Multisystemic inflammatory syndrome following COVID-19 mRNA vaccine in children: a national post-authorization pharmacovigilance study

ImportanceMultisystem inflammatory syndrome in children (MIS-C) is the most severe life-threatening clinical entity associated with pediatric SARS-CoV-2 infection. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. ObjectiveTo assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children. Design, Setting, and ParticipantsPost-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 15th, 2021 and January 1st, 2022, were reported. Each case was assessed for WHO MIS-C criteria. Causality assessment followed 2019 WHO recommendations. ExposureCOVID-19 mRNA vaccine. Main Outcome and MeasuresThe main outcome was the reporting rate of post-vaccine hyper-inflammatory syndrome per 1,000,000 COVID-19 mRNA vaccine doses in 12-17-year-old children. This reporting rate was compared to the MIS-C rate per 1,000,000 12-17-year-old children infected by SARS-CoV-2. Secondary outcomes included the comparison of clinical features between post-vaccine hyper-inflammatory syndrome and post SARS-CoV-2 MIS-C. ResultsFrom June 2021 to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12-17-year-old children. Among them, 9 presented a multisystemic hyper-inflammatory syndrome. All cases fulfilled MIS-C WHO criteria. Main clinical features included male predominance (8/9, 89%), cardiac involvement (8/9, 89%), digestive symptoms (7/9, 78%), coagulopathy (5/9, 54%), cytolytic hepatitis (4/9, 46%), and shock (3/9, 33%). 3/9 (33%) required intensive care unit transfer, and 2/9 (22%) hemodynamic support. All cases recovered. Only three cases had evidence of previous SARS-CoV-2 infection. The reporting rate was 1.1 (95%CI [0.5; 2.1]) per 1,000,000 doses injected. 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. Clinical features (inflammatory parameters, cytopenia) slightly differed from post-SARS-CoV-2 MIS-C, along with short-term outcomes (less PICU transfer than MIS-C). Conclusion and RelevanceVery few cases of hyper-inflammatory syndromes 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 MIS-C among same age children infected by SARS-CoV-2, supports the benefit of SARS-CoV-2 vaccination in children. Further studies are required to explore specific pathways of this entity compared to post-SARS-CoV-2 MIS-C. Key pointsO_ST_ABSQuestionC_ST_ABSIs COVID-19 mRNA vaccine in 12-17-year-old children associated with subsequent multisystemic hyper-inflammatory syndrome? FindingsThe French national pharmacovigilance system identified 9 children with a hyper-inflammatory syndrome with multi-organ involvement following COVID-19 mRNA vaccination (reporting rate 1.1 [0.5; 2.1] per 1,000,000 doses), of which only three had evidence of previous SARS-CoV-2 infection. All cases fulfilled WHO definition for MIS-C, but clinical and immunological features, along with short-term outcomes, slightly differed from classical post SARS-CoV-2 MIS-C. MeaningVery rare cases of hyper-inflammatory syndrome can occur following COVID-19 mRNA vaccine in 12-17-year-old children. The very low rate of this entity, compared to classical post-SARS-CoV-2 MIS-C, supports the benefit of SARS-CoV-2 vaccination in children.

Association between the COVID-19 pandemic and pertussis in France using multiple nationwide data sources

BackgroundInterventions to mitigate coronavirus disease 19 (COVID-19) pandemic may impact other respiratory diseases such as pertussis. We aimed to study the course of pertussis in France over an 8-year period and its association with COVID-19 mitigation strategies, using multiple nationwide data sources. MethodsWe analyzed the number of French pertussis cases between 2013 and 2020, using the PCR test results from nationwide outpatient laboratories (Source 1) and the pediatric network of 41 hospitals (Source 2), and using the reports of an office-based pediatric national network (Source 3). We conducted a quasi-experimental interrupted time-series analysis, relying on negative binomial regression models. The models accounted for seasonality, long-term cycles, and secular trend, and included a binary variable for the first national lockdown (ordered on March 16, 2021). ResultsWe identified 19,039 cases of pertussis from the three data sources during the study period. There was a significant decrease of pertussis cases following the implementation of mitigation measures, with adjusted incidence rate ratios of 0.102 (95% CI 0.040-0.256) and 0.216 (95% CI 0.071-0.656) for Source 1 and Source 2, respectively. The association was confirmed in Source 3 (median of 1 [IQR 0-2] vs. 0 [IQR 0-0] pertussis cases per month before and after lockdown, respectively, p=0.0048). ConclusionThe drastic reduction of outpatient and hospitalized cases of pertussis strongly suggests an impact of COVID-19 mitigation measures and their consequences on pertussis epidemiology. Pertussis vaccination recommendations should be carefully followed, and disease monitoring should be continued to detect any resurgence after relaxation of mitigation measures. FundingThere was no specific funding for the study.

