Immunogenicity, effectiveness and safety of COVID-19 vaccine in older adults living in nursing homes: A real-life study.

INTRODUCTION: BNT162b2 (BioNTech and Pfizer) is a nucleoside-modified mRNA vaccine that provides protection against SARS-CoV-2 infection and is generally well tolerated. However, data about its efficacy, immunogenicity and safety in people of old age or with underlying chronic conditions are scarce. PURPOSE: To describe BNT162b2 (BioNTech and Pfizer) COVID-19 vaccine immunogenicity, effectiveness and reactogenicity after complete vaccination (two doses), and immunogenicity and reactogenicity after one booster, in elders residing in nursing homes (NH) and healthy NH workers in real-life conditions. METHODS: Observational, ambispective, multicenter study. Older adults and health workers were recruited from three nursing homes of a private hospital corporation located in three Spanish cities. The primary vaccination was carried out between January and March 2021. The follow-up was 13 months. Humoral immunity, adverse events, SARS-CoV-2 infections, hospitalizations and deaths were evaluated. Cellular immunity was assessed in a participant subset. RESULTS: A total of 181 residents (mean age 84.1 years; 89.9% females, Charlson index ≥2: 45%) and 148 members of staff (mean age 45.2 years; 70.2% females) were surveyed (n:329). After primary vaccination of 327 participants, vaccine response in both groups was similar; ≈70% of participants, regardless of the group, had an antibody titer above the cut-off considered currently protective (260BAU/ml). This proportion increased significantly to ≈ 98% after the booster (p<0.0001 in both groups). Immunogenicity was largely determined by a prior history of COVID-19 infection. Twenty residents and 3 workers were tested for cellular immunity. There was evidence of cellular immunity after primary vaccination and after booster. During the study, one resident was hospitalized for SARS-CoV-2. No SARS-CoV-2-related deaths were reported and most adverse events were mild. CONCLUSIONS: Our results suggest that the BNT162b2 mRNA COVID-19 vaccine is immunogenic, effective and safe in elderly NH residents with underlying chronic conditions.

[Vaccination against coronavirus disease 2019 (COVID-19)]. / Impfung gegen coronavirus disease 2019 (COVID-19).

The clinical presentation of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2) is very heterogeneous and the risk of a severe course clearly increases with age. Therefore, older adults are an important target group for vaccinations. Several vaccines are currently licensed in Europe for older adults, namely two mRNA vaccines, two adenoviral vector vaccines and a protein-based vaccine. The immunogenicity and clinical efficacy of these vaccines in the first approval trials were equal or only slightly reduced for older adults compared to younger age groups; however, the concentration of neutralizing antibodies and protection against infection greatly declined over time and the latter is substantially reduced for virus variants, particularly for the Omicron variant. Nevertheless, protection against severe disease and hospitalization is maintained at a high level for longer time periods, and after three vaccine doses (2 + 1 schedule) also for the Omicron variant. Additional booster vaccinations are currently recommended for patients with risk factors, especially older adults. With respect to the currently valid recommendations for different age and risk groups, the publications and notifications of the national vaccine advisory bodies should be referred to.All currently available vaccines target the original virus strain. New vaccines, which are adapted to virus variants are currently being developed and tested, and it is highly likely that they will be used in the near future; however, viral evolution is ongoing and a continuous development of adapted vaccines will probably be necessary.

