Off-label use of dalbavancin in children: a case series.

INTRODUCTION: Dalbavancin is an antibiotic active against most Gram-positive bacteria approved for acute bacterial skin and skin structure infections (ABSSSI). Owing to its long half-life, it is being increasingly used for other indications. PATIENTS AND METHODS: We present a case series of children and adolescents treated with dalbavancin for osteoarticular, catheter-related and other non-ABSSSI infections. RESULTS: Dalbavancin was prescribed to 15 patients. Six (40%) were female and median age at prescription was 11.9 (IQR 1.3-18.0) years. Most of them (12/15) had significant comorbidities. Patients presented mainly with deep surgical site infections, osteoarticular infections and central-line-associated bloodstream infections. The most common isolate was Staphylococcus aureus followed by Staphylococcus epidermidis. Major reasons to prescribe dalbavancin were to ensure compliance and patients' convenience. Two patients discontinued the drug due to adverse events possibly related to it. The rest of the patients completed the treatment with dalbavancin, with a median duration of 56 days (IQR 17.5, 115.5). All achieved complete resolution and present no relapse after a median follow-up of 9.9 months (IQR 4.8, 16.6). CONCLUSIONS: Dalbavancin was a safe, effective and convenient alternative in selected paediatric patients with complicated non-ABSSSI infections caused by Gram-positive bacteria.

SARS-CoV-2 transmission in teenagers and young adults in Fútbol Club Barcelona's Multidisciplinary Sports Training Academy.

Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020-2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 (p < 0.01). A Basketball team showed a significant higher AR.  Conclusion: Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential. What is Known: • Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum. • The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings. What is New: • Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied. • Routine and semi-professional sports activities seem safe environments to promote during this pandemic.

Treatments for multi-system inflammatory syndrome in children - discharge, fever, and second-line therapies.

Scarce evidence exists about the best treatment for multi-system inflammatory syndrome (MIS-C). We analyzed the effects of steroids, intravenous immunoglobulin (IVIG), and their combination on the probability of discharge over time, the probability of switching to second-line treatment over time, and the persistence of fever 2 days after treatment. We did a retrospective study to investigate the effect of different treatments on children with MIS-C from 1 March 2020 to 1 June 2021. We estimated the time-to-event probability using a Cox model weighted by propensity score to balance the baseline characteristics. Thirty of 132 (22.7%) patients were initially treated with steroids alone, 29/132 (21.9%) with IVIG alone, and 73/132 (55%) with IVIG plus steroids. The probability of early discharge was higher with IVIG than with IVIG plus steroids (hazard ratio [HR] 1.65, 95% CI 1.11-2.45, p = 0.013), but with a higher probability of needing second-line therapy compared to IVIG plus steroids (HR 3.05, 95% CI 1.12-8.25, p = 0.028). Patients on IVIG had a higher likelihood of persistent fever than patients on steroids (odds ratio [OR] 4.23, 95% CI 1.43-13.5, p = 0.011) or on IVIG plus steroids (OR 4.4, 95% CI 2.05-9.82, p < 0.001). No differences were found for this endpoint between steroids or steroids plus IVIG.    Conclusions: The benefits of each approach may vary depending on the outcome assessed. IVIG seemed to increase the probability of earlier discharge over time but also of needing second-line treatment over time. Steroids seemed to reduce persistent fever, and combination therapy reduced the need for escalating treatment. What is Known: • Steroids plus intravenous immunoglobulin, compared with intravenous immunoglobulin alone for multi-system inflammatory syndrome (MIS-C) might reduce the need for hemodynamic support and the duration of fever, but the certainty of the evidence is low. What is New: • Intravenous immunoglobulin, steroids, and their combination for MIS-C may have different outcomes. • In this study, intravenous immunoglobulin increased the probability of discharge over time, steroids reduced persistent fever, while combination therapy reduced the need for second-line treatments.

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Children in Summer Schools Applying Stringent Control Measures in Barcelona, Spain.

