Highlights1. What is already known about this topic? SARS-CoV-2 causes asymptomatic or mild infection in about 80% of humans, while an excessive immune response has killed millions. Differential susceptibility and risk factors became a concern early in the pandemic. Several monogenic defects that involve innate viral sensors or affect interferon response pathways, as well as autoantibodies against type 1 interferons, have been identified in 14% of patients with life-threatening COVID-19. The impact of the novel betacoronavirus infection in patients with known inborn errors of immunity is less clear. Case series and reports from different countries have suggested a minor impact or even a potential protective effect of the IEI for some patients.2. What does this article add to our knowledge? We describe findings and outcomes of COVID-19 in 31 pediatric and adult patients with known IEI from Mexico, 84% of whom survived. Pediatric patients had a higher hospitalization rate. Inpatient mortality was 40%, and ICU mortality was 63%. Six patients died of secondary bacterial infection or uncontrolled systemic inflammation, but not from overwhelming viral infection. One patient with an autoinflammatory disorder under treatment with anakinra had a catastrophic clinical course. Eighty percent of patients received IVIG as part of their treatment for acute SARS-CoV-2 infection.3. How does this study impact current management guidelines? We recommend continued and/or high-dose IVIG in patients with known IEI seeking care for COVID-19. Patients with autoinflammatory disorders, especially those with inflammasome dysregulation, should probably take extreme measures to prevent exposure, while doctors taking care of SARS-CoV-2 infected patients with immune deficiencies must do everything they can to prevent secondary bacterial infections. The high survival of patients with COVID-19 in the context of inborn errors of immunity worldwide (over 80%) might be the result of patientphysician awareness and special care.

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Mutations in the genes coding for cytokines, receptors, second messengers, and transcription factors of interferon gamma (IFN-γ) immunity cause Mendelian susceptibility to mycobacterial disease (MSMD). We report the case of a 7-year-old male patient with partial dominant (PD) IFN-γ receptor 1 deficiency who had suffered from multifocal osteomyelitis attributable to bacille Calmette–Guérin vaccination since the age of 18 months. He developed hemophagocytic lymphohistiocytosis (HLH), a hyper-inflammatory complication, and died with multiorgan dysfunction, despite having been diagnosed and treated relatively early. Patients with PD IFN-γR1 deficiency usually have good prognosis and might respond to human recombinant subcutaneous IFN-γ. Several monogenic congenital defects have been linked to HLH, a catastrophic “cytokine storm” that is usually ascribed to lymphocyte dysfunction and thought to be triggered by interferon gamma. This is the sixth patient with both MSMD and HLH of whom we are aware. The fact that patients with macrophages that cannot respond to IFN-γ still develop HLH, bring these assumptions into question.

Autosomal recessive (AR) DOCK8 deficiency is a well-known actinopathy, a combined primary immune deficiency with impaired actin polymerization that results in altered cell mobility and immune synapse. DOCK8-deficient patients present early in life with eczema, viral cutaneous infections, chronic mucocutaneous candidiasis, bacterial pneumonia, and abscesses, together with eosinophilia, thrombocytosis, lymphopenia, and variable dysgammaglobulinemia that usually includes Hyper-IgE. In fact, before its genetic etiology was known, patients were described as having a form of Hyper-IgE syndrome, a name now deprecated in favor of genetic defects. We describe a school-age male patient with a clinical picture suggestive of DOCK8 deficiency, except for high serum IgE or a family history: early onset, failure to thrive, eczema, warts, condyloma, bronchiolitis, pneumonia, recurrent otitis media, bronchiectasis, candidiasis, leukocytosis, eosinophilia, high IgA, low IgG, and low CD4+ T cells. We were able to confirm the diagnosis through protein expression and whole-exome sequencing. We review the clinical, laboratory, and genetic features of 200 DOCK8-deficient patients; at least 4 other patients have had no elevated IgE, and about 40% do not have Hyper-IgE (above 1,000 IU/mL). Despite this, the constellation of signs, symptoms, and findings allow the suspicion of DOCK8 deficiency and other actinopathies.

Background:  The diagnosis and treatment of diarrhea in liver transplant recipients often pose a challenge owing to the variety of infectious and non‐infectious causes. However, diagnosis is principally focused on ruling out an infectious etiology. Tacrolimus, an immunosuppressive agent generally used after liver transplantation, is absorbed mainly from the duodenum through the upper jejunum. It can be assumed that metabolism of the drug will be influenced by diarrhea. Methods:  Four liver transplant recipients who developed an episode of acute gastroenteritis. Infectious etiology was confirmed; trough tacrolimus levels were measured before, during and after gastroenteritis. Results:  All patients presented a two‐ to three‐fold increase in blood tacrolimus levels after the onset of gastroenteritis. Conclusions:  Until the role played by the intestine in the metabolism of tacrolimus is fully understood, it is prudent to recommend early dose reduction of tacrolimus and careful monitoring of trough levels during diarrheal disorders of any nature in pediatric liver‐transplanted patients.

Introducción. La enfermedad de Pompe es una miopatía metabólica rara con espectro clínico heterogéneo, especialmente la de inicio tardío, cuya sintomatología es de progresión más lenta y representa un gran reto diagnóstico. Objetivo. Describir el genotipo y las características clínicas de pacientes mexicanos con Pompe de inicio tardío (LOPD). Material y métodos. Se incluyó a 19 pacientes mexicanos con LOPD confirmada mediante actividad enzimática y estudio molecular del gen GAA . Se evaluaron datos clínicos y se revisaron las mutaciones en bases de datos genómicas. Resultados. La mediana de edad de inicio de los síntomas fue de 19 años (rango: 2-43 años), y la edad de diagnóstico, de 36 años (rango: 9-52 años). Los síntomas más frecuentes fueron debilidad axial y proximal ( n = 17; 89,5%), marcha basculante ( n = 17; 89,5%) e hiperlordosis ( n = 7; 36,8%). A 16 pacientes (84,2%) se les realizó electromiografía; 11 (57,8%) describieron patrón miopático y sólo en cinco pacientes (26%) se incluyó la valoración de los músculos paraespinales. Las variantes patogénicas más frecuentes en nuestra casuística fueron c.-32-13T>G, c.1799G>A y c.1082C>T. Conclusiones. Parecido a lo comunicado en publicaciones internacionales, la LOPD en México es clínicamente heterogénea; los pacientes pueden tardar años en llegar al diagnóstico. La debilidad muscular axial y proximal es el dato clínico más frecuente, por lo que la electromiografía debe incluir valoración de los músculos paraespinales. A excepción de una, las mutaciones encontradas en nuestra serie de casos se encuentran previamente descritas en las bases de datos de enfermedad de Pompe.

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Less than 20% of pediatric physicians have a positive attitude towards death. Most didn't value death as a passage or transition to a better life, or as a solution to life's problems.