COVID-19 and Autism Research: Perspectives from Around the Globe.

Abstract

David G. Amaral, Evdokia Anagnostou, Vanessa H. Bal, Josephine Barbaro, Angela B. Barber, Ricardo Canal-Bedia, Nola Chambers, Stephen R. Dager, Geraldine Dawson, John-Joe Dawson-Squibb, Petrus J. de Vries, Gabriel Dichter, Cheryl Dissanayake, Gauri Divan, Annette Estes, Dani Fallin, Lauren Franz, Naoufel Gaddour, Alan H. Gerber, Melissa Gilbert, Rebecca M. Girard, Ofer Golan, Johathan Green, Michal Harty, Jill Howard, Darren Hedley, Caitlin M. Hudac, Susan M. Hayward, Lisa V. Ibanez, Hiroshi Ishiguro, Angelina Kakooza Mwesige, Yoko Kamio, Rajesh K. Kana, Jennifer L. Keluskar, Daniel P. Kennedy, Connor M. Kerns, Jessica Kinard, Genevieve Konopka, Frank Kooy, Hirokazu Kumazaki, Janet E. Lainhart, Lauren P. Lawson, Kathy Leadbitter, Matthew D. Lerner, Katherine A. Loveland, Maria Magan-Maganto, Masaru Mimura, Peter Mundy, Taro Muramatsu, Declan Murphy, Bethany Oakley, Sarah O'Kelley, Kally C. O'Reilly, Seon-Hye E. Park, Alexia Rattazzi, Melanie Ring, Reetabrata Roy, Amber Ruigrok, Nancy Sadka, Diana Schendel, Liezl Schlebusch, Alison Singer, Tanya St. John, Wendy L. Stone, Helen Tager-Flusberg, Carol Taylor, Julian Tillmann and the AIMS-2-TRIALS Consortium, Theodore S. Tomeny, Danielle Toth, Katy Unwin, Vivek Vajaratkar, Jeremy Veenstra-VanderWeele, Marisa Viljoen, Heather Volk, Susan W. White, Andrew J. O. Whitehouse, Christine Wu Nordahl, Yuichiro Yoshikawa Last year around this time, in preparation for the INSAR2019 meeting in Montreal, we asked members of the Autism Research editorial board as well as the Associate Editors to write short comments on what they considered to be the major gaps in autism research. The resulting Commentary was well received with nearly 3000 downloads. The INSAR meeting scheduled for Seattle in 2020 was, of course, cancelled due to the coronavirus pandemic. The pandemic has forced the reorganization and rethinking of all science, including autism research. To get a sense of how autism researchers are dealing with this unprecedented situation around the world, we asked for short comments about the situation from editorial board members, Associate Editors and from the INSAR Global Senior Leaders in Autism Research Committee, a relatively new INSAR initiative chaired by Petrus de Vries (South Africa) and Declan Murphy (UK). We will present perspectives by World Health Organization (WHO) Region. Before going further, we must acknowledge that over and above the hardships for autism researchers across the globe, the pandemic has cost so much more to the more than 400,000 families worldwide that have suffered the death of a loved one. We offer our condolences to those families and to those who will befall a similar fate in the future. We also acknowledge the global economic burden of the pandemic, both as a result of COVID-19 and as a consequence of lockdown. This too will have a major impact on everyone, and perhaps disproportionately so on families who live with disabilities and those in low- and middle-income countries. The contributions that make up the remainder of this commentary are in equal parts frightening and inspiring. On the down side, they talk about the difficulties in conducting autism research when social distancing is in place and when participants must wear masks. How does one recruit young subjects if the ADOS cannot be done with masked individuals? There is also the concern that, given the overall frightening environment of the current situation, it may be difficult to interpret behavioural research results. For example, are measures of anxiety now reflecting a trait of an individual or the state of heightened angst resulting from dealing with the virus? Others worry that the enormous costs of dealing with controlling the spread of the virus will eliminate academic positions and autism research funding in the future. This is a real concern. The state of California has gone from a $14 billion surplus to a projected $54 billion deficit. Public higher education in the state is now slated for a 10% reduction in funding. There are also implications for prevalence of autism in the future. One of the prominent, proposed nongenetic causes of autism is maternal immune activation [Patterson et al., 2011]. Naturally occurring pathogen exposures offer the strongest evidence of environmental etiology. The best example is maternal rubella (German measles) infection during pregnancy. Before development and widespread dissemination of effective vaccines, major pandemics occurred every 10 to 30 years [Duszak, 2009]. The last of these was from 1963 to 1965 and infected an estimated 10 percent of pregnant women, resulting in more than 13,000 fetal or early infant deaths; 20,000 infants born with major birth defects and 10,000 to 30,000 infants born with moderate to severe neurodevelopmental disorders. Stella Chess, a child psychiatrist at New York University, studied 243 children exposed to rubella