Snotwatch COVID-toes: An ecological study of chilblains and COVID-19 diagnoses in Victoria, Australia

The COVID-19 pandemic has caused widespread illness with varying clinical manifestations. One less-commonly-reported presentation of COVID-19 infection is chilblain-like lesions. We conducted an ecological analysis of chilblain presentations in comparison with confirmed and suspected COVID-19 infections in a primary care setting to establish that a relationship exists between the two. Our study collated data from three Primary Health Networks across Victoria, Australia, from 2017–2021, to understand patterns of chilblain presentations prior to and throughout the pandemic. Using a zero-inflated negative binomial regression analysis, we estimated the relationship between local minimum temperature, COVID-19 infections and the frequency of chilblain presentations. We found a 5.72 risk ratio of chilblain incidence in relation to COVID-19 infections and a 3.23 risk ratio associated with suspected COVID-19 infections. COVID-19 infections were also more strongly associated with chilblain presentations in 0-16-year-olds throughout the pandemic in Victoria. Our study statistically suggests that chilblains are significantly associated with COVID-19 infections in a primary care setting. This has major implications for clinicians aiming to diagnose COVID-19 infections or determine the cause of a presentation of chilblains. Additionally, we demonstrate the utility of large-scale primary care data in identifying an uncommon manifestation of COVID-19 infections, which will be significantly beneficial to treating physicians.

Pediatric Hepatitis and Respiratory Viruses: A Spatiotemporal Ecologic Analysis.

INTRODUCTION: Beginning in early 2022, clusters of severe pediatric hepatitis were reported in Europe and the United States. To date, no cause has been identified although human adenovirus 41 has been proposed in a proportion of cases. We examined population data >11 years for hepatitis clusters in Victoria, Australia, and whether any were spatiotemporally associated with community transmission of common respiratory viruses. METHODS: We used SaTScan to analyze for clusters of pediatric hepatitis and respiratory adenoviruses in Victoria. Negative binomial regression analysis was performed to determine any associations between hepatitis and respiratory viruses across Victoria between July 1, 2011, and June 30, 2022. RESULTS: A number of positive associations were observed in Victoria between pediatric hepatitis clusters and respiratory viruses in our spatiotemporal analysis. A positive association was not found with respiratory adenoviruses or SARS-CoV-2. Increased hepatitis clusters were observed in 2021 and 2022 as noted internationally. CONCLUSION: The current hepatitis outbreak is novel and, although respiratory viruses are broadly associated with hepatitis, SARS-CoV-2 and respiratory adenoviruses are unlikely to be related.

Maternal SARS-CoV-2 exposure alters infant DNA methylation.

Background: Infection during pregnancy can increase the risk of neurodevelopmental disorders in offspring. The impact of maternal SARS-CoV-2 infection on infant neurodevelopment is poorly understood. The maternal immune response to infection may be mimicked in rodent models of maternal immune activation which recapitulate altered neurodevelopment and behavioural disturbances in the offspring. In these models, epigenetic mechanisms, in particular DNA methylation, are one pathway through which this risk is conferred in utero to offspring. We hypothesised that in utero exposure to SARS-CoV-2 in humans may alter infant DNA methylation, particularly in genes associated with neurodevelopment. We aimed to test this hypothesis in a pilot sample of children in Victoria, Australia, who were exposed in utero to SARS-CoV-2. Methods: DNA was extracted from buccal swab specimens from (n = 4) SARS-CoV-2 in utero exposed and (n = 4) non-exposed infants and methylation status assessed across 850,000 methylation sites using an Illumina EPIC BeadChip. We also conducted an exploratory enrichment analysis using Gene Ontology annotations. Results: 1962 hypermethylated CpG sites were identified with an unadjusted p-value of 0.05, where 1133 CpGs mapped to 959 unique protein coding genes, and 716 hypomethylated CpG sites mapped to 559 unique protein coding genes in SARS-CoV-2 exposed infants compared to non-exposed. One differentially methylated position (cg06758191), located in the gene body of AFAP1 that was hypomethylated in the SARS-CoV-2 exposed cohort was significant after correction for multiple testing (FDR-adjusted p-value <0.00083). Two significant differentially methylated regions were identified; a hypomethylated intergenic region located in chromosome 6p proximal to the genes ZP57 and HLA-F (fwer <0.004), and a hypomethylated region in the promoter and body of the gene GAREM2 (fwer <0.036). Gene network enrichment analysis revealed differential methylation in genes corresponding to pathways relevant to neurodevelopment, including the ERBB pathway. Conclusion: These pilot data suggest that exposure to SARS-CoV-2 in utero differentially alters methylation of genes in pathways that play a role in human neurodevelopment.