BACKGROUND: Understanding the role of children in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is critical to guide decision-making for schools in the pandemic. We aimed to describe the transmission of SARS-CoV-2 among children and adult staff in summer schools. METHODS: During July 2020, we prospectively recruited children and adult staff attending summer schools in Barcelona who had SARS-CoV-2 infection. Primary SARS-CoV-2 infections were identified through (1) a surveillance program in 22 summer schools of 1905 participants, involving weekly saliva sampling for SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) during 2-5 weeks; and (2) cases identified through the Catalonian Health Surveillance System of children diagnosed with SARS-CoV-2 infection by nasopharyngeal RT-PCR. All centers followed prevention protocols: bubble groups, handwashing, face masks, and conducting activities mostly outdoors. Contacts of a primary case within the same bubble were evaluated by nasopharyngeal RT-PCR. Secondary attack rates and the effective reproduction number in summer schools (Re*) were calculated. RESULTS: Among the >2000 repeatedly screened participants, 30 children and 9 adults were identified as primary cases. A total of 253 close contacts of these primary cases were studied (median, 9 [interquartile range, 5-10] for each primary case), among which 12 new cases (4.7%) were positive for SARS-CoV-2. The Re* was 0.3, whereas the contemporary rate in the general population from the same areas in Barcelona was 1.9. CONCLUSIONS: The transmission rate of SARS-CoV-2 infection among children attending school-like facilities under strict prevention measures was lower than that reported for the general population. This suggests that under preventive measures schools are unlikely amplifiers of SARS-CoV-2 transmission, supporting current recommendations for school opening.

Dynamics of Reverse Transcription-Polymerase Chain Reaction and Serologic Test Results in Children with SARS-CoV-2 Infection.

OBJECTIVES: To determine the time to reverse transcription-polymerase chain reaction (RT-PCR) negativity after the first positive RT-PCR test, factors associated with longer time to RT-PCR negativity, proportion of children seroconverting after proven severe acute respiratory syndrome coronavirus 2 infection, and factors associated with the lack of seroconversion. STUDY DESIGN: The Epidemiological Study of Coronavirus in Children of the Spanish Society of Pediatrics is a multicenter study conducted in Spanish children to assess the characteristics of coronavirus disease 2019. In a subset of patients, 3 serial RT-PCR tests on nasopharyngeal swab specimens were performed after the first RT-PCR test, and immunoglobulin G serology for severe acute respiratory syndrome coronavirus 2 antibodies was performed in the acute and follow-up (<14 and ≥14 days after diagnosis) phase. RESULTS: In total, 324 patients were included in the study. The median time to RT-PCR negativity was 17 days (IQR, 8-29 days), and 35% of patients remained positive more than 4 weeks after the first RT-PCR test. The probability of RT-PCR negativity did not differ across groups defined by sex, disease severity, immunosuppressive drugs, or clinical phenotype. Globally, 24% of children failed to seroconvert after infection. Seroconversion was associated with hospitalization, persistence of RT-PCR positivity, and days of fever. CONCLUSIONS: Time to RT-PCR negativity was long, regardless of the severity of symptoms or other patient features. This finding should be considered when interpreting RT-PCR results in a child with symptoms, especially those with mild symptoms. Seroprevalence and postimmunization studies should consider that 11 in 4 infected children fail to seroconvert.

Multi-inflammatory Syndrome in Children Related to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Spain.

Some clusters of children with a multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection.

Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain.

BACKGROUND: Surveillance tools to estimate viral transmission dynamics in young populations are essential to guide recommendations for school opening and management during viral epidemics. Ideally, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We aimed to estimate SARS-CoV-2 infection rates in children and adult populations in a school-like environment during the initial COVID-19 pandemic waves using an antibody-based field-deployable and non-invasive approach. METHODS: Saliva antibody conversion defined as ≥ 4-fold increase in IgM, IgA, and/or IgG levels to five SARS-CoV-2 antigens including spike and nucleocapsid constructs was evaluated in 1509 children and 396 adults by high-throughput Luminex assays in samples collected weekly in 22 summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st, 2020. RESULTS: Saliva antibody conversion between two visits over a 5-week period was 3.22% (49/1518) or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) assessed by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. CONCLUSION: Saliva antibody profiling including three isotypes and multiplexing antigens is a useful and user-friendlier tool for screening pediatric populations to detect low viral load exposures among children, particularly while they are not vaccinated and vulnerable to highly contagious variants, and to recommend public health policies during pandemics.