during pregnancy [Chess, 1971; Chess, 1977] and found that the largest category of neurodevelopmental disorder was intellectual disability, which affected 37 percent of the sample. Nine of these children were also diagnosed with autism; another, without intellectual disability, had a possible diagnosis; and eight a partial syndrome of autism. These numbers would translate to an autism prevalence of 741 per 10,000 rubella-exposed children, just over seven percent which was strikingly different from the 2-3 per 10,000 typically found at the time in the general population. It is concerning therefore, that a recent survey of two New York hospitals found that 15% of pregnant woman coming for the delivery of their child were positive for coronavirus [Breslin et al., 2020] and many of these were asymptomatic. Given the inadequate testing in many countries, the true number of pregnant woman infected with the virus may not be known for some time and the implication for the prevalence of autism will undoubtedly be the basis for much future research. But, the contributions below also reflect an up side of resilience and resolve by the autism research community. Many investigators describe how testing and even clinical trials were rapidly converted from in person to telehealth strategies. Development of more efficient and technology driven assessment tools has been fast-tracked due to the pandemic. Could robots provide a mechanism for providing therapy without the risk of viral exposure? The use of teleconferencing platforms like Zoom have transformed how scientists are communicating their research results leading some to suggest that this may also be a strategy to reduce air travel and global warming in the future. Here too the disparity between access to digital technology in richer countries relative to under resourced countries is amplified. One hopefully positive take-a-way message relates to the importance of science in solving problems such as pandemics. The development of diagnostic tests, vaccines and medications related to COVID-19 highlights the work of the millions of scientists who labor, generally in obscurity, to gather knowledge about the natural world. We hope that you enjoy the thoughtful comments of many of our colleagues who are engaged in research dedicated to decreasing disability in individuals with autism spectrum disorder. Breslin, N., Baptiste, C., Gyamfi-Bannerman, C., Miller, R., Martinez, R., Bernstein, K., …, Goffman, D. (2020). COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals. American Journal of Obstetrics and Gynecology MFM. 100118. Epub 2020/04/16. http://dx.doi.org/10.1016/j.ajogmf.2020.100118. PubMed PMID: 32292903; PMCID: PMC7144599 Chess, S. (1971). Autism in children with congenital rubella. Journal of Autism and Child Schizophrenia, 1(1), 33–47. PubMed PMID: 5172438 Chess, S. Follow-up report on autism in congenital rubella. Journal of Autism and Child Schizophrenia, 1977;7(1):69-81. PubMed PMID: 576606 Duszak RS. (2009) Congenital rubella syndrome – major review. Optometry, 80(1), 36–43. http://dx.doi.org/10.1016/j.optm.2008.03.006. PubMed PMID: 19111256 Patterson, P.,H. (2011). Maternal infection and immune involvement in autism. Trends Mol Med. 2011;17(7):389-94. http://dx.doi.org/10.1016/j.molmed.2011.03.001. PubMed PMID: 21482187; PMCID: PMC3135697 The year 2020 brought new challenges and terminology to the globe, as the COVID-19 pandemic started to spread, first in China, then Europe and the USA, before expanding to Africa. New words and phrases like “social distancing”, “the new normal”, and “lockdown” were introduced, and the whole world turned towards technology for information (true and fake), to connect with one another, for online classrooms, and for research, including autism research. But, unlike the rapid technological transformation in high-income countries, in Africa the pandemic has simply magnified the pre-existing inequalities. In contrast to the UK or USA, only a small proportion of African households have internet access [World Bank, 2016]. Data costs are disproportionately high and speed disproportionately low. The World Bank refers to this as the “digital divide”. They have warned (long before the arrival of COVID-19) that this gap is increasing between Africa and high-income countries [World Bank, 2016]. The sudden drive towards technology during the pandemic has accelerated and magnified this digital disparity. Of course, technology can improve access, availability, and quality of services and clinical research. In low-resource settings, technology can facilitate the delivery of empirically supported interventions by providers that do not have substantial prior training. However, for technology to be feasible and fair in diverse African settings, it should be tailored to the local context, integrated within existing systems, and be accessible and affordable. This is why autism research has to consider not only these digital disparities, but