When a Viral Pneumonia Becomes a Hematology Problem: Birth of the ASH COVID-19 Research Agenda for Hematologists

For many hematologists, our first awareness of COVID-19 was in early January 2020 via reports of a new viral pneumonia with similarities to the severe acute respiratory syndrome (SARS) that caused the pandemic of 2002. Initial data suggested that the disease caused by SARS-CoV-2 was mild. On January 14, Science reported “no evidence that the virus is easily passed between humans.”¹  In essence, COVID-19 was something best addressed by our counterparts at the American Society of Virology or American Lung Association while we watched from our already busy hematology-focused offices, clinics, and laboratories. Plans for the 2020 ASH Annual Meeting were fully underway, with exciting educational and scientific sessions in hematologic malignancies, hematopoiesis, precision medicine, and other hematologic disciplines.

By March 1, the world had changed. The World Health Organization had identified SARS-CoV-2 infections in almost 60 countries,²  bringing COVID-19 straight to the doorstep of ASH. Always vigilant about the impact of infection on patients with blood disease, hematologists quickly raised concerns about patients with malignancy, and the ASH Research Collaborative COVID-19 Registry (www.ashresearchcollaborative.org/s/covid-19-registry) was mobilized to better define these risks. At the same time, ominous clinical features raised additional concerns among the ASH community. The recognition that COVID-19 disproportionally impacts African Americans sounded alarms about people living with sickle cell disease and the potential bidirectional relationship of these diseases. Reports of abnormal biomarkers of coagulation (e.g., D-dimer) and high rates of blood clots in patients with COVID-19 immediately captured the attention of thrombosis specialists. Concerns intensified after fibrin and platelet aggregates were observed in the lungs of patients who died of COVID-19, suggesting that thrombosis contributed directly to COVID-19 lung pathology and death. Subsequent reports of a Kawasaki-like multisystem inflammatory syndrome in children, “COVID toes,” and cutaneous manifestations signaled that COVID-19 can cause an underlying vasculopathy, even in patients without overt symptoms. Collectively, the diverse and complicated sequelae seen in patients with COVID-19 exposed significant gaps in our understanding of infection, inflammation, and blood disease, placing ASH at the forefront of the battle with COVID-19.

The ASH Research Agenda (www.hematology.org/research/ash-agenda-for-hematology-research) is a forward-looking document used as a roadmap to prioritize research and enlist support for the hematology community. This umbrella document articulates fundamental questions that experts in hematology and blood research deem critically important to researchers, physicians, and patients. Recognizing the importance in hematology of understanding COVID-19 infection, the ASH Committee on Scientific Affairs developed the ASH COVID-19 Research Agenda for Hematology (www.hematology.org/research/ash-agenda-for-hematology-research/ash-covid-19-research-agenda-for-hematology). This curated list identifies urgent questions related to COVID-19 diagnosis, pathogenesis, and therapy, that call on the expertise of ASH members and scientific committees. Action items posed by the agenda seek to understand the underlying blood and vascular biology of COVID-19, define particular risks of COVID-19 infection for patients with hematologic diseases, and develop anticoagulant and immunotherapy-based treatment and prevention paradigms for patients with COVID-19. The agenda focuses on six major themes, summarized below:

• 1. Coagulation, thrombosis, and COVID-19. The mechanisms leading to arterial thrombosis, venous thromboembolism, and small vessel thrombosis; optimizing the intensity and duration of anticoagulant therapy.

• 2. Epidemiology and health disparities. How age, underlying health issues, and socioeconomic factors influence testing, care, and treatment influence risk of infection and outcomes in populations with hematologic diseases.

• 3. Inflammatory signaling, cytokine release, and COVID-19 disease. The (patho)biological basis of inflammatory mediators, therapeutic potential for immunomodulators, and implications for adverse outcomes in patients with hematologic diseases.

• 4. Impact of hematopoiesis and hematopoietic dysfunction on COVID-19 infection and illness. The effects of COVID-19 on stem cell, myeloid, and lymphoid function, and how disorders in hematopoiesis influence infection pathogenesis.

• 5.Transfusion medicine and convalescent plasma. The effect of convalescent plasma and immunotherapy on treatment and/or protection against COVID-19.

• 6. Hematologic malignancies and COVID-19. The impact of malignancies and their treatment on COVID-19 susceptibility and response, and whether COVID-19 impacts cancer development, progression, and treatment.

The ASH COVID-19 Research Agenda for Hematology will be used to guide the development of webinars, podcasts, and scientific and educational content at the 2020 ASH Annual Meeting and beyond. It will also be used as a framework to support advocacy efforts, ensuring that hematologists have the resources needed for patient care and the support for clinical and translational studies in COVID-19 infection.

The ASH Research Agenda is a living document that undergoes review and revision at least every three years. Given the rapidly changing landscape of the current pandemic, the ASH COVID-19 Research Agenda for Hematology will surely require even more frequent revisions. We remain vigilant of new information as the disease unfolds, and we welcome suggestions to make the COVID-19 Agenda a valuable resource for the ASH community.