Welcome to the ESPID 2022 Meeting Calendar

Backgrounds:

The COVID-19 pandemic has brought numerous challenges. One of them is multisystem inflammatory syndrome in children (MIS-C), developing two to six weeks after acute SARS-CoV-2 infection. This study aimed to describe the clinical characteristics of patients who met the criteria for MIS-C, and compare them with the features of Kawasaki disease (KD) and toxic shock syndrome (TSS).

Methods

This retrospective study was conducted at the Children's Clinical University Hospital in Riga, Latvia, and involved children <18 years old who were hospitalized during the period from 2012 to 2021 with MIS-C, KD or TSS. Clinical data was collected from medical records and analysed using descriptive parametric and non-parametric statistics. A statistically significant difference between groups was assumed where p value <0.05.

Results:

In all, 81 children were included in the study: 39 (48.1%) with KD (mean age 3.9 (SD 3.7) years; 23 boys (59%)), 29 (35.8%) with MIS-C (mean age 9.8 (SD 4.5) years; 16 boys (55.2%)) and 13 (16.1%) with TSS (mean age 11.3 (SD 5.2) years; 5 boys (38.5%)). The time from symptom onset to diagnosis was shorter in TSS compared with MIS-C and KD (p<0.001). Patients with MIS-C differ from those with KD, with more frequent gastrointestinal symptoms (e.g., abdominal pain, vomitting, diarrhoea), neurological manifestations (e.g., headache, meningism/photophobia, hyperaesthesia) and cardiac involvement at onset (i.e., valvular insufficiency, pericardial effusions, systolic dysfunction)(p<0.01). Meanwhile, cervical lymphadenopathy, synovitis and arthralgia were significantly more common in KD compared with MIS-C and TSS (p<0.05).

Conclusions/Learning Points:

Children with MIS-C display specific clinical features when compared with those with KD and TSS. The overlapping signs and symptoms of these childhood diseases make an appropriate diagnosis challenging.

Backgrounds:

SARS-CoV-2 variant Omicron (B.1.1.529) is causing the actual wave in Spain, leading to the highest cumulative incidence across the pandemic. It is not known whether this variant causes more severe disease in children.

Methods

Clinical features were collected from children attended at the Emergency Room (ER) at a secondary center in Madrid from December 20^th 2021 to January 2^nd 2022. Charts were reviewed 1 week after diagnosis to check potential complications. Data were compared to children with other variants included in the national COVID-19 database EPICO-AEP. In this comparison, 17 ambulatory patients with Omicron from other center were also included to make data more robust.

Results:

94/1360 children (9.6%) had COVID-19. In 16% of them, variant was identified: 87% Omicron, 13% Delta. Median age was 6.5 years, only 7% were >12 years. Final diagnosis were upper respiratory tract infection (URTI) 61/94 (65%), flu-like syndrome 15/94 (16%), gastroenteritis 7/94 (7%), fever without source (FWS) 3/94 (3%), and migraine or asthma flare 2/94 each (2%). Only 2/94 (2%) patients were hospitalized: a 3-year girl with features of bacterial pneumonia and an Omicron variant; and a 40-days-old infant with whooping-like cough with negative RT-PCR for both Bordetella pertussis and RSV. Hospitalization rate was similar in Omicron and Alpha variant waves (2% vs 4%, p=0.656). Compared to other waves, URTI, headache and fever were more frequent in the Omicron wave, while pneumonia and FWS were in previous waves.

Conclusions/Learning Points:

Children with COVID-19 and Omicron variant seem to have similar profile as other variants, only more fever and URTI and less pneumonia.. Most children were <12 years, which may be related to the high proportion of vaccinated adolescents in our population.

Backgrounds:

Studies on clinical outcomes of children with COVID-19 are scarce, particularly in those with asymptomatic and mild disease. We aimed to describe COVID-19 persistent symptoms in patients presenting to a tertiary hospital and to search risk factors for the development of long COVID.

Methods

A retrospective study was performed including all the patients under 18 years that presented at our tertiary hospital between March 2020 and September 2021 that had a positive SARS-CoV-2 PCR test. At admission they were monitored on a home-care basis by telephone and then, with an appointment at 4,12 and 24 weeks to evaluate persistent symptoms.

