19”, “vaccine”, and “dialysis” but no peer-reviewed studies to date assessed both SARS-CoV-2 specific B- and T-cell responses, mucosal immunoglobulins, and considered the impact of SARS-CoV-2 variants of concern in this at risk population.Added value of the studyWe provide a comprehensive functional characterization of both T- and B-cell responses following a two-dose regimen of BNT162b2 in at risk patients on maintenance hemodialysis. More importantly, to the best of our knowledge, we assess for the first time binding and neutralization capacity of vaccination-induced circulation and mucosal antibodies towards emerging SARS-CoV-2 variants of concern in an immunocompromised population.Implications of all the available evidencePatients on maintenance hemodialysis develop a substantial cellular and humoral immune response following the BNT162b2 vaccine. These findings should encourage patients on intermittent hemodialysis to receive the vaccine. However, we suggest continuing additional protection measures against variants of concern in this at risk population until longevity of the vaccine response is fully evaluated.

Background Vaccine-induced neutralizing antibodies are key in combating the coronavirus disease 2019 (COVID-19) pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and prolonged or severe disease courses. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC)—B.1.1.7 (United Kingdom), B.1.351 (South Africa), and P.1 (Brazil)—may exacerbate this issue, as the latter two are able to evade control by antibodies. Methods We assessed humoral and T-cell responses against SARS-CoV-2 wild-type (WT), VOC, and endemic human coronaviruses (hCoVs) that were induced after single and double vaccination with BNT162b2. Results Despite readily detectable immunoglobulin G (IgG) against the receptor-binding domain of the SARS-CoV-2 S protein at day 14 after a single vaccination, inhibition of SARS-CoV-2 S-driven host cell entry was weak and particularly low for the B.1.351 variant. Frequencies of SARS-CoV-2 WT and VOC-specific T cells were low in many vaccinees after application of a single dose and influenced by immunity against endemic hCoV. The second vaccination significantly boosted T-cell frequencies reactive for WT and B.1.1.7 and B.1.351 variants. Conclusions These results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19., We assessed single vaccine shot–induced B- and T-cell responses against SARS-CoV-2, variants of concern, and human coronaviruses to determine protection against COVID-19. Our results provide important information about surrogates of protection, test result interpretation, and clinical decision-making.

Vaccine-induced neutralizing antibodies are key in combating the COVID-19 pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and disease for prolonged periods. The emergence of SARS-CoV-2 variants of concern (VOC), B.1.1.7 (United Kingdom), B.1.351 (South Africa) and P.1 (Brazil), may reinforce this issue with the latter two being able to evade control by antibodies. We assessed humoral and T cell responses against SARS-CoV-2 WT and VOC and endemic human coronaviruses (hCoV) that were induced after single and double vaccination with BNT162b2. Despite readily detectable IgG against the receptor-binding domain (RBD) of the SARS-CoV-2 S protein at day 14 after a single vaccination, inhibition of SARS-CoV-2 S-driven host cell entry was weak and particularly low for the B.1.351 variant. Frequencies of SARS-CoV-2 specific T cells were low in many vaccinees after application of a single dose and influenced by immunity against endemic hCoV. The second vaccination significantly boosted T cell frequencies reactive for WT, B.1.1.7 and B.1.351 variants. These results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19.

Rapid spread of SARS-CoV-2 variants C.1.2 and B.1.621 (Mu variant) in Africa and the Americas, respectively, as well as a high number of mutations in the viral spike proteins raised concerns that these variants might pose an elevated threat to human health. Here, we show that C.1.2 and B.1.621 spike proteins mediate increased entry into certain cell lines but do not exhibit increased ACE2 binding. Further, we demonstrate that C.1.2 and B.1.621 are resistant to neutralization by bamlanivimab but remain sensitive to inhibition by antibody cocktails used for COVID-19 therapy. Finally, we show that C.1.2 and B.1.621 partially escape neutralization by antibodies induced upon infection and vaccination, with escape of vaccine-induced antibodies being as potent as that measured for B.1.351 (Beta variant), which is known to be highly neutralization resistant. Collectively, C.1.2 and B.1.621 partially evade control by vaccine-induced antibodies, suggesting that close monitoring of these variants is warranted.

BackgroundSerology testing is explored for epidemiological research and to inform individuals after suspected infection. During the COVID-19 pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist.MethodsIn a large German university hospital, we performed weekly questionnaire assessments and anti-SARS-CoV-2 IgG measurements with various commercial tests, a novel surrogate virus neutralization test, and a neutralization assay using live SARS-CoV-2.ResultsFrom baseline to week six, n=1,080 screening measurements for anti-SARS CoV-2 (S1) IgG from n=217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12·4 % in week six, pConclusionWhen assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, we suggest confirming positive results from single measurements by alternative serology tests or functional assays. Our data highlight the need for a methodical serology screening approach in regions with low SARS-CoV-2 infection rates.

Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells using surface-expressed angiotensin-converting enzyme 2 (ACE2). We developed a surrogate neutralization test (sVNT) to assess at what degree serum antibodies interfere with the binding of SARS-CoV-2-S-RBD to ACE2. The sVNT revealed neutralizing anti-SARS-CoV-2-S antibodies in the sera of 90% of mildly and 100% of severely affected coronavirus-disease-2019 (COVID-19) convalescent patients. Importantly, sVNT results correlated strongly to the results from pseudotyped-vesicular stomatitis virus-vector-based neutralization assay and to levels of anti-SARS-CoV-2-S1 IgG and IgA antibodies. Moreover, levels of neutralizing antibodies also correlated to duration and severity of clinical symptoms, but not patient age or gender. These findings together with the sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.