Fever without source as the first manifestation of SARS-CoV-2 infection in infants less than 90 days old.

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good. What is Known: • Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI). • The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce. What is New: • SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission. • Bacterial coinfection rarely coexists in those infants. • Inflammatory markers were not increased in children without bacterial coinfection. • Outcome is good in most patients.

The Use of Quinacrine in Nitroimidazole-resistant Giardia Duodenalis: An Old Drug for an Emerging Problem.

Background: There is little evidence regarding the management of refractory giardiasis after treatment with nitroimidazoles. This study estimates the proportion of persistent giardiasis in 3 hospitals in Barcelona, describes associated risk factors and genotype, and evaluates the efficacy rate of quinacrine in those with persistent giardiasis. Methods: A clinical, prospective, observational study was conducted in patients with giardiasis treated with nitroimidazoles. Those with persistent giardiasis were provided quinacrine. Molecular characterization of Giardia isolates was performed by polymerase chain reaction amplification of a fragment of tpi and bg genes. Results: Seventy-seven patients were recruited and treated with nitroimidazoles, and in 14 of 71 (20%) of patients followed up, Giardia persisted. Refractory giardiasis was associated with malaise (P = .007) and anorexia (P = .02), with previous giardiasis (P = .03), and with previous antibiotic (P = .02) or antiparasitic(P = .04) use. Quinacrine had an effectiveness rate of 100% in refractory giardiasis (n = 13; 95% confidence interval = 75-100). Molecular characterization showed that 17 (25%) Giardia isolates belonged to assemblage A, and 31 (43%) belonged to assemblage B. In refractory giardiasis, assemblage A and B were found responsible in 4 and 6 cases, respectively. Conclusions: Almost 20% of patients presented persistent giardiasis, belonging to both assemblages A and B, after nitroimidazole. Short course of quinacrine was effective in treating refractory cases. Further controlled studies should evaluate its efficacy and safety.

Towards a New Strategy for Diagnosis of Congenital Trypanosoma cruzi Infection.

The immigration of Latin American women of childbearing age has spread the congenital transmission of Chagas disease to areas of nonendemicity, and the disease is now a worldwide problem. Some European health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy common to all laboratories. Our aims were to (i) analyze the trend of passive IgG antibodies in the newborn by means of five serological tests for the diagnosis and follow-up of congenital Trypanosoma cruzi infection, (ii) assess the utility of these techniques for diagnosing a congenital transmission, and (iii) propose a strategy for a prompt, efficient, and cost-effective diagnosis of T. cruzi infection. In noninfected newborns, a continuous decreasing trend of passive IgG antibodies was observed, but none of the serological assays seroreverted in any the infants before 12 months. From 12 months onwards, serological tests achieved negative results in all the samples analyzed, with the exception of the highly sensitive chemiluminescent microparticle immunoassay (CMIA). In contrast, in congenitally infected infants, the antibody decline was detected only after treatment initiation. In order to improve the diagnosis of congenital T. cruzi infection, we propose a new strategy involving fewer tests that allows significant cost savings. The protocol could start 1 month after birth with a parasitological test and/or a PCR. If negative, a serological test would be carried out at 9 months, which if positive, would be followed by another at around 12 months for confirmation.

[Paediatric Chagas in a non-endemic area]. / Chagas pediátrico en zona no endémica.

