Welcome to the ESPID 2022 Meeting Calendar

Backgrounds:

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe SARS-CoV-2 related disease occurring in children and adolescents. Its pathophysiology is incompletely unraveled, although superantigen-driven hyperinflammation is presumed. Currently approved pediatric vaccines against coronavirus disease 2019 (COVID-19) are mRNA-based and encode the SARS-CoV-2 spike protein. Theoretically, in children with previous MIS-C, re-exposure to the same viral protein could trigger hyperinflammation. However, to date, no specific safety data for COVID-19 vaccination are available for children with a history of MIS-C.

Methods

We conducted an international electronic questionnaire, running from 1 Nov 2021 to 15 Dec 2021.

Results:

We collected data from 83 healthcare professionals involved with MIS-C, originating from 32 countries. Respondents provided information for 5673 MIS-C patients, of which 1750 (30.8%) were eligible for vaccination. Vaccination was documented in 273 (15.6%) children. For 420 additional cases, no contra-indication was in place and, therefore, respondents presumed vaccination without formal registration and vigilance of the procedure.

MIS-C was declared as a contra-indication for COVID-19 vaccination in multiple regions (Belgium/France/Italy/India/Mexico/Pakistan/Turkey/USA), accounting for 1144 patients (20.2% of the cohort). Reasons for contra-indication included national/regional guidelines (9/14 regions) and safety concerns (9/14).

In those vaccinated, mild/moderate adverse events (AE) were reported similarly to those published in healthy controls. Besides one patient experiencing Bell’s palsy, no severe/serious AE were described. In particular, no relapse MIS-C or other similar inflammatory conditions were reported.

Conclusions/Learning Points:

MIS-C is not regarded as a universal contra-indication for COVID-19 vaccination in most countries. In those vaccinated, no particular AE and no relapse MIS-C was reported. At the time of the survey, less than one-third of MIS-C patients were eligible for vaccination and at most 40 percent of those eligible were vaccinated. Further follow-up is warranted.

Backgrounds:

Long-term data regarding the association of antibody levels after immunization with the BNT162b2 mRNA COVID-19 vaccine with epidemiological and clinical parameters are limited. We prospectively measured the total(TAbs) and neutralizing antibodies(NAbs) against the receptor binding domain(RBD) of SARS-CoV-2 spike protein in healthcare workers(HCWs) 1, 4 and 8 months after the 2^nd dose of the BNT162b2 vaccine.

Methods

Serum samples from 462 HCWs of ‘‘Aghia Sophia’’ Children’s Hospital, Greece were collected and tested for TAbs-RBD using the Elecsys® Anti-SARS-CoV-2 S reagent and for NAbs-RBD using the Food and Drug Administration (FDA) approved blocking ELISA cPass^TM SARS-CoV-2 neutralization antibody detection kit. A statistical analysis for possible association of antibodies’ levels with epidemiological and clinical parameters was performed.

Results:

The mean age (±SD) of the participants was 48.33 years (± 12.98) and 361(77.1%) were females. No significant differences in TAbs-RBD and NAbs-RBD were detected regarding gender and history of autoimmune diseases. A statistically significant negative association of NAbs-RBD was detected for age (β=-0.046, P<0.001). Smokers had significantly lower TAbs-RBD and NAbs-RBD (P<0.05) than non-smokers in each time-point of the study. TAbs-RBD in HCWs with underlying diseases significantly declined in all time points (P=0.005). HCWs with allergies showed higher TAbs-RBD in 1 and 4 months after the 2^nd dose (P=0.003 and P=0.008 respectively). HCWs with AB blood type had lower TAbs-RBD than the other blood types in all time-points (P=0.044), especially 4 months after the 2^nd dose (P=0.014).

Conclusions/Learning Points:

A significant gradual decline in TAbs and NAbs was detected within the first 8 months after the 2^nd dose. Our findings support that older age and smoking negatively affect antibody levels, thus the administration of a booster dose in those groups is highly recommended.

Backgrounds:

Multisystem inflammatory syndrome in children (MIS-C) is a condition characterized by a dysregulated response of the immune system 2-6 weeks after a SARS-CoV-2 infection. Some authors hypothesized that the COVID-19 vaccine could trigger a new exaggerated response in these children.

Our aim was to assess the proportion of vaccinated children and the incidence of new MIS-C or myocarditis after vaccination in adolescents with previous MIS-C.

Methods

From the Epidemiological Study of COVID-19 in Children of the Spanish Pediatric Association, we contacted researchers from centers with ≥3 MIS-C patients aged 12-18 years old by October 31, 2021, hospitalized from March 2020, through October 2021 and fulfilling WHO criteria for MIS-C.