also the contextual and socio-economic challenges experienced by Africans. South Africa, for example, is recognised by the World Bank as the most unequal society in the world, and this manifests in both economic and health disparities [Sullah and Zikhali, 2018]. Mindful of the pre-existing digital disparities, South African academic centres have been sensitive to the needs of staff and students during the time of COVID-19. They provided devices, data, and negotiated with mobile telecommunication companies for free access to academic websites. Yet, providing online access is only part of the answer. We still make many contextual assumptions. Many students and researchers have been severely affected by the contextual challenges of “working from home,” when “home” may be an environment very different from a classroom, clinic or laboratory. For example, staff have experienced significant difficulties with internet access during the lockdown, and a number of students had devices stolen after they received them from their universities. The contextual challenges of families participating in research have had direct impacts on the ethics of our research. How appropriate is it to conduct research during a pandemic (even if it may help families), when many of them were struggling to feed their children? Fortunately, Africa is a resilient and an innovative place, and good things have emerged. Many families have become more motivated and skilled to use internet-based training and remote coaching. Whatsapp support groups and Zoom coffee mornings have sprung up, and excellent online resources have been produced in record time. In one particular study, we struggled for many months in 2019 to encourage non-specialist facilitators to participate in online training. COVID-19 changed that for good and showed that these approaches might be feasible, but only with the right online and offline supports in place. COVID-19 has magnified the disparities in African communities and emphasised the importance of context, not only for autism research, but for all health research in low-resource settings to ensure that we reduce, rather than increase, pre-existing disparities. The time of COVID-19 has forced autism researchers in Africa to reflect on our goals and methods for socially-responsive and socially responsible research. We acknowledge funding from NIMH 5K01MH104370, NIMH 1R21MH120696 and from the South African Department of Social Development. Sulla, V., Zikhali, P. (2018). Overcoming poverty and inequality in South Africa: An assessment of drivers, constraints and opportunities. Washington, DC: The World Bank Group. World Bank. (2016). World Development Report 2016: Digital Dividends. Washington, DC: World Bank. doi:10.1596/978-1-4648-0671-1. License: Creative Commons Attribution CC BY 3.0 IGO The coronavirus disease 2019 (COVID-19) is described as the once-in-a-century pandemic of the 21st century (Gates, 2020), with over 6.9 million infections and 400,000 deaths globally to date (WHO, 2020). Governments and Ministries of Health have currently focused on the prevention and treatment of COVID-19 patients, with minimal consideration of other services especially for children with disabilities or chronic illnesses. These children are also prone to the effects of social disruption and the lock down measures created as a means to curb the pandemic (United Nations, 2020). While COVID-19 continues to spread across the globe, public health strategies to curb the pandemic including social distancing, public travel restriction measures that many countries including Uganda have implemented, have caused disruptions to daily routines [Uganda Ministry of Health, 2020]. For children with cognitive disabilities such as Autism Spectrum Disorder (ASD) and their families, such measures mean a lack of access to the resources they usually have through clinics, schools, habilitation or rehabilitation services. There is also a higher risk of children with ASD becoming frustrated and short-tempered when their daily routines are interrupted [Lee, 2020]. It is anticipated that the COVID- 19 pandemic may create overwhelming havoc to the health and social economic sectors in Africa, in view of the challenges of weak health systems, inadequate health infrastructure, lack of appropriate medicines, inefficient surveillance systems and laboratory capacity and scarcity of trained personnel to adequately respond to the pandemic [Gates, 2020]. Everyone has had their lives changed as a result of the raging COVID-19 pandemic. However, the degree by which their lives are affected may vary from one person to another based on context and at what stage of the pandemic they are. It is also important to realize that children (especially those with cognitive disabilities) are less likely to adhere to some behavioural and hygienic practices such as routine hand washing that prevent, or reduce the risk of, infection or the consistent wearing of face masks due