Uncertain rates of asymptomatic infections have raised concerns about potentially high rates of thus far undiagnosed SARS-CoV-2 infections. Serological testing for SARS-CoV-2 specific IgG can be helpful in identification of asymptomatic infections. We report baseline results of the CVOID-19 Contact (CoCo) Study, which follows 217 frontline healthcare workers at a university hospital and performs weekly SARS-CoV-2 specific serology (IgA/IgG). The majority of participants had direct contact to patients with infectious respiratory diseases. Study participants estimated their personal likelihood of having had a SARS-CoV-2 infection with a mean of 20.9% (range 0 to 90%). In contrast, anti-SARS-CoV-2-IgG prevalence was in the range of 1-2% among health care workers. The CoCo Study is not fully representative for other hospitals and the sensitivity of anti-SARS-CoV-2 serology in low prevalence conditions may require further improvement. Taken together, low rates of SARS-CoV-2 specific IgG in healthcare workers in Northern Germany are in sharp contrast to the high personal risk perception. Regular anti-SARS-CoV-2 IgG testing of health-care workers may aid in monitoring the pandemic, assessing the quality of immune responses, directing resources for protective measures, and assuring CVID-19 care in the long run.

There have been concerns about high rates of thus far undiagnosed SARS-CoV-2 infections in the health-care system. The COVID-19 Contact (CoCo) Study follows 217 frontline health-care professionals at a university hospital with weekly SARS-CoV-2-specific serology (IgA/IgG). Study participants estimated their personal likelihood of having had a SARS-CoV-2 infection with a mean of 21% [median 15%, interquartile range (IQR) 5–30%]. In contrast, anti-SARS-CoV-2 IgG prevalence was about 1–2% at baseline. Regular anti-SARS-CoV-2 IgG testing of health-care professionals may aid in directing resources for protective measures and care of COVID-19 patients in the long run.

The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike-protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by Sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent or BNT162b2-vaccinated individuals with 10- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1/BNT162b2-vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant., The SARS-CoV-2 Omicron variant is rapidy spreading worldwide and a public health concern. Experiments show that this variant resistant against several therapeutic antibodies for COVID-19 and efficiently evades antibodies induced upon infection or double BNT162b2 vaccination, however not triple BNT162b2 or ChAdOx1/BNT162b2 vaccination.

Background:Use of telemedicine in Germany has increased due to the COVID-19 lockdown. Between March and May 2020, government restrictions led to cancellation of routine outpatient appointments to limit viral spread and optimize resources.Objectives:This study assesses patient satisfaction of follow-up telemedicine appointments among patients known to be in disease remission, attending either secondary or tertiary care Rheumatology clinics. Appointments were conducted either by a rheumatologist or a qualified medical assistant for rheumatology (RFA). Additional data regarding perceived concerns arising from the COVID-19 pandemic as well as attitudes to vaccination were collected.Methods:Methods: Patients not requiring adjustment of their DMARDs at the two previous attendances were considered stable. At cancellation of the planned attendance, patients were offered participation in the study and provided verbal informed consent. Participants were randomized to a telemedicine appointment by either a physician or RFA. Telemedicine appointments consisted of a standardized patient interview, including assessment of disease activity (modified CDAI score), attitudes to vaccination as well as current vaccine status and concerns about COVID-19. Following participation, all patients received a pseudonymized postal questionnaire to evaluate appointment satisfaction (FAPI-Score).Results:In total 112/116 (96%) patients that were offered appointments, participated in the study (RA 50%, axSpA 30%, PsA 20%). Of these 88/112 (79%) returned their postal questionnaires. Overall patient satisfaction was excellent (mean 4.3/5 modified FAPI score) and did not differ between care setting or clinical status of the interviewer. RFAs conducted 19/112 (17%) of appointments, 6 (32%) of which required additional physician intervention. Change of DMARDs occurred in 19/112 (17%) appointments. Patients reporting a pain score ≥7 (VAS 1-10) were most dissatisfied with the telemedicine appointment (p=0.036). Concerns about COVID-19 correlated with disease activity: high disease activity (p = 0.031), presence of tender joints (p=0.001), high pain levels (p=0.009) correlated with concern of contracting COVID-19 or experiencing severe disease course. Only 38% of the patients had been vaccinated against pneumococci in the past 5 years and 54% had been vaccinated against influenza in 2019/2020.Conclusion:Telemedicine can contribute to patient care in stable patients. RFAs can also contribute to patient care especially for follow-up appointment when patients are in remission. Vaccination rates and motivation needs to be improved as influenza and pneumococcal vaccination is recommended to all patients with rheumatic diseases without contraindications.Disclosure of Interests:None declared

Background Patients with chronic renal insufficiency on maintenance haemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only a few studies have addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population. Methods We assessed immunogenicity of the mRNA vaccine BNT162b2 in at-risk dialysis patients and characterised systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants Alpha, Beta, Epsilon and Cluster 5 by ACE2-RBD competition assay. Findings Patients on maintenance haemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to a vaccinated non-dialysed control population. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished. Interpretation Quantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on maintenance haemodialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in the face of emerging variants of concern may favour this at-risk population for re-vaccination using modified vaccines at the earliest opportunity. Funding Initiative and Networking Fund of the Helmholtz Association of German Research Centres, EU Horizon 2020 research and innovation program, State Ministry of Baden-Wurttemberg for Economic Affairs, Labour and Tourism.