INTRODUCTION: Immigration has introduced new diseases into Spanish society, one of which is Chagas disease. Young women of childbearing age and children infected with Trypanosoma cruzi from endemic areas are at risk of developing the disease years later, and pregnant women can transmit the infection through the placenta. METHODS: Serological screening for anti-T.cruzi antibodies was performed on all immigrant children coming from a Chagas endemic area and seen in our Pathology Unit between 2003 and 2008, as well as on newborns of T.cruzi positive infected pregnant women coming from Latin America. Two ELISA tests were used (bioelisa Chagas Biokit® with recombinant antigens, and an 'in house' ELISA with crude antigen). Patients with sufficient sample were also screened by nested PCR (TCZ3/Z4). RESULTS: A total of 202 children, aged 1 day to 14 years old were included in the study, of whom 22 (10.8%) were diagnosed with asymptomatic infection, 5 of which were congenital as they were born in this country. All infected patients received treatment with benznidazole, with three of them currently with a serologically negative result after treatment. CONCLUSION: Chagas disease is a new imported paediatric disease that can affect children from endemic countries, but can also be acquired in our country by vertical transmission. Therefore, we believe that it is essential to perform serological screening on all children and pregnant women in the prenatal care from endemic areas, and provide specific treatment for those infected patients, given the good results observed in the paediatric population.

Deciphering the Longevity and Levels of SARS-CoV-2 Antibodies in Children: A Year-Long Study Highlighting Clinical Phenotypes and Age-Related Variations.

BACKGROUND: Identifying potential factors correlated with the sustained presence of antibodies in plasma may facilitate improved retrospective diagnoses and aid in the appraisal of pertinent vaccination strategies for various demographic groups. The main objective was to describe the persistence of anti-spike IgG one year after diagnosis in children and analyse its levels in relation to epidemiological and clinical variables. METHODS: A prospective, longitudinal, observational study was conducted in a university reference hospital in the Metropolitan Region of Barcelona (Spain) (March 2020-May 2021). This study included patients under 18 years of age with SARS-CoV-2 infection (positive PCR or antigen tests for SARS-CoV-2). Clinical and serological follow-up one year after infection was performed. RESULTS: We included 102 patients with a median age of 8.8 years. Anti-spike IgG was positive in 98/102 (96%) 12 months after the infection. There were higher anti-spike IgG levels were noted in patients younger than 2 years (p = 0.034) and those with pneumonia (p < 0.001). A positive and significant correlation was observed between C-reactive protein at diagnosis and anti-spike IgG titre one-year after diagnosis (p = 0.027). CONCLUSION: Anti-SARS-CoV-2 IgG antibodies were detected in almost all paediatric patients one year after infection. We also observed a positive correlation between virus-specific IgG antibody titres with SARS-CoV-2 clinical phenotype (pneumonia) and age (under 2 years old).

Serological Outcome in the First Months of Life of Children Born to Mothers with SARS-CoV-2 Infection during Pregnancy.

BACKGROUND: The objective of this study is to analyze the transplacental transmission of SARS-CoV-2 antibodies, their persistence in newborns, the factors that may influence this transmission, and the protection these antibodies confer over time. METHODS: This prospective cohort was conducted in a tertiary pediatric hospital in the Barcelona Metropolitan Region, Spain. It included neonates born to mothers who had SARS-CoV-2 infection during pregnancy or delivery between August 2020 and January 2022. We followed the recruited children for at least six months, and blood tests were performed to determine the presence of SARS-CoV-2 antibodies. RESULTS: A total of 101 children were recruited. Among the serologies performed on children under three months of age, 44/82 were positive (53.7%). Newborns whose mothers presented more severe disease exhibited higher seropositivity odds (coefficient 9.747; p = 0.002). There were increased preterm deliveries when maternal infection occurred closer to the time of delivery. No severe SARS-CoV-2 infections were detected in children during the follow-up. CONCLUSIONS: Slightly more than half of the SARS-CoV-2 serologies performed in the first three months were positive. This appears to confer protection during early childhood. The severity of maternal infection is the most significant factor influencing the transmission of antibodies in children born to unvaccinated mothers.