to their age, maturity and evolving capacities [Thompson, 1994]. In Africa, specialized centres that take care of patients with autism are few, quite expensive and commonly placed in the urban setting requiring those caregivers able to afford these services to often travel long distances in order to access them. In the health unit I work in, the patient turn up has shrunk by over 25%. The current restrictions on public transport, in addition to the poor road networks, a rudimentary ambulance system and existing poverty may further prohibit their access to the required medications and services during this time [United Nations, 2020]. For those with ASD, the added major interruptions in their children's usual health services, such as speech and language, cognitive behavioural or rehabilitation therapy may create feelings of helplessness and stress for both patient and caregiver with the potential risk of their deteriorating mental well-being [United Nations, 2020]. These circumstances may subsequently result in worsening of the existing chronic conditions as a result of not being properly managed, with the child developing severe complications [United Nations, 2020]. Measures to mitigate the risks of the pandemic and promote continuing chronic care to these children is hence critical. Whereas Uganda had closed down due to the COVID-19 impact, and has begun to ease the lockdown, it is not clear what bearing this will have had on the weak healthcare systems with minimal emergency facilities and capacity like that found in many similar areas in Africa? What happens when contingency planning is almost absent and resources are inadequate? In particular, what happens to those children on chronic care management like those with ASD, how has the pandemic affected their care? What factors have facilitated or hindered access to care? What actions are needed to strengthen the health system to meet the needs of such vulnerable groups in times of pandemics? COVID-19 effects extend beyond the pandemic and are expected to transform healthcare and subsequently research in various, many yet unknown ways. With social distancing becoming the mainstay for prevention, could telemedicine perhaps become the preferred communication channel between caregivers and patients? Implications for patients with ASD present a unique challenge within this transformation. How will some of our patients on the spectrum practice social distancing if they live in a one or two room dwelling in slum areas; are cognitively impaired and are unable to understand instructions or wash hands without clean water? Telemedicine is the primary way of providing services for chronic conditions during the pandemic in many developed countries and is expected to expand beyond pre-Coronavirus era use. The question remains though, how can digital health care be employed as an accelerator for participatory medicine, including networked patients and families, as responsible drivers of their health in areas such as Africa where issues of internet connectivity are still a challenge? Another challenge is how prepared is the health care system to handle the greater uncertainties associated with ASD related research during this outbreak? The potential acceptability of the various risks will definitely vary, depending on numerous factors including the type of research and the context in which it takes place. We should be cognizant of the fact that a “one size fits all” approach towards the implementation of ASD research may not be appropriate and therefore it is important that global priorities are contextualized, and protocols and planned interventions are adapted to local needs and experiences. All these are important gaps for research that need to be explored as the COVID-19 pandemic rages on and radically disrupts the schedules and access to services that those on the spectrum have grown to rely on. Gates, B. (2020). Responding to Covid-19 — A Once-in-a-Century Pandemic? New England Journal of Medicine, Feb 28. http://dx.doi.org/10.1056/NEJMp2003762. [Epub ahead of print] Lee, J. (2020). Mental health effects of school closures during COVID-19. www.thelancet.com/child-adolescent. Published online April 14, 2020. http://dx.doi.org/10.1016/S2352-4642(20)30109-7 Thompson, S. (1994). Infectious diarrhoea in children: controlling transmission in the child care setting. Journal of Paediatrics and Child Health, 30(3), 210–219. Uganda Ministry of Health. Coronavirus (pandemic) Covid 19. [cited May 15 2020] Available from: https://www.health.go.ug/covid/ United Nations Policy Brief: The impact of COVID-19 on children. 