Re-vaccination against SARS-COV2 in allogeneic HSCT patients: Repeated primary vaccines doses increases seroconversion rates

Patients undergoing treatment for haematological malignancies have been shown to have reduced antibody responses to vaccination against SARS-COV2. This is particularly important in patients who have undergone allogeneic haemopoietic stem cell transplantation (HSCT), in whom there is limited data about vaccine efficacy. In this retrospective single-centre analysis, we present data on serologic responses following one, two, three or four doses of either Pfizer-BioNTech (PB), AstraZeneca (AZ) or Moderna (MU) SARS-CoV- 2 vaccines from a series of 75 patients who have undergone allogeneic HSCT within 2 years from the time they were revaccinated. The seroconversion rates following post-HSCT vaccination were found to be 50.7%, 78%, 79% and 83% following the first, second, third and fourth primary post -HSCT vaccine doses, respectively. The median time from allograft to first revaccination was 145 days (range 79-700). Our findings suggest that failure to respond to the first SARS-CoV- 2 vaccine post-HSCT was associated with the presence of acute GVHD (p = 0.042) and treatment with rituximab within 12 months of vaccination (p = 0.019). A statistical trend was observed with the presence of chronic GVHD and failure to seroconvert following the second (p = 0.07) and third (p = 0.09) post-HSCT vaccine doses. Patients who had received one or more SARS-CoV- 2 vaccines prior to having an allogeneic stem cell transplant were more likely to demonstrate a positive antibody response following the first dose of revaccination against Sars-CoV- 2 (p = 0.019) and retained this seropositivity following subsequent doses. The incidence of confirmed COVID-19 diagnosis among this cohort at the time of analysis was 16%. 17% of these were hospitalised and there was one recorded death (8%) secondary to COVID-19 in a patient who was 15.7 months post allogeneic transplant. In summary, this study suggests that despite the initial low seroconversion rates observed postallogeneic transplant, increasing levels of antibody response are seen post the second primary vaccine dose. In addition, there seems to be lower risk of mortality secondary to COVID-19 in this vaccinated population, compared to what was reported in the earlier phases of the pandemic prior to use of SARS-COV2 vaccination. This adds support to the widely adopted policy of early full revaccination with repeat of primary vaccine doses and boosters post-HSCT to reduce mortality in this population. Finally, we have identified rituximab use and active GVHD as potential risk factors influencing serological responses to SARS-COV2 vaccination and further work should focus on further characterising this risk and optimum dosing schedule both pre-and post-transplant.

Factors Associated with Hospitalization with Symptomatic Coronavirus Disease 2019 among Pregnant Individuals: A Multicenter Retrospective Cohort Study

Background: Pregnant individuals are at increased risk of coronavirus disease 2019 (COVID-19) hospitalization and death, and primary and booster COVID-19 vaccination is recommended for this population. Method(s): Among a cohort of pregnant individuals who received prenatal care at 3 healthcare systems in the United States, we estimated the cumulative incidence of hospitalization with symptomatic COVID-19 illness. We also identified factors associated with COVID-19 hospitalization using a multivariable Cox proportional hazards model with pregnancy weeks as the timescale and a time-varying adjustor that accounted for severe acute respiratory syndrome coronavirus 2 circulation;model covariates included site, age, race, ethnicity, insurance status, prepregnancy weight status, and selected underlying medical conditions. Data were collected primarily through medical record extraction. Result(s): Among 19 456 pregnant individuals with an estimated due date during 1 March 2020-28 February 2021, 75 (0.4%) were hospitalized with symptomatic COVID-19. Factors associated with hospitalization for symptomatic COVID-19 were Hispanic ethnicity (adjusted hazard ratio [aHR], 2.7 [95% confidence interval {CI}, 1.3-5.5]), Native Hawaiian or Pacific Islander race (aHR, 12 [95% CI, 3.2-45.5]), age <25 years (aHR, 3.1 [95% CI, 1.3-7.6]), prepregnancy obesity (aHR, 2.1 [95% CI, 1.1-3.9]), diagnosis of a metabolic disorder (aHR, 2.2 [95% CI, 1.2-3.8]), lung disease excluding asthma (aHR, 49 [95% CI, 28-84]), and cardiovascular disease (aHR, 2.6 [95% CI, 1.5-4.7]). Conclusion(s): Although hospitalization with symptomatic COVID-19 was uncommon, pregnant individuals should be aware of risk factors associated with severe illness when considering COVID-19 vaccination. Copyright © 2022 Published by Oxford University Press on behalf of Infectious Diseases Society of America. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Evaluation of Corticosteroid Use and Secondary Infection Rates in Critically Ill Covid-19 Patients

