Welcome to the ESPID 2022 Meeting Calendar

Backgrounds:

Multisystem inflammatory syndrome in children (MIS-C) is the most severe clinical entity associated with pediatric SARS-CoV-2 infection with a putative role of the spike protein into the immune system activation. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. We aimed to assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children.

Methods:

We conducted a post-authorization national population-based surveillance using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines. All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12–17-year-old children between June 15^th, 2021 and January 1^st, 2022, were reported. The reporting rate of this syndrome was compared to the MIS-C rate per 1,000,000 12–17-year-old children infected by SARS-CoV-2.

Results:

Up to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12–17-year-old children. Among them, 12 presented a hyper-inflammatory syndrome with multisystemic involvement. Main clinical features included male predominance (10/12, 83%), cardiac involvement (10/12, 83%), digestive symptoms (10/12, 83%), coagulopathy (7/12, 58%), cytolytic hepatitis (6/12, 50%), and shock (5/12, 42%). 4/12 (33%) required intensive care unit transfer, and 3/12 (25%) hemodynamic support. All cases recovered. In eight cases, no evidence of previous SARS-CoV-2 infection was found. The reporting rate was 1.5 (95%CI [0.8; 2.6]) per 1,000,000 doses injected, i.e. 2.9 (95%CI [1.5; 5.1]) per 1,000,000 12–17-year-old vaccinated children. As a comparison, 113 MIS-C (95%CI [95; 135]) occurred per 1,000,000 12–17-year-old children infected by SARS-CoV-2.

Conclusions/Learning Points:

Very few cases of hyper-inflammatory syndrome with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12–17-year-old children. The low reporting rate of this syndrome, compared to the rate of post-SARS-CoV-2 MIS-C in the same age-group, largely supports the vaccination in a context of an important circulation of SARS-CoV-2.

Backgrounds:

To evaluate the outcomes of neonates exposed to SARS-CoV-2 in pregnancy, the dynamics of maternal IgG placental transfer and its persistence during the first months of life.

Methods:

Prospective study enrolling neonates born to mothers with SARS-CoV-2 infection in pregnancy at IRCCS Azienda Ospedaliero Universitaria di Bologna, Italy, between March 2020 and September 2021. Neonates born to women with peripartum infection were excluded. All infants were enrolled in a 12-month follow-up. Quantitative IgG to S1/S2 subunits of spike protein were assessed in mother-neonates dyads within 48 hours post-delivery and during follow-up until negative. Transplacental IgG transfer ratio in relation to the trimester of maternal infection was assessed.

Results:

One hundred and forty neonates were included. No clinical, laboratory and cerebral abnormalities were detected at birth or during follow-up, until a median age of 11 months (range 6-12). Median SARS-CoV-2 S1/S2 IgG level at birth was 22 AU/mL (IQR 11-52.5) for neonates and 35 AU/mL (IQR 19-62.5) for mothers. Median IgG level at birth was not different between neonates born to asymptomatic or symptomatic mothers (18 AU/mL, IQR 9-49, versus 23.5 AU/mL, IQR 11-61.7, P=0.26) and was not different in relation to trimester of maternal infection (P= 0.9). Transplacental transfer ratio was higher following second trimester maternal infections (0.99±0.45 versus 1.05±0.61 versus 0.74±0.43, P=0.02). Maternally derived IgG were rapidly weaned: all infants had no detectable antibodies within 8 months of life.

Conclusions/Learning Points:

Neonatal and long-term outcomes of infants SARS-CoV-2 exposed in utero in all trimesters of gestation were favorable. IgG transplacental transfer was higher following second trimester maternal infections, which could be relevant to inform studies on appropriate vaccination strategies. All infants lost maternal antibodies within 8 months of life.

Backgrounds:

Multisystem Inflammatory Syndrome in Children (MIS-C, also known as PIMS-TS) typically occurs 2-6 weeks after exposure to SARS-CoV-2. Early estimates suggested a risk of MIS-C of 1 in 3-4000 infected children. Whether this risk is sustained with new SARS-CoV-2 variants remains unknown.

Methods:

We utilised prospective data from the NHS South Thames Paediatric Network (STPN), which manages all cases of MIS-C amongst 1·5 million children in South-East England, to assess trends over time. We compared MIS-C cases with two independent SARS-CoV-2 infection datasets. We used publicly available UK Health Security Agency case numbers weighted to child population distributions according to area population estimates from the Office for National Statistics (ONS). To avoid bias due to evolving testing behaviour, we also compared MIS-C cases to community infection rates, obtained from the ONS COVID-19 Infection Survey, which randomly selects individuals for fortnightly PCR tests. All three datasets were normalised to the peak of the Alpha wave, and plotted against time. MIS-C cases were plotted 40 days prior to hospitalisation, corresponding to the best fit of rising SARS-CoV-2 infection and MIS-C cases during the Alpha wave.

Results:

Compared with the Alpha wave, we found fewer cases of MIS-C relative to SARS-CoV-2 infections during both initial and subsequent Delta waves. This relative reduction continued into the Omicron wave.

Conclusions/Learning Points:

Re-infection rates with the Alpha or Delta variants and vaccination rates were very low during the Delta wave. As a result, lower MIS-C rate relative to SARS-CoV-2 infections during the Delta wave is unlikely to be explained by population level immunity from prior infection or vaccination. It is most likely due to viral mutations in key antigenic epitopes responsible for triggering the hyperinflammatory response observed with MIS-C.

