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

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

Attitude towards and perception of individual safety after SARS-CoV-2 vaccination among German cancer patients.

PURPOSE: Refusal to receive SARS-CoV-2 vaccination poses a threat to fighting the COVID-19 pandemic. Little is known about German cancer patients' attitude towards and experience with SARS-CoV-2 vaccination. METHODS: Patients were enrolled between 04-11/2021. They completed a baseline questionnaire (BLQ) containing multiple choice questions and Likert items ranging from 1 ("totally disagree") to 11 ("totally agree") regarding their attitude towards vaccination and COVID-19. A follow-up questionnaire (FUQ) was completed after vaccination. RESULTS: 218 patients (43% female) completed BLQ (110 FUQ; 48% female). Most patients agreed to "definitely get vaccinated" (82%) and disagreed with "SARS-CoV-2 vaccination is dispensable due to COVID-19 being no serious threat" (82%; more dissent among men, p = 0.05). Self-assessment as a member of a risk group (p = 0.03) and fear of COVID-19 (p = 0.002) were more common among women. Fear of side effects was more common among women (p = 0.002) and patients with solid or GI tumors (p = 0.03; p < 0.0001). At FUQ, almost all (91%) reported their vaccination to be well tolerated, especially men (p = 0.001). High tolerability correlated with confidence in the vaccine being safe (r = 0.305, p = 0.003). Most patients would agree to get it yearly (78%). After vaccination, patients felt safe meeting friends/family (91%) or shopping (62%). Vacation (32%) or work (22%) were among others considered less safe (less frequent among men, p < 0.05). CONCLUSION: Acceptance of SARS-CoV-2 vaccination is high and it is well tolerated in this sensitive cohort. However, concerns about vaccine safety remain. Those and gender differences need to be addressed. Our results help identify patients that benefit from pre-vaccination consultation.

Mental burden and moral distress among oncologists and oncology nurses in Germany during the third wave of the COVID-19 pandemic: a cross-sectional survey.

PURPOSE: There is evidence for mental burden and moral distress among healthcare workers during the pandemic. However, there is scarcity of analyses regarding possible correlations of mental burden and moral distress in this context. This study provides data to quantify mental burden and possible associations with moral distress among physicians and nurses working in oncology in Germany. METHODS: We conducted a cross-sectional online survey with physicians and nurses working in oncology in Germany between March and July 2021. Next to sociodemographic characteristics and working conditions, mental burden and moral distress were assessed using standardized instruments. Binary multivariate logistic regression using the enter method was performed in order to explore the relationship between mental burden and moral distress. RESULTS: 121 physicians and 125 nurses were included in the study. Prevalence of clinically relevant depressive symptoms, anxiety, somatic symptoms, burnout symptoms and moral distress was 19.2, 14.5, 12.7, 46.0 and 34.7% in physicians and 41.4, 24.0, 46.8, 46.6 and 60.0% in nurses respectively. Mental burden was significantly associated with moral distress, being female/diverse, younger age < 40 and increase in workload. Nurses who felt sufficiently protected from COVID-19 reported significantly less moral distress. CONCLUSION: To improve pandemic resilience, there is a need to ensure safe working environment including psychosocial support. Further evidence on risk and protective factors for moral distress is needed to be able to develop and implement strategies to protect healthcare workers within and beyond the pandemic.

Impact of SARS-CoV-2 vaccination on systemic immune responses in people living with HIV.

Despite the development of vaccines, which protect healthy people from severe and life-threatening Covid-19, the immunological responses of people with secondary immunodeficiencies to these vaccines remain incompletely understood. Here, we investigated the humoral and cellular immune responses elicited by mRNA-based SARS-CoV-2 vaccines in a cohort of people living with HIV (PLWH) receiving anti-retroviral therapy. While antibody responses in PLWH increased progressively after each vaccination, they were significantly reduced compared to the HIV-negative control group. This was particularly noteworthy for the Delta and Omicron variants. In contrast, CD4+ Th cell responses exhibited a vaccination-dependent increase, which was comparable in both groups. Interestingly, CD4+ T cell activation negatively correlated with the CD4 to CD8 ratio, indicating that low CD4+ T cell numbers do not necessarily interfere with cellular immune responses. Our data demonstrate that despite the lower CD4+ T cell counts SARS-CoV-2 vaccination results in potent cellular immune responses in PLWH. However, the reduced humoral response also provides strong evidence to consider PLWH as vulnerable group and suggests subsequent vaccinations being required to enhance their protection against COVID-19.

Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination.

Objective: The pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells via anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood. Methods: We here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls. Results: We show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain CD4+ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1). Interpretation: In summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity.

Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination

Objective The pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells via anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood. Methods We here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls. Results We show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain CD4+ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1). Interpretation In summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity.

Low Serological Prevalence of SARS-CoV-2 Antibodies in Cancer Patients at a German University Oncology Center.

BACKGROUND: Coronavirus disease 2019 (COVID-19) cases in Germany, as in most other places in Europe or worldwide, are still highly prevalent. Vaccination rates currently remain low, putting cancer patients at a continued risk of infection with SARS-CoV-2, while prevalence of SARS-CoV-2 antibodies among cancer patients in Germany remains essentially unknown. METHODS: Between August 2020 and February 2021, patients admitted to our hospital were prospectively enrolled in our COVID-19 biobank. Collected sera were analyzed for SARS-CoV-2-IgM/IgG using Elecsys Anti-SARS-CoV-2 assay. RESULTS: One hundred and ten patients with cancer were included in this study. With 71 (65%) patients, most had active cancer treatment, mainly chemotherapy (56%). The most frequent diagnosis was gastrointestinal cancer (54%) with pancreatic cancer being the most common cancer type (24%). Hematologic malignancies were present in 21 patients (17%). Among the cancer patients first diagnosed during the pandemic, the rate of palliative treatment situations tended to be higher (76% vs. 67%, p = 0.17). A history of SARS-CoV-2 infection was documented in 15 (14%) patients; however, SARS-CoV-2 antibodies were detected in 10 (67%) patients only. Of the patients without a history of SARS-CoV-2 infection, none displayed SARS-CoV-2 antibodies. CONCLUSION: In the present single-center experience, a low serological prevalence of SARS-CoV-2 antibodies among cancer patients even after SARS-CoV-2 infection was found. The results support continued strict preventive measures as well as efforts toward faster vaccination, due to a low immunity level in the population.