We performed a semi-structured telephonic interview with the caregivers and/or the adolescents, about vaccination acceptance and adverse events after vaccination.

Results:

An interview was possible in 42/48 (87.5%) selected adolescents, being mainly male (30/42, 71.4%) and, at MIS-C diagnosis, their median age was 13.1 years old. 32/42 (76.2%) patients had received COVID-19 vaccine. The median time between MIS-C diagnosis and vaccination was 42 weeks and the telephonic interview took place after a median of 10.0 weeks (range 5.3-19.7) post-vaccination. After vaccination, 22/32 (68.8%) patients reported adverse events, being 86.7% mild and 3.3% moderate (Table1). No new MIS-C or myocarditis or pericarditis episodes were reported.

Conclusions/Learning Points:

In this study, we describe a high acceptance and low incidence of relevant adverse events after COVID-19 vaccines in a population of adolescents with a previous MIS-C diagnosis. No new MIS-C episodes or myocarditis occurred after a median of 10 weeks post-vaccination. The results of this study are reassuring and may help to decide for patients with previous MIS-C who are considering COVID-19 vaccination.

Backgrounds:

There is a need to assess the immunogenicity and duration of immune response to SARS-CoV-2 mRNA vaccination in HIV-infected patients. Scarce data exist on HIV-infected adolescents.

Methods

A prospective ongoing observational study is being conducted in HIV-infected patients > 12 years of age after the introduction of mRNA vaccination in Spain. Blood samples were drawn 3-10weeks after the first or second dose (according to prior SARS-CoV2 infection) of BNT162b2 (Pfizer/BioNTech) and CoV-2-mRNA-1273 (Moderna) vaccines in 20 HIV-infected adolescents and compared to 20 matched healthy-control subjets. Humoral response was assesed by detection of SARS-CoV-2 antibodies by chemiluminescent-microparticle-immunoassay (CMIA) (Alinity® Quant assay-Abbott) to detect IgG against S1-region of the spike-protein of SARS-CoV-2 (≥50U/mL considered reactive). T-Cell response to SARS-CoV-2 was measured by an interferon-gamma-released-assay (IGRA,Euroimmun) of S1 peptide-stimulated T-cells in whole blood (≥200mlU/ml considered reactive).

Results:

Blood samples from 20 HIV-infected adolescents were drawn after vaccination (15 Pfizer/BioNTech, 5 Moderna), see figure one. Mean age was 16.7±3.9 and 14.3±3.9 years in patients and controls, respectively (p:0.06). Mean intervals since last vaccine dose in HIV-infected and controls were 44.0±15.1 and 38.5±12.6 days,(p>0.05). Two HIV-infected patients and 6 controls had documented past SARS-CoV-2 infection.

All patients and controls had reactive humoral and celular responses. HIV-infected subjects had lower anti-Spike antibodies titers (mean 14251±8270 U/mL) than controls (mean 27716±15768 U/mL)(p:0.013). Likewise, cellular immune responses were lower in HIV-infected adolescents (mean 1609±418 mlU/ml) than in controls (mean 1777±356 mlU/ml),(p:0.024).

Conclusions/Learning Points:

Perinatally HIV-infected adolescents with good immunologic and virological status elicit appropriate specific antispike-antibody levels and cellular immune responses against SARS-CoV-2 shortly after mRNA vaccination, but of lower amount than healthy control subjects. More prolonged studies are underway to determine the evolution of humoral and cellular immune responses after vaccination.

Backgrounds:

Immunization of vulnerable populations with distinct immunity often results in suboptimal immunogenicity, durability and efficacy.

Methods

To investigate the safety and the immunogenicity profiles of BNT162b2 mRNA COVID-19 vaccine among people living with HIV, we enrolled 28 HIV-infected patients under ART and 65 healthy controls (HCs) with no previous history of COVID-19. Immunogenicity was evaluated by measuring anti-RBD and anti-trimeric Abs, along with the frequency of SARS-CoV-2 specific CD4+CD40L+T cells. Samples were collected before vaccination (baseline, D0), at the second dose (D21), at 4 weeks (D28) and 6 months (D180) after the first dose. T and B cell phenotypes were investigated. Proteomic profiles at D0 and D28 were assessed with a Proximity Extension Assay (Olink) on plasma samples.

