Understanding COVID-19 in children: immune determinants and post-infection conditions.

Coronavirus disease 2019 in children presents with milder clinical manifestations than in adults. On the other hand, the presence of a wide range of inflammatory manifestations, including multisystem inflammatory syndrome in children (MIS-C), in the period after infection suggests a particular susceptibility of some children toward severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Both protective factors that prevent evolution to severe forms and risk factors for post-infectious conditions are likely to be found in age-related differences in the immune system. The prompt innate response with type I IFN production and the generation of neutralizing antibodies play a crucial role in containing the infection. The greater number of naive and regulatory cells in children helps to avoid the cytokine storm while the causes of the intense inflammatory response in MIS-C need to be elucidated. This review aims to analyze the main results of the recent literature assessing immune response to SARS-CoV-2 over the pediatric age group. We summarized such observations by dividing them into innate and acquired immunity, then reporting how altered immune responses can determine post-infectious conditions. IMPACT: The main immune markers of acute SARS-CoV-2 infection in children are summarized in this review. This paper reports a broad overview of age-related differences in the immune response to SARS-CoV-2 and emerging post-infection conditions. A summary of currently available therapies for the pediatric age group is provided.

Higher Troponin Levels on Admission are associated With Persistent Cardiac Magnetic Resonance Lesions in Children Developing Myocarditis After mRNA-Based COVID-19 Vaccination.

BACKGROUND: Acute pericarditis/myocarditis is a rare complication of the mRNA-based vaccines and although mostly self-limiting, long-term sequelae remain unclear. METHODS: We enrolled all patients admitted to the emergency department between September 2021 and February 2022 meeting the CDC work case definition, with symptoms onset after mRNA-based COVID-19 vaccine. Alternative virologic causes were excluded. Clinical data, laboratory values, cardiologic evaluation, electrocardiogram (ECG), and echocardiogram (ECHO) were collected on admission, at discharge, and during follow-up in all patients. Cardiac Magnetic Resonance (CMR) was performed only in those with signs consistent with myocarditis. RESULTS: We observed 13 patients (11M and 2F), median age 15 years, affected by acute pericarditis/myocarditis after COVID-19 mRNA vaccination (11 after Comirnaty® and 2 after Spikevax®). Symptoms'onset occurred at a median of 5 days (range, 1 to 41 days) after receiving mRNA vaccine (13 Prizer 2 Moderna): 4 patients (31%) after the 1st dose, 6 (46%) after the 2nd, and 3 (23%) after 3rd dose. Increased levels of high-sensitive troponin T (hsTnT) (median 519,5 ng/mL) and N-terminal-pro hormone BNP (NT-proBNP) (median 268 pg/mL) and pathognomonic ECG and ECHO abnormalities were detected. On admission, 7 of 13 (54%) presented with myopericarditis, 3 (23%) with myocarditis, and 3 (23%) with pericarditis; CMR was performed in 5 patients upon pediatric cardiologist prescription and findings were consistent with myocarditis. At 12 weeks of follow-up, all but one patient (92%), still presenting mild pericardial effusion at ECHO, were asymptomatic with normal hsTnT and NT-proBNP levels and ECG. On CMR 6 of 9 patients showed persistent, although decreased, myocardial injury. Higher hsTnT levels on admission significantly correlated with persistent CMR lesions. CONCLUSION: Evidence of persistent CMR lesions highlights the need for a close and standardized follow-up for those patients who present high hsTnT levels on admission.

Two Pediatric Cases of Multisystem Inflammatory Syndrome with Overlapping Neurological Involvement Following SARS-CoV-2 Vaccination and Unknown SARS-CoV2 Infection: The Importance of Pre-Vaccination History.

The SARS-CoV-2 vaccine roll-out has been successful around the world. However, there are increasing concerns about adverse events. We report two pediatric cases of Multisystem-Inflammatory-Syndrome (MIS-C) with neurological involvement that occurred after SARS-CoV-2 vaccination and unknown recent SARS-CoV-2 infection. Brain magnetic resonance revealed mild-encephalopathy with reversible-splenial-lesion in both cases and complete resolution within 4 weeks. In conclusion, this report aims to describe rare emerging clinical entities that can help pediatricians to make an early diagnosis and to provide appropriate treatment. Multisystem-Inflammatory-Syndromes following COVID-19 vaccination remain rare events. When a history of a recent contact with SARS-CoV-2 is present, a careful evaluation by the clinicians in charge of immunization activities is suggested prior to proceeding with the vaccination.

Evaluation of Safety and Immunogenicity of BNT162B2 mRNA COVID-19 Vaccine in IBD Pediatric Population with Distinct Immune Suppressive Regimens.

Patients affected by Inflammatory Bowel Disease (IBD) present higher risk for infection and suboptimal response upon vaccination. The immunogenicity of SARS-CoV2 vaccination is still largely unknown in adolescents or young adults affected by IBD (pIBD). We investigated the safety and immunogenicity of the BNT162B2 mRNA COVID-19 vaccine in 27 pIBD, as compared to 30 healthy controls (HC). Immunogenicity was measured by anti-SARS-CoV2 IgG (anti-S and anti-trim Ab) before vaccination, after 21 days (T21) and 7 days after the second dose (T28). The safety profile was investigated by close monitoring and self-reported adverse events. Vaccination was well tolerated, and short-term adverse events reported were only mild to moderate. Three out of twenty-seven patients showed IBD flare after vaccination, but no causal relationship could be established. Overall, pIBD showed a good humoral response upon vaccination compared to HC; however, pIBD on anti-TNFα treatment showed lower anti-S Ab titers compared to patients receiving other immune-suppressive regimens (p = 0.0413 at first dose and p = 0.0301 at second dose). These data show that pIBD present a good safety and immunogenicity profile following SARS-CoV-2 mRNA vaccination. Additional studies on the impact of specific immune-suppressive regimens, such as anti TNFα, on immunogenicity should be further investigated on larger cohorts.

Characteristics of COVID-19 patients up to 6 months of age admitted to a paediatric emergency department.

Very young age could be a potential risk factor for community-acquired severe acute respiratory syndrome coronavirus 2, due to immature immune systems. We retrospectively enrolled 39 infants up to 6 months of age who had presented to our tertiary Italian children's hospital emergency room between 9 March 2020 and 8 March 2021 and tested positive for the virus. Of those, 38 had a non-specific mild or asymptomatic clinical course and only one patient was admitted to intensive care with severe symptoms. We concluded that very young infants with COVID-19 had a generally favourable disease course.