Adolescents at risk of mental health problems in the COVID-19 pandemic: A prospective population-based study of the effects of government mandates and school closures

There is increasing evidence that the COVID-19 pandemic has had substantial mental health impacts for adolescents. Yet, few definitive studies have investigated which adolescents were at higher risk of poor mental health and well-being during the pandemic. Data were drawn from the Childhood to Adolescence Transition Study, a prospective cohort study of students in Australia (N = 1211). Prevalence of mental health outcomes (depressive symptoms, anxiety symptoms, self-harm and good subjective well-being) was estimated in school Years 5–12, where Years 11 (2020) and 12 (2021) coincided with the pandemic. The age- and sex-adjusted relative risk of each mental health outcome for each priority group during the pandemic were estimated. During the pandemic, over 50% of study participants reported depressive symptoms, and one quarter reported anxiety symptoms. There was a decrease in good subjective well-being compared with pre-pandemic years, while self-harm prevalence remained similar. History of mental health problems, school disengagement and frequent peer victimisation increased the risk of experiencing mental health problems during the pandemic. Schools play a central role in maintaining the mental health and good subjective well-being of students, and this is particularly important during periods of social disruption, such as the COVID-19 pandemic. © 2022 The Authors. Australian Journal of Social Issues published by John Wiley & Sons Australia, Ltd on behalf of Australian Social Policy Association.

Immunogenicity of Covid-19 vaccination in patients with myelodysplastic syndromes

Many patients with haematological cancers remain incompletely protected from SARS-CoV-2 following two doses of vaccine with Pfizer-BioNTech BNT162b2 nCoV-19 or ChAdOx1. Myelodysplastic syndrome (MDS) represents a spectrum of clonal bone marrow neoplasms. The response of patients with MDS to the COVID-19 vaccines remains unknown. Here, we report the humoral and T-cell responses of patients with low-and high-risk myelodysplastic syndrome (MDS), 2 weeks following completion of the second-dose schedules of ChAdOx1 or BNT162b2 nCoV-19 vaccines. Patients with MDS ( n = 38) followed up at Kings College Hospital, London were vaccinated with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccine. Written informed consent was provided. Eligibility criteria included the diagnosis of MDS as per the WHO classification and age ≥18 years. Healthy volunteers (HV;n = 30) served as a reference group. Blood samples were collected 2 weeks after the second vaccine dose. Plasma samples were tested for SARS-CoV-2-specific antibody aimed at the SARS-CoV-2 spike (S) protein receptor-binding domain and neutralisation assays against pseudotypes with SARS-CoV-2 Wuhan strain (WT), VOC.B.1.1.7 (alpha) or VOC.B.1.617.2 (delta) Spike. Cellular responses were assessed using IFNγ ELISPOT and flow cytometry (CD25 and CD69 expression) after 24 h peptide stimulation. IFNγ ELISpot analysis was performed ex vivo for assessment of T-cell response. 32% of the MDS patients received BNT162b2 and 58% received ChAdOx1 nCoV-19 vaccines. All HV received BNT162b2. Overall serological responses were as follows: HV BNT162b2 100% (26/26);MDS BNT162b2 100% (15/15) and MDS ChAdOx1 76.2% (16/21). Notably, the MDS ChAdOx1 cohort demonstrated significantly decreased serological titres to the MDS BNT162b2 cohort. The functional implications of seroconversion were assessed by neutralisation assays for SARS-CoV-2 WT and VOC alpha and delta. All but four MDS patients could neutralise all variant strains, but MDS cohorts showed significantly reduced median neutralisations for all three variant strains compared to HV. Five MDS ChAdOx1 patients who did not have a serological response were able to mount T-cell responses. Additionally, treatment with either azacytidine or calcineurin inhibitor cyclosporin did not impair appropriate T-cell responses. The numbers of individuals who were both serological and T-cell responders were as follows: HV 95% (20/21), MDS BNT162b2 71.4% (10/14) and MDS ChAdOx1 52.9% (9/17). Overall serological responses in the MDS cohorts were 100% for those who had completed the two-dose BNT162b2 vaccine schedule compared to 76.2% of patients vaccinated with the ChAdOx1 vaccine. It may be advisable that MDS patients are boosted with an mRNA-based vaccine to promote enhanced immunity in this specific population. We observed that neutralisation in seroconverted patients was significantly weaker for both the ChAdOx-1 and BNT162b2 MDS cohorts compared to HV. This highlights the continued need for a third primary dose for this clinically vulnerable patient group and our further work will analyse the cohort's response to this.

