Controversies about immunoglobulin replacement therapy in HSCT recipients with hypogammaglobulinemia.

The efficacy of immunoglobulin replacement therapy (IgRT) has been demonstrated for primary immune deficiency diseases and hematological malignancies such as chronic lymphocytic leukemia (CLL) or multiple myeloma with hypogammaglobulinemia. Clinical development of anti-B cell therapies including a monoclonal antibody, bispecific antibody, or chimeric antigen receptor T-cell therapy which could result in severe hypogammaglobulinemia accelerates the argument of prophylactic use of IgRT. Clinical guidelines for CLL describe immunoglobulin administration in patients with a low IgG who have experienced a severe/repeated bacterial infection. The utility in hematopoietic stem-cell transplantation (HSCT) remains unknown. Although an early randomized trial demonstrated that IgRT decreased infection risk and transplant-related mortality after HSCT, subsequent clinical trials could not validate the benefit. Consequently, a meta-analysis did not show the benefit of IgRT in HSCT. Most of the available data derives from matched-related HSCT using myeloablative regimen, and the impact in haploidentical and cord blood transplantation, or reduced-intensity HSCT remains unknown. One crucial issue is that no studies exist for patients with only hypogammaglobulinemia after HSCT. Other challenges are heterogeneous patient characteristics, or immunoglobulin formulation, dosage, schedule, route and duration of IgRT. Without evidence in HSCT, it would be reasonable to follow the guidelines for other diseases with hypogammaglobulinemia.

Update on Infections in Primary Antibody Deficiencies.

Bacterial respiratory tract infections are the hallmark of primary antibody deficiencies (PADs). Because they are also among the most common infections in healthy individuals, PADs are usually overlooked in these patients. Careful evaluation of the history, including frequency, chronicity, and presence of other infections, would help suspect PADs. This review will focus on infections in relatively common PADs, discussing diagnostic challenges, and some management strategies to prevent infections.

The Clinical Course of COVID-19 Pneumonia in a 19-Year-Old Man on Intravenous Immunoglobulin Replacement Therapy for X-Linked Agammaglobulinemia.

BACKGROUND Since the emergence of coronavirus disease 2019 (COVID-19), patients with the illness have presented with considerable variation in severity. Some infected individuals present mild or no symptoms, while others present severe illness with some fatal outcomes. Multiple lines of management have been suggested for critically ill patients, such as intravenous immunoglobulin (IVIG) and steroids. IVIG is the main treatment for patients with X-linked agammaglobulinemia. Multiple studies have reported that these patients have excellent outcomes when they contract COVID-19. This report describes the clinical course of COVID-19 pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a 19-year-old man on IVIG replacement therapy for X-linked agammaglobulinemia (XLA). CASE REPORT A patient with XLA receiving a monthly dose of IVIG and having bronchiectasis managed by prophylactic azithromycin presented with fever, shortness of breath, productive cough, and diarrhea. He was admitted to our hospital with SARS-CoV-2 infection. His treatment course for COVID-19 was uncomplicated and had excellent results. He completed a 10-day course of piperacillin/tazobactam and his symptoms resolved 3 days after admission, without complications, oxygen supplementation, or intensive care unit admission. CONCLUSIONS Patients with XLA have weakened immunity and therefore may present with an infection as a first symptom. This report describes the mild course of COVID-19 pneumonia in an immunologically vulnerable patient with XLA who presented with SARS-CoV-2 infection while undergoing IVIG replacement therapy. Currently, IVIG is one of many supportive immune therapies undergoing clinical evaluation in patients with severe COVID-19.

Two X-linked agammaglobulinemia patients develop pneumonia as COVID-19 manifestation but recover.

BACKGROUND: The recent SARS-CoV-2 pandemic, which has recently affected Italy since February 21, constitutes a threat to normal subjects, as the coronavirus disease-19 (COVID-19) can manifest with a broad spectrum of clinical phenotypes ranging from asymptomatic cases to pneumonia or even death. There is evidence that older age and several comorbidities can affect the risk to develop severe pneumonia and possibly the need of mechanic ventilation in subjects infected with SARS-CoV-2. Therefore, we evaluated the outcome of SARS-CoV-2 infection in patients with inborn errors of immunity (IEI) such as X-linked agammaglobulinemia (XLA). METHODS: When the SARS-CoV-2 epidemic has reached Italy, we have activated a surveillance protocol of patients with IEI, to perform SARS-CoV-2 search by nasopharyngeal swab in patients presenting with symptoms that could be a manifestation of COVID-19, such as fever, cough, diarrhea, or vomiting. RESULTS: We describe two patients with X-linked agammaglobulinemia (XLA) aged 34 and 26 years with complete absence of B cells from peripheral blood who developed COVID-19, as diagnosed by SARS-CoV-2 detection by nasopharyngeal swab, while receiving immunoglobulin infusions. Both patients developed interstitial pneumonia characterized by fever, cough, and anorexia and associated with elevation of CRP and ferritin, but have never required oxygen ventilation or intensive care. CONCLUSION: Our report suggests that XLA patients might present with high risk to develop pneumonia after SARS-CoV-2 infection, but can recover from infection, suggesting that B-cell response might be important, but is not strictly required to overcome the disease. However, there is a need for larger observational studies to extend these conclusions to other patients with similar genetic immune defects.