Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults (preprint)

Heterogeneity in SARS-CoV-2 vaccine responses is not understood. Here, we identify four patterns of live-virus neutralizing antibody responses: individuals with hybrid immunity (with confirmed prior infection); rare individuals with low responses (paucity of S1-binding antibodies); and surprisingly, two further groups with distinct serological repertoires. One group - broad responders - neutralize a range of SARS-CoV-2 variants, whereas the other - narrow responders - neutralize fewer, less divergent variants. This heterogeneity does not correlate with Ancestral S1-binding antibody, rather the quality of the serological response. Furthermore, IgDlowCD27-CD137+ B cells and CCR6+ CD4+ T cells are enriched in broad responders before dose 3. Notably, broad responders have significantly longer infection-free time after their third dose. Understanding the control and persistence of these serological profiles could allow personalized approaches to enhance serological breadth after vaccination.

Non-hospitalised, vaccinated adults with COVID-19 caused by Omicron BA.1 and BA.2 present with changing symptom profiles compared to those with Delta despite similar viral kinetics (preprint)

Introduction The impact of COVID-19 vaccination on disease in the community has been limited, as a result of both SARS-CoV-2 Variants of Concern that partially escape vaccine-induced immunity. We sought to characterise symptoms and viral loads over the course of COVID-19 infection in otherwise-healthy vaccinated adults, representative of the general population, to assess whether current self-isolation guidance remains justified. Methods In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive PCR or lateral flow test, self-swabbed on alternate days until day 10. We compared symptoms and viral kinetics between infections caused by VOCs Delta and Omicron (sub-variants BA.1 and BA.2) and investigated applicability of UK NHS isolation guidelines to these newer VOCs. Results 373 infection episodes were reported among 349 participants. Across VOCs, symptom duration was similar, however symptom profiles differed significantly among infections caused by Delta, Omicron BA.1 and BA.2. Anosmia was reported in <10% of participants with BA.1 and BA.2, compared to 42% with Delta infection, coryza fatigue and myalgia predominated. Most notably, viral load trajectories and peaks did not differ between Delta, BA.1 and BA.2, irrespective of symptom severity, VOC or vaccination status. Conclusion COVID-19 isolation guidance should not differ based on symptom severity or febrile illness and must remain under review as new SARS-CoV-2 VOCs emerge and population immunity changes. Our study emphasises the ongoing transmission risk of Omicron sub-variants in vaccinated adults with mild symptoms that may extend beyond current isolation periods.

Immune responses following third COVID-19 vaccination are reduced in patients with hematologic malignancies compared to patients with solid cancer (preprint)

Not all patients with cancer, in particular those with hematogic malignancies, develop functional immunity against SARS-CoV-2 variants of concern (VOC) following COVID-19 vaccines. Durability of vaccine-induced immunity after two doses and the impact of a third dose were evaluated in CAPTURE (NCT03226886), a longitudinal prospective cohort study of vaccine responses in patients with cancer. In evaluating 316 patients, at a median of 111 days following two doses of either BNT16b2 or ChadOX, we observed a time-dependant decline in neutralising antibody titres (NAbT) in a proportion of patients, where NAbTs became undetectable against Delta and Beta in 17% and 15% of patients, respectively. Vaccine-induced T cell responses declined in 44% of patients. Patients with breakthrough infections following two vaccines doses were characterised by absent/low NAbT to Delta prior to infection. Administration of the third vaccine dose boosted NAb responses against VOC in the majority of patients with cancer, especially those with solid cancer. In patients with hematologic malignancies who had undetectable NAbT against Delta after two vaccine doses, 54% did not develop NAb against both Beta and Delta following the third dose. Third vaccine dose boosted T cell responses were boosted in patients with both solid and hematologic malignancies. These results provide critical information on vaccine responses in patients with cancer, especially against VOCs and support widespread access to a third COVID-19 vaccination in this patient group.

Getting our voice heard: empowering people with a learning disability to influence adult safeguarding policy

PurposeThe purpose of this paper is to present an examination of the development of adult safeguarding policy from the perspectives of both policymakers and those who have sought to influence policy, to empower individuals with a learning disability to have a say in how policies, that influence their life and impact their right to independence, are developed.Design/methodology/approachThis paper is based on a project which was led by a UK-wide interdisciplinary and multi-agency team, which included the central involvement of peer researchers who had lived experience of learning disability. It was based on a participatory disability research design.FindingsFactors which enabled or restrained individuals with a learning disability, and their supporting organisations, from getting their voice heard in policy development, are identified.Originality/valueThis paper builds on policy theory and research, making recommendations for policy makers, disabled people and their supporting organisations as to how adult safeguarding policy, could be more effectively informed and influenced.

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study (preprint)

CAPTURE (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable neutralizing antibody titers (NAbT) against SARS-CoV-2 variants of concern (VOCs) vs wild-type (WT). Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT vs solid cancers against both WT and VOCs. In comparison with individuals without cancer, patients with haematological, but not solid, malignancies had reduced NAb responses. Seroconversion showed poor concordance with NAbT against VOCs. Prior SARS-CoV-2 infection boosted NAb response including against VOCs, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T-cell responses were detected in 80% of patients, and were comparable between vaccines or cancer types. Our results have implications for the management of cancer patients during the ongoing COVID-19 pandemic.

Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections (preprint)

BackgroundRoutine asymptomatic testing using RT-PCR of people who interact with vulnerable populations, such as medical staff in hospitals or care workers in care homes, has been employed to help prevent outbreaks among vulnerable populations. Although the peak sensitivity of RT-PCR can be high, the probability of detecting an infection will vary throughout the course of an infection. The effectiveness of routine asymptomatic testing will therefore depend on testing frequency and how PCR detection varies over time. MethodsWe fitted a Bayesian statistical model to a dataset of twice weekly PCR tests of UK healthcare workers performed by self-administered nasopharyngeal swab, regardless of symptoms. We jointly estimated times of infection and the probability of a positive PCR test over time following infection, we then compared asymptomatic testing strategies by calculating the probability that a symptomatic infection is detected before symptom onset and the probability that an asymptomatic infection is detected within 7 days of infection. FindingsWe estimated that the probability that the PCR test detected infection peaked at 77% (54 - 88%) 4 days after infection, decreasing to 50% (38 - 65%) by 10 days after infection. Our results suggest a substantially higher probability of detecting infections 1-3 days after infection than previously published estimates. We estimated that testing every other day would detect 57% (33-76%) of symptomatic cases prior to onset and 94% (75-99%) of asymptomatic cases within 7 days if test results were returned within a day. InterpretationOur results suggest that routine asymptomatic testing can enable detection of a high proportion of infected individuals early in their infection, provided that the testing is frequent and the time from testing to notification of results is sufficiently fast. FundingWellcome Trust, National Institute for Health Research (NIHR) Health Protection Research Unit, Medical Research Council (UKRI)