Investigation of SARS-CoV-2 RNA in milk produced by women with COVID-19 and follow-up of their infants: A preliminary study.

OBJECTIVES: Studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily transmitted from person to person via airborne droplets. It is unclear whether it can be shed into human milk and transmitted to a child via breastfeeding. We investigated the presence of SARS-CoV-2 RNA in human milk samples of 15 mothers with coronavirus disease 19 (COVID-19) and in the throat swab samples of their infants. METHODS: This is a prospective observational study in which breast milk samples were collected from 15 mothers with COVID-19. The presence of SARS-CoV-2 RNA in the whole human milk samples of the patients was investigated using RT-qPCR. All of the infants underwent a clinical follow-up during their 14-day isolation and their throat swab samples were tested for SARS-CoV-2 RNA. RESULTS: Of 15 mothers with COVID-19, SARS-CoV-2 RNA was detected in milk samples from 4 mothers. The throat swab samples from these mothers' infants were found to be positive for SARS-CoV-2 RNA. Three of the four mothers were breastfeeding. In addition, during the 14-day isolation, all but three of the mothers breastfed their infants. Of the 12 breastfed infants, while the test for SARS-CoV-2 RNA in throat swab samples was negative in 6 of the infants, the other 6 infants, who had mild COVID-19 symptoms, tested positive for SARS-CoV-2 RNA. Clinical outcomes of all mothers and infants were uneventful. CONCLUSION: To our knowledge, this is the first case series with the largest number of cases with SARS-CoV-2 RNA positivity in human milk samples of mothers with COVID-19. However, we believe that the benefits of breastfeeding may outweigh the risk of SARS-CoV-2 infection in infants.

BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies.

BACKGROUND: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. OBJECTIVES: We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. METHODS: An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. RESULTS: Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/µL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/µL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001). CONCLUSIONS: BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.

Combined immunodeficiency due to purine nucleoside phosphorylase deficiency: Outcome of three patients.

Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine salvage pathway. PNP deficiency, caused by the autosomal recessive mutations in the PNP gene, can lead to severe combined immunodeficiency (SCID). PNP deficiency patients typically have profound T-cell deficiency with variable B and NK cell functions. They present clinically with recurrent infections, failure to thrive, various neurological disorders, malignancies, and autoimmune diseases. Hematopoietic stem cell transplantation (HSCT) is the only available cure for patients with PNP deficiency. We present three patients, two of whom were successfully treated with HSCT. One patient died prior to HSCT due to EBV-associated lymphoma. Over the course of post-HSCT, there was no further aggravation of the patients' neurological symptoms. Although both of the patients still had mild developmental delay, new developmental milestones were achieved.

Allele *1 of HS1.2 enhancer associates with selective IgA deficiency and IgM concentration.

Selective IgA deficiency (IGAD) is the most common primary immunodeficiency, yet its pathogenesis is elusive. The IG (heavy) H chain human 3' Regulatory Region harbors three enhancers and has an important role in Ig synthesis. HS1.2 is the only polymorphic enhancer of the 3' RRs. We therefore evaluated HS1.2 allelic frequencies in 88 IGAD patients and 101 controls. Our data show that IGAD patients have a highly significant increase of homozygousity of the allele *1 (39% in the IGAD patients and 15% in controls), with an increase of 2.6-fold. Allele *4 has a similar trend of allele *2, both showing a significant decrease of frequency in IGAD. No relationship was observed between allele *1 frequencies and serum levels of IgG. However, allele *1 was associated in IGAD patients with relatively low IgM levels (within the 30th lowest percentile of patients). The HS1.2 polymorphism influences Ig seric production, but not IgG switch, in fact 30th lowest or highest percentile of IgG in patients did not associate to different frequencies of HS1.2 alleles. The control on normal healthy subjects did not correlate high or low levels of IgM or IgG with HS1.2 allelic frequence variation. Overall our candidate gene approach confirms that the study of polymorphisms in human diseases is a valid tool to investigate the function of these Regulatory Regions that confers multiple immune features.

Occupational injuries admitted to the Emergency Department.

