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.

Lessons of the month 2: Meningococcal epiglottitis and connective tissue disease associated with C2 deficiency.

CASE PRESENTATION: A 68-year-old woman was referred for immunological investigation following an episode of meningococcal epiglottitis with associated septicaemia. Several years previously, she had been diagnosed with undifferentiated connective tissue disease. On investigation, alternative pathway complement function was normal; however, classical pathway complement activation was reduced. C1q, C3 and C4 levels were all measured and found to be within their respective normal ranges, but C2 levels were low. Sequencing of the C2 gene was subsequently performed, confirming a diagnosis of type 1 C2 deficiency (C2D). DISCUSSION: C2D is usually hereditary and inherited in an autosomal recessive manner. C2D is often asymptomatic, however, some patients suffer from infections with encapsulated bacteria and/or autoimmune diseases, particularly systemic lupus erythematosus. Recognition of complement pathway deficiency is important due to the predisposition to severe and/or recurrent infections by encapsulated bacteria. Immunisations have the potential to reduce both mortality and morbidity not only for the patient but also for any affected relatives.