Hospital contact patterns and vulnerability to SARS-CoV-2 outbreaks

The transmission risk of SARS-CoV-2 within hospitals can exceed that in the general community because of more frequent close proximity interactions (CPIs). Heterogeneity of risk across wards is still poorly described. We measured CPIs in 15 clinical wards across three hospitals using wearable sensors over 36 hours in spring 2020. This data was combined with a transmission model to estimate and compare transmission risks across wards. We found a four-fold range of epidemic risk between wards, with patients frequently presenting high risk to patients and healthcare workers (HCWs). Using a simulation study, we then assessed the potential impact on global risk of targeting individuals for prevention based on their contact patterns. We found that targeting individuals with the highest cumulative contact hours was most impactful. This study reveals patterns of interactions between individuals in hospital during a pandemic and opens new routes for research into airborne nosocomial risk. One Sentence SummaryWe measured contacts between staff, patients and visitors in 15 hospital wards, and used models to predict epidemic risk and evaluate interventions.

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.

A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis

SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-{kappa}B activity, TNF- signaling, associated with decreased gene expression of NF-{kappa}B inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1 and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.

Prior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children

BackgroundChildren have a lower rate of COVID-19, potentially related to cross-protective immunity conferred by seasonal coronaviruses (HCoVs). We tested if prior infections with seasonal coronaviruses impacted SARS-CoV-2 infections and related Multisystem Inflammatory Syndrome (MIS). MethodsThis cross-sectional observational study in Paris hospitals enrolled 739 pauci or asymptomatic children (HOS group) plus 36 children with suspected MIS (MIS group). Prevalence, antigen specificity and neutralizing capability of SARS-CoV-2 antibodies were tested. Antibody frequency and titres against Nucleocapsid (N) and Spike (S) of the four seasonal coronaviruses (NL63, HKU1, 229E, OC43) were measured in a subset of seropositive patients (54 SARS-CoV-2 (HOS-P subgroup) and 15 MIS (MIS-P subgroup)), and in 118 matched SARS-CoV-2 seronegative patients (CTL subgroup). FindingsSARS-CoV-2 mean prevalence rate in HOSP children was 11.7% from April 1 to June 1. Neutralizing antibodies were found in 55{middle dot}6% of seropositive children, and their relative frequency increased with time (up to 100 % by mid-May). A majority of MIS children (25/36) were SARS-CoV-2 seropositive, of which all tested (n=15) had neutralizing antibodies. On average, seropositive MIS children had higher N and S1 SARS-CoV-2 titres as compared to HOS children. Patients from HOS-P, MIS-P, and CTL subgroups had a similar prevalence of antibodies against the four seasonal HCoVs (66{middle dot}9 -100%). The level of anti-SARS-CoV-2 antibodies was not significantly different in children who had prior seasonal coronavirus infection. InterpretationPrior infection with HCoVs does not prevent SARS-CoV-2 infection and related MIS in children. Children develop neutralizing antibodies after SARS-CoV-2 infection. Evidence before this studyChildren seem to be less likely affected by SARS-CoV-2 infection and clinical course of COVID-19 is less severe than in adults. As those asymptomatic or mildly symptomatic children are underdiagnosed and their viral loads are comparable to those of adults, they may act as an asymptomatic reservoir for the spread of the virus. One explanation of the difference between the adult and the pediatric infectious profile might be that infection with seasonal human coronaviruses, which is very frequent from a very young age, could lead to cross protective immunity. We searched in PubMed, MedRxiv and BioRxiv for publications from inception to June 15, 2020, using the terms "COVID-19, SARS-CoV-2, children, serology, Kawasaki, Corona Virus". Added value of this studySARS-CoV-2 mean prevalence rate was 11.7% from April 1 to June 1 and neutralizing antibodies were found in 55% of the tested seropositive children. Among patients with a Multisystem Inflammatory Syndrome, Kawasaki-like disease, 70% were SARS-CoV-2 seropositive and had neutralizing antibodies. COVID-19 and MIS attack rates, and anti-SARS-CoV-2 antibodies titres were not significantly impacted by prior seasonal coronavirus infection. Implications of all the available evidencePrior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children As antibodies against seasonal coronaviruses are very frequent and as these viruses circulate efficiently in human populations every winter, our results question to what extent the concept of herd immunity based on circulating antibodies can be applied to seasonal coronaviruses and possibly SARS-CoV-2.

