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 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.

SummaryVaccine‐specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens, but interpretation may be complicated. Typhim Vi®, a polysaccharide vaccine for Salmonella typhoid fever, may be an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multi‐centre study describing the analytical and clinical performance of a Typhi Vi immunoglobulin (Ig)G enzyme‐linked immunosorbent assay (ELISA) calibrated to an affinity‐purified Typhi Vi IgG preparation. Intra‐ and interassay imprecision was low and the assay was linear, between 7·4 and 574 U/ml (slope = 0·99–1·00; R 2 > 0·99); 71% of blood donors had undetectable Typhi Vi IgG antibody concentrations. Of those with antibody concentrations  > 7·4 U/ml, the concentration range was 7·7–167 U/ml. In antibody‐deficient patients receiving antibody replacement therapy the median Typhi Vi IgG antibody concentrations were  < 25 U/ml. In vaccinated normal healthy volunteers, the median concentration post‐vaccination was 107 U/ml (range 31–542 U/ml). Eight of eight patients (100%) had post‐vaccination concentration increases of at least threefold and six of eight (75%) of at least 10‐fold. In an antibody‐deficient population (n = 23), only 30% had post‐vaccination concentration increases of at least threefold and 10% of at least 10‐fold. The antibody responses to Pneumovax II and Typhim Vi® correlated. We conclude that IgG responses to Typhim Vi® vaccination can be measured using the VaccZyme Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a useful additional test to accompany Pneumovax II responses for the assessment of antibody deficiencies.

Electrical Impedance Tomography (EIT) has successive wide range in impedance imaging, but still it is difficult to extract cardiac-related conductivity changes and respiratory-related conductivity changes in spontaneous breathing subjects. Quite a few methods are attempted to extract these two signals such as electrocardiogram gated averaging, frequency domain filtering and principal component analysis. However, such methods are not able to take apart these components properly or put some effort in real time imaging and have their own limitations. The purpose of this paper is to introduce a new method in the EIT clinical application field, Independent Component Analysis (ICA) to extract cardiac and respiratory related signals in electrical impedance tomography. Independent component analysis has been introduced to use in electrical impedance tomography but this is the first attempt ever to implement this method to separate these two signals and image those independent conductivity distribution of respiration and cardiac changes independently. Data has been collected from a spontaneous breathing subject. Filtration technique has been used to remove random noise and multi level spatial ICA has been applied to obtain independent component signals which has been later used in reconstruction algorithm for imaging.

Purpose To define the burden of morbidity and mortality arising from COVID-19 in individuals with primary (PID) and secondary immunodeficiency (SID) in the United Kingdom. Methods 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. Anonymised demographic data, pre-SARS-CoV-2 infection lymphocyte counts, co-morbidities, targeted treatments and outcomes were collected. Three groups were analysed in further detail: individuals with common variable immunodeficiency (CVID), individuals with any PID, including CVID, receiving immunoglobulin replacement therapy (IgRT) and individuals with secondary immunodeficiency. Results 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 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. Conclusion 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.

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