Results:

All vaccinated HIV-infected patients mounted anti-SARS-CoV-2 humoral responses between D21 and D28 similarly to HCs, albeit lower titers of anti-trimeric S Abs were detected at D28 compared to HC (p=0.0098). Only PBMCs of HIV+ demonstrated at D28 an impaired ability to expand their specific (CD40L+) CD4+ T populations. At 6 months, follow-up HIV+ showed similar maintenance of anti-SARS-CoV-2 Abs to HC. To explore whether these immunogenicity results could be linked to a particular proteomic outline, we correlated baseline protein levels to either humoral or cellular responses, identifying clusters of molecules involved in immune response regulation with inverse profiles between the two study groups.

Conclusions/Learning Points:

Responses of ART-treated HIV+ compared to HC, characterized by distinct features especially within the proteomic compartment, supporting their eligibility to an additional dose scheduled at 6 months, similarly to HC.

Backgrounds:

Emerging evidence suggests COVID-19 vaccination during pregnancy may reduce risk of newborn SARS-CoV-2 infection; however, safety concerns remain a potential obstacle to achieving high coverage during pregnancy. This study aimed to assess the risk of preterm birth, small-for-gestational-age (SGA) birth, and stillbirth after COVID-19 vaccination during pregnancy.

Methods:

We used provincial databases in Ontario, Canada to identify all live and stillbirths ≥20 weeks’ gestation (birth registry), linked to COVID-19 vaccination data (vaccine registry) for May 1 to November 30, 2021. Using Cox regression, we estimated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for preterm birth, SGA birth (<10^th percentile), and stillbirth treating COVID-19 vaccination as a time-varying exposure. Models were adjusted for calendar time, COVID-19 illness, sociodemographic factors, health behaviours, and pregnancy-related factors.

Results:

Among 69,650 births, 33,295 (47.8%) were born to individuals who received ≥1 dose of COVID-19 vaccine during pregnancy. The incidence of preterm birth was 6.5% among those who received ≥1 dose of COVID-19 vaccine during pregnancy and 7.0% among unvaccinated. The risk of preterm birth was not associated with COVID-19 vaccination during pregnancy (adjusted HR [aHR] 0.96, 95% CI, 0.91 to 1.02), nor was spontaneous preterm birth or very preterm birth (<32 weeks). Similarly, there was no increased risk of SGA birth in vaccinated vs. unvaccinated individuals (8.7% vs. 9.2%; aHR, 1.00; 95% CI, 0.95 to 1.05) or stillbirth (1.6 vs. 2.8 per 1000; aHR, 0.64; 95% CI, 0.46 to 0.90). Results did not differ by trimester of vaccination, mRNA vaccine product, or number of doses received during pregnancy.

Conclusions/Learning Points:

In this large population, COVID-19 vaccination during pregnancy was not associated with a higher risk of preterm birth, SGA birth, or stillbirth.

Backgrounds:

Few data are published on immune responses against SARS-CoV-2 induced by COVID-19 vaccines in people under the age of 18 years compared with adults.

Methods:

COV006 is a phase 1/2, single-blind, randomised controlled trial of ChAdOx1 nCoV-19 (ChAd) in children and adolescents aged 6-17 years in the UK. Participants were randomised 4:1:4:1 to receive two doses of ChAd or control (capsular group B meningococcal) vaccine (4:1), 28 days (short-interval) or 84 days (long-interval) apart. The primary outcome was safety and tolerability, with immunogenicity in the baseline-seronegative participants as the secondary outcome. Due to the restrictions in the use of ChAd introduced during the study, only participants aged 12-17 years randomised to the short-interval were vaccinated as planned (D28). The remaining participants received their second dose at D112.

Results:

Of 262 participants, 211 and 51 were randomised to the ChAd and control arms, respectively. No serious adverse events related to ChAd administration were recorded. Solicited adverse reactions were reported more frequently after the first dose compared with the second dose, across all age and interval groups.

In participants aged 12-17 years, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at D28 post-second dose were higher in the long-interval arm (geometric mean ratios (GMR): 1.70, 95%CI: 1.27-2.26 and 1.99, 95%CI: 1.39-2.86, respectively) than after a short-interval.

Humoral responses were higher in participants aged 6-11 years than those aged 12-17 years (GMR: 1.48, 95%CI: 1.07-2.07 and 2.96, 95%CI: 1.89-4.62 for anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres, respectively). Cellular responses peaked after a first dose of ChAd across all age and interval groups.

Conclusions/Learning Points:

ChAdOx1 nCoV-19 is well-tolerated and immunogenic in children aged 6-17 years. No safety concerns were raised in this trial.