Severe malnutrition among children under the age of 5 years admitted to a rural district hospital in southern Mozambique.

OBJECTIVE: To describe the burden, clinical characteristics and prognostic factors of severe malnutrition in children under the age of 5 years. DESIGN: Retrospective study of hospital-based data systematically collected from January 2001 to December 2010. SETTING: Rural Mozambican district hospital. SUBJECTS: All children aged <5 years admitted with severe malnutrition. RESULTS: During the 10-year long study surveillance, 274 813 children belonging to Manhiça's Demographic Surveillance System were seen at out-patient clinics, almost half of whom (47 %) presented with some indication of malnutrition and 6% (17 188/274 813) with severe malnutrition. Of these, only 15% (2522/17 188) were eventually admitted. Case fatality rate of severe malnutrition was 7% (162/2274). Bacteraemia, hypoglycaemia, oral candidiasis, prostration, oedema, pallor and acute diarrhoea were independently associated with an increased risk of in-hospital mortality, while malaria parasitaemia and breast-feeding were independently associated with a lower risk of a poor outcome. Overall minimum communitybased incidence rate was 15 cases per 1000 child-years at risk and children aged 12­23 months had the highest incidence. CONCLUSIONS: Severe malnutrition among admitted children in this Mozambican setting was common but frequently went undetected, despite being associated with a high risk of death. Measures to improve its recognition by clinicians responsible for the first evaluation of patients at the out-patient level are urgently needed so as to improve their likelihood of survival. Together with this, the rapid management of complications such as hypoglycaemia and concomitant co-infections such as bacteraemia, acute diarrhoea, oral candidiasis and HIV/AIDS may contribute to reverse the intolerable toll that malnutrition poses in the health of children in rural African settings.

[Recommendations for the diagnosis, treatment and follow-up of the pregnant woman and child with Chagas disease. Sociedad Española de Infectología Pediátrica. Sociedad de Enfermedades Infecciosas y Microbiología Clínica. Sociedad Española de Ginecología y Obstetricia]. / Recomendaciones para el diagnóstico, seguimiento y tratamiento de la embarazada y del niño con enfermedad de Chagas.

Congenital transmission of Chagas disease now occurs in areas where the disease is non-endemic, and also from one generation to another. According to epidemiological data from Latin America, the prevalence of the disease in pregnant women is 0.7%-54%, and the prevalence of vertical transmission is around 5%-6%. Congenital T. cruzi infection is an acute infection in newborns that should be treated with anti-parasitic therapy. The treatment of pregnant women could also have an impact on the control of the disease. This article has been prepared following the recommendations suggested by a group of experts in Infectious Diseases, Microbiology, Gynaecology and Paediatrics.

Travel-associated extensively drug-resistant typhoid fever: a case series to inform management in non-endemic regions.

BACKGROUND: Extensively drug-resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem and encourage preventive interventions as well as appropriate empiric antimicrobial use. METHODS: Cases were extracted from the GeoSentinel database, microbiologic laboratory records of two large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin and trimethoprim-sulfamethoxazole. RESULTS: Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1) and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only one patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhoea. Antimicrobial therapy was started on Day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2 days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR S. typhi phenotype, and whole genome sequencing on three isolates confirmed their belonging to the XDR variant of the H58 clade. CONCLUSIONS: XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for visiting friends and relatives travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology.

Acute and long-term immune responses to SARS-CoV-2 infection in unvaccinated children and young adults with inborn errors of immunity.