15 April 2020. [cited May 15 2020] Available from: https://unsdg.un.org/resources/policy-brief-impact-covid-19-children. World Health Organization. (2020). Coronavirus disease (COVID-19) Pandemic. Rolling updates. [cited May 15 2020]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019 The definition of autism is highly related to social life. Covid-19 crisis, beyond the infectious aspects, brought a dramatic change in social life either through the lockdown for several weeks in many countries or through a drastic limitation of physical contact that will probably prevail for an important period of time. Therefore, studying the social impact of Covid-19 on autism seems compelling. The COVID-19 pandemic has had an enormous impact on our region, with notable repercussions on practically all areas of social and community life. The reports worldwide inform that no vaccination or cure for the COVID-19 will be available for at least the next 12-18 months. This fact is already changing the way that society is conducted and the autism communities which support people with ASD will be challenged to understand the situation and develop new ways of participating, alongside people with ASD, in social life while maintaining the physical distance needed for prevention. The context has changed for research and although the research questions that have been raised previously will likely remain largely untouched, it is possible that some topics will become more relevant than before (e.g. tele-healthcare procedures in screening, evaluation and intervention). New questions will also arise due to this situation (e.g. research focused on situations of crisis). We are now witnessing a great proliferation of studies aiming to understand the experience of families in the context of confinement with limited access to community services [Kong, 2020; Narzisi, 2020; Stankovic et al., 2020; Szabo et al., 2020]. Furthermore, it will be necessary to adapt working procedures within labs to make them more hygienic as well as redoubling efforts to make people feel comfortable and trusted within the health services, research, and facilities. Another aspect observed not only in our field, but in the field of biomedical and health research in general, is the risk of losing scientific rigor in these moments of crisis. It is true that we are living in times when science is asked to respond quickly by providing actionable information to help society deal with this situation effectively. However, It is a great challenge that should not lead us to fall into the real risk of throwing caution to the wind in such an exceptional situation, at the cost of overgeneralizing effective treatments tested on small samples or relaxing criteria for randomization procedures and blind systems in clinical trials in response to these circumstances [London & Kimmelman, 2020]. Lastly, the effect of this pandemic varies from country to country. Countries with less resources are affected especially regarding the provision of essential services. It is important to highlight the responsibility of researchers to create new networks of cooperation to develop research projects that can bring essential resources to where they are needed without overlooking the perspective of people with autism and their families. We hope that inclusive international cooperation efforts will be established in order to develop capabilities such as new, less costly evaluation methods, and intervention models that can be implemented with affordable technologies. Society will need to re-learn how to work together at a distance, even if it means reflecting on what has been done thus far, because it is paramount that we better understand our current and future situations and their changing needs. Kong, M. (2020). What COVID-19 means for non-neurotypical children and their families. Pediatric Research, 1-3. http://dx.doi.org/10.1038/s41390-020-0913-7 London, A. J., & Kimmelman, J. (2020). Against pandemic research exceptionalism. Science, 368(6490), 476-477. http://dx.doi.org/10.1126/science.abc1731 Narzisi, A. (2020). Handle the autism spectrum condition during Coronavirus (COVID-19) stay at home period: Ten tips for helping parents and caregivers of young children. Brain Science, 10(4), 207. http://dx.doi.org/10.3390/brainsci10040207 Stankovic, M., Jelena, S., Stankovic, M., Shih, A., Stojanovic, A., & Stankovic, S. (2020). The Serbian Experience of Challenges of Parenting Children with Autism Spectrum Disorders During the COVID-19 Pandemic and the State of Emergency with the Police Lockdown. Available at SSRN 3582788. Szabo, T. G., Richling, S., Embry, D. D., Biglan, A., & Wilson, K. G. (2020). From helpless to hero: Promoting values-based behavior and positive family interaction in the midst of Covid-19. Behavior Analysis in Practice, 1-9. The COVID-19 pandemic presented ASD clinicians and clinical researchers with unique challenges. With social communication as the defining feature of ASD, both diagnostic examination and therapeutic intervention suffer in the absence of direct social contact in this era of social distancing. The need for diagnostic assessments (e.g., for educational placements or state-funded support) has not diminished, and the need for intervention may have even increased (albeit with changes in focus). In Israel, a central