INTRODUCTION: Corticosteroids have shown to decrease mortality and increase ventilator-free days in the treatment of COVID-19. The incidence of and risk factors for secondary infections (SI) associated with corticosteroid use in COVID-19 patients are not well defined. The purpose of this study was to assess the incidence and impact of dose and duration of corticosteroids on the rate of secondary infections (SI) in critically-ill COVID-19 patients. METHOD(S): This multi-center, single health-system, retrospective cohort study evaluated adults (>=18 years) admitted to an intensive care unit (ICU) who received corticosteroid(s) for the treatment of COVID-19 between March 2020 and August 2021. Patients were excluded for ICU stay < 24 hours or if the patient transferred from another hospital. The primary endpoint was rate of SI defined as a positive microbiological result after initial corticosteroid administration and at least 48 hours after admission. Secondary endpoints were compared in those who did and did not develop SI and included but not limited to: cumulative corticosteroid dose, duration of corticosteroid, receipt of recommended corticosteroid regimen(s), ICU length of stay (LOS), hospital LOS, in-hospital mortality, 90-day mortality, and ventilator-free days. Secondary outcomes were adjusted for pre-specified variables. RESULT(S): Of the 910 patients included in analyses, 300 patients (32%) experienced SI. Patients who developed SI had higher use of prolonged corticosteroid courses (79.3% vs 44.9%, p< 0.001) and higher cumulative steroid doses (238 vs 124 mg dexamethasone equivalents;aOR 1.008;95% CI, 1.006-1.009;p< 0.001) and longer median (IQR) corticosteroid duration 16 days (11-25) vs 11 days (9-17);aOR 1.12, 1.09-1.14;p< 0.001). The use of recommended corticosteroid regimen was lower in patients with SI 11.7% vs. 39.3% (p< 0.001). Patients with SI had more ventilator days, longer ICU and hospital LOS and increased in-hospital and 90-day mortality (p< 0.001). CONCLUSION(S): In patients who received corticosteroids for COVID-19, exceeding recommended dosing strategies by either prolonging treatment or receiving higher cumulative doses was associated with increased rates of SI. Patients with SI were more likely to experience increased ICU LOS, ventilator days and mortality.

Paediatric hospital admissions for psychiatric and psychosocial reasons during the first year of the COVID-19 pandemic.

Increases in youth psychiatric presentations to out-patient and emergency department settings during COVID-19 have been reported. This study, using data from five hospitals in Ireland, examines changes in the number and type of paediatric admissions during COVID-19 (March 2020 - February 2021) compared to the previous two years. ICD-10 classification was used to establish admissions with mental, behavioural, neuro-developmental disorders and psychosocial reasons (MBN-PS). Overall hospital admissions fell by 25.3%, while MBN-PS fell by only 2.6%, mostly during an initial lockdown. Admissions for MBN-PS increased in July-August (9.2%), increased further in September-December (28.3%), returning to pre-COVID-19 levels in January-February 2021. Significant increases were observed among youths with anorexia nervosa (47.8%), other eating disorders (42.9%), and admissions for anxiety (29.6%), with these effects relating to females only. Although admissions for self-harm increased (3%) and rates of ASD admissions reduced (17%), these were not statistically significant. The disproportionate increase in admissions for MBN-PS compared to medical admissions suggests an adverse effect of COVID-19 on youth mental health, for females in particular, and supports previous reports of a pandemic specific increase in eating psychopathology. Combined community and acute service delivery and capacity planning are urgently needed given the prior underfunding of services pre-pandemic.

