Antibody prevalence after 3 or more COVID-19 vaccine doses in 23,000 immunosuppressed individuals: a cross-sectional study from MELODY (preprint)

Objectives: To investigate the prevalence of spike-protein antibodies following at least 3 COVID-19 vaccine doses in immunocompromised individuals. Design Cross-sectional study using UK national disease registries of individuals with solid organ transplants (SOT), rare autoimmune rheumatic diseases (RAIRD) and lymphoid malignancies (LM). Setting: Participants were identified, invited and recruited at home by accessing the NHS Blood and Transplant Registry for those UK individuals who had received a SOT; and the National Disease Registration Service at NHS Digital for identifying individuals within England with RAIRD or LM. Participants: 101972 people were invited, 28411 recruited, and 23036 provided serological data, comprising 9927 SOT recipients, 6516 with RAIRD, and 6593 with LM. Interventions: Participants received a lateral flow immunoassay for spike-protein antibodies to perform at home together with an online questionnaire. Main outcome measures Odds of detectable IgG spike-protein antibodies in immunosuppressed cohorts following at least three COVID-19 vaccine doses by participant demographic, disease type, and treatment related characteristics Results: IgG spike-protein antibodies were undetectable in 23.3%, 14.1% and 20.7% of the SOT, RAIRD and LM cohorts, respectively. Participants had received three, four or [≥]five vaccine doses at the time of testing in 28.5%, 61.8%, and 9.6%, respectively. In all groups, seropositivity was associated with younger age, higher number of vaccine doses and previous COVID-19 infection. Immunosuppressive medication reduced the likelihood of seropositivity: the lowest odds of seropositivity were found in SOT recipients receiving an anti-proliferative agent, calcineurin inhibitor and steroid concurrently, and those treated with anti-CD20 in the RAIRD and LM cohorts. Conclusions: Approximately one in five individuals with SOT, RAIRD and LM have no detectable IgG spike-protein antibodies despite three or more vaccines, but this proportion reduces with sequential booster doses. Choice of immunosuppressant and disease-type is strongly associated with serological response. Antibody testing could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions.

COVID-19 infection, hospitalisation and death Amongst People with Rare Autoimmune Rheumatic Disease in England. Results from the RECORDER Project. (preprint)

ObjectivesTo calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared to the general population. MethodsWe used Hospital Episode Statistics to identify all people alive 01 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths. ResultsWe identified a cohort of 168,680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardised infection rate was 1.54 (95% CI 1.50-1.59) times higher than in the general population. 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardised mortality rate for COVID-19-related death was 2.41 (2.30 - 2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. ConclusionsDuring the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared to the general population. These increases were seen despite shielding policies. Key MessagesO_LIPeople with RAIRD were at increased risk of COVID-19 infection during the first wave. C_LIO_LICompared to the general population, they had over twice the risk of COVID-19-related death. C_LIO_LIThese increased risks were seen despite shielding policies in place in England. C_LI

Risk of death during the 2020 UK COVID-19 epidemic among people with rare autoimmune diseases compared to the general population. Preliminary results from the RECORDER project. (preprint)

Objectives: To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 epidemic compared with baseline risk and the risk of death in the general population during COVID-19. Design A cohort study using data from the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS). We used ONS published data for general population mortality rates. Setting: Hospital Episode Statistics for England 2003 onwards, and linked data from the NHS Personal Demographics Service. Participants: 168,691 people with RAIRD who were alive on 1 March 2020. Their median age was 61.7 (IQR 41.5-75.4) years, and 118,379 (70.2%) were female. Our case ascertainment methods had a positive predictive value >85%. Main outcome measure: Age-standardised mortality rates for all-cause death. Secondary outcome measures were age-sex standardised mortality rates, and age-stratified mortality rates. Results: 1,815 (1.1%) participants died during March and April 2020. The age-standardised mortality rate (ASMR) among people with RAIRD (3669.3, 95% CI 3500.4-3838.1 per 100,000 person-years) was 1.44 (95% CI 1.42-1.45) times higher than the average ASMR during the same months of the previous 5 years, whereas in the general population of England it was 1.38 times higher. Compared to the general population, the age-specific mortality rates in people with RAIRD compared to the pre-COVID rates were higher from the age of 35 upwards, whereas in the general population the increased risk began from age 55 upwards. Sex-specific rates were similar in males and females, whereas in the general population females had a lower rate than males. Conclusions: The risk of all-cause death is more prominently raised during COVID-19 among people with RAIRD than among the general population. We urgently need to quantify how much risk is due to COVID-19 infection and how much is due to disruption to healthcare services, in order to inform better guidance about shielding, access to healthcare and vaccine priorities for people with rare diseases.