platform that has been widely used is video conferencing which has been harnessed for the provision of diagnostic and therapeutic services. This method presented clinicians with new challenges, which by themselves call for research examination. Diagnosticians faced the challenge of real-time assessment of the client. How could gold standard instruments such as the ADOS [Lord et al., 2012] be administered online? How could non-verbal behaviours and social reciprocity be assessed this way? What constitutes a normative behaviour and what could be marked as abnormal? Could online platforms conceal subtle symptom manifestations that might have been tracked face-to-face? Therapists of different disciplines, employing a wide variety of intervention programs, faced their own dilemmas, to name a few: How could an early intervention program be implemented without its trained team? How could treatments requiring clinic-based equipment be implemented? What does social-skills training look like at a time of social distancing? Recently, Israeli clinicians have been allowed to meet clients face to face again. However, the lessons that could be learned from the current crisis may project far beyond its emergency context and extend the availability of diagnostic and intervention services for individuals with ASD even when routine is regained. If clinicians continue to use technological platforms for the provision of services, many families who are geographically distant, or are deterred from coming to clinical centers could benefit from services that have previously been scarcely provided. The provision of technology-based, or telehealth, training and therapy services for individuals with ASD and their families is not new, and its effectiveness has received some support by research [Antezana et al., 2017; Sutherland et al., 2018]. Another form of distant intervention is available through research supported technology-aided intervention programs, supporting skill acquisition in various areas of functioning [Steinbrenner et al., 2020]. With regards to diagnostic assessment, some work has supported the effectiveness of online screening of ASD [e.g., Halim et al., 2020] though others have warned against the sole reliance on online formats [Kanne & Bishop, 2020]. Indeed, research validating an online diagnostic assessment is still needed. A major lesson of COVID-19 may be the need for the mainstreaming of online clinical services. To maintain high service quality, clinical research would need to provide better understanding of normative (and age and gender appropriate) online social behaviour, to provide artificial intelligence tools to support online clinical decision making, and to examine the efficacy of diagnostic assessments and interventions provided online, compared to research-supported clinic-based services. Contrary to raised worries, such services do not necessarily exclude clinicians from the picture, but could rather support their work, extend their reach, and provide high-quality services online, in sickness and in health. Antezana, L., Scarpa, A., Valdespino, A., Albright, J., & Richey, J. A. (2017). Rural trends in diagnosis and services for autism spectrum disorder. Frontiers in Psychology, 8, 590. Halim, A., Ford, G., Liu-Mayo, S., Glover, E., & Wall, D. P. (2020). Multi-modular AI Approach to Streamline Autism Diagnosis in Young Children. Scientific Reports, 10:5014. http://dx.doi.org/10.1038/s41598-020-61213-w Kanne, S. M., & Bishop, S. L. (2020). Editorial Perspective: The autism waitlist crisis and remembering what families need. Journal of Child Psychology and Psychiatry. http://dx.doi.org/10.1111/jcpp.13254 Lord, C., Rutter, M., DiLavore, P.C., Risi, S., Gotham, K., & Bishop, S. (2012). Autism diagnostic observation schedule, second edition (ADOS-2). Torrance, CA: Western Psychological Services. Sutherland, R., Trembath, D., & Roberts, J. (2018). Telehealth and autism: A systematic search and review of the literature. International Journal of Speech-Language Pathology, 20(3), 324-336. Steinbrenner, J. R., Hume, K., Odom, S. L., Morin, K. L., Nowell, S. W., Tomaszewski, B., Szendrey, S., McIntyre, N. S., Yücesoy-Özkan, S., & Savage, M. N. (2020). Evidence-based practices for children, youth, and young adults with Autism. The University of North Carolina at Chapel Hill, Frank Porter Graham Child Development Institute, National Clearinghouse on Autism Evidence and Practice Review Team. What struck me most is how sudden the whole situation changed. On Friday March 6, 2020, I gathered with about 300 fellow Belgian geneticists in a conference hall in the capital city of Brussels for our annual meeting. Except that perhaps fewer kisses were shared as a typical Belgian greeting ceremony, the meeting format was entirely like it always had been. Exactly one week later, on Friday the 13, I was lecturing to about 20 students, as teaching for smaller groups was still allowed (!), be it in a bigger hall to a