Impact of vaccination on hospitalization and mortality from COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience

Abstract

BackgroundIndividuals with primary and secondary immunodeficiency (PID/SID) were shown to be at risk of poor outcomes during the early stages of the SARS-CoV-2 pandemic. SARS-CoV-2 vaccines demonstrate reduced immunogenicity in these patients.ObjectivesTo understand whether the risk of severe COVID-19 in individuals with PID or SID has changed following the deployment of vaccination and therapeutics in the context of the emergence of novel viral variants of concern.MethodsThe outcomes of two cohorts of patients with PID and SID were compared: the first, infected between March and July 2020, prior to vaccination and treatments, the second after these intervention became available between January 2021 and April 2022.Results22.7% of immunodeficient patients have been infected at least once with SARS-CoV-2 since the start of the pandemic, compared to over 70% of the general population. Immunodeficient patients were typically infected later in the pandemic when the B.1.1.529 (Omicron) variant was dominant. This delay was associated with receipt of more vaccine doses and higher pre-infection seroprevalence. Compared to March-July 2020, hospitalization rates (53.3% vs 17.9%, p<0.0001) and mortality (Infection fatality rate 20.0% vs 3.4%, p=0.0003) have significantly reduced for patients with PID but remain elevated compared to the general population. The presence of a serological response to vaccination was associated with a reduced duration of viral detection by PCR in the nasopharynx. Early outpatient treatment with antivirals or monoclonal antibodies reduced hospitalization during the Omicron wave.ConclusionsMost individuals with immunodeficiency in the United Kingdom remain SARS-CoV-2 infection naïve. Vaccination, widespread availability of outpatient treatments and, possibly, the emergence of the B.1.1.529 variant have led to significant improvements in morbidity and mortality followings SARS-CoV-2 infection since the start of the pandemic. However, individuals with PID and SID remain at significantly increased risk of poor outcomes compared to the general population; mitigation, vaccination and treatment strategies must be optimized to minimize the ongoing burden of the pandemic in these vulnerable cohorts.

Dose reductions in immunoglobulin replacement are associated with increased antibiotic usage in patients with antibody deficiency

“…Following immunoglobulin dose reduction, total antibiotic use in the dose-reduced cohort increased from 62 to 121 courses of antibiotics in the 12 months before and after dose reduction, respectively (rate ratio 1.95 (95% CI 1.42-2.70), p < 0.0001). Although COVID-19 shielding policies may have contributed to a reduced burden of infectious disease in this cohort prior to July 2021, 8 no significant increase in antibiotic use was observed in the control cohort, despite the relaxation of non-pharmacological interventions from July 2021 onwards, strengthening the association between reduced trough IgG and infections requiring antibiotic use.…”

Clinical and laboratory characteristics of patients with symptomatic secondary immunodeficiency following the treatment of haematological malignancies

“…The loss of humoral immunity to Pn14 and HiB may be a surrogate marker for the disruption of the reservoir of high-quality humoral immunity and therefore provide valuable insight into the severity of the immune deficiency. CoV-2 vaccination schedule, rising to 76.0% after three doses [23][24][25].…”

The protection of CoronaVac against the infection of wild‐type SARS‐CoV‐2 (WH‐09) or Omicron variant in nude‐hACE2 mice

“…7 The World Health Organization states that immunization plans should give preference to vulnerable groups, including the elderly, people with immune deficiencies, and those with underlying health. 8 It should be noted that there are many types of such diseases, and we…”

“… 4–6 One of the important reasons for excluding immune‐deficient individuals is that immune deficiency can impair the humoral immune responses and cellular immune responses induced by vaccines, making it difficult to measure the effectiveness on the immune system 7 . The World Health Organization states that immunization plans should give preference to vulnerable groups, including the elderly, people with immune deficiencies, and those with underlying health 8 . It should be noted that there are many types of such diseases, and we have not yet fully understood the pathogenesis.…”

“…| DISCUSS IONImmunocompromised individuals often experience inflammation and are at an increased risk of contracting SARS-CoV-2. They are more likely to develop severe illness as a result of infection 8,[14][15][16]. Rodents have been widely used to study the pathogenesis and vaccination response of SARS-CoV-2 due to their wide availability and short growth cycle.…”