Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK.

In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.

A National Survey of Hereditary Angioedema and Acquired C1 Inhibitor Deficiency in the United Kingdom.

BACKGROUND: Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care. OBJECTIVE: To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients. METHODS: A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data. RESULTS: The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home. CONCLUSIONS: Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients.

Clinical associations of the positive anti Ro52 without Ro60 autoantibodies: undifferentiated connective tissue diseases.

AIMS: Autoantibodies targeting Ro52 and Ro60 antigens are historically reported as anti SSA/Ro. In general anti SSA/Ro results are either anti Ro52+Ro60+ or anti Ro52-Ro60+ antibodies. Anti Ro52 without anti Ro60 (Ro52+ Ro60-) antibodies are often not reported routinely. This study intends to review the potential significance of these autoantibodies in the management of connective tissue diseases. METHOD: A retrospective survey of Ro52+Ro60- was carried out as part of the service evaluation of extractable nuclear antigen antibodies (ENA) reporting from the immunology laboratory, the NHS Greater Glasgow and Clyde (GGC), UK. The clinical documents and laboratory results of 97 patients with Ro52+Ro60- and 100 patients with Ro52+Ro60+ were reviewed. RESULTS: Seventy-one patients (73%) with anti Ro52+Ro60- antibodies have been diagnosed with autoimmune conditions including undifferentiated connective tissue diseases (n=14, 14%), systemic lupus erythematosus (n=10, 10%), Sjögren's syndrome (n=10, 10%) and rheumatoid arthritis (n=13, 13%). Twenty-three patients (24%) with anti Ro52+Ro60- antibodies have no autoimmune features but were found to have significant clinical conditions including malignancies. In contrast, 87 patients (87%) with anti Ro52+Ro60+ antibodies have autoimmune conditions including Sjögren's syndrome (n=34, 34%), systemic lupus erythematosus (SLE; n=23, 23%), undifferentiated connective tissue diseases (n=12, 12%) and rheumatoid arthritis (n=6, 6%). CONCLUSION: Anti Ro52 without anti Ro60 (Ro52+Ro60-) antibodies should be reported. In the majority of patients these autoantibodies were associated with various autoimmune diseases. Anti Ro52+Ro60- antibodies were also found in patients with significant clinical conditions including malignancies even though there was no suggestion of autoimmunity at the time of testing.