Results:

A total of 242 patients were included, 55.0% of them females, mean age of 77 months, with 38.0% of adolescents. Chronic conditions were identified in 36.0% and 7.4% were obese. At admission, 5.8% had moderate disease and 2.9% severe. At 4 weeks, 20.1% had persistent symptoms (Graph 1): fatigue (8.7%), chronic cough (6.7%) and rhinorrhea (6.6%). At 12 weeks, 13.1% had symptoms: fatigue (7.4%), behavioral changes (4.4%) and sleep disturbance (3.7%). At 24 weeks, 6.5% had symptoms: sleep disturbance (3.6%) and fatigue (2.9%). Symptoms’ persistence was more frequent in patients with chronic conditions (12x more at 24 weeks, p<0.05). Persistent fatigue was more prevalent in adolescents (p=0.013), obese (p<0.01) and with severe disease (p<0.01). Behavioral changes were also more frequent in adolescents (p=0.021).

Conclusions/Learning Points:

In our cohort, an important proportion of patients presented symptoms after COVID infection, being respiratory symptoms more frequent in the first weeks and neuropsychiatric symptoms over time. Chronic conditions and obesity were risk factors for persistent symptoms at 6 months after illness and adolescents were the group with greater risk for long-COVID. Persistent fatigue was of utmost importance.

Backgrounds:

Patients produce systemic and mucosal antibodies after SARS-CoV-2 infection. In the context of ongoing public health measures and vaccination programs, it is crucial to explore practical methods to monitor this humoral immunity. Following our earlier findings of heterogeneity in serum and saliva SARS-CoV-2 antibodies in 2020, we now describe antibody prevalence in serum and saliva of children one year after the beginning of the pandemic and explore associations.

Methods

We assessed SARS-CoV-2 antibody prevalence in serum and saliva of 223 children attending medical services in the Netherlands (irrespective of COVID-19 exposure) from May - October 2021. The cohort included vaccinated and unvaccinated children (< 18 years old) and was compared to 517 unvaccinated children from the April - October 2020 cohort. We measured SARS-CoV-2 spike- and nucleocapsid-specific IgG prevalence in serum and saliva.

Results:

Our cohort contained 75% unvaccinated children, 18% with a PCR-proven history of COVID-19, and a 1:1 male-female ratio. Antibody prevalence increased from 3-4% in both serum and saliva in 2020 to 38% (95% CI 31 - 45) in serum and 31% (95% CI 25 - 38) in saliva in 2021. Paired analysis (figure 1) showed positive titers in both serum and saliva in 53/196 (27%). Prevalence of spike and nucleocapsid-specific IgG was significantly lower in saliva compared to serum (P<0.05). Girls showed a higher prevalence of saliva antibodies as compared to boys (OR 2.26 corrected for age, vaccination status, comorbidity, positive PCR).

Conclusions/Learning Points:

SARS-CoV-2 antibody prevalence in children increased in serum and saliva between 2020 and 2021 in the Netherlands. We observed lower SARS-CoV-2 antibody prevalence in saliva compared to serum, which should be taken into account when evaluating humoral immunity.

Backgrounds:

Infants may develop severe viral respiratory tract infections because their immune system is still undeveloped. Human milk provides passive humoral immunity during the first months of life. During the COVID-19 pandemic, circulation of common respiratory viruses was virtually absent due to the preventative measures resulting in reduced maternal exposure. Therefore, we hypothesized that this might result in lower antibody levels in human milk during the pandemic and, subsequently, decreased protection of infants against viral respiratory tract infections.

Methods

We assessed antibody levels against respiratory syncytial virus (RSV), Influenza virus, and several seasonal coronaviruses in different periods of the COVID-19 pandemic in serum and human milk using a Luminex assay.

Results:

IgG levels against RSV, Influenza, HCoV-OC43, HCoV-HKU1, and HCoVNL63 in human milk were reduced with a factor of 1.7 (p<0.001), 2.2 (p<0.01), 2.6 (p<0.05), 1.4 (p<0.01), and 2.1 (p<0.001), respectively, since the introduction of the COVID-19 restrictions. Furthermore, we observed that human milk of mothers that experienced COVID-19 contained increased levels of IgG and IgA binding to other respiratory viruses.

Conclusions/Learning Points:

Passive immunity via human milk against common respiratory viruses was reduced during the COVID-19 pandemic, which may put breastfed infants at increased risk for respiratory infections.

Backgrounds:

Vaccination of lactating women against COVID-19 may protect not only themselves but also their breast-fed infant through human milk. Therefore, it is important to gain insight into the human milk antibody response after immunization with the various vaccines that are currently widely used. The aim of this study is to determine and compare the antibody response in human milk following vaccination with mRNA- and vector-based vaccines up to over 2 months post-vaccination.

Methods

In this prospective cohort study, human milk samples from women receiving four different SARS-CoV-2 vaccines were collected longitudinally during a period of 70 days. SARS-CoV-2-specific antibodies were measured using an enzyme-linked immunosorbent assay. The area under the curve of the antibody response was determined over 15 and 70 days following vaccination and compared between the different vaccines.

