Abstract
COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In this review, we highlight the potential role of additional factors in CCP that can be either beneficial (e.g., AT-III, alpha-1 AT, ACE2+ extracellular vesicles) or detrimental (e.g., anti-ADAMTS13, anti-MDA5 or anti-interferon autoantibodies, pro-coagulant extracellular vesicles). Variations in these factors in CCP may contribute to varied outcomes in patients with COVID-19 and undergoing CCP therapy. We advise careful, retrospective investigation of such co-factors in randomized clinical trials that use fresh frozen plasma in control arms. Nevertheless, it might be difficult to establish a causal link between these components and outcome, given that CCP is generally safe and neutralizing antibody effects may predominate.
Highlights
At the end of 2019, a novel flu-like coronavirus (CoV), named severe acute respiratory syndrome (SARS)-CoV-2 causing Coronavirus Disease 2019 (COVID-19), was associated with an epidemic initially focused on Wuhan, China
Several randomized and nonrandomized controlled trials were published last year, overall documenting that COVID-19 convalescent plasma (CCP), if administered at high-titer (>1:160 anti-SARS-CoV-2 neutralizing antibodies and at early onset (
We focus on large case series that help assess the prevalence of autoantibodies
Summary
At the end of 2019, a novel flu-like coronavirus (CoV), named severe acute respiratory syndrome (SARS)-CoV-2 causing Coronavirus Disease 2019 (COVID-19), was associated with an epidemic initially focused on Wuhan, China. As a consequence of worldwide spread, COVID-19 was declared a pandemic by the World Health Organization (WHO, Geneva, Switzerland) on 11 March 2020 [1] This new virus represented a major challenge for clinicians because it had no specific pre-existing therapy. Therapeutic efforts were initially focused on optimizing respiratory care, managing thrombotic and inflammatory complications using anticoagulation and corticosteroids, and repurposing existing antiviral therapies [2]. Most these initially promising agents (i.e., hydroxychloroquine and lopinavir/ritonavir) showed limited clinical benefit [3].
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