COVID-19 vaccination in patients with cancer receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICI) can cause off-target inflammatory and immune-related adverse events (irAE). Conceivably, COVID-19 vaccination could trigger an inflammatory and immune response that could induce or aggravate irAE. METHODS: The objective of this systematic review is to appraise the efficacy and safety of COVID-19 vaccination in patients with cancer treated with ICI. The literature search was performed in PubMed and Embase in English from December 2019 to February 2022. The review included clinical trials, observational cohort studies, case series, and case reports reporting on the clinical efficacy and safety of COVID-19 vaccines on patients with cancer treated with ICI. Outcomes of interest included seroconversion, SARS-CoV-2 infection rate, severe COVID-19, COVID-19 mortality rate. Incidence of ICI irAEs was also ascertained as well as vaccine adverse events. A meta-analysis was conducted to estimate the pooled effect sizes of the outcomes when possible, using random effects models. RESULTS: Overall, 19 studies were included for the analysis (n=10 865 with 2477 receiving ICI). We analyzed 15 cohort studies, 1 cross-sectional study, and 3 case reports. There were no statistically significant differences in seroconversion rates after the second dose of the vaccine when comparing patients with cancer receiving ICI with patients without cancer (risk ratio, RR 0.97, 95% CI 0.92 to 1.03) or with patients with cancer without active treatment (RR 1.00, 95% CI 0.96 to 1.04). There was a higher probability of seroconversion in patients with cancer treated with ICI compared with patients with cancer treated with chemotherapy (RR 1.09, 95% CI 1.00 to 1.18). In a single study in patients receiving ICI, no differences were observed in risk of irAE between those receiving inactivated vaccine and those unvaccinated (pneumonitis RR 0.88, 95% CI 0.33 to 2.3; rash RR 1.03, 95% CI 0.66 to 1.62; arthralgia RR 0.94, 95% CI 0.51 to 1.75). There were no studies for other types of vaccines comparing vaccinated vs not vaccinated in patients treated with ICI. The most common vaccine-related adverse events were local pain or fatigue. Overall, the quality of evidence was rated as very low. CONCLUSION: COVID-19 vaccination appears to be effective and safe in patients with cancer receiving ICI.

Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries.

BACKGROUND: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer. METHODS: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19. FINDINGS: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 109 cells/L, p=0.0098). CONCLUSION: Anti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2.

Does Cytomegalovirus (CMV) Status Impact the Host Response to SARS-CoV-2?

Background Cytomegalovirus (CMV) seropositivity has a significant immunomodulating over the life course, both with respect to responses to infections and responses to vaccines. For example, influenza vaccine response is known from multivariate analyses to be reduced by CMV seropositivity in elderly individuals. In patients with COVID-19, evidence suggests there are interactions between SARS-CoV-2 and CMV. CMV seropositives may have more severe COVID disease, and patients recovering from COVID often reactivate latent CMV, leading to end-organ CMV disease. This study aimed to test two hypotheses: 1) that vectored vaccines based on attenuated arenaviruses demonstrate equivalent immunogenicity to adjuvanted protein subunit spike (S) vaccines in a guinea pig vaccine model;2) that CMV seropositivity impacts the immune response to S protein-based vaccines. Method Guinea pigs (n=3 per group) were vaccinated with a 2-dose series of an attenuated arenavirus (Pichinde virus) S protein-vectored vaccine by intranasal (IN;n=4) or intramuscular (IM) route at a dose of 1x10

Antibody and T cell responses to COVID-19 vaccination in patients receiving anticancer therapies.

BACKGROUND: Patients with cancer were excluded from phase 3 COVID-19 vaccine trials, and the immunogenicity and side effect profiles of these vaccines in this population is not well understood. Patients with cancer can be immunocompromised from chemotherapy, corticosteroids, or the cancer itself, which may affect cellular and/or humoral responses to vaccination. PD-1 is expressed on T effector cells, T follicular helper cells and B cells, leading us to hypothesize that anti-PD-1 immunotherapies may augment antibody or T cell generation after vaccination. METHODS: Antibodies to the SARS-CoV-2 receptor binding domain (RBD) and spike protein were assessed in patients with cancer (n=118) and healthy donors (HD, n=22) after 1, 2 or 3 mRNA vaccine doses. CD4+ and CD8+ T cell reactivity to wild-type (WT) or B.1.617.2 (delta) spike peptides was measured by intracellular cytokine staining. RESULTS: Oncology patients without prior COVID-19 infections receiving immunotherapy (n=36), chemotherapy (n=15), chemoimmunotherapy (n=6), endocrine or targeted therapies (n=6) and those not on active treatment (n=26) had similar RBD and Spike IgG antibody titers to HDs after two vaccinations. Contrary to our hypothesis, PD-1 blockade did not augment antibody titers or T cell responses. Patients receiving B-cell directed therapies (n=14) including anti-CD20 antibodies and multiple myeloma therapies had decreased antibody titers, and 9/14 of these patients were seronegative for RBD antibodies. No differences were observed in WT spike-reactive CD4+ and CD8+ T cell generation between treatment groups. 11/13 evaluable patients seronegative for RBD had a detectable WT spike-reactive CD4+ T cell response. T cells cross-reactive against the B.1.617.2 variant spike peptides were detected in 31/59 participants. Two patients with prior immune checkpoint inhibitor-related adrenal insufficiency had symptomatic hypoadrenalism after vaccination. CONCLUSIONS: COVID-19 vaccinations are safe and immunogenic in patients with solid tumors, who developed similar antibody and T cell responses compared with HDs. Patients on B-cell directed therapies may fail to generate RBD antibodies after vaccination and should be considered for prophylactic antibody treatments. Many seronegative patients do develop a T cell response, which may have an anti-viral effect. Patients with pre-existing adrenal insufficiency may need to take stress dose steroids during vaccination to avoid adrenal crisis.

