Publications - September 2021
Preprint and peer-reviewed publications from RECOVER’s studies
Does 2 units of ABO-compatible, high-titer convalescent plasma, administered to critically ill patients with COVID-19, improve organ support–free days up to day 21 (a composite end point of in-hospital mortality and the duration of intensive care unit–based respiratory or cardiovascular support)? This international bayesian randomized clinical trial that included 2011 participants treated with 2 units of high-titer convalescent plasma, compared with no convalescent plasma, resulted in a posterior probability of futility of 99.4% for the primary outcome of organ support–free days up to day 21.
The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) is a global federation of clinical research networks that work collaboratively to prevent illness and deaths from infectious disease outbreaks. In 2014, we proposed that effective and timely research during outbreaks of emerging infections would benefit from pre-prepared research tools, global collaboration, and research-ready clinical networks.1 After applying this research model to several outbreaks, and particularly the COVID-19 pandemic, we can now explore what has been achieved to date.
The animal reservoir of SARS-CoV-2 is unknown despite reports of various SARS-CoV-2-related viruses in Asian Rhinolophus bats, including the closest virus from R. affinis, RaTG13. Several studies have suggested the involvement of pangolin coronaviruses in SARS-CoV-2 emergence. SARS-CoV-2 presents a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain (RBD) to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range. SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 pathway have not yet been identified, though they would be key in understanding the origin of the epidemics. Here we show that such viruses indeed circulate in cave bats living in the limestone karstic terrain in North Laos, within the Indochinese peninsula.
The majority of emerging infectious diseases originate in animals. Current routine surveillance is focused on known diseases and clinical syndromes, but the increasing likelihood of emerging disease outbreaks shows the critical importance of early detection of unusual illness or circulation of pathogens - prior to human disease manifestation. In this Viewpoint, we focus on one key pillar of preparedness—the need for early warning surveillance at the human, animal, environmental interface.