Adaptive immunity to SARS-CoV-2 in cancer patients: The CAPTURE study

There is a pressing need to characterise the nature, extent and duration of immune response to SARS-CoV-2 in cancer patients, to inform risk-reduction strategies and preserve cancer outcomes. CAPTURE is a prospective, longitudinal cohort study of cancer patients and healthcare workers (HCWs) integrating immune profiles and clinical annotation. We evaluated 529 blood samples and 1051 oronasopharyngeal swabs from 144 cancer patients and 73 HCWs and correlated with >200 clinical variables. In patients with solid cancers and HCWs, S1-reactive and neutralising antibodies to SARS-CoV-2 were detectable five months post-infection. In these participants, SARS-CoV-2-specific T-cell responses were detected. CD4+ T-cell response correlated with S1 antibody levels. Patients with haematological malignancies had impaired but partially compensated immune responses, depending on malignancy and therapy. Overall, cancer stage, disease status, and therapies did not correlate with immune responses. These findings have implications for understanding individual risks and potential effectiveness of SARS-CoV-2 vaccination in this population.

COVID-19 Infection of HSCT Recipients Is Associated with High Mortality but No Detectable Cytokine Storm at Presentation

Introduction The clinical manifestations of COVID-19 infection in recipients of allogeneic hematopoietic stem cell transplantation (HSCT) have been reported in multiple retrospective cohorts of patients, but there have been no prospective studies to date. Previous studies report that HSCT recipients are at higher risk, with cumulative incidence of death between 17-35%. Although an excessive pro-inflammatory viral response has been documented in the general population, its role in the immune incompetent HSCT setting has not been documented. We present a combined prospective and retrospective national study run through the UK IMPACT trial network to characterize the clinical and immunological features of COVID-19 infection in 96 adult and pediatric recipients of HSCT in the United Kingdom. Methods HSCT recipients of any age and transplanted for any indication, with an RT-PCR-proven COVID-19 infection, were eligible for this study. Patients within 72 hours of COVID-19 diagnosis, who had not received cytokine-targeted treatment, were recruited to a prospective cohort. All other patients were eligible for a retrospective cohort. Prospective patients provided blood samples within 72 hours of COVID-19 diagnosis, and again within 72 hours of clinical deterioration (defined as requirement for oxygen administration) if applicable. Follow-up data were collected on patients 30 and 100 days after COVID-19 diagnosis. Results 100 patients were recruited from 16 sites across the UK between May 2020-June 2021, comprising 12 in a prospective cohort and 88 recruited retrospectively. 96 patients were evaluable, as 4 proved ineligible post-registration. Patients were diagnosed with COVID-19 at a median of 11 months after HSCT. Patient/HSCT characteristics are shown Table 1. The most common symptoms associated with the onset of COVID-19 were fever in 8 prospective (73%) and 35 (41%) retrospective patients, followed by cough in 5 (45%) prospective and 35 (41%) retrospective patients and dyspnea in 4 (36%) prospective and 16 (19%) retrospective patients. 8 (73%) prospective and 40 (47%) retrospective patients were actively immunosuppressed at the time of COVID-19 infection. 16% of the patients had moderate/severe disease at baseline. At day 30 (±2 days) after COVID-19 diagnosis, 2 prospective and 8 retrospective patients continued to demonstrate SARS-CoV-2 positivity on respiratory PCR testing. The median time to viral clearance was 40 (IQR 17-78) days for the prospective and 34 (IQR 15-70) days for the retrospective cohort. Prolonged (more than 14 days) neutropenia was reported in 4 (5%) patients in the retrospective cohort, prolonged thrombocytopenia in 2 (18%) prospective and 11 (13%) retrospective patients. 1 retrospective patient developed secondary hemophagocytic lymphohistiocytosis, and graft rejection was reported in 1 (1%) retrospective patient, within 30 days of COVID-19 diagnosis. In the prospective cohort, 3 (27%) patients died, all by day 30, and all due to COVID-19. In the retrospective cohort, 13 (17%) patients died by day 30, rising to 18 (21%) by day 100, 61% of deaths were attributed to COVID-19. Lower baseline platelets (p=0.013, Mann-Whitney U test), lymphocytes (p=0.012), albumin (p=0.028), and higher baseline CRP (p=0.007), were seen in patients who died following COVID-19 diagnosis. Additionally, exploratory univariate logistic regression of the retrospective cohort found mortality at day 100 to be associated with increased age at diagnosis (OR 1.04, 95% CI 1.01-1.08, p=0.04), and no requirement compared with requirement for invasive ventilation (OR 0.02, 95% CI 0.00-0.16, p=0.001). The 11 prospective patients showed normal levels of interleukin (IL)-2, -4, -10, interferon gamma and tumor necrosis factor alpha at COVID-19 presentation. IL-6 was minimally raised (up to 127 pg/ml, nv<50) in 3/11 pts at presentation. Respiratory deterioration was not associated with detectable cytokine storm. Conclusion Our study confirms a significant mortality rate in patients affected by COVID-19 post HSCT and confirms age as well s requirement for invasive ventilation to be independent risk factors associated with death at day 100. Baseline laboratory data at disease presentation can identify patients at higher risk of COVID-19 related death. In the prospective cohort of our study, pathophysiology of the viral disease did not seem related to cytokine storm-mediated inflammation. [Formula presented] Disclosures: Protheroe: Jazz Pharmaceuticals: Honoraria;Astellas: Honoraria;Kite Gilead: Honoraria. Peggs: Autolus: Consultancy, Current equity holder in publicly-traded company. Craddock: Novartis Pharmaceuticals: Other: Advisory Board;Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nicholson: BMS/Celgene: Consultancy;Kite, a Gilead Company: Other: Conference fees, Speakers Bureau;Novartis: Consultancy, Other: Conference fees;Pfizer: Consultancy. Amrolia: ADC Therapeutics: Other: Named inventor on a patent which is being transferred to ADCT.;Autolus: Patents & Royalties.

