Convalescent plasma therapy for COVID-19

As of April 2nd, 2020, the total number of confirmed COVID-19 cases in the United States exceeds 200,000 andis escalating rapidly. The Institute for Health Metrics and Evaluation projects that COVID-19 cases in the US willsurge mid-to-late April, leading to hospitalization of as many as 2.4 to 21 million people; numbers that willoverwhelm the US healthcare system. Confronted with a pandemic that threatens the lives of millions, with novaccines or effective drugs in sight, the clinical community is evaluating convalescent plasma/serum as an urgentcountermeasure to thwart new infections and ameliorate COVID-19 related morbidity and mortality.The number of recovered individuals in the US is at present 8,500 and as these numbers continue to grow, sowill the availability of plasma rich in SARS antibodies from recovered donors. Infusion of convalescent plasmaprophylactically could immunize health care workers against nascent infections and therapeutic infusion coulddecrease the likelihood of severe disease in infected patients. As a result, several academic medical centersacross the nation have begun trials to use convalescentplasma to treat patients, with many hospitals in NewYork starting treatments this week.Given the potential for broad implementation of convalescent plasma therapy in the US in the coming weeksthere is an urgent need to evaluate the prophylactic and therapeutic ability of convalescent plasma as a stand-alone treatment against COVID-19 using an animal model where timing and dose of infection can be controlled;immunopathology to organ systems can be rigorously assessed by collection of tissue biopsies, and where re-challenge experiments can critically evaluate long-term impact of convalescent plasma therapy on protectiveimmunity.The goals of this study are to determine if human plasma from convalescent COVID 19 patients preventsprimary infection, decreases viremia in the event of breakthrough infections, and alters susceptibility toa secondary challenge. We are collaborating with UCD Health clinicians who are conducting human trial titled:Convalescent Plasma to Stem Coronavirus. We will use an aliquot of the same plasma used in human trials forour rhesus studies. We will inoculate rhesus monkeys with the Davis SARS-CoV-2 isolate (2019-nCoV/USA-CA9/2020; GenBank: MT118835.1) to address these questions within a timeline of 30 days.Urgency and relevance to Emergency Guide Notice: Our animal studies will critically inform efficacy in theshort term and potential risks in the long term of convalescent plasma therapy within 30 days. These criticalanswers can only be rigorously obtained in the setting of controlled animal experiments, and therefore thesestudies are highly urgent as convalescent plasma use becomes a widespread medical countermeasure againstCOVID-19 in the coming weeks. The proposed studies will lay the groundwork for evaluating the "window ofopportunity" during which time plasma therapy would be effective post-infection so that plasma infusion maybe maximized for clinical benefit as these animal studies will provide answers within a month.