New primary immunodeficiencies 2021 context and future.

PURPOSE OF REVIEW: Primary immunodeficiency diseases (PIDs), also called inborn errors of immunity (IEI), are genetic disorders classically characterized by an increased susceptibility to infection and/or disruption in the regulation of an immunologic pathway. This review summarizes and highlights the new IEI disorders in the IUIS 2019 report and 2020 interim report and discusses the directions for the future management of PIDs. RECENT FINDINGS: Since 2017, the International Union of Immunologic Societies (IUIS) IEI committee has updated the IUIS classification of IEIs with 88 new gene defects and 75 new immune disorders. The increased utilization of genetic testing and advances in the strategic evaluation of genetic variants have identified, not only novel IEI disorders, but additional genetic causes for known IEI disorders. Investigation of potential immune susceptibilities during the ongoing COVID-19 pandemic suggests that defects in Type I interferon signalling may underlie more severe disease. SUMMARY: The rapid discovery of new IEIs reflects the growing trend of applying genetic testing modalities as part of medical diagnosis and management.In turn, elucidating the pathophysiology of these novel IEIs have enhanced our understanding of how genetic mutations can modulate the immune system and their consequential effect on human health and disease.

Immunodeficient patient experience of emergency switch from intravenous to rapid push subcutaneous immunoglobulin replacement therapy during coronavirus disease 2019 shielding.

PURPOSE OF REVIEW: Welsh immunodeficient patients on immunoglobulin replacement therapy (IgRT) who were considered high risk for severe coronavirus disease 2019 (COVID-19) were directed to shield. Consequently, patients receiving hospital-based intravenous immunoglobulin (IVIg) quickly transitioned to home-based self-administered subcutaneous immunoglobulin (SCIg). This evaluation aimed to assess patients' perceptions and experiences and laboratory outcomes of emergency IgRT transition during COVID-19. RECENT FINDINGS: A quick transition from in-hospital IVIg to home-based rapid push SCIg is achievable, however, patient IgRT administration preference remains key outside of emergency shielding measures. SUMMARY: Subjective self-reported experiences ( n  = 23) and objective immunoglobulin G (IgG) concentration ( n  = 28) assessments were prospectively collected from patients pre/post-IgRT switch. In total, 41/55 (75%) patients transitioned from IVIg to rapid push SCIg and all completed training to self-administer subcutaneously within 24 days. Twenty-two percent ( n  = 5) of patients preferred SCIg and 35% ( n  = 8) wanted to return to hospital-based IVIg at 6 weeks post-transition. Mean IgG levels were similar pre vs. post-SCIg switch (10.3 g/l vs. 10.6 g/l, respectively). Patients reported greater infection anxiety during COVID-19 and adapted behaviours to mitigate risk. Although a third of patients wished to return to IVIg following cessation of shielding, over time the percentage electing to remain on SCIg rose from 22% to 59%.

Treatment of chronic or relapsing COVID-19 in immunodeficiency.

BACKGROUND: Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown. OBJECTIVE: Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting ≥21 days) or relapsing (≥2 episodes) of COVID-19. RESULTS: We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of ≤20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise.

Advances in clinical outcomes: What we have learned during the COVID-19 pandemic.

Our understanding of risk factors and interventions influencing outcomes from coronavirus disease 2019 (COVID-19) has continued to evolve, revealing advances emerging from hypotheses formed at the start of the pandemic. Epidemiologic studies have shown that asthma control, rather than a diagnosis of asthma, is a determinant of COVID-19 severity. Clinical outcomes in patients with primary immunodeficiencies, even in those with impaired cellular immunity, are variable. IL-6 has emerged as a reliable biomarker of COVID-19 severity, and large clinical trials have shown the potential for improving outcomes through inhibition of IL-6 signaling in some patients. Studies of genetic risk factors for severe COVID-19 have also revealed the importance of interferon homeostasis in the defense against severe acute respiratory syndrome coronavirus 2. Because COVID-19 vaccines constitute the primary tool for ending this pandemic, strategies have been developed to address potential allergic and immune-mediated reactions. Here, we discuss advances in our understanding of COVID-19 risk factors and outcomes within the context of allergic and immunologic mechanisms.

Managing childhood allergies and immunodeficiencies during respiratory virus epidemics - The 2020 COVID-19 pandemic: A statement from the EAACI-section on pediatrics.

While the world is facing an unprecedented pandemic with COVID-19, patients with chronic diseases need special attention and if warranted adaptation of their regular treatment plan. In children, allergy and asthma are among the most prevalent non-communicable chronic diseases, and healthcare providers taking care of these patients need guidance. At the current stage of knowledge, children have less severe symptoms of COVID-19, and severe asthma and immunodeficiency are classified as risk factors. In addition, there is no evidence that currently available asthma and allergy treatments, including antihistamines, corticosteroids, and bronchodilators, increase the risk of severe disease from COVID-19. Most countries affected by COVID-19 have opted for nationwide confinement, which means that communication with the primary clinician is often performed by telemedicine. Optimal disease control of allergic, asthmatic, and immunodeficient children should be sought according to usual treatment guidelines. This statement of the EAACI Section on Pediatrics puts forward six recommendations for the management of childhood allergies and immunodeficiencies based on six underlying facts and existing evidence.