Poor Outcome of Patients with COVID-19 after CAR T-Cell Therapy for B-Cell Malignancies: Results from a Multicenter Study on Behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Background The ongoing Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is having an enormous impact on society worldwide and is especially posing a threat to health in vulnerable patients, such as patients with immune deficiencies. It is expected that patients who received Chimeric Antigen Receptor T-cell (CAR T-cell) therapy for hematologic malignancies are at risk for poor outcomes after COVID-19 due to their severely immunocompromised state caused by prior cumulative immunochemotherapy, on-target/off-tumor B-cell depletion, hypogammaglobulinemia and ongoing cytopenias. Current data are limited to small case series and case reports. This study describes the clinical characteristics and outcomes of CAR T-cell therapy recipients after developing COVID-19 in the largest cohort to date. Methods In response to the COVID-19 pandemic, the European Society for Blood and Marrow Transplantation (EBMT) developed a special COVID-19 report form to capture data from all patients with COVID-19 after treatment with CAR T-cell therapy for hematologic malignancies. Only PCR positive SARS-CoV-2 diagnosed patients before June 1 st, 2021 were included. The aim of this study was to describe the clinical course after COVID-19 diagnosis and evaluate overall survival. Overall survival probabilities were calculated using the Kaplan Meier method. Factors associated with mortality after COVID-19 diagnosis were examined using a Cox proportional hazard model. Results A total of 57 patients from 11 countries were reported to the EBMT. One patient with incomplete data at diagnosis and without any follow up information had to be excluded from the analysis. The median age of these 56 patients was 57.7 years (min-max 5.2 - 72.8) including 55 adults and one child. Of these patients, 32 were male. CAR T-cell therapy was given to 46 patients with B-cell-non-Hodgkin lymphoma, 7 patients with B-cell acute lymphoblastic leukemia, and 3 patients with multiple myeloma. The median time from CAR T-cell infusion to COVID-19 diagnosis was 7.4 months (min-max 0.03 - 25.3). At the time of COVID-19 diagnosis, 62.5% of patients were in complete remission, 12.5% of patients had a partial response and 25% of patients had relapsed/refractory disease. Forty-five patients (80%) were admitted to hospital (median 26,5 days, min-max 3-171) due to COVID-19. Of the admitted patients, 24 (53%) needed oxygen support. Twenty-two (49%) patients were admitted to the intensive care unit (median 14 days, min - max 2-65) and 16 (73%) of these patients received invasive ventilation. At the time of analysis, 25 of the 56 patients had died (44.6%), most (23/25) due to COVID-19, resulting in a COVID-19 attributable mortality rate of 41%. The Kaplan-Meier estimate of overall survival is shown in Figure 1. The median follow-up from COVID-19 diagnosis was 20.9 weeks. In 1 of the 32 alive patients there was no resolution of COVID-19 at the time of analysis. In multivariate analysis, older age (hazard ratio (HR) 1.50, 95% CI 1.11-2.03, p=0.009) and comorbidities (HR 2.56, 95% CI 1.05-6.23, p=0.001) had a negative impact on overall survival. Better performance status at time of admission (HR 0.72, 95% CI 0.59-0.88, p=0.038) had a positive impact on overall survival. Sex, time from CAR T-cell therapy to COVID-19 diagnosis, disease remission status and the occurrence of neurotoxicity or cytokine release