Backgrounds:

Cardiomyopathy is one of the significant features of SARS-CoV-2 induced multi-system inflammatory syndrome in children (MIS-C) and it is also a rare complication of mRNA COVID-19 vaccination in young adults. MIS-C occurs 4-6 weeks following SARS-CoV-2 infection; we therefore postulated that antibodies might play a role in the cardiac immunopathology. The mechanism of vaccine-induced myocarditis is currently being explored. We investigated the role of anti-cardiac antibodies in post SARS-CoV-2 vaccine myocarditis and MIS-C.

Methods:

Clinical cohort: Pre-treatment acute MIS-C (n=10), acute COVID-19 vaccination-induced myocarditis (n=10), Pre-COVID-19 pandemic healthy children (n=10) and healthy COVID-19 vaccinated adults (10).

Immunohistochemistry was performed on human left ventricular tissue sections from 2 donor hearts (deemed unsuitable for donation) for assessment of auto-antibody binding. Sera from patients and controls were used as primary antibodies. FITC-conjugated anti-human-IgG (1:150), IgM (1:150) and IgA (1:50) were used for detection. 10 images were taken at random from each section and immunoglobulin deposition was quantified by calculating mean fluorescent intensity using ImageJ/Fiji. This method has previously shown specific binding of IgG to cardiac tissue following treatment with serum obtained from an adult myocarditis patient.

Results:

No specific binding was seen in left ventricular tissue treated with sera from paediatric patients with either MIS-C or COVID-19 vaccine-induced myocarditis. There was no significant difference in the mean fluorescent intensity of IgG, IgM and IgA in patients compared to controls (Figure 1).

Conclusions/Learning Points:

Our study did not find evidence for a role of an anti-cardiac antibody-mediated inflammatory process in MIS-C cardiomyopathy and COVID-19 vaccine induced myocarditis.

Backgrounds:

Antibody titres decline in the months following COVID-19 in adults. COVID-19 is typically milder in children and there is limited data on durability of humoral responses following natural infection in this cohort.

Methods:

Children aged ≤17 years old with SARS-CoV-2 infection diagnosed by RT-PCR at our centre were recruited between January and July 2021. Subjects underwent serological testing for anti-Spike and anti-N-capsid Immunoglobulin G (IgG) antibodies at time of diagnosis. Subjects underwent point of care testing (POCT) (ASSURE® SARS-CoV-2 IgG/IgM Rapid Test) for total SARS-CoV-2 IgG at 0-6 weeks post diagnosis. POCT testing was repeated with serological testing and testing for SARS-CoV-2 neutralising antibodies (cPASS™ assay) at 3-6 months, 12 months, and 24 months post-diagnosis. Subjects were allowed to be recruited into the study at any timepoint.

Results:

The results summarise preliminary data for 23 children. Median age of the cohort was 5.9 years (range 8 months -17 years). None were immunosuppressed or had significant co-morbidities. 21 children had a positive household contact. 12 children were asymptomatic at time of diagnosis; all eventually had asymptomatic or mild disease. There were no cases of multisystem inflammatory syndrome in children, or re-infection in the child or their household contacts. 7/18 (39%) children were already seropositive at time of diagnosis on serology testing. On POCT, at 0-6 weeks, 5/6 (83%) children were seropositive; seropositivity persisted in all children at 3-6 months (n=8) and in 5/6 (83%) children at 12 months (figure 1). The study of temporal kinetics for anti-Spike and anti-N-capsid IgG antibodies, and neutralising antibody titres is still ongoing.

Conclusions/Learning Points:

Even mild COVID-19 infection induces durable seroconversion in children with detectable IgG levels at 1 year after infection in the majority.

Backgrounds:

We aim to describe outcomes (focusing on hearing and neurological findings) and transfer of maternal antibodies in infants born from mothers with SARS-CoV-2 infection during pregnancy.

Methods:

Observational prospective study performed in a tertiary hospital in Madrid (Spain). Infants born from mothers with SARS CoV-2 infection during pregnancy from March to September 2020 were included. SARS-CoV-2 RT-PCT on nasopharyngeal swab (NPS) was performed at birth to infants born from mother with acute infection at delivery. A follow-up visit with physical and neurological examination, SARS-CoV-2 RT-PCR on NPS, SARS-CoV-2 serology, and a cranial ultrasound (cUS) was performed within 3 months of life. Automated auditory brainstem response (A-ABR) exams were performed at birth, and auditory steady-state response (ASSR) at six months of life.

Results:

95 infants born from 94 mothers were included. Median gestational age was 39+3 (IQR 38-40) and 10 (10.5%) were preterm. Thirteen (13.7%) newborns required hospital admission after birth, none of them with a COVID-19 infection. Rates of vertical (1/28; 3.6%) and horizontal (1/93; 1.1%) transmitted infections were low, with mild symptoms. In follow-up visit, neurological examination was normal in all infants. Cranial ultrasound was normal in 81/85 (95.3%) infants, with mild abnormalities in four infants. 47/ 95 (50%) infants had a positive serology. Serology result was not related to the severity of the maternal infection, skin-to-skin care at birth or breastfeeding. There was a progressive decrease in SARS-CoV-2 antibody titers with the age (figure 1). No hearing loss was detected.

Conclusions/Learning Points:

In this cohort, most infants born from mothers with SARS-CoV-2 infection during pregnancy had normal cUS, hearing screening and neurological examinations in the follow-up. There is a rapid decrease in transferred maternal antibodies in the first months of life.