Results:

This study enrolled 134 vaccinated lactating women, who provided a total of 1887 human milk samples. After vaccination with an mRNA-based vaccine, almost all participants (96/97%) showed detectable SARS-CoV-2-specific antibodies in their milk, whereas only 37-50% of the participants who received a vector-based vaccine showed human milk antibodies. The mean area under the curve of SARS-CoV-2-specific antibodies in human milk over 70 days was the highest after vaccination with an mRNA-based vaccine.

Conclusions/Learning Points:

Maternal vaccination during lactation with an mRNA-based vaccine resulted in higher SARS-CoV-2 IgA and IgG responses in human milk compared to vector-based vaccines. Therefore, vaccination with mRNA-based vaccines might not only provide better immunological protection for the mother but also for her breast-fed infant.

Backgrounds:

Cystic fibrosis (CF) patients constitute a high-risk group for severe COVID-19. We prospectively measured total (TAbs-RBD; U/ml) and neutralizing (NAbs-RBD; %) antibodies of SARS-CoV-2 spike-RBD protein before immunization, 20 days after the 1^st and 30 days after the 2^nd dose of the BNT162b2 vaccine in CF patients and healthy controls.

Methods

Serum samples were tested using the Elecsys® Anti-SARS-CoV-2 S reagent. Values of ≥0.8 U/ml are positive. The determination of anti-RBD neutralization titers was carried out using the Food and Drug Administration(FDA) approved blocking ELISA cPass^TM SARS-CoV-2 neutralization antibody detection kit. Percentages of ≥ 30% were positive. A statistical analysis was performed for the comparison of the two groups and the possible association of antibody levels with epidemiological and clinical parameters.

Results:

A total of 33 patients with CF and 66 healthy controls were included in the study. The median age (IQR) of the CF group was 19.6 (17.6-24.3) years and 18 (54.5%) were females. CF patients had statistically significant higher antibody responses regarding TAbs-RBD and NAbs-RBD after both doses (P-value<0.001). One month after the 2^nd dose, CF and controls had TAbs-RBD (IQR): 3396 (2443) and 1452 (1231) U/ml, respectively. Similarly, the NAbs-RBD (%) were: 97.30 (1.00) and 95.70 (3.71) (%), respectively. Among CF patients no statistically significant differences were detected for TAbs-RBD or NAbs-RBD regarding gender, pancreatic status, CFTR genotype of CF, use of CFTR modulators and chronic Pseudomonas Aeruginosa infection.

Conclusions/Learning Points:

The BNT162b2 vaccine was more immunogenic in patients with CF patients compared to healthy controls regardless of the CFTR genotype, related comorbidities, treatment type or severity of disease. Longitudinal studies regarding the kinetics of antibodies will be important to determine the appropriate timing for a booster dose in this population.

Backgrounds:

Australia has utilized two mRNA vaccines as part of its COVID-19 vaccine strategy in 12-17 year-olds, namely Comirnaty BNT162b2 COVID-19 (Pfizer-BioNTech) and Spikevax mRNA-1273 (Moderna).

Of particular interest in the young adult population is post-vaccination myocarditis causally associated with COVID-19 mRNA vaccines. Post-licensure observational and report-based case studies confirmed the highest risk group is young males (<24 years old) following the 2^nd vaccine dose.

Due to this AESI signal, the risk, clinical manifestations and follow-up of myocarditis has been of particular interest. This study describes clinical presentation and evaluation of myocarditis AESI following mRNA COVID-19 vaccination in 12–17-year-old adolescents in Victoria, Australia.

Methods

Identified reports of myocarditis in 12–17-year-old vaccinees submitted to SAEFVIC, the state-wide vaccine safety service, between 22 February and 30 November 2021 were assessed. Diagnostic test results were obtained to confirm the diagnoses. Each case was categorized by two independent experts utilizing the Brighton Collaboration definition with graded levels of certainty.

Results:

Rigorous clinical review demonstrated definite (Brighton level 1) or probable (level 2) diagnoses in 53 cases, with one case possible (level 3). As of 30th November 2021, the 54 reports of confirmed myocarditis, equated to a rate of 7.0 per 100,000 doses in this age group.

Cases were predominantly male (n=48, 88.9%) and post dose 2 (n=44, 81.5%). Rates peaked in the 16–17-year-old age group and were higher in males than females (12.2 v 1.6 per 100,000, p=<0.001).

Troponin levels differed between sexes, with males recording substantially higher levels.

Conclusions/Learning Points:

Accurate evaluation and confirmation of episodes of COVID-19 mRNA vaccine associated myocarditis enabled understanding of clinical phenotypes in the pediatric and adolescent age group. Any potential vaccination and safety surveillance policies needs to consider age and gender differences.