BACKGROUND: We aimed to identify the characteristics, causes and rates of injuries associated with occupational accidents. METHODS: Patients who presented to the Emergency Department due to injuries occurring as a result of occupational accidents were determined retrospectively. In occupational injuries, several parameters were evaluated, such as gender, occurrence mechanism, injury type, injury localization, severity score of the injury, and the type of profession. RESULTS: The number of occupational injury admissions in the Emergency Departments of our two centers during 2006 was 1038. Mean age of the cases was 31.6+/-9.6. The most common mechanism of injuries was determined to be caught-in-machinery, at 31.5%, followed by blunt object injury (21.5%), fall from height (18.9%), penetrating-sharp object injury (17%), ocular foreign body (3.9%), and others. Isolated extremity injuries (74.2%) were the most common injury site, followed by multiple bodily injuries (8.5%), facial injuries (5.5%) and head-neck injuries (4.6%). While 90% of cases were discharged after treatment in the Emergency Department, 7% were referred to various departments for hospitalization. CONCLUSION: In the majority of cases, patients with injuries associated with occupational accidents presented to Emergency Departments. Observations in Emergency Departments may help reveal details of occupational injuries and prevent workplace-related accidents.

The efficacy of immunoglobulin replacement therapy in the long-term follow-up of the B-cell deficiencies (XLA, HIM, CVID).

Immunoglobulin replacement therapy is the essential treatment of B-cell deficiencies. Because of the high expense of therapy, optimal dose, infusion intervals and serum IgG levels should be well defined. Data of 19 X-linked agammaglobulinemia (XLA), 7 hyper-IgM syndrome (HIM) and 20 common variable immunodeficiency (CVID) patients were analyzed. Infection frequencies and hospitalization requirements were correlated with the immunoglobulin doses used and serum IgG levels achieved. The characteristics before diagnosis and after treatment were compared among the XLA, HIM and CVID groups. By using a median dose of 370 mg/kg/month immunoglobulin, which maintained serum IgG levels at a median concentration of 440 mg/dl, the annual incidence of infections dropped from 12.4 to 3.2 and annual hospitalization requirements decreased from 1.6 to 0.16 per patient. Serum IgG levels of 300-500 mg/dl were found to be satisfactory, except in the CVID group. Increasing the level over 500 mg/dl neither prevented pneumonia further nor decreased the need for hospitalization. Monthly replacement was found to be adequate, except for XLA patients. Serum IgG levels between 300-500 mg/dl are sufficient for effective treatment of hypogammaglobulinemias. These concentrations can be maintained with 300-400 mg/kg/month doses. Higher doses and IgG levels are not needed.

Value of serum and bronchoalveolar fluid lavage pro- and anti-inflammatory cytokine levels for predicting bronchopulmonary dysplasia in premature infants.

OBJECTIVE: The aim of this study was to determine the value of pro- and anti-inflammatory cytokine levels in both blood and tracheal aspirate (TA) samples that were obtained within 24 h after birth for predicting bronchopulmonary dysplasia (BPD) development in premature infants. MATERIAL AND METHODS: Premature infants, who were born before 32 weeks of gestation, weighing less than 1,500 g, and admitted with respiratory distress between September 2009 and December 2010, were enrolled. Tracheal aspirate samples and serum were obtained from all infants on the first day of admittance for evaluation of pro- and anti-inflammatory cytokine levels using ELISA. RESULTS: The study included 102 premature babies of whom 31 (30%) had BPD diagnosed in the follow-up. Mild, moderate and severe BPD was diagnosed in 10 (32%), 14 (45%) and seven (23%) infants, respectively. Both serum and TA sample pro-inflammatory cytokine (TNF-α, IL-1ß, IL-6) levels were significantly higher, and anti-inflammatory cytokine (IL-10) levels were significantly lower in infants who developed BPD compared with those who had no BPD. No significant differences were detected in either serum or TA sample pro- and anti-inflammatory cytokine concentrations in preterm infants with BPD in terms of BPD severity. Cut-off values of both serum and TA sample pro- and anti-inflammatory cytokine concentrations for predicting BPD were also determined. CONCLUSION: It is suggested that higher serum and TA pro-inflammatory cytokine (TNF-α, IL-1ß, IL-6) concentrations, along with lower anti-inflammatory cytokine (IL-10) concentrations, might be used for predicting the development of BPD in premature infants with respiratory distress at birth.

Primary B cell immunodeficiencies: comparisons and contrasts.

Sophisticated genetic tools have made possible the identification of the genes responsible for most well-described immunodeficiencies in the past 15 years. Mutations in Btk, components of the pre-B cell and B cell receptor (lambda5, Igalpha, Igbeta), or the scaffold protein BLNK account for approximately 90% of patients with defects in early B cell development. Hyper-IgM syndromes result from mutations in CD40 ligand, CD40, AID, or UNG in 70-80% of affected patients. Rare defects in ICOS or CD19 can result in a clinical picture that is consistent with common variable immunodeficiency, and as many as 10% of patients with this disorder have heterozygous amino acid substitutions in TACI. For all these disorders, there is considerable clinical heterogeneity in patients with the same mutation. Identifying the genetic and environmental factors that influence the clinical phenotype may enhance patient care and our understanding of normal B cell development.