Purpose: To describe SARS-CoV-2 infection outcome in unvaccinated children and young adults with inborn errors of immunity (IEI) and to compare their specific acute and long-term immune responses with a sex-, age-, and severity-matched healthy population (HC). Methods: Unvaccinated IEI patients up to 22 years old infected with SARS-CoV-2 were recruited along with a cohort of HC. SARS-CoV-2 serology and ELISpot were performed in the acute phase of infection (up to 6 weeks) and at 3, 6, 9, and 12 months. Results: Twenty-five IEI patients (median age 14.3 years, min.-max. range 4.5-22.8; 15/25 males; syndromic combined immunodeficiencies: 48.0%, antibody deficiencies: 16.0%) and 17 HC (median age 15.3 years, min.-max. range 5.4-20.0; 6/17 males, 35.3%) were included. Pneumonia occurred in 4/25 IEI patients. In the acute phase SARS-CoV-2 specific immunoglobulins were positive in all HC but in only half of IEI in whom it could be measured (n=17/25): IgG+ 58.8% (10/17) (p=0.009); IgM+ 41.2% (7/17)(p<0.001); IgA+ 52.9% (9/17)(p=0.003). Quantitative response (index) was also lower compared with HC: IgG IEI (3.1 ± 4.4) vs. HC (3.5 ± 1.5)(p=0.06); IgM IEI (1.9 ± 2.4) vs. HC (3.9 ± 2.4)(p=0.007); IgA IEI (3.3 ± 4.7) vs. HC (4.6 ± 2.5)(p=0.04). ELISpots positivity was qualitatively lower in IEI vs. HC (S-ELISpot IEI: 3/11, 27.3% vs. HC: 10/11, 90.9%; p=0.008; N-ELISpot IEI: 3/9, 33.3% vs. HC: 11/11, 100%; p=0.002) and also quantitatively lower (S-ELISpot IEI: mean index 3.2 ± 5.0 vs. HC 21.2 ± 17.0; p=0.001; N-ELISpot IEI: mean index 9.3 ± 16.6 vs. HC: 39.1 ± 23.7; p=0.004). As for long term response, SARS-CoV-2-IgM+ at 6 months was qualitatively lower in IEI(3/8, 37.5% vs. 9/10 HC: 90.0%; p=0.043), and quantitatively lower in all serologies IgG, M, and A (IEI n=9, 1.1 ± 0.9 vs. HC n=10, 2.1 ± 0.9, p=0.03; IEI n=9, 1.3 ± 1.5 vs. HC n=10, 2.9 ± 2.8, p=0.02; and IEI n=9, 0.6 ± 0.5 vs. HC n=10, 1.7 ± 0.8, p=0.002 -respectively) but there were no differences at remaining time points. Conclusions: Our IEI pediatric cohort had a higher COVID-19 pneumonia rate than the general age-range population, with lower humoral and cellular responses in the acute phase (even lower compared to the reported IEI serological response after SARS-CoV-2 vaccination), and weaker humoral responses at 6 months after infection compared with HC.

Association between soluble angiotensin-converting enzyme 2 in saliva and SARS-CoV-2 infection: a cross-sectional study.

This study aimed to investigate the association between saliva soluble angiotensin-converting enzyme 2 (sACE2) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adults. We selected a convenience sample of adults with post-acute SARS-CoV-2 infection and their household children living in quarantined family households of the metropolitan Barcelona region (Spain) during the spring 2020 pandemic national lockdown. Participants were tested for saliva sACE2 quantification by western blot and nasopharyngeal SARS-CoV-2 RT-PCR detection. A total of 161 saliva samples [82 (50.9%) from children; 79 (49.1%) from females] yielded valid western blot and RT-PCR results. Saliva sACE2 was detected in 79 (96.3%) children and 76 (96.2%) convalescent adults. Twenty (24.4%) children and 20 (25.3%) convalescent adults were positive for SARS-CoV-2 in nasopharynx by RT-PCR. SARS-CoV-2 RT-PCR-negative children had a significantly higher mean proportional level of saliva sACE2 (0.540 × 10-3%) than RT-PCR-positive children (0.192 × 10-3%, p < 0.001) and convalescent adults (0.173 × 10-3%, p < 0.001). In conclusion, children negative for nasopharyngeal SARS-CoV-2 RT-PCR appear to exhibit a higher concentration of saliva sACE2 than SARS-CoV-2 RT-PCR-positive children and convalescent adults. Release of adequate levels of sACE2 in saliva could play a protective role against SARS-CoV-2.