syndrome after CAR T-cell infusion did not have a significant effect on overall survival in the multivariate analysis. Conclusion Patients with COVID-19 after B-cell-targeted CAR T-cell therapy have a very poor outcome. As it remains uncertain whether currently applied vaccination strategies against SARS-CoV-2 are effective after CAR T-cell therapy, vaccination of health-care personnel and family members in combination with protective measures against viral exposure are likely to play the most important role in protecting this vulnerable group of patients. Better treatment strategies are urgently needed. [Formula present d] Disclosures: Ljungman: OctaPharma: Other: DSMB;Enanta: Other: DSMB;Janssen: Other: Investigator;Takeda: Consultancy, Other: Endpoint committee, speaker;AiCuris: Consultancy;Merck: Other: Investigator, speaker. De La Camara: IQONE: Consultancy;Roche: Consultancy. Ortiz-Maldonado: Kite, Novartis, BMS, Janssen: Honoraria. Barba: Novartis: Honoraria;Gilead: Honoraria;BMS: Honoraria;Amgen: Honoraria;Pfizer: Honoraria. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria. Sesques: Novartis: Honoraria;Chugai: Honoraria;Kite, a Gilead Company: Honoraria. Bachy: Kite, a Gilead Company: Honoraria;Novartis: Honoraria;Daiishi: Research Funding;Roche: Consultancy;Takeda: Consultancy;Incyte: Consultancy. Di Blasi: Kite, a Gilead Company: Consultancy, Honoraria;Novartis: Consultancy, Honoraria;Janssen: Consultancy, Honoraria. Thieblemont: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding;Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees;Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Hospira: Research Funding;Bayer: Honoraria;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Mutsaers: BMS: Consultancy;AstraZeneca: Research Funding. Nicholson: Kite, a Gilead Company: Other: Conference fees, Speakers Bureau;Novartis: Consultancy, Other: Conference fees;BMS/Celgene: Consultancy;Pfizer: Consultancy. Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfizer: Consultancy;Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Ribera: NOVARTIS: Consultancy, Speakers Bureau;TAKEDA: Consultancy, Research Funding, Speakers Bureau;ARIAD: Consultancy, Research Funding, Speakers Bureau;SHIRE: Consultancy, Speakers Bureau;AMGEN: Consultancy, Research Funding, Speakers Bureau;Pfizer: Consultancy, Research Funding, Speakers Bureau. Sanderson: Kite, a Gilead Company: Honoraria;Novartis: Honoraria. Bloor: Kite, a Gilead Company: Honoraria;Novartis: Honoraria. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Ayuk: Novartis: Honoraria;Janssen: Honoraria;Takeda: Honoraria;Mallinckrodt/Therakos: Honoraria, Research Funding;Gilead: Honoraria;Miltenyi Biomedicine: Honoraria;Celgene/BMS: Honoraria. Kröger: Novartis: Research Funding;Riemser: Honoraria, Research Funding;Sanofi: Honoraria;Neovii: Honoraria, Research Funding;Jazz: Honoraria, Research Funding;Gilead/Kite: Honoraria;Celgene: Honoraria, Research Funding;AOP Pharma: Honoraria. Kersten: Celgene: Research Funding;Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support;Roche: Consultancy, Honoraria, Other: Travel support, Research Funding;BMS/Celgene: Consultancy, Honoraria;Takeda: Research Funding;Novartis: Consultancy, Honoraria, Other: Travel support;Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding. Mielke: DNA Prime SA: Speakers Bureau;Im unicum: Other: Data safety monitoring board;Novartis: Speakers Bureau;Miltenyi: Other: Data safety monitoring board;Gilead/KITE: Other: Travel support, Expert panel;Celgene/BMS: Speakers Bureau.

Adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients: The CAPTURE study

Background: Patients with cancer are at increased risk of severe outcomes from COVID-19. Understanding the impact of SARS-CoV-2 infection and vaccination induced-immunity is an area of unmet need. Methods: CAPTURE (NCT03226886) is a prospective longitudinal cohort study of COVID-19 vaccine or SARS-CoV-2 infection-induced immunity. SARS-CoV-2 infections were confirmed by RT-PCR and ELISA. Neutralising antibody titres (NAbT) against wild-type (WT) SARS-CoV-2 and variants of concern (VOC;Alpha, Beta, Delta) and SARS-CoV-2 specific T-cells (SsT-cells) were quantified. Results: 118 patients (89% solid malignancy, [SM]) were SARS-CoV-2-positive (median follow-up: 154 days). 85% patients were symptomatic;2 died of COVID-19. 82% had S1-reactive antibodies, of whom 89% had neutralising antibodies (NAbs);NAbT were lower against all VOCs. While S1-reactive antibody levels declined over time, NAbT remained stable up to 329 days. Most patients had detectable SsT-cells (76% CD4+, 52% CD8+). Haematological malignancy (HM) patients had impaired immune responses that were disease and treatment-specific (anti-CD20), but with evidence suggestive of compensation from T-cells. 585 patients were evaluated following 2 doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after 2 doses were 85% and 54% in patients with SM and HM, respectively. A lower proportion of patients had detectable NAbs against SARS-CoV-2 VOC (Alpha 62%, Beta 54%, Delta 49%) vs WT (84%), with corresponding significantly lower NAbT. Patients with HM were more likely to have an undetectable NAb and had lower NAbT vs solid malignancies to both WT and VOCs. Seroconversion showed poor concordance with NAbTs against VOCs. Prior SARS-CoV-2 infection boosted NAbT including against VOCs. Anti-CD20 treatment was associated with severely diminished NAbTs. Vaccine-induced T-cell responses were detected in 80% of patients, with no differences between vaccines or cancer types. Conclusions: Patients with HM had blunted humoural responses to infection and vaccination, particularly against VOCs, but preserved cellular responses might contribute to protection. Our results lend support to prioritisation of all cancer patients for further booster vaccination. Clinical trial identification: NCT03226886. Legal entity responsible for the study: The Royal Marsden NHS Foundation Trust. Funding: The Royal Marsden Charity;The National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at the Royal Marsden Hospital and Institute for Cancer Research (ICR). Disclosure: All authors have declared no conflicts of interest.

Increased mental health presentations by children aged 5-15 at emergency departments during the first 12 months of covid-19

Aims To determine changes in mental health (MH) attendance at Emergency Departments (ED) by children aged five to 15 during the COVID-19 pandemic. Methods Analysis of MH presentations during the first year of the pandemic compared with prior year for three public paediatric EDs serving the greater Dublin area with a paediatric population of 430,000. Results Overall, ED attendance during the 12 months to 28th February 2021 was 34.3% below prior year, while MH presentations were 8.9% above prior year. MH attendances initially decreased by 26.8% (2020: 303;2019: 414) during the first four months of the pandemic (March to June), lower than the corresponding decrease of 47.9% for presentations for any reason (2020: 11,530;2019: 22,128). However, MH presentations increased by 52.4% in July and August (2020: 218;2019: 143), and by 45.6% in September to December (2020: 552;2019: 379), dropping 28.1% below prior year in January (2021: 87;2020: 121) before returning to prior year levels in February 2021 (2021: 107;2020: 106). Conclusion Following the initial COVID-19 lockdown, ED presentations by children for acute MH care increased significantly over prior year, with this increase sustained throughout 2020. Long-term stressors linked to the pandemic may be leading to chronic MH problems, warranting increased funding of MH services as part of the response to COVID-19.