Covid-19 research: Infection and transmission in children

The role of children in infection and transmission of COVID-19 is still not well understood, especially as it doesn’t follow the typical trends of other respiratory viruses in which children play a large role in transmission. Understanding the ability of children to both become infected and subsequently transmit SARS-CoV-2 is crucial to help understand the role of children in this pandemic, and better inform relevant policy.

The program of work at MCRI is extensively monitoring the COVID-19 presentations of children, from asymptomatic to the most severe hospital presentations, to understand how COVID-19 infects them. The project led by A/Prof Nigel Crawford and Dr Shidan Tosif is investigating the extent to which an infected family member can spread COVID-19 and aim to define the role of children in transmission within their household. This work has also led to further work on campus that is analysing multiple specimens collected over the course of the study to describe key immunological and virological characteristics of COVID-19.

Webinar

COVID-19 and kids: understanding infection and transmission

In this webinar, we heard from Prof Sarath Ranganathan, Dr Shidan Tosif, and Dr Melanie Neeland about what we know about children and COVID-19, the role of children in COVID-19 transmission, and COVID-19 immunity in children, compared to adults. Prof Fiona Russell joined the speakers for a panellist discussion and Q&A, led by Prof Andrew Steer.

Research

The COVID-19 household transmission study

Dr Shidan Tosif and A/Prof Nigel Crawford are leading the study aiming to examine key clinical and epidemiological characteristics and transmission within families who have a SARS-CoV-2 positive household member. By analysing the transmission within a household, they aim to understand the extent to which an infected family member can spread COVID-19 to other household members, including children. They aim to characterise any secondary infections that occur, including asymptomatic presentations, to understand the risk factors that may make one more susceptible to subsequent infection. By analysing multiple specimens collected over the course of the study, they also aim to describe key immunological and virological characteristics of COVID-19.

COVID-19 in Hospitalised Children

Dr Danielle Wurzel and A/Prof Nigel Crawford are leading the paediatric-specific component of the Doherty Institute’s Sentinel Travellers and Research Preparedness for Emerging Infectious Diseases (SETREP-ID) study. They will examine any COVID-19 patient admitted to the Royal Children’s Hospital and aim to follow the clinical course and outcome of the infection, as well as conduct epidemiological, virology and immunology studies. By investigating the characteristics of inpatients, they will evaluate the predictors for severe COVID-19 infection in children, particularly in those with underlying chronic diseases.

Age-specific coagulation

Professors Paul Monagle and Vera Ignjatovic are investigating the contribution of age-specific differences in blood clotting to the age-specific epidemiology of COVID-19. To do this, they will compare COVID-19, non-COVID-19 coronavirus and influenza infected patients, as well as healthy participants, to understand the changes in the coagulation system observed in COVID-19. Understanding the mechanisms of clot formation in patients with COVID-19 will identify drug targets that could alleviate the devastating blood clot-related complications in infected patients.

Genetic susceptibility to severe COVID-19

Professor John Christodoulou, a key member of the international COVID-19 Human Genetic Effort consortium, together with NSW’s Garvan Institute will conduct whole genome sequencing to screen for genetic variants in biological pathways that could be functionally relevant, but not obvious until exposed to COVID-19. This work will identify underlying genetic variations that could help to predict the severity of the disease, potentially uncovering new opportunities for personalised approaches to treatment of individuals exposed to the virus. In addition, they aim to identify pathways that play a major role in modulating COVID-19 disease severity, which could potentially allow the identification of existing drugs that could be used in a targeted manner to reduce disease severity in specific cohorts of patients or even more generally.

See Inborn errors of type I IFN immunity in patients with life-threatening COVID-19 and Autoantibodies against type I IFNs in patients with life-threatening COVID-19 for more details.

The EPICENTRE - international registry of children and newborns needing critical care for SARS-CoV-2 infection

Led by A/Professor David Tingay, the MCRI has launched the EPICENTRE (ESPNIC Covid pEdiatric Neonatal Registry), an international, multi-center and multidisciplinary initiative to study the epidemiology, clinical course and outcomes of children and newborns needing critical care for SARS-CoV-2 infection. EPICENTRE will contain symptom, treatment and outcome data on the largest number of paediatric COVID-19 intensive care cases worldwide. This initiative is a joint collaboration with European Paediatric and Neonatal Intensive Care Society partners in France and Italy. The MCRI was chosen to lead this initiative due to our international reputation for running trials and registries in children, and because Australia is not experiencing the same acute healthcare pressures.

Stem cell-derived tissues for SARS-CoV-2 research

Professor Melissa Little heads the team at MCRI who are leading a project that uses human stem cells to better understand the effects of COVID-19 on different organ systems in the body including the lungs, heart, kidneys, brain, immune system and blood vessels, to support the development of targeted treatments. This work can help to support research facilities across Australia that have established live COVID-19 cultures for the purpose of assessing viral infectivity to facilitate rapid repurposing of existing drugs and accelerate the evaluation of new drugs prior to clinical trial. The research has already deepened our understanding on how coronavirus impacts on the heart, the team identified issues with the heart muscle as a result of the virus disrupting oxygen supply. This research has been expanded to include emerging strains of SARS-CoV-2, long-term symptoms and potential links between COVID-19 and unborn children.

Associated Resources

• Kids mount a COVID-19 immune response without detection of the SARS-CoV-2 virus
• First month of Australian data shows children at low risk of COVID-19 infection, no hospitalisations
• Dr Melanie Neeland spoke to ABC about her work finding that children's innate immune system is protecting them from severe COVID. Article available here. Radio available here. TV interview here.
• Murdoch Children's Research Institute studies family with coronavirus to find out why their children were immune

Associated Campus Papers

• Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19
• Understanding COVID-19 in children may provide clues to protect at-risk populations
• SARS-CoV-2 testing and outcomes in the first 30 days after the first case of COVID-19 at an Australian children's hospital
• Update on the COVID-19-associated inflammatory syndrome in children and adolescents; paediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2
• Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections
• Understanding COVID-19 in children may provide clues to protect at-risk populations
• Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children
• The use of dried blood spots for the serological evaluation of SARS-CoV-2 antibodies
• Systems serology detects functionally distinct coronavirus antibody features in children and elderly
• Sense and sensitivity: can an inaccurate test be better than no test at all?
• Testing children with COVID-19 symptoms: what are parents' intentions?