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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.

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

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.

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.

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.

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.

Background: Patients who are post-COVID-19 will require more treatment soon. Therefore, it is important to understand the root cause of their psychological and somatic conditions. Previous studies showed contradictory results on the influence of pre-existing mental conditions. The present study examines the influence of these pre-existing conditions and their pre-treatment on the severity of post-COVID-19 symptoms. Methods: This analysis employs questionnaire data from a large study sample in Germany. Overall, 801 participants were included. All participants rated their health status on a scale from 0 to 100. Fatigue, depression, and anxiety were measured using the FAS, PHQ-9, and GAD-7 scales. Results: All pre-pandemic values showed no significant differences between the groups. The current health status was rated similarly by the recovered patients (μ = 80.5 ± 17.0) and the control group (μ = 81.2 ± 18.0) but significantly worse by acutely infected (μ = 59.0 ± 21.5) and post-COVID-19 patients (μ = 54.2 ± 21.1). Fatigue, depression, and anxiety were similar for recovered patients and the control group. By contrast, there were significant differences between the control and the post-COVID-19 groups concerning fatigue (45.9% vs. 93.1%), depression (19.3% vs. 53.8%), and anxiety (19.3% vs. 22.3%). Conclusion: Fatigue and psychological conditions of post-COVID-19 patients are not associated with pre-existing conditions.

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.

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 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.