[Prevention by vaccination of adult patients with pulmonary diseases]. / Prävention durch Impfung pneumologisch vorerkrankter Erwachsener: Pneumokokkenpneumonie, Influenza, Pertussis, Herpes Zoster und "coronavirus disease 2019".

The key priority in patients with chronic lung diseases is currently immunization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); all vaccines approved for this showed high effectiveness against severe infections. For patients with chronic pulmonary diseases the recommendations by the Standing Committee on Vaccination include not only the standard vaccinations in adulthood but also the so-called indication vaccinations. These include vaccinations against pneumococci and influenza. Advances include the recent development of new pneumococcal conjugate vaccines containing additional serotypes and the recommendation of a more effective high-dose vaccine against influenza for persons over 60 years old. With the next scheduled booster vaccination against tetanus and diphtheria a combination vaccine with pertussis antigen should be used. For patients with chronic lung disease the herpes zoster vaccine is recommended over the age of 50 years.

[Effectiveness of BNT162b2 vaccine to preventing COVID-19 in healthcare personnel]. / Efectividad de la vacuna BNT162b2 para prevenir la COVID-19 en personal sanitario.

OBJECTIVE: To assess the effectiveness of the vaccine against SARS-CoV-2 (BNT162b2) in healthcare personnel of a health department. METHOD: Test-negative case̶control study. Healthcare personnel with suspected COVID-19 and healthcare personnel close contacts of COVID-19 cases were included between January 27th and June 6th, 2021. They were PCR tested for SARS-CoV-2; those with positive PCR were considered cases and those with negative PCR were considered controls. The adjusted vaccine effectiveness (aVE) to prevent COVID-19 cases and their 95% confidence interval (95%CI) were calculated using the formula VE=(1-odds ratio)×100. RESULTS: 624 healthcare personnel were included, of which 43 (6.9%) were considered cases and 581 (93.8%) controls. The aVE of the complete regimen was 96.3% (95%CI: 82.5̶99.2). The aVE of the incomplete pattern was 68.0% (95%CI: 30.0̶85.4). CONCLUSIONS: The administration of the complete pattern of BNT162b2 vaccine against SARS-CoV-2 is effective for the prevention of cases of COVID-19 in healthcare personnel.

Can reactogenicity predict immunogenicity after COVID-19 vaccination?

BACKGROUND/AIMS: This study aimed to assess the association between local and systemic reactogenicity and humoral immunogenicity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS: Adverse events were prospectively evaluated using an electronic diary in 135 healthy adults who received a SARS-CoV-2 vaccine (AZD1222, AstraZeneca/Oxford, n = 42; or BNT162b2, Pfizer/BioNTech, n = 93). We semi-quantitatively measured anti-S1 immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay at baseline, 3 weeks after the first dose of AZD1222 or BNT162b2, and 2 weeks after the second dose of BNT162b2. We evaluated the association between the maximum grade of local or systemic adverse events and the anti-S1 IgG optical density using multivariate linear regression with adjustment for age, sex, and use of antipyretics. RESULTS: The median age of the 135 vaccinees was 30 years (36 years in the AZD1222 group and 29 years in the BNT162b2 group) and 25.9% were male (9.5% in the AZD1222 group and 33.3% in the BNT162b2 group). Local and systemic adverse events were generally comparable after the first dose of AZD1222 and the second dose of BNT162b2. The grades of local and systemic adverse events were not significantly associated with anti-S1 IgG levels in the AZD1222 or BNT162b2 group. CONCLUSION: Local and systemic reactogenicity may not be associated with humoral immunogenicity after SARS-CoV-2 vaccination.