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.

Outbreak of Kawasaki disease in children during COVID-19 pandemic: a prospective observational study in Paris, France

BackgroundAcute clinical manifestations of SARS-CoV-2 infection are less frequent and less severe in children than in adults. However, recent observations raised concerns about potential post-viral severe inflammatory reactions in children infected with SARS-CoV-2. MethodsWe describe an outbreak of cases of Kawasaki disease (KD) admitted between April 27 and May 7, 2020, in the general paediatrics department of a university hospital in Paris, France. All children prospectively underwent nasopharyngeal swabs for SARS-CoV-2 RT-PCR, SARS-CoV-2 IgG serology testing, and echocardiography. The number of admissions for KD during the study period was compared to that observed since January 1, 2018, based on discharge codes, using Poisson regression. ResultsA total of 17 children were admitted for KD over an 11-day period, in contrast with a mean of 1.0 case per 2-week period over 2018-2019 (Poisson incidence rate ratio: 13.2 [95% confidence interval: 7.3-24.1], p <0.001). Their median age was 7.5 (range, 3.7-16.6) years, and 59% of patients originated from sub-Saharan Africa or Caribbean islands. Eleven patients presented with KD shock syndrome (KDSS) requiring intensive care support, and 12 had myocarditis. All children had marked gastrointestinal symptoms at the early stage of illness and high levels of inflammatory markers. Fourteen patients (82%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR 7/17, positive IgG antibody detection 14/16). All patients received immunoglobulins and some received corticosteroids (5/17). The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 cases (29%) during hospitalisation. ConclusionsThe ongoing outbreak of KD in the Paris might be related to SARS-CoV2, and shows an unusually high proportion of children with gastrointestinal involvement, KDSS and African ancestry.

COVID-19-related mortality by age groups in Europe: A meta-analysis

Background and ObjectivesTo date, more than 1,000,000 confirmed cases and 65,000 deaths due to coronavirus disease 2019 (COVID-19) have been reported globally. Early data have indicated that older patients are at higher risk of dying from COVID-19 than younger ones, but precise international estimates of the age-breakdown of COVID-19-related deaths are lacking. Materials and MethodsWe evaluated the distribution of COVID-19-related fatalities by age groups in Europe. On April 6, 2020, we systematically reviewed COVID-19-related mortality data from 32 European countries (European Union/European Economic Area and the United Kingdom). We collated official reports provided by local Public Health or Ministry of Health websites. We included countries if they provided data regarding more than 10 COVID-19-related deaths stratified by age according to pre-specified groups (i.e., < 40, 40-69, [≥] 70 years). We used random-effects meta-analysis to estimate the proportion of age groups among all COVID-19-related fatalities. ResultsThirteen European countries were included in the review, for a total of 31,864 COVID-19-related deaths (range: 27-14,381 per country). In the main meta-analysis (including data from Germany, Hungary, Italy, Netherlands, Portugal, Spain, Switzerland; 21,522 COVID-19-related fatalities), the summary proportions of persons < 40, 40-69, and [≥] 70 years of age among all COVID-19-related deaths were 0.1% (0.0-0.2%; I2 24%), 12.8% (10.3-15.6%; I2 94%), and 84.8% (81.3-88.1%; I2 96%), respectively. ConclusionsPeople under 40 years of age represent a small fraction of the total number of COVID-19-related deaths in Europe. These results may help health authorities respond to public concerns and guide future physical distancing and mitigation strategies.