Assessment of spread of SARS-CoV-2 by RT-PCR and concomitant serology in children in a region heavily affected by COVID-19 pandemic

BackgroundSeveral studies indicated that children seem to be less frequently infected with SARS-CoV-2 and potentially less contagious. To examine the spread of SARS-CoV-2 we combined both RT-PCR testing and serology in children in the most affected region in France, during the COVID-19 epidemic. MethodsFrom April 14, 2020 to May 12, 2020, we conducted a cross-sectional prospective, multicenter study. Healthy controls and pauci-symptomatic children from birth to age 15 years were enrolled by 27 ambulatory pediatricians. A nasopharyngeal swab was taken for detection of SARS-CoV-2 by RT-PCR and a microsample of blood for micro-method serology. ResultsAmong the 605 children, 322 (53.2%) were asymptomatic and 283 (46.8%) symptomatic. RT-PCR testing and serology were positive for 11 (1.8%) and 65 (10.7%) of all children, respectively. Only 3 children were RT-PCR-positive without any antibody response have been detected. The frequency of positivity on RT-PCR for SARS-CoV-2 was significantly higher in children with positive serology than those with a negative one (12.3% vs 0.6%, p<0.001). Contact with a person with proven COVID-19 increased the odds of positivity on RT-PCR (OR 7.8, 95% confidence interval [1.5; 40.7]) and serology (15.1 [6.6;34.6]). ConclusionIn area heavily affected by COVID-19, after the peak of the first epidemic wave and during the lockdown, the rate of children with positive SARS-CoV-2 RT-PCR was very low (1.8%), but the rate of positive on serology was higher (10.7%). Most of PCR positive children had at the same time positive serology. What is already known on this topic?- As compared with adults, children seem to be less frequently infected with SARS-CoV-2 and potentially less contagious according to several studies. - Most of the studies were based on RT-PCR SARS-CoV-2 testing, without antibody assays. What this study adds?- This study combining RT-PCR and serologic testing, assessed the spread of SARS-CoV-2 infection in children in area heavily affected by COVID-19 pandemic. - Among a large cohort of children (>600), 11 (1.8%) were positive on RT-PCR for SARS-CoV-2 and 65 (10.7%) were positive on serology. - The only factor affecting positivity of RT-PCR for SARS-CoV-2 or serology was the household contact COVID-19.

Changes in RT-PCR-positive SARS-CoV-2 rates in adults and children according to the epidemic stages

AimTo describe the trends of RT-PCR positive SARS-CoV-2 rates in children and adults according to the time of COVID-19 epidemic. MethodsIn this prospective multicenter study involving 45 pediatric units, we collected the results of nasopharyngeal swabs in France from March 2, 2020 to April 26, 2020. ResultsDuring the study period, 52,588 RT-PCR tests for SARS-CoV-2 were performed, 6,490 in children and 46,098 in adults. The risk ratio of RT-PCR positive SARS-CoV-2 tests for adults compared to children was 3.5 (95% CI [3.2;3.9]) for the whole study period. These rates varied according to the time of the epidemic and were higher at the peak. The lower rates of positive test in children persisted during the surveillance period but varied according to the time in the epidemic. ConclusionThe rate of positive RT-PCR positive SARS-CoV-2 tests for children was always less than that for adults but vary according to the epidemic stage.