Immunogenicity of Covid-19 Vaccination in Subjects with Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) represent a spectrum of clonal bone marrow neoplasms from low risk disease through to those transforming into acute myeloid leukaemia. The COVID-19 pandemic has presented a great risk to those with hematological malignancies who are at higher risk of severe disease and death than the general population. Previous studies looking at the immune response to influenza vaccination in those with MDS had shown promising results, with immune responses not differing from those of healthy family members. Whilst some data exist to reassure the MDS community that majority of patients show seroconversion following Covid-19 vaccination, little data exists on their neutralizing capacity or post vaccination T-cell responses in this cohort. In addition, the majority of patients in these studies received BNT162b2 and there is little published data on vaccine response to the ChAdOx1 nCoV-19 vaccine. We have investigated the humoral and T-cell response of 39 patients with MDS two to four weeks following Covid-19 booster vaccination with BNT162b2 or ChAdOx1 nCoV-19 through the SOAP study (Sars-cov-2 fOr cAncer Patients, IRAS project ID:282337). Plasma and PBMCs from MDS cases and healthy controls have been collected, and are being assessed for both humoral and cellular responses to SARS_CoV_2, the alpha (B.1.1.7) and delta (B.1.617.2) variants. Humoral responses will be assessed using ELISA (peptide binding) and functional viral neutralization assays. Cellular responses will be assessed using IFNy ELISPOT and flow cytometry (CD25 and CD69 expression) after 24h peptide stimulation. All data at time point 1 (2 - 4 weeks following booster vaccination) have been collected and will subsequently be collected at 6 months and 12 months post-vaccination. We also report on the safety data for these vaccines within this patient population. Of this cohort 64% were male with a median age of 65 years (range 21-84). 54% received vaccination with ChAdOx1 nCoV-19 and 44% received BNT162b2 (2% unrecorded). The vaccines were well tolerated with no serious adverse events to date. The mean interval between doses was 70.7 days (range 50 - 90 days). 71% of the cohort were receiving no disease modifying therapy at the time of vaccination, half of whom were receiving supportive therapy and the other half no intervention for their MDS. Of those receiving disease modifying therapy;5 were receiving azacitidine, (1 in conjunction with low-dose cytarabine) and 3 ciclosporin. We will report the largest study of the humoral and T-cell mediated response to the Covid-19 vaccine in MDS patients to date. This will include cellular response to the delta variant and immunogenicity of both the BNT162b2 and ChAdOx1 nCoV-19 vaccines. Given the vulnerability of these patients to severe disease, investigating the immune response to the vaccines begins to build an evidence base for advising MDS patients on their ongoing risk of infection during the pandemic and going forward. The SOAP study will reassess the immune response at 6 and 12 months post-vaccination to continue to investigate post-vaccine immunity in this cohort. Disclosures: Kulasekararaj: F. Hoffmann-La Roche Ltd.: Consultancy, Honoraria, Speakers Bureau;Apellis: Consultancy;Akari: Consultancy, Honoraria, Speakers Bureau;Biocryst: Consultancy, Honoraria, Speakers Bureau;Achilleon: Consultancy, Honoraria, Speakers Bureau;Alexion: Consultancy, Honoraria, Speakers Bureau;Ra Pharma: Consultancy, Honoraria, Speakers Bureau;Amgen: Consultancy, Honoraria, Speakers Bureau;Novartis: Consultancy, Honoraria, Speakers Bureau;Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau;Alexion, AstraZeneca Rare Disease Inc.: Consultancy, Honoraria, Other: Travel support. Patten: JANSSEN: Honoraria;NOVARTIS: Honoraria;GILEAD SCIENCES: Honoraria, Research Funding;ROCHE: Research Funding;ASTRA ZENECA: Honoraria;ABBVIE: Honoraria.