A prospective, longitudinal, case-control study to evaluate the neurodevelopment of children from birth to adolescence exposed to COVID-19 in utero.

BACKGROUND: The Coronavirus disease (COVID-19) pandemic has created unprecedented acute global health challenges. However, it also presents a set of unquantified and poorly understood risks in the medium to long term, specifically, risks to children whose mothers were infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Infections during pregnancy can increase the risk of atypical neurodevelopment in the offspring, but the long-term neurodevelopmental impact of in utero COVID-19 exposure is unknown. Prospective, longitudinal studies are needed to evaluate children exposed in utero to SARS-CoV2 to define this risk. METHODS: We have designed a prospective, case-controlled study to investigate the long-term impacts of SARS-CoV2 exposure on children exposed in utero. Women infected with SARS-CoV-2 during pregnancy will be recruited from Monash Health, the Royal Women's Hospital and Western Health (Melbourne, Australia) and Londrina Municipal Maternity Hospital Lucilla Ballalai and PUCPR Medical Clinical (Londrina, Brazil). A control group in a 2:1 ratio (2 non-exposed: 1 exposed mother infant dyad) comprising women who gave birth in the same month of delivery, are of similar age but did not contract SARS-CoV-2 during their pregnancy will also be recruited. We aim to recruit 170 exposed and 340 non-exposed mother-infant dyads. Clinical and socio-demographic data will be collected directly from the mother and medical records. Biospecimens and clinical and epidemiological data will be collected from the mothers and offspring at multiple time points from birth through to 15 years of age using standardised sample collection, and neurological and behavioural measures. DISCUSSION: The mapped neurodevelopmental trajectories and comparisons between SARS-CoV-2 exposed and control children will indicate the potential for an increase in atypical neurodevelopment. This has significant implications for strategic planning in the mental health and paediatrics sectors and long-term monitoring of children globally.

Snotwatch COVID-toes: An ecological study of chilblains and COVID-19 diagnoses in Victoria, Australia.

The COVID-19 pandemic has caused widespread illness with varying clinical manifestations. One less-commonly-reported presentation of COVID-19 infection is chilblain-like lesions. We conducted an ecological analysis of chilblain presentations in comparison with confirmed and suspected COVID-19 infections in a primary care setting to establish that a relationship exists between the two. Our study collated data from three Primary Health Networks across Victoria, Australia, from 2017-2021, to understand patterns of chilblain presentations prior to and throughout the pandemic. Using a zero-inflated negative binomial regression analysis, we estimated the relationship between local minimum temperature, COVID-19 infections and the frequency of chilblain presentations. We found a 5.72 risk ratio of chilblain incidence in relation to COVID-19 infections and a 3.23 risk ratio associated with suspected COVID-19 infections. COVID-19 infections were also more strongly associated with chilblain presentations in 0-16-year-olds throughout the pandemic in Victoria. Our study statistically suggests that chilblains are significantly associated with COVID-19 infections in a primary care setting. This has major implications for clinicians aiming to diagnose COVID-19 infections or determine the cause of a presentation of chilblains. Additionally, we demonstrate the utility of large-scale primary care data in identifying an uncommon manifestation of COVID-19 infections, which will be significantly beneficial to treating physicians.